IMMUNOLOGY INTRODUCTION

L.A.A.L Immunology. Branch of biomedical science

Concepts of the immune system. that covers the study of all aspects of immune
system in all organisms
Case analysis -​ Host defense reaction to foreign
Seminar type SGD (non-self) entities knowns as antigens,
antigen recog molecules, and
1 INTRO TO IMMUNOLOGY cell-mediated host defense functions

2 COMPONENTS OF IMMUNE SYSTEM Immunity

-​ Refers to all mechanisms used by the
3 INNATE IMMUNITY body as protection against foreign
environmental agents
4 ADAPTIVE IMMUNITY
IMMUNE SYSTEM
5 ANTIGEN-ANTIBODY INTERACTIONS Refers to a collection of cells, chemicals, and
processes that function to protect against
6 IMMUNE SYSTEM COMMUNICATION foreign antigens, such as microbes and other
microorganisms that are not generally part of
7 IMMUNOLOGICAL DISORDERS the body’s environment.

8 APPLICATION OF IMMUNOLOGY IN Immune response - generated against a

MEDICINE potential pathogen or its products
Collective and coordinated response to intro of
9 TUMOR IMMUNOLOGY foreign substances
Produces antibodies , which are proteins
10 ADVANCES IN IMMUNOLOGY produced in response to pathogens.
Activated by antigens (ANTIbody GENerator)

Significance of immune system

BENEFICIAL - protection from invaders,
vaccine helps build up immune defenses
agaisnt specific infections
Elimination of abonormal/altered self
-​ Potential for immunotherapy in the
treatment of tumors

DETRIMENTAL - discomfort due to

inflammation, Damage to self (autoimmunity)
Additional problems in transplantation and
gene therapy
 4. Natural Killer (NK) Cells
("Assassins")

I. CELLS OF THE ●​ Function: Destroy virus-infected cells

and cancer cells without needing prior
IMMUNE SYSTEM activation.
●​ Key Role: Recognize "stressed" cells
lacking MHC I (self-marker).
A. Innate Immune Cells ●​ Secretes: Perforins (poke holes in
target cells) and granzymes (induce
(First Responders) apoptosis).

These cells are part of the nonspecific immune 5. Eosinophils (Parasite Killers)
response, meaning they react quickly to any
foreign invader without prior exposure. ●​ Function: Specialized in attacking
parasites (especially
1. Macrophages ("Big Eaters") helminths/worms).
●​ Secretes: Toxic proteins (e.g., major
●​ Function: Engulf (phagocytose) and basic protein) that break down
destroy pathogens, dead cells, and parasites.
debris. ●​ Involvement in Allergies: Release
●​ Key Role: Present antigens to T cells, histamine in response to allergens.
linking innate and adaptive immunity.
●​ Secretes: Cytokines (e.g., IL-1, 6. Basophils & Mast Cells (Allergy
TNF-α) to recruit other immune cells.
Inducers)
2. Neutrophils (Frontline Soldiers) ●​ Function: Involved in allergic
reactions and inflammation.
●​ Function: The first immune cells to
●​ Secretes:
arrive at infection sites, highly
○​ Histamine (causes swelling,
efficient at phagocytosis.
redness, itching).
●​ Lifespan: Short-lived (hours to days),
○​ Leukotrienes (enhance
die after fighting infection.
inflammation).
●​ Secretes: Enzymes like
○​ Cytokines that recruit other
myeloperoxidase to kill microbes.
immune cells.
●​ Forms Pus: Dead neutrophils
●​ Mast Cells: Found in tissues (skin,
accumulate as pus at infection sites.
lungs, gut); Basophils: Circulate in
blood.
3. Dendritic Cells ("Messengers")

●​ Function: Best antigen-presenting

cells (APCs), capture antigens and
present them to T cells.
●​ Key Role: Bridge between innate and
adaptive immunity.
●​ Location: Found in tissues like the
skin (Langerhans cells) and lymph
nodes.
 ●​ Function: Prevent autoimmunity by
suppressing excessive immune
responses.
B. Adaptive Immune Cells ●​ Secretes: Anti-inflammatory
(Targeted, Memory-Based cytokines like IL-10 and TGF-β.

Defense)
These cells develop specific immunity and 8. B Lymphocytes (B Cells)
provide long-lasting protection.
("Antibody Factories")
7. T Lymphocytes (T Cells) Originate and mature in the bone marrow.

