Innate and acquired immunology Innate and acquired (also known as Cell Types of Innate and Adaptive Immunity

ive Immunity Innate Immunity Cells

adaptive) immunity are the two main categories of the immune system in Macrophages: Engulf and digest cellular debris and pathogens. They also
vertebrates, including humans. Each serves distinct functions and present antigens to T cells, linking innate and adaptive immunity.
operates through different mechanisms. Here’s a detailed look at both: Neutrophils: The most abundant type of white blood cells that rapidly
Innate Immunity; respond to sites of infection by ingesting and killing pathogens. Dendritic
Characteristics: Non-specific: Innate immunity provides a generalized Cells: Capture antigens and deliver them to lymph nodes, serving as antigen-
defense against pathogens, not targeted to any specific organism. presenting cells that activate T cells. Natural Killer (NK) Cells: Recognize
Immediate response: It is the body's first line of defense, responding and kill virus-infected cells and tumor cells by detecting the lack of "self"
immediately or within hours after exposure to an antigen.No memory: It markers and stress molecules released by infected cells. Basophils and
does not have immunological memory; hence the response is the same Eosinophils: Involved in the response to allergens and parasitic infections,
each time the body encounters a pathogen. Components: Physical respectively, and contribute to inflammation and allergic reactions
barriers: Skin, mucous membranes, and the epithelial lining of the Adaptive Immunity Cells
gastrointestinal, respiratory, and genitourinary tracts. Chemical barriers: B Cells: Produce antibodies that neutralize pathogens or mark them for
Acids in the stomach, enzymes in tears and saliva, and various destruction. They are essential for humoral immunity. , Lymphocyte
antimicrobial peptides. Cellular defenses: Phagocytes (like Trafficking Lymphocyte trafficking is the process by which lymphocytes
macrophages and neutrophils), natural killer (NK) cells, and dendritic
circulate from blood to various tissues and lymphoid organs, a mechanism
cells. Inflammatory response: Triggered by tissue damage and
infection, leading to redness, heat, swelling, and pain, which help isolate critical for effective immune surveillance and response. Key steps include:
infected areas and recruit immune cells Homing: Lymphocytes use specific adhesion molecules to enter lymphoid
. Acquired (Adaptive) Immunity Characteristics: tissues (like lymph nodes) from the bloodstream. Chemokines and
Specificity: Acquired immunity is highly specific to particular antigens. Cytokines: These molecules guide the movement of lymphocytes within
Once an antigen is recognized, the immune system can target it
tissues and towards sites of infection or inflammation.
precisely. Memory: After an initial response to a specific pathogen, the
adaptive immune system creates an army of immune cells specifically Phagocytosis Phagocytosis is a form of endocytosis where cells (primarily
designed to attack that pathogen if it enters the body again. Slower macrophages, neutrophils, and dendritic cells) engulf large particles or
response: It takes time to develop on the first exposure to a new antigen microbes. Steps include: Recognition and Attachment: Phagocytes
but provides a rapid response upon subsequent exposures. recognize pathogens through pattern recognition receptors (PRRs) that
Components: Lymphocytes: B cells and T cells are the primary cells
detect pathogen-associated molecular patterns (PAMPs). Engulfment: The
involved. B cells (Humoral Immunity): Produce antibodies that are
released into the bloodstream and lymph, binding to antigens to phagocyte membrane surrounds the pathogen, forming a phagosome.
neutralize them or mark them for destruction. T cells (Cell-mediated Killing and Degradation: The phagosome fuses with lysosomes to form a
Immunity): Helper T cells (CD4+): Activate other T cells and B cells and phagolysosome, where the pathogen is killed and digested by enzymes.
regulate the immune response. Cytotoxic T cells (CD8+): Destroy virus- Inflammation Inflammation is an essential part of the innate immune
infected cells and cancer cells. Regulatory T cells: Modulate the
response to infection and injury, characterized by: Redness, Heat, Swelling,
immune response and help prevent autoimmunity. Antigens: Substances
that can elicit an immune response, typically proteins or polysaccharides Pain, and Loss of Function: These classical signs are due to increased blood
on the surfaces of viruses, bacteria, or other pathogens. flow, vascular permeability, and the influx of immune cells to the site of
injury or infection.

Humoral immuni , Antibody Production and Function:

Neutralization: Antibodies can neutralize pathogens by binding to and
Humoral immunity is one of the main branches of the adaptive blocking the parts of the pathogen essential for infecting cells.
immune system, primarily involving B cells and the production of Opsonization: Antibodies coat pathogens, making them more attractive
antibodies. This type of immunity is critical for defending against targets for phagocytes like macrophages and neutrophils.
bacteria, viruses, and other pathogens present in extracellular fluids
like blood and lymph. Here’s a detailed look at how humoral immunity Complement Activation: Antibody binding can initiate the complement
works: Key Components of Humoral Immunity B Cells: These are cascade, a series of protein interactions that results in the lysis (bursting) of
receptor (BCR) on its surface, which can bind to a specific antigen. the pathogen’s cell membrane.

Antibodies (Immunoglolymphocytes that develop and mature in the Antibody-dependent cellular cytotoxicity (ADCC): Natural killer (NK) cells
bone marrow. Each B cell expresses a unique B cell bulins): These are recognize antibodies on the surface of infected cells and kill them.
proteins produced by plasma cells (differentiated B cells) in response
to an antigen. Antibodies are secreted into the bloodstream and Types of Antibodies Humans produce several classes of antibodies, each
lymphatic system, where they bind to pathogens and neutralize them with a specific function:
or mark them for destruction by other components of the immune IgM: First antibody produced in response to an antigen, prominent in early
system. immune responses.
IgG: Most abundant in blood and extracellular fluid, providing the majority
Process of Humoral Immunity of antibody-based immunity against pathogens.
IgA: Found in mucosal areas, such as the gut, respiratory tract, and
Antigen Encounter and Activation: When a B cell's receptor recognizes urogenital tract, as well as in saliva, tears, and breast milk.
and binds to its specific antigen (such as a part of a virus or bacteria), IgE: Involved in allergic reactions and responses to parasitic infections.
the B cell is activated. This process is often aided by helper T cells IgD: Functions mainly as a receptor on immature B cells, and its role is not
(CD4+ T cells), which provide necessary additional signals through fully understood.
direct contact and cytokine release.
Memory in Humoral Immunity
B Cell Proliferation and Differentiation: Once activated, B cells
proliferate (clone) and differentiate into plasma cells and memory B Memory B cells play a crucial role in the long-term protection provided by
cells. Plasma cells are short-lived cells that produce large quantities of vaccines and previous infections. Upon re-exposure to the same antigen,
antibodies. Memory B cells remain in the body for years, ready to memory B cells rapidly differentiate into plasma cells and produce
respond more rapidly and robustly should the same antigen be antibodies much quicker and in greater quantities than during the first
encountered again. exposure, often
The B Cell Activation and Differentiation Primary Humoral Response When an antigen is encountered for the first
B cells, a fundamental component of the adaptive immune system, time, it initiates the primary humoral response. Here’s how it typically
undergo a complex process of activation, proliferation, and unfolds: Lag Phase: There is an initial period, typically lasting several days,
differentiation upon encountering their specific antigen. during which no significant antibody production is detected. This period is
Here’s how this process unfolds: necessary for the antigen to activate naïve B cells that have receptors
1. Activation specific for that antigen. Activation of Naïve B Cells: B cells with receptors
Antigen Recognition: Each B cell bears unique B cell receptors (BCRs) that recognize the antigen are activated. This process often requires help
on its surface. Activation begins when a BCR specifically binds to an from T helper cells (CD4+ T cells), which recognize the antigen presented
antigen. This is a precise match; each BCR recognizes a distinct on MHC-II molecules on B cells and provide necessary additional signals.
antigenic determinant or epitope. Receptor-Mediated Endocytosis: Clonal Expansion and Differentiation: Activated B cells proliferate and
After antigen binding, the BCR-antigen complex is internalized into the differentiate into plasma cells and memory B cells in lymphoid tissues.
B cell. This allows the B cell to process the antigen and present Plasma cells start producing antibodies, while memory B cells will persist
peptide fragments of it on its surface bound to major long-term. Antibody Production: The first antibodies produced are
histocompatibility complex class II (MHC-II) molecules. T Cell Help: For predominantly of the IgM class, followed by a class switch to IgG, IgA, or
most antigens, particularly proteins, B cell activation requires help IgE, depending on cytokine signals from helper T cells and the nature of
from T cells (specifically, helper T cells, CD4+). These T cells recognize the antigen. The overall amount of antibodies produced in the primary
the antigen-MHC-II complex on the B cell. They provide additional response is relatively modest. Peak and Decline: Antibody levels rise over a
activation signals through direct contact (via CD40 ligand binding to period of 1-2 weeks, peak, and then gradually decline as the antigen is
CD40 on B cells) and secreting cytokines like IL-4 and IL-21. 2. cleared and plasma cells begin to die off. Secondary
Proliferation and Differentiation Humoral Response - Upon re-exposure to the same antigen, the immune
Clonal Expansion: Once fully activated, B cells proliferate, producing system mounts a secondary humoral response, which is more rapid and
clones of themselves that all recognize the same antigen. effective than the primary response: Rapid Activation: Memory B cells
Differentiation into Plasma Cells and Memory B Cells: Plasma Cells: generated during the primary response are quickly reactivated. Because
Most of the proliferated B cells differentiate into plasma cells, which these cells are already primed to recognize the antigen, the lag phase is
are highly specialized for producing and secreting large quantities of significantly shortened or absent. Higher Antibody Levels: The secondary
antibodies. These antibodies are soluble forms of the BCRs and have response produces a much higher concentration of antibodies than the
the same antigen specificity. Memory B Cells: A smaller fraction of the primary response. This is due to the larger number of memory B cells and
cells becomes memory B cells. These cells do not secrete antibodies their readiness to differentiate into antibody-secreting plasma cells.
but remain in the lymphoid tissues, ready to initiate a rapid and Antibody Class and Affinity: The antibodies produced during the secondary
robust response if the antigen is encountered again. response are predominantly IgG in many cases, though IgA or IgE might
predominate depending on the site and type of antigen. These antibodies
generally have a higher affinity for the antigen due to affinity maturation