Originate from the bone marrow but mature ●​ Function: Produce antibodies against
in the thymus. specific antigens.
●​ Key Role: Humoral immunity
a. Helper T Cells (CD4⁺) ("Commanders") (antibody-mediated response).
●​ Recognizes: Antigens directly,
●​ Function: Coordinate immune
without needing MHC molecules.
responses by activating B cells,
●​ Can Differentiate Into:
macrophages, and cytotoxic T cells.
○​ Plasma Cells – Secrete large
●​ Recognizes: Antigens presented on
amounts of antibodies.
MHC II molecules.
○​ Memory B Cells – Provide
●​ Subtypes:
long-term immunity.
○​ Th1 Cells – Activate
macrophages (intracellular
infections).
○​ Th2 Cells – Activate
eosinophils (parasites,
allergies). II. CHEMICALS
○​ Th17 Cells – Promote
inflammation (autoimmunity). INVOLVED IN
b. Cytotoxic T Cells (CD8⁺) ("Killers") IMMUNE
●​ Function: Directly kill virus-infected
cells and cancer cells.
RESPONSE
●​ Recognizes: Antigens presented on
MHC I molecules. A. Cytokines ("Immune
●​ Mechanism:
○​ Releases perforin (creates Signals")
pores in target cells).
○​ Releases granzymes (triggers Small proteins that help cells communicate
apoptosis). during an immune response.

c. Regulatory T Cells (Tregs) ("Immune 1. Pro-Inflammatory Cytokines

Suppressors") (Increase Immune Activity)
 ●​ Interleukin-1 (IL-1) – Fever, 2. Complement Activation Pathways:
inflammation.
●​ Interleukin-6 (IL-6) – Stimulates 1.​ Classical Pathway – Triggered by
acute phase proteins (liver). antibody-antigen complexes (IgG,
●​ Tumor Necrosis Factor-alpha IgM).
(TNF-α) – Key in inflammation, 2.​ Alternative Pathway – Triggered by
fever, and cell death. microbial surfaces (LPS, fungal
●​ Interferons (IFNs, esp. IFN-α and walls).
IFN-β) – Fight viral infections. 3.​ Lectin Pathway – Triggered by
mannose-binding lectin (detects
2. Anti-Inflammatory Cytokines pathogens).
(Reduce Immune Activity)

●​ IL-10 – Suppresses inflammation

(Treg function). C. Antibodies ("Targeted
●​ TGF-β (Transforming Growth
Factor-beta) – Promotes immune Weapons")
tolerance.
Produced by B cells, antibodies help neutralize
3. Chemokines ("Immune Traffic pathogens.
Controllers")
Types of Antibodies:
Guide immune cells to infection sites.
Examples: ●​ IgG – Most abundant, crosses
placenta, provides long-term
●​ CXCL8 (IL-8) – Attracts neutrophils. immunity.
●​ CCL2 (MCP-1) – Recruits ●​ IgA – Found in mucosal surfaces
monocytes/macrophages. (tears, saliva, gut).
●​ IgM – First antibody produced in an
infection, best at forming antigen
complexes.
●​ IgE – Involved in allergies and
B. Complement System parasitic infections.
("Molecular Weapons") ●​ IgD – Involved in B cell activation
(function not well understood).
A set of plasma proteins that enhance the
immune response.

1. Functions of Complement: Conclusion:

✅ Opsonization – Coats microbes to The immune system is an intricate defense

network involving:
✅ Lysis of Pathogens – Forms the
enhance phagocytosis (C3b).​
1.​ Cells – Each with specific roles in
Membrane Attack Complex (MAC) to poke
detecting and destroying threats.

✅
holes in bacteria (C5b-9).​
2.​ Cytokines – Signaling proteins that
Inflammation – Promotes recruitment of
coordinate responses.
immune cells (C3a, C5a).
 3.​ Complement – Molecular tools to Antibodies (specific)
enhance pathogen destruction.
4.​ Antibodies – Specialized proteins SOLUBLE MEDIATORS
targeting specific invaders. Lymphocyte derived cytokines like interferon
gamma

INNATE IMMUNITY (THE RACIST IMMUNE CELLS

COPS, THE DONUT HOGGERS) T and B lymphocytes
GEN DIFF.
Natural native non adaptve
Antigen independent and non specific INNATE IMMUNITY
Immediate maximal response ( no lag time) First line of defense
Rapid response -​ Rapidly mobilized at the site of
No immunologic memory infection
​ -​ There is immediate maximal response
INSANELY FUCKING RACISTS​ (no time lag)