Cell-mediated immunity is a critical component of the adaptive T-cell development and activation are fundamental processes in the
immune system, primarily involving T cells rather than antibodies adaptive immune system, ensuring that T cells are equipped to recognize
(which are central to humoral immunity). This type of immunity is and respond to specific antigens. Here's an overview of T-cell development
essential for fighting intracellular pathogens such as viruses, some and activation: T-Cell Development: T-cell development takes place
bacteria, and fungi, as well as for combating tumor cells. It also plays a primarily in the thymus, a specialized organ located in the chest. The
role in transplant rejection and in the regulation of immune process involves several stages of maturation and selection to generate a
responses. diverse repertoire of functional T cells: Thymic Entry: Immature T cells,
called thymocytes, originate from hematopoietic stem cells in the bone
Key Features of Cell-Mediated Immunity
marrow. They migrate to the thymus through the bloodstream. Positive
T Cells: The primary cells involved in cell-mediated immunity are T Selection: Thymocytes undergo positive selection in the thymic cortex,
lymphocytes, which mature in the thymus and are distinguished by where they are tested for their ability to recognize self-major
their T-cell receptors (TCR). There are several types of T cells, each histocompatibility complex (MHC) molecules. Only thymocytes that express
playing unique roles: T-cell receptors (TCRs) capable of weakly binding to self-MHC molecules
survive this selection process. Negative Selection: Thymocytes that strongly
CD8+ Cytotoxic T Cells: These cells directly kill infected or bind to self-MHC molecules presenting self-antigens undergo negative
dysfunctional cells by recognizing antigens presented by MHC class I selection, leading to apoptosis (cell death). This process occurs in the
molecules. thymic medulla and helps prevent the development of T cells that could
cause autoimmune reactions. Maturation: Surviving thymocytes mature
CD4+ Helper T Cells: They assist other cells of the immune system, into CD4+ helper T cells or CD8+ cytotoxic T cells, depending on the type of
including B cells and CD8+ T cells, by producing cytokines and co-receptor (CD4 or CD8) they express in addition to the TCR. Exit from the
enhancing their responses. Regulatory T Cells (Tregs): These cells help Thymus: Mature T cells leave the thymus and enter the circulation, where
maintain immune tolerance and prevent autoimmune responses by they can encounter antigens and become activated in peripheral lymphoid
suppressing other immune cells. Antigen Presentation: Unlike B cells, tissues. T-Cell Activation:T-cell activation occurs when mature T cells
T cells do not recognize free-floating antigens. Instead, they recognize encounter specific antigens presented by antigen-presenting cells (APCs),
small peptides presented on the surface of cells by major such as dendritic cells, macrophages, or B cells. The process involves
histocompatibility complex (MHC) molecules. MHC Class I: Found on several steps: Antigen Recognition: T-cell activation begins when the T-cell
all nucleated cells, present peptides derived from intracellular receptor (TCR) on a mature T cell binds to a specific peptide antigen
proteins to CD8+ cytotoxic T cells. presented by an MHC molecule on the surface of an APC. CD4+ T cells
recognize peptides presented by MHC class II molecules, while CD8+ T cells
MHC Class II: Expressed mainly on professional antigen-presenting recognize peptides presented by MHC class I molecules. Co-stimulation: In
cells (APCs) like dendritic cells, macrophages, and B cells, present addition to TCR engagement, co-stimulatory signals are required for full T-
peptides derived from extracellular proteins to CD4+ helper T cells. cell activation. Co-stimulatory molecules on the APC, such as CD80 and
CTL and NK cell mediated immunity : Cytotoxic T lymphocytes (CTLs) CTL and NK cell mediated immunity : Cytotoxic T lymphocytes (CTLs) and
and natural killer (NK) cells are key players in the immune system's natural killer (NK) cells are key players in the immune system's defense
defense against infected or abnormal cells. While both are involved in against infected or abnormal cells. While both are involved in cell-
cell-mediated immunity and share some similarities, they have mediated immunity and share some similarities, they have distinct
distinct origins, mechanisms, and roles in immune responses. Let's origins, mechanisms, and roles in immune responses. Let's explore CTL
explore CTL and NK cell-mediated immunity: CTL (Cytotoxic T and NK cell-mediated immunity: CTL (Cytotoxic T Lymphocytes): Origin
Lymphocytes): Origin and Development: CTLs develop from immature and Development: CTLs develop from immature T cells (thymocytes) in
T cells (thymocytes) in the thymus during T-cell maturation. They the thymus during T-cell maturation. They mature into cytotoxic effector
mature into cytotoxic effector cells under the influence of cytokines cells under the influence of cytokines and antigen recognition.
and antigen recognition. Activation: CTLs are activated when their T- Activation: CTLs are activated when their T-cell receptors (TCRs)
cell receptors (TCRs) recognize specific peptide antigens presented by recognize specific peptide antigens presented by major
major histocompatibility complex class I (MHC-I) molecules on the histocompatibility complex class I (MHC-I) molecules on the surface of
surface of infected or abnormal cells. Co-stimulatory signals, such as infected or abnormal cells. Co-stimulatory signals, such as those from
those from CD28 binding to CD80/86 on antigen-presenting cells, are CD28 binding to CD80/86 on antigen-presenting cells, are also required
also required for full activation. Effector Functions: Upon activation, for full activation. Effector Functions: Upon activation, CTLs release
CTLs release cytotoxic granules containing perforin and granzymes, cytotoxic granules containing perforin and granzymes, which induce
which induce apoptosis (programmed cell death) in target cells. CTLs apoptosis (programmed cell death) in target cells. CTLs can also express
can also express cell surface death receptors, such as Fas ligand (FasL), cell surface death receptors, such as Fas ligand (FasL), which bind to
which bind to death receptors on target cells, triggering apoptosis death receptors on target cells, triggering apoptosis through the
through the extrinsic pathway. Role in Immune Response: CTLs play a extrinsic pathway. Role in Immune Response: CTLs play a crucial role in
crucial role in eliminating virus-infected cells, intracellular bacteria, eliminating virus-infected cells, intracellular bacteria, and cancer cells.
and cancer cells. They are particularly effective against cells They are particularly effective against cells expressing foreign or
expressing foreign or aberrant antigens on their surfaces, such as aberrant antigens on their surfaces, such as those derived from viruses
those derived from viruses or tumor-specific antigens. NK (Natural or tumor-specific antigens.
Killer) Cells: Origin and Development: NK cells develop from common
lymphoid progenitor cells in the bone marrow. Unlike T cells, NK cell
maturation does not require thymic education or antigen-specific
activation. Activation: NK cells are activated by a balance of activating
and inhibitory signals received through their cell surface receptors.
Activating receptors, such as NKG2D and NKp46, recognize stress-
induced ligands on target cells, signaling for NK cell activation.
Inhibitory receptors, such as killer cell immunoglobulin-like receptors
(KIRs) and CD94/NKG2A, recognize self-MHC-I molecules on healthy
NK (Natural Killer) Cells: Origin and Development: NK cells develop Antigens are substances that can elicit an immune response in the body
from common lymphoid progenitor cells in the bone marrow. Unlike T by interacting with components of the immune system, such as
cells, NK cell maturation does not require thymic education or antibodies, B cells, and T cells. These substances can vary widely in
antigen-specific activation. Activation: NK cells are activated by a nature and origin. Here's a breakdown of the different types of antigens:
balance of activating and inhibitory signals received through their cell Protein Antigens: Proteins are among the most potent and diverse
surface receptors. Activating receptors, such as NKG2D and NKp46, antigens in nature. They can be: Microbial Proteins: Found on the
recognize stress-induced ligands on target cells, signaling for NK cell surface or within pathogens such as bacteria, viruses, fungi, and
activation. Inhibitory receptors, such as killer cell immunoglobulin-like parasites. Examples include viral capsid proteins, bacterial cell wall
receptors (KIRs) and CD94/NKG2A, recognize self-MHC-I molecules on proteins, and toxins. Self-Proteins: Normally present in the body's own
healthy cells, preventing NK cell activation and self-recognition. tissues. Abnormal or altered self-proteins, such as those found in cancer
Effector Functions: Upon activation, NK cells release cytotoxic cells or autoimmune diseases, can also serve as antigens. Foreign
granules containing perforin and granzymes, similar to CTLs, leading Proteins: Introduced into the body from outside sources, such as foods,
to target cell apoptosis. NK cells can also induce target cell death drugs, or allergens. Carbohydrate Antigens: Carbohydrates can also act
through death receptor-mediated pathways, similar to CTLs. Role in as antigens, especially in the context of: Microbial Carbohydrates:
Immune Response: NK cells provide rapid and non-specific immune Present on the surface of bacteria, fungi, and parasites. Examples
responses against virus-infected cells, tumor cells, and cells include bacterial lipopolysaccharides (LPS) and fungal cell wall
undergoing stress or transformation. They serve as the first line of polysaccharides. Blood Group Antigens: Found on the surface of red
defense against infected or abnormal cells before antigen-specific T- blood cells and other tissues, determining blood type compatibility for
cell responses are fully activated. Comparison: CTLs require antigen- transfusions. Lipid and Nucleic Acid Antigens: While less common than
specific activation and recognition of MHC-I-presented antigens, protein and carbohydrate antigens, lipids and nucleic acids can also
whereas NK cells can recognize stressed or abnormal cells without induce immune responses: Lipid Antigens: Found in the cell membranes
prior sensitization. CTLs are part of the adaptive immune system and of certain pathogens and in some allergenic substances. Nucleic Acid
undergo clonal expansion upon activation, while NK cells are innate Antigens: DNA and RNA from pathogens or damaged cells can trigger
immune effectors and do not undergo clonal expansion. Both CTLs immune responses, especially in the context of viral infections. Haptens
and NK cells utilize similar mechanisms, such as the release of and Conjugated Antigens: Some molecules are too small to be
cytotoxic granules and death receptor-mediated pathways, to induce immunogenic on their own but can become antigens when bound to
target cell apoptosis. larger carrier molecules: Haptens: Small molecules such as drugs,
chemicals, or environmental pollutants. When bound to carrier proteins,
they can elicit immune responses. Conjugated Antigens: Antigens
formed by the combination of haptens with carrier proteins, enhancing
their immunogenicity. Autoantigens: These are self-antigens derived
from the body's own tissues. Normally, the immune system is tolerant to
self-antigens and does not mount an immune response against them.
"Skylark" is a poem by water security - conservation of surface and ground water wildlife and causes of extinction