PHYSICAL BARRIERS
Skin gut villi lung cilia etc

CIRCULATING MOLECULES INNATE IMMUNITY

Complements First line of defense, rapid mobilization at site
of infection. Present at birth, (natural and
SOLUBLE MEDIATORS native), no immunologic memory
Macrophage derived cytokines such as
interferon gamma and alph, TNF NON-SPECIFIC
Used virtually against every possible invader.
IMMUNE CELLS Exceptions include HPV and dermatophytes
Phagocytes, NK cells
Eosinophils, K cells NON SPECIFIC DEFENSE MECHANISMS
OF HEALTHY INDIVIDUALS ICNLUDE:
Physical barriers (skin and mucosal
ADAPTIVE IMMUNITY (THE GOOD membrane)
COPS, THE INTELLIGENCE NERDS) Antimicrobial substances present in mucous
GEN DIFF. membranes include:
Acquired, antigen dependent and specific, has
lag time between exposure and maximal Antimicrobial Peptides (AMPS):
response 1.​ Cathelicidins - Pro-peptides (inactive
Slow response protein precursors) that disrupt
Antigen specific pathogen membranes
Exposure results to immunologic memory 2.​ Defensins - short amphipathic peptides
that are positively charged that disrupt
PHYSICAL BARRIERS bacterial membranes. 21 diff types
Cutaneous and mucosal immune systems 3.​ Histatins - found in saliva, effective
-​ Especially antibodies in mucosal against pathogenic fungi
secretions

CIRCULATING MOLECULES
DEFENSIN -fatty acid on skin tends to eliminate
-positively charged peptide in GL and lower pathogenic organisms
respiratory tract
-can disrupt bacterial viral and fungal cell Also include immune components important
membrane In adaptive immunity such as
Phagocytic cells and eosinophils in the blood
●​ Alpha-defensin and tissues
-​ produced by neutrophils of
small intestine A class of of lymphocytes called NK cells
-​ Released following TLR Toll-like receptors (TLRs)
activation Various blood borne molecules cytokines and
-​ Also possesses antiviral complement
activity
-​ Inhibit HIV binding to the CHARACTERISTICS OF INNATE
CXCR4 receptor to interfere IMMUNITY
with viral entry Present prior to exposure to infectious agents
or other forms of macromolecules
●​ Beta-defensin Unlike acquired immunity, exposure to
-​ epithelial cells in the antigens to enhance function cause exposure
respiratory tract. Normally does not make sense to them (not need cause
comprised of lysozymes (lysis no immunologic memory)
of bacteria by cleaving
polysaccharide backbone of Not antigen specific
the peptidoglycan of Response is antigen-independent
gram-positive bacteria) and
Lactoferrin (deprives Does not discriminate among any foreign
microbes of free iron by substances
binding to them) PAMPs on the cells of the intestine
-​ Proteolytic enzymes continuously see the LPS LTA , flagella and
(intestine) and acidic pH other components of the bacteria within the
(stomach) lumen

MUCUS Equilibrium a state maintained between the

In the mucosal epithelium of the respiratory innate immune regulatory responses and their
tract microbial stimuli

Complex mixture of mucins, proteins, BARRIER DEFENSES

proteases, and protease inhibitors ​ Generally lined by epithelial cells
connected by tight junctions that prevent entry.
Limits bacterial adhesion All barrier surfaces have a distinct microbiome
Remove entrapped organisms by cilliary that are beneficial and prevent pathogens from
clearance colonizing the body. They also possess certain
Limiting microbial adhesion and exposure chemicals that fight off pathogens too like
time antimicrobial peptides.

SWEAT AND OIL SITE COMPONENT FUNCTIONS

-acidic pH in sweat and sebaceuous secretions 1.​ Skin - stratified squamous cells, sweat
glands, sebaceous glands -
 desquamation flushing fatty acids.
Skin microbiomes (commensals) fight INNATE IMMUNE
against pathogens, like production of
antibiotics and proteases or SYSTEM PROCESS
stimulation of AMP production.
Pathogens like viruses need living 1.)​ENTRY, ALARM, AND
cells to proliferate, hence why the skin
is a perfect counter against them.
RECRUITMENT

2.​ GI tract - columnar cells - peristalsis When an invading microbe/pathogen gets in,
(flush out contents, making it hard for PRR’s (Microbial Sensors) detect PAMPs
pathogens to colonize intestinal (Pathogen-Associated Molecular Patterns).
epithelium) low pH bile salts digestive Microbial sensors: three major groups: TLRs,
enzymes defensis, fatty acids. Rapid NOD-like receptors NLRs and RIG-1 like
turnover every 4-5 days fights off helicases and MDA-5
pathogens. M cells sample antigen
from gut to present to adaptive 1.)​ TLRs
immune cells on the basolateral side, Class of PRRs (pattern recognition receptors)
but can be hijacked. GALT. Gastric that recognize pathogen-associated molecular
acid also kills microbes. patterns PAMPs

3.​ Respiratory airways and lungs - Critical in initiating immune response and
tracheal cillia - mucocilliary elevator, initiates inflamm response
surfactants, defensins. Small hair TYPE 1 transmembrane proteins
lining of cilia mucosa and mucus that -with an extracellular domain
traps pathogens via the mucociliary -a single transmembrane a-helix
escalator to take up trapped pathogens - a cytoplasmic domain
and be cleared out by compensatory
mechanisms like coughing or Starts a signal transduction cascade - generate
sneezing. inflammatory response marked by cellular
activation and cytokine release
4.​ Nasopharynx and eye - mucus, saliva,
tears - flushing lyzozyme. Saliva has
defensins too and antimicrobial TLR types
enzymes like lysozymes. 1.​ TLR1 and 6 - recognize multiple
diacyl peptides ex.mycoplasma
5.​ Blood and lymphoid - phagocytes, 2.​ TLR2 - recognize various ligands (eg.
killer (K), natural killer - phagocytosis lipotechoic acid) expressed by gram +
and intracellular killing, direct and bacteria
antibody dependent cytolysis 3.​ TLR3 - engages double-stranded RNA
(dsRNA) in viral replication
6.​ Serum and other serous fluids - 4.​ TLR4 - is specific for gram -
interferons TNF-alpha, fibronectin, lipopolysaccharides (LPS)
complement, lyzozymes, lactoferrin, 5.​ TLR7 and 8 - interact with ssRNA in
transferrin - antiviral proteins viral replication
opsonization, enhanced phagocytosis 6.​ TLR9 - bind bacterial and viral DNA
inflammation, peptidoglycan 7.​ TLR10 - remains an orphan receptor
hydrolysis, iron deprivation
 2.)​ NOD-Like receptors (NLRs) Nitric oxide NO - increases vascular
Located in the cytoplasm, serve as intracellular permeability. Causing swelling.
sensors for microbial products
Activates nuclear factor kappa light chain KININ SYSTEM - promotes bradykinin, a
enhancer of activated B cells NF-kB pathway factor for pain.
Drive inflammatory responses similar to TLRs
During infection, circulating phagocytes
3.)​ RIG-1 like helicases and MDA-5 increase and can participate in chemotaxis,
Cytoplasmic sensors of viral ssRNA migration, ingestion, and microbial killing
(single-stranded RNA)
Triggers type I IFN production, which are Phagocytes include:
highly effective inhibitors of viral replication
Cellular components and phagocytosis A.​ Monocytes and macrophages
-​ Mono mature into macro
-​ Macro contain cathelicidin (disrupts
ALARM bacterial membrane) and macrophage
Invading microbe then triggers: elastase-derived peptides
●​ Release of complement and numerous -​ Kupffer cells in the liver
cytokines -​ Microglial cells in the nervous tissue
●​ IL-1, TNF-a, IL-6, and IFN -​ Macrophages = engulf and kill
●​ Induced through TLR pathogen, process and present antigen,
regulate immune reactivity by
This kicks off an inflammation process from producing cytokines
the cytokines themselves. The inflammation
calls in the recruitment of immune response B.​ Granulocytes
cells to the site. Sort of an alarm being B.E.N cells
triggered and cops being mobilized to the site Neutro - contain alpha and beta
of the urgency. defensins, cathelicidins, as well as
lactoferrin. Phagocytic destroys
Signals sent by the host or pathogen: pathogens within intracellular vesicle
●​ IL8 (CXCCL8) - potent, attracts -​ Has secretory granules
neutrophil -​ Eosinophils and Basophils are
●​ IL-17 induces IL-8 which recruits less abundant than
immune cells to peripheral tissue Neutrophils. They contain
granules that contain enzymes
and toxic proteins
C.​ Dendritic cells - phagocytic and can
INFLAMMATION
degrade pathogens. Main role is to
Pain (dolor)
activate T cells in adaptive immunity
Swelling (tumor)
Redness (rubor)
Non-phagocytic:
Heat (calor)
D.​ NK cells
Large, granular lymphocytes. Detects
Leukotrienes, prostaglandins, PAF, Nitric
virus infected cells and tumors.
oxide, etc are released to induce vasodilation,
thereby increasing blood volume while
Contains granzyme (induce cell
slowing blood flow.
apoptosis) and perforin (make holes