Antigenicity: Immunogenicity:

Antigenicity refers to the ability of a substance, called an antigen, to Immunogenicity refers to the ability of an antigen to induce an immune
specifically bind to components of the immune system, such as response, specifically the production of antibodies or the activation of T
antibodies, B cells, or T cells, and initiate an immune response. Not all cells. While all immunogens are antigens, not all antigens are
antigens are equally antigenic, meaning they do not all evoke the same immunogenic. Factors influencing immunogenicity include: Antigenicity:
level of immune response. Factors influencing antigenicity include: Immunogenicity requires antigenicity, but not all antigenic substances are
sufficiently immunogenic to induce an immune response. For example,
Size and Complexity: Larger and more complex molecules tend to be some antigens may be poorly recognized by the immune system or may
more antigenic because they contain multiple epitopes (antigenic not elicit a strong enough response.
determinants) that can be recognized by different parts of the immune
system. Adjuvants: Substances called adjuvants can enhance the immunogenicity
of antigens by stimulating the immune system and promoting the
Chemical Composition: Certain chemical properties, such as the maturation of antigen-presenting cells (APCs), leading to more robust
presence of specific functional groups or molecular motifs, can enhance immune responses. Common adjuvants include aluminum salts, oil-in-
or diminish antigenicity. For example, proteins and carbohydrates are water emulsions, and toll-like receptor agonists.
generally more antigenic than simple molecules like sugars or lipids.
Genetic Factors: Genetic differences between individuals can influence
Foreignness: Antigens that are perceived as foreign to the body's their immune responses to antigens. Some people may have genetic
immune system, such as those from pathogens or transplanted tissues, variations that predispose them to stronger or weaker immune responses
are typically more antigenic than self-antigens. However, self-antigens to specific antigens.
can become immunogenic in autoimmune diseases.
Dose and Route of Administration: The dose and route of antigen
Stability: Antigens that are stable and resistant to degradation are more exposure can impact immunogenicity. Higher doses or repeated
likely to persist in the body and stimulate a prolonged immune exposures to an antigen may lead to stronger immune responses, while
response. certain routes of administration may enhance immune activation.

Route of Exposure: The route through which an antigen enters the body Patient Characteristics: Factors such as age, health status, and immune
can influence its antigenicity. For example, antigens encountered in the competence can influence an individual's ability to mount an immune
bloodstream or lymphatic system may elicit stronger immune response to antigens. For example, infants and elderly individuals may
responses compared to those encountered in the skin or mucous have weaker immune responses compared to healthy adults.
membranes.

B cell epitopes are specific regions within antigens that are recognized T Cell Epitopes:
by B cells triggering an immune response. Haptens, on the other hand,
are small molecules that are not immunogenic on their own but can Linear Epitopes: Similar to B cell epitopes, T cell epitopes can be linear
become immunogenic when they bind to carrier molecules. Here are sequences of amino acids within the antigenic protein. They are
the characteristics of B and T cell epitopes and haptens: recognized by the T cell receptor (TCR) on the surface of T cells. MHC
Binding: T cell epitopes must be presented by major histocompatibility
complex (MHC) molecules on the surface of antigen-presenting cells
(APCs) for recognition by T cells. MHC class I molecules present peptides
B Cell Epitopes: to CD8+ cytotoxic T cells, while MHC class II molecules present peptides
to CD4+ helper T cells. Processing and Presentation: T cell epitopes are
Linear Epitopes: These epitopes consist of a continuous sequence of
generated through the degradation of proteins by proteases within APCs.
amino acids within the antigenic protein. They are typically recognized
The resulting peptides are then loaded onto MHC molecules and
by the B cell receptor (BCR) on the surface of B cells.
presented on the cell surface for T cell recognition. Activation of T Cells:
Upon recognition of an epitope-MHC complex, T cells become activated
Conformational Epitopes: Also known as discontinuous epitopes, these
and undergo clonal expansion. CD4+ T cells provide help to B cells and
epitopes are formed by spatially adjacent amino acids that come
other immune cells, while CD8+ T cells directly kill infected or abnormal
together when the protein folds into its native conformation. They are
cells.
recognized by the BCR when the antigen is in its native three-
dimensional structure.
Haptens: Small Size: Haptens are small molecules that are typically too
small to elicit an immune response on their own. Examples include drugs,
Antigenic Specificity: B cell epitopes can be specific to certain regions or
chemicals, and environmental pollutants. Lack of Immunogenicity:
domains of a protein, depending on the antigen's structure and the
Haptens do not possess the necessary complexity or structure to directly
arrangement of its amino acids.
interact with immune receptors such as BCRs or TCRs. Binding to Carrier
Recognition by Antibodies: Upon recognition of an epitope, B cells are Molecules: Haptens become immunogenic when they bind covalently or
activated and differentiate into plasma cells, which produce antibodies non-covalently to larger carrier molecules, such as proteins or
specific to the epitope. These antibodies can bind to the epitope and polysaccharides. The carrier molecule provides the necessary complexity
mediate immune responses, such as neutralization, opsonization, or and structure for immune recognition. Induction of Immune Response:
complement activation. Once bound to a carrier molecule, haptens can induce the production of
antibodies or T cell responses specific to the hapten-carrier complex.
These immune responses can lead to allergic reactions, contact
hypersensitivity, or autoimmune responses.
Super antigen and its role in T cell activation::: Superantigens are a class Antigen processing and presentation:: Antigen processing and
of antigens that have the unique ability to activate a large proportion of T presentation is a crucial aspect of the immune system's ability to
cells, regardless of their specificity for the antigen being presented. recognize and respond to pathogens, abnormal cells, and foreign
Unlike conventional antigens, which are processed and presented by substances. This process involves the digestion of antigens into peptide
antigen-presenting cells (APCs) to specific T cell receptors (TCRs), fragments, their loading onto major histocompatibility complex (MHC)
superantigens bypass the normal antigen processing pathway and directly molecules, and the presentation of these peptide-MHC complexes to T
interact with T cells and MHC molecules. Here's how superantigens cells for recognition. Here's an overview of antigen processing and
function and their role in T cell activation: Mechanism of Superantigen presentation: Antigen Processing: Endogenous Antigen Processing (MHC
Activation: Binding to MHC and TCR: Superantigens bind simultaneously Class I Pathway): Proteasomal Degradation: Intracellular pathogens,
to MHC class II molecules on APCs and to specific variable regions of the abnormal proteins, or proteins synthesized within the cell are degraded
β-chain of the TCR on T cells. This interaction occurs outside of the by the proteasome into short peptide fragments. Transport into
peptide-binding groove of the MHC molecule and outside of the antigen- Endoplasmic Reticulum (ER): The peptide fragments are transported into
binding site of the TCR. Crosslinking and Activation: By simultaneously the ER by transporter proteins, such as TAP (transporter associated with
binding to MHC and TCR molecules, superantigens crosslink multiple TCRs antigen processing). Loading onto MHC Class I Molecules: Within the ER,
on different T cells, as well as MHC molecules on APCs. This crosslinking the peptide fragments are loaded onto newly synthesized MHC class I
leads to the activation of a large number of T cells, regardless of their molecules. Transport to the Cell Surface: The peptide-MHC class I
antigen specificity. Activation of T Cells: The activation of T cells by complexes are transported to the cell surface and presented to CD8+
superantigens results in the release of cytokines, such as tumor necrosis cytotoxic T cells (CTLs). CTLs recognize these complexes and can kill the
factor-alpha (TNF-α), interferon-gamma (IFN-γ), and interleukins (IL-1, IL- presenting cell if the peptides are derived from foreign or abnormal
2, IL-6), among others. This massive cytokine release can lead to systemic proteins. Exogenous Antigen Processing (MHC Class II Pathway):
effects, including fever, shock, and inflammation. Role in T Cell Activation:
Polyclonal T Cell Activation: Superantigens activate a large proportion of T Antigen Presentation:
cells indiscriminately, leading to polyclonal T cell activation. This is in Recognition by T Cells: CD8+ Cytotoxic T Cells (CTLs) recognize peptide-
contrast to conventional antigens, which activate only antigen-specific T MHC class I complexes presented on the surface of infected or abnormal
cells. Overactivation of the Immune System: The activation of a large cells. This recognition triggers CTL activation and the killing of the
number of T cells by superantigens can result in an exaggerated and presenting cell. CD4+ Helper T Cells (Th cells) recognize peptide-MHC
dysregulated immune response. This can lead to the development of class II complexes presented on the surface of antigen-presenting cells
conditions such as toxic shock syndrome and certain autoimmune (APCs). Th cell activation leads to the release of cytokines and the
diseases. Modulation of Immune Responses: Superantigens can modulate activation of other immune cells. Co-stimulation: In addition to TCR
immune responses by skewing cytokine production towards recognition of peptide-MHC complexes, co-stimulatory signals provided
inflammatory or anti-inflammatory profiles, depending on the context of by interaction between co-stimulatory molecules on APCs (such as
the immune response and the specific superantigen involved. Potential as CD80/86) and their receptors on T cells (such as CD28) are required for
Immunomodulatory Agents: Because of their ability to activate T cells in a full T cell activation.