 on the surface of the pathogen), kill In the main, these cells play a major
bacteria and lyse proteins of virus role in protecting the individual,
Two surface receptors with both however, recently they have been
activation and inhibition properties: implicated in pathogenesis of certain
●​ Lectin-like Nk-cell receptors - inflammatory skin disorders such as
binds proteins psoriasis (associated with ILC3
●​ Killer immunoglobulin-like dysfunction and excess IL-17A/IL-22
receptors (KIR) - recognize overproduction)
MHC class I molecules
2.) EFFECTOR RESPONSE,
NOTE: NK Cells are critical in
antibody dependent cytotoxicity AND SUPPORTING
(chemical mediators that are toxic to ACTIONS
cells) (ADCC).
1.) PHAGOCYTOSIS
●​ NK Fc receptor that binds to Process:
Fc portion of antibody 1.​ Pathogen enters blood/tissue
●​ Inhibit replication 2.​ Dependent on chemoattractant signals
●​ NK Cells and the IFN system by the host or pathogen
●​ NK cells are one of the three -​ IL8 (CXCCL8) - potent,
primary sources of attracts neutrophil
IFN-gamma -​ IL-17 induces IL-8 which
recruits immune cells to
E. Innate lymphoid cells (ILCs) peripheral tissue
Innate immune cells that regulate 3.​ Initial stage of migration to the tissue
tissue immunity. Found in lymphoid 4.​ Neutrophils attach to endothelial cell
and non-lymphoid organs via adhesion molecules (like
P-selectin)
Also preferentially populate the barrier 5.​ Phagocyte recognizes the pathogen
tissues of the skin, intestine, and lungs 6.​ Ingests pathogen
Because of their unique location, ILCs -​ Internalise pathogen into an
are among the first immune cells to endocytic vesicle called
respond to pathogens. phagosome
7.​ Destroys engulfed pathogen
Defined by their lymphoid -​ Acidification of phagosome
morphology and their lack of cell (to about pH 3.5-4.0, which
lineage markers for T cells, B cells, can be bactericidal, if not just
and other immune cells bacteriostatic)
-​ Production of toxic
Three types of ILCs identified by their oxygen-derived products
cytokine profile and distinct (superoxide O2, H202, singlet
transcription factors: O2)
1.​ ILC1 produces IFN-gamma -​ Nitrogen oxides (NO is
2.​ ILC2 produces IL-5 and IL-13 formed)
3.​ ILC3 produces IL-17A and -​ Antimicrobial peptide
IL-22 8.​ Apoptosis
-​ Once it completes its mission
 creating C4b and C2a respectively
NOTE: Can be independent of antibodies, which then bind to each other, creating
though is more efficient in their presence C4sb2a complex or C3
CONVERTASE and cleaves
circulating C3 into C3a and C3b
2.​ ALTERNATIVE
2.) OPSONIZATION (ENHANCE Proceed in the absence of the antibody
PHAGOCYTOSIS) Critical first lines of defenses and
-​ Antibody alone can act as opsonin provide immediate protection against
-​ Antibody and antigen can trigger the microorganisms (use C3, instead of
complement system (via the classical antibody). C3bBb
pathway) to generate opsonin 3.​ LECTIN
-​ Opsonin may be produced when the Bypasses antibody and uses a lectin,
alternative pathway is activated and mannose-binding lectin (MBL), to
C3 is generated initiate events. Can recognize
Macrophage have receptors on their pathogen sugars
membranes for Fc portion of an antibody and Critical first lines of defense and
for the complement component C3 provide immediate protection against
-​ Both of these receptors facilitate the microorganisms
phagocytosis of the antibody-coated Mannose binding causes activation of
pathogen MASP2 that will cleave C4 and C2 to
C4b and C2a, interconnecting with the
3.) COMPLEMENT SYSTEM classical pathway
Initiates a series of biochemical reactions that
result in cellular lysis of the pathogen
NOTE: However, some microbes have ways to
9 main complement proteins, named with a C sabotage this and evade immune response
with a given number. Once cleaved, it is either Ex.
a or b Poxviruses encode a soluble protein that
A - fragment with smaller anaphylatoxin regulates complement activity - inhibition
B - fragment with larger binding portion complement system

There are three pathways but all result in the 3.) HOMEOSTASIS AND
pathogen lysis. All three pathways are
common in cleaving C3. RESOLUTION

1.​ CLASSICAL Once the pathogen is eliminated, regulatory

Opsonization (tagging pathogens for mechanisms turn off the immune response to
immune response), pathogen lysis, or prevent excessive inflammation.
amplification of inflammatory
responses. Begin with C1 (made of Anti-inflammatory cytokines that regulate
C1q, C1r, C1s proteases). C1q can immune response:
bind to some bacterial surfaces, ●​ Interleukin-10 (IL-10) – Suppresses
antibodies, or acute phase C-reactive immune response and prevents tissue
protein. Once bound, C1q causes damages.
informational change and activation of ●​ Transforming Growth Factor-beta
C1r, then cleaves and activates C1s. (TGF-β) – Promotes tissue repair and
C1s activation cleaves C4 and C2, immune suppression.
 ●​ Failure to regulate inflammation can irritant. This migration (chemotaxis) is
lead to chronic inflammation, stimulated by proteins in the
autoimmunity, or excessive tissue inflammatory exudate, including some
damage. chemokines
-​ Chemokines produced by macrophage
and endothelial cell
Fever induced by:
MEDIATORS OF -​ Cytokines (IL-1, IL-6, TNF-alpha, and
the interferons)
INFLAMMATION AND THE
INTERFERONS
2.)​ INTERFERONS
1.)​ CYTOKINES IFN family has three groups
Cytokines are responsible for the regulation of 1.​ Type 1
inflammatory response. Also include, ●​ Comprise numerous genes and
chemokines, adhesion molecules, and growth primarily include IFN-1alpha
factors. THEY ARE NOT RELEASED IN and IFN-beta
JUST ONE STAGE, THEY OCCUR IN ALL ●​ Virus infection itself triggers
STAGES OF THE RESPONSE the production of type 1 IFNs

NOT PHAGOCYTIC, they are chemical

mediators released by macrophages and 2.​ Type II
lymphocytes to recruit more cells for ●​ Consists of a single gene that
phagocytic activity produces IFN-gamma
-​ Cytokine derived from macrophages ●​ Produced by activated Nk
and lymphocytes are different cells in innate immune
responses and by specifically
During immune response, leukocytes sensitized T cells in adaptuve
(macrophages) release cytokine such as IL-1, immune responses
TNF-alpha, iL-6
-​ Other mediators released by
macrophages include prostaglandins 3.​ Type III
and leukotrienes ●​ Interferon lambda
-​ These mediators regulate changes in ●​ Produced by T cells triggered
local blood vessels by cytokines IL-2 and IL-12
-​ Dilation of blood arterioles and
capillaries
-​ Plasma escape IFN SYSTEM
-​ Fibrin formed occludes lymphatic -​ IFN binds to its specific receptor on
channels, limiting spread of organism the surface of uninfected cells
-​ Activates JAK STAT pathways
Changes in the expression of adhesion -​ Activation of genes that initiate
molecules (selectins and integrins) on the production of selected genes.
surfaces of endothelial cells and leukocytes. -​ insert: Multiple Sclerosis
-​ Cells stick to the capillary walls and
then migrate out (extravasation) of the
capillaries in the direction of the
 the bone marrow may diff into cells of
ADAPTIVE IMMUNITY myeloid, or lymphoid series
Synonymous terms: acquired or specific Lymphoid progenitor cells: develop into B
immunity and T cells
Elicited by contact with antigens
-​ Responses is antigen dependent B lympho - stems cells developed in the bone
marrow
2nd line of defense against infection -​ Rearrange their immunoglobulin
-​ Exposure results from immunologic genes and express a unique receptor
memory for antigen on their cell surface.
-​ Antigen specific -​ After which , they migrate to a
Soluble forms of antibody in the blood, body secondary lymphoid organ like spleen
fluids, or secreted from the mucosal membrane and when the encountered an antigen
can inactivate and promote the elimination of could be activated into antibody
toxins and microbes secreting plasma cells
-can be antibody-mediated (humoral), or cell T lympho - produced in the bone marrow but
mediate travel to the thymus for maturation

COMPONENTS OF THE ADAPTIVE TWO IMPORTANT PROPERTIES OF

IMMUNE SYSTEM ADAPTIVE IMMUNITY
Components: antigens antibodies lymph -​ Immunologic memory
systems, lymphocytes; B cells, T cells, NK -​ Acquired immunity remembers and
cells recognizes each encounter with a
A monoclonal antibody recognizes a single microbe or foreign antigens
epitope - subsequent encounters stimulate
-​ Antigenic determinant that interacts increasingly effective mechanism
with a single antibody molecule or
T-cell antigen receptor -​ Basis of Vaccination
Components or variants of
Thymus -differentiation site of bone marrow microorganisms of a particular disease
stem cells (T cell precursor) from bone (measles polio) are introduced to the
marrow factory, produce T cells that interact individual and the body remembers
with the pathogen that then release of the foreign antigen
cytokines and elicit immune responses.
Release of cytokines can elicit or activate SPECIFICITY
other T cells to repeat the immune response of -​ Amplifies the protective
releasing more cytokines: macrophage mechanisms of natural
activation, inflammation, differentiation of immunity.
cytotoxic T cells -​ Directs or focuses these
mechanisms to the site of
B cell differentiate from Bone marrow. antigen entry lead to
Interaction with the cytokines produced from a elimination of the foreign
T cell leads to the release of antibodies from antigen
plasma cells. -​ Depends on the receptor of the
antigen (dengue strains of 4 -
Lymphoid cells: significant role in adaptive you need to be exposed to all
immunity response. Stem cells differentiate in 4 strains to confer complete
immunity against dengue)
TYPES OF ADAPTIVE IMMUNITY Administered to provide IMMEDIATE
A.​ Active immunity immunity to prevent incubation of deadly
Induced via stimulation of specific immune viruses
response stimulated by exposure or contact Advantage: prompt availability or large
with foreign antigens amounts of antibody
Regardless of antigen introduced, the host Con: short lifespan of antibodies and possible
actively produces antibodies, and lymphocytes hypersensitivity reactions if antibodies from
will acquire the ability to defend the said other species is administered
antigens
NATURAL ACTIVE: infection
ARTIFICIAL ACTIVE: vaccination HUMORAL IMMUNITY - mediated in the
-​ Dead organism (cholera, typhoid) blood responsible for specific recognition and
-​ Attenuated/weakened (BCG) elimination of antigens. Antibodies. Can be
-​ Live organism (smallpox) transferred to unimmunized individuals by cell
-​ Toxoid (tetanus) free portions of the blood (plasma/serum)
-​ Modified virus (polio) Secreted by B lymphocytes
Principal defense against extracellular
ADVANTAGE : long term protection (based microbes
on memory of prior contact with antigen and
the capacity to respond faster and to a greater Naive individuals - non vaccinated
extent on subsequent contact with same
antigen