Structure and functions of Antibodies :: Antibodies, also known as

immunoglobulins (Ig), are large Y-shaped proteins produced by B cells of
MHC complex:: The Major Histocompatibility Complex (MHC), also
known as the Human Leukocyte Antigen (HLA) system in humans, is a the immune system in response to the presence of foreign substances
group of genes that encode cell surface proteins essential for the called antigens. Antibodies play a central role in the adaptive immune
immune system's ability to recognize and respond to foreign antigens. response by recognizing and binding to specific antigens, thereby
MHC molecules play a central role in antigen presentation, self/non-self marking them for destruction or neutralization. Here's an overview of the
discrimination, and the initiation of immune responses. Here's an structure and functions of antibodies: Structure of Antibodies: Basic
overview of the MHC complex: Structure and Genetics: Genetic Loci: The
Structure: Antibodies are composed of four polypeptide chains—two
MHC complex is located on chromosome 6 in humans (chromosome 17
in mice) and contains a cluster of highly polymorphic genes. Class I and identical heavy chains and two identical light chains—linked together by
Class II Molecules: MHC molecules are classified into two main classes, disulfide bonds. Variable Regions: The amino-terminal regions of both the
MHC class I and MHC class II, based on their structure, function, and heavy and light chains contain hypervariable regions, also known as
distribution on cell types. Function: Antigen Presentation: The primary complementarity-determining regions (CDRs), which form the antigen-
function of MHC molecules is to present peptide antigens to T cells, binding site. These regions are highly variable in sequence and are
thereby initiating adaptive immune responses. MHC class I molecules responsible for the specificity of antibody-antigen interactions.Functions
present endogenous antigens derived from intracellular proteins to CD8+
of Antibodies:Antigen Recognition: Antibodies specifically recognize and
T cells, while MHC class II molecules present exogenous antigens derived
from extracellular proteins to CD4+ T cells. Self/Non-Self Discrimination: bind to antigens through interactions between their variable regions
MHC molecules play a crucial role in distinguishing between self and non- (CDRs) and epitopes (antigenic determinants) on the surface of the
self antigens. T cells are educated in the thymus to recognize self- antigen. Neutralization: Antibodies can neutralize pathogens and toxins
peptides presented by MHC molecules, leading to the deletion of by binding to their surface epitopes, thereby preventing them from
autoreactive T cells and the establishment of self-tolerance. Clinical infecting host cells or exerting their harmful effects. Opsonization:
Relevance: Autoimmune Diseases: Genetic variations in MHC genes are
Antibodies can coat pathogens with molecules that enhance their
associated with an increased risk of autoimmune diseases, such as
recognition and uptake by phagocytic cells, such as macrophages and
rheumatoid arthritis, type 1 diabetes, and multiple sclerosis. Infectious
Diseases: MHC polymorphism influences susceptibility to infectious neutrophils, leading to their destruction through phagocytosis.
diseases by affecting the ability of the immune system to recognize and Complement Activation: Antibodies can activate the complement system,
respond to pathogens. Immunotherapy: MHC molecules are targets for a group of proteins that promotes inflammation, opsonization, and lysis
immunotherapy in cancer treatment, as they play a crucial role in tumor of target cells. Binding of antibodies to antigens can initiate the classical
antigen presentation and T cell-mediated anti-tumor immune responses. pathway of complement activation. Antibody-Dependent Cell-Mediated
Cytotoxicity (ADCC): Antibodies can recruit immune cells, such as natural
killer (NK) cells and eosinophils, to target cells expressing surface
antigens. These immune cells recognize the Fc portion of antibodies
bound to target cells and induce their destruction. Regulation of Immune
Responses: Antibodies play a role in regulating immune responses by
 The interaction between antigens and antibodies, also known as antigen- Complement System: Activation Pathways: The complement system can
antibody binding or immune complex formation, plays a central role in be activated through three main pathways: the classical pathway, the
the immune response. When antibodies encounter their specific alternative pathway, and the lectin pathway. The classical pathway is
initiated by antigen-antibody complexes, whereas the alternative and
antigens, they can bind to them with high specificity and affinity, leading
lectin pathways can be activated by microbial surfaces. Cascading
to the formation of antigen-antibody complexes. The complement
Activation: Activation of the complement system involves a cascade of
system is a group of proteins that becomes activated by these immune proteolytic cleavage events, leading to the sequential activation of
complexes, leading to a cascade of events that enhance the immune complement proteins, including C1 through C9, as well as other
response against pathogens. Here's an overview of antigen-antibody regulatory proteins. Biological Functions: The complement system has
interaction and the complement system: Antigen-Antibody Interaction: several biological functions, including opsonization of pathogens for
Recognition: Antibodies (immunoglobulins) are produced by B cells in phagocytosis, direct lysis of target cells through the formation of the
membrane attack complex (MAC), recruitment and activation of immune
response to the presence of specific antigens. The variable regions of the
cells, and modulation of inflammation. Enhancement of Immune
antibody bind to complementary epitopes on the antigen surface, Response: Activation of the complement system enhances the immune
forming a stable antigen-antibody complex. Specificity and Affinity: response against pathogens by promoting their recognition and
Antibodies exhibit high specificity for their target antigens, meaning they elimination by phagocytic cells and facilitating the clearance of immune
can distinguish between different antigens based on their unique complexes. Regulation: The complement system is tightly regulated to
molecular structures. They also have high affinity, meaning they bind prevent excessive or inappropriate activation, which could lead to tissue
tightly to their antigens. Epitope Binding: The region of the antigen damage or autoimmune reactions. Regulatory proteins, such as factor H
and C1 inhibitor, control complement activation and prevent self-
recognized and bound by the antibody is called an epitope, or antigenic
damage. Interplay with Antigen-Antibody Complexes: Antigen-antibody
determinant. Epitopes can be linear or conformational, depending on the complexes serve as platforms for complement activation, particularly
antigen's structure. Types of Interactions: Antigen-antibody binding through the classical pathway. Binding of C1q to antigen-antibody
involves various types of interactions, including hydrogen bonds, complexes initiates the classical pathway, leading to the generation of C3
electrostatic interactions, van der Waals forces, and hydrophobic convertase and subsequent activation of downstream complement
interactions. Functional Consequences: Antigen-antibody binding can components. Complement activation enhances the clearance of
pathogens and immune complexes, promotes inflammation, and helps
lead to neutralization of pathogens or toxins, opsonization for
orchestrate the immune response against infections. The interplay
phagocytosis, activation of the complement system, or cross-linking of
between antigen-antibody complexes and the complement system
antigens for agglutination or precipitation. represents a crucial aspect of the immune response, contributing to host
defense against pathogens and the maintenance of immune
homeostasis. Understanding these interactions is essential for developing
strategies for the diagnosis, treatment, and prevention of infectious and
autoimmune diseases.

Antibody affinity and antibody avidity are two related but distinct Precipitation reactions involve the formation of insoluble aggregates,
concepts that describe the strength and stability of the interaction known as precipitates, when soluble antigens and antibodies combine in
between an antibody and its antigen. Both properties are essential for solution. These reactions are commonly used in immunology for
understanding the effectiveness of antibodies in recognizing and binding diagnostic purposes and to study antigen-antibody interactions. Here's an
to their target antigens. Here's an explanation of antibody affinity and overview of precipitation reactions: Mechanism: Formation of Antigen-
avidity: Antibody Affinity: Definition: Antibody affinity refers to the Antibody Complexes: Soluble antigens (usually proteins) and their
strength of the binding interaction between a single antigen-binding site corresponding antibodies are mixed together in a suitable buffer solution.
on an antibody and a single epitope on an antigen. Measurement: Affinity If the antigen and antibody are complementary, they bind to form
is typically quantified by the equilibrium dissociation constant (Kd), which immune complexes. Precipitation of Immune Complexes: When the
represents the concentration of antigen required to occupy half of the concentration of immune complexes exceeds their solubility threshold,
available antibody binding sites at equilibrium. A lower Kd value indicates insoluble aggregates, known as precipitates, form. The precipitates
higher affinity (tighter binding) between the antibody and antigen. consist of cross-linked antigen-antibody complexes that are no longer
Antibody Avidity: Definition: Antibody avidity refers to the overall soluble in the solution. Visualization: Precipitation reactions can be
strength of the binding interaction between an antibody and a visualized macroscopically as visible clumps or turbidity in the solution.
multivalent antigen, taking into account the cumulative effects of Applications: Diagnosis of Infectious Diseases: Precipitation reactions are
multiple antigen-antibody binding interactions. Measurement: Avidity used in serological tests to detect antibodies against specific pathogens,
depends not only on affinity but also on the valency and spatial aiding in the diagnosis of infectious diseases. Quantification of Antigens
arrangement of antigenic epitopes on the multivalent antigen. It is often and Antibodies: Quantitative precipitation assays, such as SRID, can be
expressed as the overall avidity index, which considers both the affinity of used to measure the concentration of antigens or antibodies in biological
individual antibody-antigen interactions and the number of simultaneous samples. Research on Antigen-Antibody Interactions: Precipitation
interactions. Relationship between Affinity and Avidity: Affinity reactions are valuable tools for studying the specificity and affinity of
represents the intrinsic binding strength between an individual antibody antigen-antibody interactions in vitro. Quality Control in Biomedical
binding site and a single epitope. Avidity considers the cumulative effects Research: Precipitation assays are used for quality control purposes in
of multiple binding interactions between antibodies and multivalent the production of antibodies and diagnostic kits. Factors Affecting
antigens. While affinity influences the initial binding event, avidity Precipitation Reactions: Concentration of Antigen and Antibody:
reflects the overall stability and effectiveness of the antibody-antigen Precipitation depends on the relative concentrations of antigen and
interaction, particularly in the context of multivalent antigens. In antibody in the reaction mixture. Affinity and Specificity of Antibody:
summary, antibody affinity and avidity are complementary properties High-affinity antibodies and specific antigen-antibody interactions favor
that collectively determine the strength, specificity, and effectiveness of the formation of precipitates. pH and Ionic Strength: Optimal pH and
antibody-mediated immune responses. Understanding these properties is ionic strength conditions are required for efficient antibody-antigen
crucial for optimizing the design and efficacy of antibodies for various binding and precipitation. Precipitation reactions provide valuable
diagnostic, therapeutic, and research applications. insights into antigen-antibody interactions and have widespread
. Agglutination reactions involve the clumping together of insoluble Complement System - activation pathway, biological function and
particles, such as cells or particles coated with antigens, in the presence complement deficiencies The complement system is a crucial part of the
of specific antibodies. These reactions are commonly used in immunology innate immune system that plays a central role in host defense against
for diagnostic purposes and to study antigen-antibody interactions. pathogens, clearance of immune complexes, and modulation of
Here's an overview of agglutination reactions: Mechanism: Coating of inflammatory responses. It consists of a complex network of soluble
Particles with Antigens: Insoluble particles, such as red blood cells (RBCs), proteins and cell surface receptors that interact to recognize and
latex beads, or microbial cells, are coated with antigens of interest. eliminate foreign invaders. Here's an overview of the complement
Addition of Antibodies: Antibodies specific to the antigens present on the system, including its activation pathways, biological functions, and
coated particles are added to the suspension. Formation of Antigen- complement deficiencies: Activation Pathways: Classical Pathway:
Antibody Complexes: If the antigens on the coated particles are Initiated by antigen-antibody complexes (mainly IgM or IgG) binding to
complementary to the antibodies, they bind to form immune complexes. C1q, which activates the classical pathway. C1q binds to the Fc portion of
Clumping of Particles: As more antibodies bind to adjacent antigen- antibodies in immune complexes, leading to activation of the C1 complex
coated particles, they cross-link them, leading to the formation of visible (C1q, C1r, and C1s), which cleaves C4 and C2 into C4a, C4b, C2a, and C2b.
aggregates or clumps known as agglutinates. Visualization: Agglutination C4b and C2a form the classical pathway C3 convertase (C4bC2a), which
can be macroscopically observed as visible clumps or aggregates in the cleaves C3 into C3a and C3b, leading to downstream complement
suspension. Alternatively, agglutination can be detected using methods activation. Biological Functions: Opsonization: Complement fragments,
such as turbidimetry, nephelometry, or microscopic examination. particularly C3b and its derivatives, coat pathogens and enhance their
Applications: Blood Typing: Agglutination reactions are used in ABO and recognition and phagocytosis by phagocytic cells (opsonization).
Rh blood typing to determine an individual's blood group based on the Inflammation: Complement activation leads to the release of
presence or absence of specific antigens on RBCs. Serological Testing: anaphylatoxins (C3a, C4a, C5a), which stimulate mast cells, basophils, and
Agglutination assays are used in serological tests to detect antibodies leukocytes to induce inflammation. Membrane Attack Complex (MAC)
against specific pathogens, aiding in the diagnosis of infectious diseases. Formation: Complement activation results in the formation of the
Detection of Autoantibodies: Agglutination assays can be used to detect membrane attack complex (MAC), consisting of C5b, C6, C7, C8, and
autoantibodies directed against self-antigens in autoimmune diseases. multiple C9 molecules, which inserts into microbial membranes, leading
Detection of Microorganisms: Agglutination assays are used to detect and to cell lysis.
identify microbial pathogens based on the presence of specific surface
antigens. Quality Control in Biomedical Research: Agglutination assays
are used for quality control purposes in the production of antibodies and
diagnostic kits. Factors Affecting Agglutination Reactions: Concentration
of Antigen and Antibody: Agglutination depends on the relative
concentrations of antigen and antibody in the reaction mixture. Affinity
and Specificity of Antibody: High-affinity antibodies and specific antigen-