CON: slow onset of protection and the indeed CELL-MEDIATED IMMUNITY

for prolonged or repeated contact with the
antigen
May cause the disease to appear in very few DIFFERENCE TABLE: HUMORAL | C-M
cases after vaccination Immunity

ANTIGEN: Extracellular microbes |

PASSIVE IMMUNITY intracellular microbes replicating within cell
Specific immunity given to an individual by
transferring whole cells or RESPONDING LYMPHOCYTES: B lympho |
immunoglobulin-containing sera from a Helper T, cytotoxic T lympho
specifically immunized individual (adoptive
transfers) EFFECTOR MECHANISM: Secretes
-​ Transmitted by antibodies or antibodies | activate the macrophage + kill
lymphocytes preformed in another infected cells
host
FUNCTIONS: Block infection and eliminate
Natural passive: transfer in vivio, colostrum extracellular microbes | Elimination of
(trans-placental, breastfeeding) phagocytosed microbes, kill infected cells and
Artificial passive: administration of immune eliminate reservoires of infection
serum
TRANSFERRED BY: Serum antibodies |
Vaccination - ex. Anti rabies and Lymphocytes
immunoglobulin vaccines
 -​ Tolerance - immunologic
unresponsiveness.
CARDINAL FEATURES OF THE IMMUNE -​ Recognize and respond to many
SYSTEM foreign Ags but normally
unresponsive to the potentially
1.)​ Specificity antigenic substance in the individual
Immune response specific for distinct Ag -​ Autoimmune diseases - abnormalities
Specific for different structural components of in the induction of self tolerance
complex proteins, polysaccharides, and other
antigens PHASES OF IMMUNE RESPONSE
Determinant of Epitopes
-​ EPITOPE - Portions of the antigen 1.​ Recognition
specifically recognized by individual 2.​ Activation
lymphocytes 3.​ Effector, development of mechanism
-​ Membrane receptor of lymphocytes that mediate the physiologic effect
distinguish subtle differences 4.​ Elimination of antigen

2.) Diversity
-​ Total number of Ag’s specificities of
the lymphocytes in an individual is
known as the Lymphocyte Repertoire 1.)​ COGNITIVE/RECOGNITION
-​ Result of variability un the strcucture PHASE
if the Ag bindings sites of lymphocyte Binding of foreign antigens to specific
receptors receptors on lymphocytes that exist prior to
-​ Different variants for different clones antigenic stimulation

3.) Memory Innate immune recognition

Exposure to a foreign Ag enhancing its ability -​ Relies on microbial sensors that
to respond upon re-exposure macrophage and other phagocytic cells
-secondary immune response - responses to possess
2nd and subsequent exposures to the same Ag Adaptive immune recognition
are usually rapid, larger, and often -​ involves specific antigen receptors
qualitatively different from the 1st response -​ Recurrent exposues can eliminated
- immunologic memory faster
- Forget? = Autoimmune manifestation B lymphocytes
-​ Produce antibody molecules on their
4.) Self Limitation surfaces that can bind to antigenic
-​ When Ags ar eliminated the stimulus proteins, polysaccharides or lipin in
is also eliminated soluble form.
-​ Lymphocytes perform these functions T lymphocytes
for brief periods after stimulation then -​ Express receptors only for short
remain as memory cells peptide sequences in protein antigens
-​ Feedback regulation -​ Recognize and respond only to
peptides present on the surface
5.) Discrimination
-​ - ability to distinguish between foreign
Ag and self Ag
 2.)​ ACTIVATION PHASE function and stimulate inflammatory
All lymphocytes undergo 2 major changes in responses
response to antigen
-​ Proliferate leading to expansion of
the clones of antigen-specific 4.) ELIMINATION-RESOLUTION
lymphocytes and amplification of the
protective response
-​ Differentiate from cells whose
primary function is cognitive into cells
that function to eliminate foreign
antigens