Complement Deficiencies: C1 Inhibitor Deficiency (Hereditary ELISA, or Enzyme-Linked Immunosorbent Assay, is a widely used
Angioedema): Results in uncontrolled activation of the classical pathway laboratory technique for detecting and quantifying the presence of
and excessive production of bradykinin, leading to episodes of proteins, peptides, antibodies, hormones, and other molecules in
angioedema. C3 Deficiency: Increases susceptibility to recurrent bacterial biological samples. ELISA is highly sensitive, specific, and versatile, making
infections due to impaired opsonization and phagocytosis. Terminal it an invaluable tool in various fields, including immunology, molecular
Pathway Deficiencies (C5-C9): Predispose individuals to recurrent biology, clinical diagnostics, and drug discovery. Here's an overview of
Neisseria infections, as they lack the ability to form the MAC and lyse the ELISA technique and its applications: Principle of ELISA: Coating: The
bacteria. Factor H and Factor I Deficiencies: Result in uncontrolled target molecule (antigen or antibody) is immobilized onto the surface of a
activation of the alternative pathway and predispose individuals to microplate well, typically by adsorption to the plastic surface or by
autoimmune diseases, such as atypical hemolytic uremic syndrome specific capture using antibodies. Blocking: Unoccupied sites on the
(aHUS). Mannose-Binding Lectin (MBL) Deficiency: Impairs the lectin microplate surface are blocked with a non-reactive protein (e.g., bovine
pathway of complement activation and may increase susceptibility to serum albumin) to prevent non-specific binding of detection reagents.
infections, particularly in early childhood. Properdin Deficiency: Leads to Binding: The sample containing the analyte of interest is added to the
increased susceptibility to infections, especially by encapsulated bacteria, well and allowed to incubate. If the analyte is present, it binds to the
due to impaired stabilization of the alternative pathway C3 convertase. immobilized capture molecule. Washing: The well is washed to remove
Treatment of Complement Deficiencies: Treatment options for unbound sample components, reducing background noise and increasing
complement deficiencies may include plasma infusions containing assay specificity. Detection: A detection molecule, typically an enzyme-
missing complement proteins, prophylactic antibiotics to prevent conjugated antibody or antigen, is added to the well. This molecule binds
infections, and targeted therapies to modulate complement activation. specifically to the captured analyte. Substrate Addition: A substrate
Understanding the complement system and its role in immunity is specific for the enzyme conjugated to the detection molecule is added.
essential for diagnosing and managing complement deficiencies and The enzyme catalyzes a colorimetric, fluorometric, or chemiluminescent
developing therapeutic interventions for complement-related disorders. reaction, generating a signal directly proportional to the amount of
analyte present. Signal Measurement: The signal generated is measured
using a spectrophotometer, fluorometer, or luminometer, and the
concentration of the analyte in the sample is determined based on a
standard curve generated from known concentrations of the analyte.
Applications of ELISA: Diagnostics: Detection of infectious agents (e.g.,
HIV, hepatitis), autoimmune antibodies, hormones, tumor markers, and
other biomarkers for disease diagnosis and monitoring. Research:
Quantification of proteins, antibodies, cytokines, and other molecules in
cell culture supernatants, tissue lysates, serum, plasma, and other
biological samples. Drug Discovery: High-throughput screening of
Cytokines are a broad and diverse group of small proteins or Cytokine Receptors: Single-Chain Receptors: Many cytokines signal
glycoproteins that play key roles in cell signaling and regulation of through receptors that have a single transmembrane domain and
immune responses. They are produced by various cell types, including activate intracellular signaling pathways via associated Janus kinases
immune cells, and act in a paracrine or autocrine manner to modulate (JAKs) and signal transducers and activators of transcription (STATs).
the behavior and function of target cells. Cytokines are classified based Example: IL-2 receptor, IFN-γ receptor. Multi-Subunit Receptors: Some
on their structure, function, and the cell types they act on. Here's an cytokines signal through receptors composed of multiple subunits, which
overview of cytokines classification, functions, and their receptors: form receptor complexes upon ligand binding and activate downstream
Classification of Cytokines: Interleukins (ILs): ILs are a large family of signaling pathways. Example: IL-4 receptor (composed of IL-4Rα and IL-
cytokines that regulate immune and inflammatory responses. They are 2Rγc subunits), IL-6 receptor (composed of IL-6Rα and gp130 subunits).
named sequentially as interleukins based on their discovery. Example: IL- Tyrosine Kinase Receptors: Certain growth factors and cytokines signal
1, IL-2, IL-6, IL-10, IL-12, IL-17, IL-23, etc. Interferons (IFNs): IFNs are through receptors with intrinsic tyrosine kinase activity, leading to
cytokines involved in antiviral defense, immune regulation, and phosphorylation of intracellular signaling molecules and activation of
modulation of cell growth and differentiation. Example: IFN-α, IFN-β, IFN- downstream pathways. Example: Epidermal Growth Factor Receptor
γ. Tumor Necrosis Factors (TNFs): TNFs are involved in inflammation, (EGFR), Platelet-Derived Growth Factor Receptor (PDGFR). G-Protein-
apoptosis, and immune regulation. Example: TNF-α, TNF-β (also known as Coupled Receptors (GPCRs): Some chemokines signal through GPCRs,
lymphotoxin-alpha). Chemokines: Chemokines regulate leukocyte which activate intracellular signaling pathways via heterotrimeric G
trafficking, inflammation, and immune cell activation by promoting proteins and downstream effectors. Example: CXCR4, CCR5. Cytokines
chemotaxis. Example: CXCL8 (IL-8), CCL2 (MCP-1), CXCL10 (IP-10), CCL5 and their receptors play critical roles in regulating immune responses,
(RANTES). Functions of Cytokines: Immune Activation: Cytokines regulate inflammation, hematopoiesis, and tissue homeostasis. Dysregulation of
immune cell proliferation, activation, and differentiation, including T cytokine signaling pathways is associated with various diseases, including
cells, B cells, natural killer (NK) cells, macrophages, and dendritic cells. autoimmune disorders, inflammatory diseases, cancer, and infectious
Inflammation: Cytokines mediate inflammatory responses by inducing diseases. Therefore, targeting cytokines and their receptors has
the production of inflammatory mediators, chemotaxis of immune cells, therapeutic potential for treating these conditions.
and activation of endothelial cells. Cell Growth and Differentiation:
Cytokines regulate cell proliferation, survival, and differentiation in
various tissues and organs, including hematopoiesis, wound healing, and
tissue repair. Hematopoiesis: Cytokines control the development and
differentiation of hematopoietic stem cells into various blood cell
lineages, including erythrocytes, leukocytes, and platelets.Antiviral
Defense: Cytokines such as interferons play critical roles in host defense
against viral infections by inducing antiviral responses in infected cells
and activating immune cells.
The organization and expression of immunoglobulin (Ig) genes are Expression of Ig Genes: Somatic Recombination: During B cell
fundamental processes that govern the development and function of B development in the bone marrow, the V, D, and J gene segments in the Ig
lymphocytes and the production of antibodies. Immunoglobulins are heavy chain locus undergo somatic recombination to generate a diverse
proteins produced by B cells and plasma cells, and they play essential repertoire of Ig heavy chain variable regions. Similarly, the V and J gene
roles in the adaptive immune response by recognizing and neutralizing segments in the Ig light chain locus undergo somatic recombination to
pathogens. Here's an overview of the organization and expression of Ig generate Ig light chain variable regions. Allelic Exclusion: B cells undergo
genes: Organization of Ig Genes: Gene Loci: Ig genes are located on allelic exclusion, meaning that only one allele of each Ig gene locus is
multiple chromosomes in humans and mice. The major loci encoding Ig expressed. This ensures that each B cell produces antibodies with a single
genes are on chromosome 14 in humans (Ig heavy chain locus) and specificity. Class Switch Recombination (CSR): After antigen activation,
chromosome 2 in mice (Igh locus), and on chromosome 2 in both species mature B cells can undergo class switch recombination, a process that
(Ig light chain locus). Heavy Chain Locus (Igh): The Ig heavy chain locus replaces the constant region of the Ig heavy chain (Cμ) with a
contains multiple gene segments that encode the variable (V), diversity downstream constant region (e.g., Cγ, Cα). CSR allows B cells to change
(D), joining (J), and constant (C) regions of the Ig heavy chain. The V, D, the effector function of the antibodies they produce without altering
and J gene segments undergo somatic recombination during B cell their antigen specificity. Somatic Hypermutation (SHM): Mature B cells
development to generate the diverse repertoire of Ig heavy chain can undergo somatic hypermutation, a process in which point mutations
variable regions. Light Chain Locus (Igk and Igl): The Ig light chain locus are introduced into the variable regions of Ig genes during clonal
contains V and J gene segments, but lacks D segments. It also contains a expansion in the germinal centers of secondary lymphoid organs. SHM
constant (C) region. In mice, there are two light chain loci: Ig kappa (Igk) increases the affinity of antibodies for their antigens, leading to the
on chromosome 6 and Ig lambda (Igl) on chromosome 16. Humans only generation of high-affinity antibodies through a process of affinity
have the Igk locus. maturation. Regulation of Ig Gene Expression: Transcriptional Regulation:
Ig gene expression is regulated at the transcriptional level by
transcription factors and cis-regulatory elements, including enhancers
and promoters, which control the activity of Ig gene promoters and
regulate the accessibility of Ig gene segments for recombination.
Epigenetic Regulation: Epigenetic modifications, such as DNA methylation
and histone modifications, play important roles in regulating the
accessibility of Ig gene segments for recombination and the
transcriptional activity of Ig genes.Cell Type-Specific Regulation: The
expression of Ig genes is tightly regulated in a cell type-specific manner,
with different regulatory mechanisms operating at different stages of B
cell development and activation. Understanding the organization and
expression of Ig genes is essential for elucidating the mechanisms of B
The generation of antibody diversity is a crucial process that allows the The generation of diversity in B cell receptors (BCRs) and T cell receptors
immune system to produce a vast array of antibodies capable of (TCRs) is essential for the adaptive immune system to recognize and
recognizing and neutralizing a diverse range of pathogens. Antibody respond to a wide range of antigens. While BCR diversity primarily arises
diversity arises primarily through three main mechanisms: V(D)J through V(D)J recombination, TCR diversity also involves this process but
recombination, somatic hypermutation (SHM), and combinatorial with additional layers of complexity due to TCRαβ chain pairing and the
diversity. Here's an overview of each mechanism: 1. V(D)J selection process in the thymus. Here's how diversity is generated in
Recombination: Process: V(D)J recombination is a somatic recombination BCRs and TCRs: B Cell Receptor (BCR) Diversity: V(D)J Recombination: BCR
process that occurs during the development of B cells in the bone diversity primarily arises through V(D)J recombination, a process that
marrow. It involves the rearrangement and joining of gene segments occurs during B cell development in the bone marrow. Multiple gene
encoding the variable (V), diversity (D), and joining (J) regions of the segments encoding variable (V), diversity (D), and joining (J) regions are
immunoglobulin heavy and light chain genes. Heavy Chain: In the Ig rearranged to form the variable region of the BCR heavy and light chains.
heavy chain locus, multiple V, D, and J gene segments are present. During By combinatorially joining different V, D, and J gene segments, a diverse
B cell development, one D segment is joined to one J segment, and then repertoire of BCRs with unique antigen-binding specificities is generated.
a V segment is joined to the DJ complex, forming the variable region of Combination of Heavy and Light Chains: Each B cell expresses both a
the heavy chain. Light Chain: In the Ig light chain locus, V and J gene heavy chain and a light chain, with each chain contributing to the
segments are rearranged to form the variable region of the light chain. antigen-binding site. The combination of diverse heavy and light chain
Result: V(D)J recombination generates enormous diversity in the antigen- variable regions further increases the diversity of BCRs, resulting in an
binding sites of antibodies by combining different V, D, and J gene extensive repertoire capable of recognizing a wide array of antigens. T
segments in various combinations. 2. Somatic Hypermutation (SHM): Cell Receptor (TCR) Diversity: V(D)J Recombination: Similar to BCRs, TCR
Process: Somatic hypermutation occurs in the germinal centers of diversity also arises through V(D)J recombination during T cell
secondary lymphoid organs (e.g., lymph nodes, spleen) during the development in the thymus. TCRα and TCRβ chains are generated
immune response to antigen stimulation. Mechanism: B cells undergo through the rearrangement of V, D, and J gene segments, resulting in the
rapid and random point mutations in the variable regions of their formation of the variable regions of the TCR chains. TCRαβ Chain Pairing:
immunoglobulin genes (both heavy and light chains). Result: These TCR diversity is further expanded by the pairing of TCRα and TCRβ chains
mutations lead to changes in the amino acid sequence of the variable to form functional TCR heterodimers. Each T cell expresses a unique
region, resulting in antibodies with altered antigen-binding affinities. B combination of TCRα and TCRβ chains, leading to a diverse repertoire of
cells producing antibodies with higher affinity for the antigen are TCRs with different antigen specificities.
selectively expanded through affinity maturation. 3. Combinatorial
Diversity: Process: Combinatorial diversity results from the numerous
possible combinations of heavy and light chain variable regions during B
cell development. Combination: Each B cell can express a unique
combination of heavy and light chain variable regions due to the random

Importance of BCR and TCR Diversity: Immunology, the study of the immune system, plays a critical role in
understanding and treating various diseases. The immune system is
Pathogen Recognition: The diversity of BCRs and TCRs allows the adaptive involved in defending the body against pathogens such as bacteria,
immune system to recognize and respond to a wide range of pathogens, viruses, fungi, and parasites, as well as in recognizing and eliminating
including viruses, bacteria, parasites, and fungi. abnormal cells, including cancer cells. Dysregulation or dysfunction of the
immune system can lead to a wide range of diseases, including infectious
Immune Memory: Diverse BCRs and TCRs enable the establishment of
diseases, autoimmune disorders, allergies, and immunodeficiencies.
immunological memory, ensuring a rapid and specific immune response
Here's how immunology is intertwined with various diseases: 1.
upon re-exposure to previously encountered antigens.
Infectious Diseases: Role of Immunology: Immunology is central to
understanding how the immune system recognizes and responds to
Protection Against Autoimmunity: The process of positive and negative
infectious agents. It involves the study of host-pathogen interactions,
selection in the thymus ensures the elimination of self-reactive T cells,
mechanisms of immune evasion by pathogens, and the development of
helping to prevent autoimmune reactions while maintaining immune
vaccines and therapeutics. Examples: HIV/AIDS, tuberculosis, malaria,
tolerance.
influenza, COVID-19, hepatitis, pneumonia, and sexually transmitted
Overall, the generation of diversity in BCRs and TCRs is critical for the infections are all infectious diseases where immunological principles play
adaptive immune system's ability to mount effective immune responses a significant role in disease progression, treatment, and prevention. 2.
and provide protection against pathogens while avoiding harmful Autoimmune Diseases: Role of Immunology: Autoimmune diseases occur
autoimmune responses. when the immune system mistakenly attacks and damages the body's
own tissues, leading to chronic inflammation and tissue destruction.
Immunology investigates the underlying mechanisms of autoimmune
diseases and explores strategies for immune modulation and tolerance
induction. Examples: Rheumatoid arthritis, systemic lupus erythematosus
(SLE), multiple sclerosis (MS), type 1 diabetes, inflammatory bowel
disease (Crohn's disease and ulcerative colitis), psoriasis, and
Hashimoto's thyroiditis are autoimmune diseases characterized by
aberrant immune responses. 3. Allergic Diseases: Role of Immunology:
Allergic diseases result from exaggerated immune responses to harmless
substances (allergens) in the environment. Immunology explores the
mechanisms of allergic sensitization, immune cell activation, and the
development of allergic reactions. Examples: Allergic rhinitis (hay fever),
allergic asthma, atopic dermatitis (eczema), food allergies, insect sting
allergies, and drug allergies are allergic diseases mediated by
Importance of BCR and TCR Diversity:

Pathogen Recognition: The diversity of BCRs and TCRs allows the adaptive
immune system to recognize and respond to a wide range of pathogens,
including viruses, bacteria, parasites, and fungi.

Immune Memory: Diverse BCRs and TCRs enable the establishment of

immunological memory, ensuring a rapid and specific immune response
upon re-exposure to previously encountered antigens.

Protection Against Autoimmunity: The process of positive and negative

selection in the thymus ensures the elimination of self-reactive T cells,
helping to prevent autoimmune reactions while maintaining immune
tolerance.

Overall, the generation of diversity in BCRs and TCRs is critical for the
adaptive immune system's ability to mount effective immune responses
and provide protection against pathogens while avoiding harmful
autoimmune responses.
Hypersensitivity reactions are exaggerated or inappropriate immune Autoimmunity refers to a condition in which the immune system
responses to harmless antigens (allergens) or self-antigens, resulting in mistakenly targets and attacks the body's own tissues and cells, leading
tissue damage and inflammation. The Gell and Coombs classification to chronic inflammation, tissue damage, and autoimmune diseases.
categorizes hypersensitivity reactions into four types based on the Normally, the immune system is able to distinguish between self and
underlying immunological mechanisms involved. Here's an overview of non-self antigens, but in autoimmunity, this tolerance mechanism breaks
each type: Type I Hypersensitivity (Immediate Hypersensitivity): down, resulting in the production of autoantibodies and/or autoreactive
Mechanism: Type I hypersensitivity reactions are mediated by T cells directed against self-antigens. Here's an overview of
immunoglobulin E (IgE)-dependent mechanisms. Upon initial exposure to autoimmunity: Mechanisms of Autoimmunity: Loss of Self-Tolerance:
an allergen, B cells produce IgE antibodies specific to the allergen. Upon Autoimmunity often results from a breakdown in self-tolerance, the
subsequent exposure, the allergen binds to IgE antibodies on mast cells immune system's ability to recognize and tolerate self-antigens while
and basophils, triggering their activation. Type II Hypersensitivity mounting effective responses against foreign antigens. Various factors,
(Cytotoxic Hypersensitivity): Mechanism: Type II hypersensitivity including genetic predisposition, environmental triggers (e.g., infections,
reactions involve antibodies (IgG or IgM) directed against cell surface drugs, stress), and dysregulation of immune checkpoints, can contribute
antigens or extracellular matrix components. Antibody binding leads to to loss of self-tolerance. Immune Dysregulation: Dysregulated immune
complement activation and/or antibody-dependent cell-mediated responses, such as defects in regulatory T cells (Tregs), cytokine
cytotoxicity (ADCC), resulting in target cell destruction. Mediators: imbalances, aberrant antigen presentation, and impaired peripheral
Complement activation, phagocytosis, and cytotoxicity mediated by tolerance mechanisms, can lead to the activation of autoreactive immune
natural killer (NK) cells, macrophages, and neutrophils contribute to cells and the production of autoantibodies. Molecular Mimicry:
tissue damage. Clinical Manifestations: Type II hypersensitivity reactions Molecular mimicry occurs when antigens from infectious agents or
can manifest as autoimmune hemolytic anemia, thrombocytopenia, drug- environmental triggers share structural similarities with self-antigens.
induced hemolytic reactions, transfusion reactions, and autoimmune Cross-reactive immune responses against both foreign and self-antigens
diseases such as Graves' disease and myasthenia gravis. Type III can lead to tissue damage and autoimmune diseases. Epigenetic Factors:
Hypersensitivity (Immune Complex-Mediated Hypersensitivity): Epigenetic modifications, such as DNA methylation and histone
Mechanism: Type III hypersensitivity reactions result from the formation modifications, play important roles in regulating gene expression and
of immune complexes composed of antigens and antibodies (IgG or IgM) immune cell function. Dysregulation of epigenetic mechanisms can
in the circulation or tissues. These immune complexes deposit in tissues, contribute to the development of autoimmunity by altering immune cell
leading to complement activation, inflammation, and tissue damage. differentiation, activation, and tolerance. Types of Autoimmune Diseases:
Type IV Hypersensitivity (Delayed-Type Hypersensitivity): Mechanism: Systemic Autoimmune Diseases: These affect multiple organs and tissues
Type IV hypersensitivity reactions are T cell-mediated responses involving throughout the body and often have systemic manifestations. Examples
antigen-specific CD4+ T cells (Th1 cells) or CD8+ cytotoxic T cells (Tc cells). include systemic lupus erythematosus (SLE), rheumatoid arthritis (RA),
Sensitized T cells recognize antigens presented by antigen-presenting Sjögren's syndrome, systemic sclerosis (scleroderma), and mixed
cells (APCs) and release cytokines, leading to recruitment of macrophages connective tissue disease (MCTD).

Immunodeficiencies are a group of disorders characterized by defects in

the immune system, resulting in increased susceptibility to infections,
impaired immune responses, and in some cases, autoimmune or
inflammatory manifestations. These disorders can be inherited (primary
immunodeficiencies) or acquired (secondary immunodeficiencies). Here's
an overview of immunodeficiencies: Primary Immunodeficiencies: B Cell
Disorders: X-Linked Agammaglobulinemia (XLA): Deficiency of Bruton's
tyrosine kinase (BTK) leads to impaired B cell maturation and antibody
production, resulting in recurrent bacterial infections, particularly of the
respiratory tract. Common Variable Immunodeficiency (CVID):
Characterized by low levels of serum immunoglobulins (IgG, IgA, or IgM)
and recurrent bacterial infections, CVID is a heterogeneous disorder with
various underlying genetic defects affecting B cell function. T Cell
Disorders: Severe Combined Immunodeficiency (SCID): A group of
disorders characterized by profound defects in both T cell and B cell
immunity, often resulting from mutations in genes involved in
lymphocyte development or signaling pathways. DiGeorge Syndrome:
Caused by deletion of a portion of chromosome 22, DiGeorge syndrome
is characterized by congenital thymic hypoplasia, leading to T cell
deficiency and increased susceptibility to infections. Combined
Immunodeficiencies: Hyper-IgM Syndromes: Various forms of hyper-IgM
syndrome result from defects in CD40 ligand (CD40L) expression or
signaling, leading to impaired class switching and antibody production,
with variable T cell defects. Wiskott-Aldrich Syndrome (WAS):
Characterized by a triad of eczema, thrombocytopenia, and recurrent
infections, WAS is caused by mutations in the WAS gene, leading to
defects in T cell and B cell function, as well as platelet abnormalities.
Phagocyte Disorders: Chronic Granulomatous Disease (CGD): Deficiency
in NADPH oxidase enzymes leads to impaired respiratory burst and
defective killing of phagocytosed bacteria by neutrophils and
macrophages, resulting in recurrent bacterial and fungal infections.
Secondary Immunodeficiencies: Acquired Immunodeficiency Syndrome
 Gross and fine structure of Antibodies::: The gross and fine structure of Classes and Sub-classes of Antibodies ::: Antibodies, also known as
antibodies refers to both the overall architecture and the detailed immunoglobulins (Igs), are classified into different classes and subclasses
composition of these immune proteins. Here's an overview of the gross based on the structure of their constant regions (C regions) and their
and fine structure of antibodies: Gross Structure: Overall Shape: biological properties. In humans, there are five main classes of
Antibodies are typically Y-shaped molecules, also known as antibodies: IgG, IgM, IgA, IgD, and IgE. Each class is further divided into
immunoglobulins (Igs), consisting of four polypeptide chains arranged in subclasses, except for IgD. Here's an overview of the classes and
a symmetrical pattern. Heavy and Light Chains: Antibodies are composed subclasses of antibodies: 1. Immunoglobulin G (IgG): Structure: IgG
of two identical heavy chains and two identical light chains, which are antibodies have a monomeric structure, consisting of two identical heavy
linked together by disulfide bonds. Fab and Fc Regions: The Y-shaped chains and two identical light chains. Distribution: IgG is the most
structure consists of two antigen-binding fragments (Fab) at the tips of abundant antibody class in the bloodstream and tissues. 2.
the Y and one crystallizable fragment (Fc) at the stem. The Fab regions Immunoglobulin M (IgM): Structure: IgM antibodies have a pentameric
contain the antigen-binding sites, while the Fc region mediates effector structure in which five monomeric units are linked together by disulfide
functions. Variable and Constant Regions: Antibodies have variable (V) bonds and a J chain. 3. Immunoglobulin A (IgA): Structure: IgA antibodies
regions at the N-terminal ends of the heavy and light chains, which exist in two forms: monomeric IgA (found in the bloodstream) and
contain hypervariable regions called complementarity-determining dimeric IgA (secreted as secretory IgA in mucosal secretions).
regions (CDRs). The constant (C) regions are located at the C-terminal Distribution: IgA is primarily found in mucosal secretions, such as saliva,
ends and determine the antibody's isotype and effector functions. Fine tears, mucus, and breast milk. Functions: IgA antibodies provide mucosal
Structure: Variable Regions (V Regions): The variable regions of the heavy immunity by neutralizing pathogens and preventing their adherence to
and light chains contain three hypervariable loops, known as mucosal surfaces. 4. Immunoglobulin D (IgD): Structure: IgD antibodies
complementarity-determining regions (CDRs), which form the antigen- have a monomeric structure similar to IgG, consisting of two identical
binding site. The diversity of amino acid sequences in the CDRs allows heavy chains and two identical light chains. Functions: The function of
antibodies to recognize a wide range of antigens. Framework Regions IgD antibodies is not well understood, but they are believed to play a role
(FRs): The variable regions also contain framework regions (FRs), which in the activation and regulation of B cells. 5. Immunoglobulin E (IgE):
provide structural support for the CDRs. The FRs are less variable than Structure: IgE antibodies have a monomeric structure similar to IgG,
the CDRs but still contribute to antigen binding. Antigen-Binding Site: The consisting of two identical heavy chains and two identical light chains.
antigen-binding site of an antibody is formed by the complementarity of Distribution: IgE is found in low concentrations in the bloodstream and
the CDRs with the epitope (antigenic determinant) on the surface of the tissues. Functions: IgE antibodies are involved in allergic reactions and
antigen. The binding affinity and specificity of the antibody for its antigen defense against parasitic infections by triggering the release of histamine
are determined by the interactions between the CDRs and the epitope. and other inflammatory mediators from mast cells and basophils. Each
Constant Regions (C Regions): The constant regions of the heavy and light class and subclass of antibodies has unique properties and functions,
chains determine the antibody's effector functions and isotype. Different contributing to the overall effectiveness of the immune response against

Antibody-mediated effector functions refer to the various mechanisms by Monoclonal Antibodies (mAbs): Production: Monoclonal antibodies are
which antibodies, also known as immunoglobulins (Igs), contribute to the produced by cloning a single B cell that produces a specific antibody of
immune response against pathogens, abnormal cells, and foreign interest. These cells are fused with myeloma cells to create hybridoma
substances. Monoclonal antibodies (mAbs) are laboratory-produced
cell lines that can continuously produce large quantities of the desired
antibodies that are designed to target specific antigens with high
antibody. Specificity and Affinity: Monoclonal antibodies are highly
specificity and affinity. Here's an overview of antibody-mediated effector
functions and the applications of monoclonal antibodies: Antibody- specific for their target antigen and have high affinity due to their
Mediated Effector Functions: Neutralization: Antibodies can neutralize homogeneous nature. This allows for precise targeting of specific cells,
pathogens, toxins, and viruses by binding to their surface epitopes, proteins, or molecules in the body. Therapeutic Applications: Monoclonal
thereby preventing them from infecting host cells or exerting their antibodies have numerous therapeutic applications in medicine,
harmful effects. Opsonization: Antibodies can coat pathogens with including the treatment of cancer, autoimmune diseases, infectious
molecules that enhance their recognition and uptake by phagocytic cells,
diseases, and inflammatory disorders. Diagnostic and Research Tools:
such as macrophages and neutrophils, leading to their destruction
through phagocytosis. Complement Activation: Antibodies can activate Monoclonal antibodies are widely used in diagnostic assays, such as
the complement system, a group of proteins that promotes enzyme-linked immunosorbent assays (ELISAs), immunohistochemistry,
inflammation, opsonization, and lysis of target cells. Binding of antibodies and flow cytometry, for the detection and quantification of specific
to antigens can initiate the classical pathway of complement activation. antigens. Immunotherapy: Monoclonal antibodies are used as
Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC): Antibodies can immunotherapeutic agents to target specific cells or molecules involved
recruit immune cells, such as natural killer (NK) cells and eosinophils, to in disease processes. Examples include immune checkpoint inhibitors for
target cells expressing surface antigens. These immune cells recognize
cancer therapy and biologics for autoimmune diseases. Drug Delivery:
the Fc portion of antibodies bound to target cells and induce their
destruction. Cross-linking and Agglutination: Antibodies can cross-link Monoclonal antibodies can be conjugated to drugs or imaging agents and
antigens, such as bacterial cells or viruses, leading to their aggregation or used as targeted delivery systems to deliver therapeutic payloads
agglutination. This facilitates their recognition and clearance by specifically to diseased cells or tissues. Monoclonal antibodies have
phagocytic cells. Modulation of Immune Responses: Antibodies can revolutionized the fields of medicine, diagnostics, and research by
modulate immune responses by interacting with immune cells and providing highly specific and effective tools for targeting and modulating
cytokines, influencing the balance between inflammatory and regulatory
immune responses and disease processes. Their versatility and precision
pathways.
make them invaluable assets in the development of novel therapeutics
and diagnostic technologies.