Antigen-recognizing B lymphocytes diff into

antibody-secreting cells
-​ Secreted antibody binds the soluble
(extracellular) antigen and triggers the
mechanisms that eliminate the antigen

If antigen is presented, by helper or accessory

cells

TWO ASPECTS
-​ Antigen recognition triggeres
numerous aplimification
-​ Lymphocytes preferentially expand in
numbers

3.)​ EFFECTOR PHASE

-​ Lymphocytes that have been
specifically activated antigens perform
the function of the elimination of the
antigen
-​ Effector cells include lymphocytes
that function in this phase

Effector functions:
1.)​ Antibodies - bind to antigens and
enhance their phagocytosis
(opsonization) by neutrophils and
mononuclear phagocytes. Activate
system of plasma proteins termed
complement. Stimulate degranulation
of mast cells and release mediators,
thus fighting infections.
2.)​ Activated T lymphocytes - secret
cytokines and enhance phagocyte
 -​ Initiate antibody-mediated immune
FINALS responses by binding specific antigens
to the B cell’s plasma
08/04/25
T cells (lymphocytes)
INNATE -​ Mature in thymus
Macrophage -​ Cell surface receptors similar to
Dendritic immunoglobulins but it is not soluble
Mast (cannot be secreted)
B.E.N -​ CYTOTOXIC T cells (CD8+ cells)
Nk cells -​ Bind to antigens on plasma membrane
Complement proteins of target
-​ HELPER T CELL (CD4+ cells)
-​ Secrete cytokines that help to activate
ADAPTIVE B cells, cytotoxic T cells, NK cells,
B cell and macrophages
T cell - CD4 and CD8 Natural killer (NK cells)
-​ Bind directly and nonspecifically to
virus-infected cells and cancer cells
IMMUNE CELLS and kill them
Leukocytes -​ Secrete cytokines that induce
-​ Various types of WBC apoptosis and inhibit viral replication
-​ Classified into two: -​ Function as killer cells in ADCC
GRANULOCYTES (B.E.N) Plasma cells (Mature B cells)
Neutrophil -​ Secrete antibodies
-​ Phagocytic capable
-​ Increased in bacterial infections MACROPHAGES
-​ Release chemical involved in inflamm -​ Phagocytic capable
-​ One fo the first to act in acute cases -​ Extracellular killing via secretion of
-​ Short lived toxic chemicals
Basophil -​ Process and present antigens to Helper
-​ Releases histamine and other chem for T cells
inflamm -​ Secrete cytokines involved in
-​ Induces allergic reactions inflamm, activation and differentiation
Eosinophil of helper T cells, and systemic
-​ Increased in parasitic infections responses to infection and injury
especially by helminth worms and (acute phase response)
other intestinal parasites Dendritic cells
-​ Participate in immediate -​ Phagocytic capable
hypersensitivity reactions -​ Antigen presentation
Monocytes Mast Cells
-​ Enter tissue and become macrophages -​ Releases granules of inflamm

LYMPHOCYTES HIERARCHY OF IMMUNE SYSTEM

B cells (lymphocytes)
-​ Mature in bone marrow 3rd line - Adaptive immune system
-​ Associated with humoral immunity 2nd line - Phagocytes NK BEN
1st LINE - Skin, mucous membrane, INFLAMMATORY RESPONSE
enzymes, natural microbial flora, complement -​ Body’s local response to infection or
injury
-​ FUNCTION: destroy/inactivate
foreign invaders and set stage for
1ST LINE tissue repair
-​ Barriers offered by surfaces exposed -​ KEY MEDIATORS: Phagocytes
to the external environments - Primarily Neutrophils and
-​ Include skin, mucous membrane, etc macrophages as well as monocytes or
-​ Cough and sneeze reflex reticuloendothelial cells and
-​ Skin glands, salivary glands, lacrimal macrophage like cells (like dendritic
glands cells)
- secrete antimicrobial chemicals such - with chemical mediators (cytokines,
as lysozymes, antibodies complement proteins, chemotactic
- Tissue macrophages factors)
​ - Resident macrophages in different
tissues GENERAL PROCESS:
Histiocytes in skin 1.)​ Surface wound introduces bacteria
Kupffer in liver which activate resident effector cells
Alveolar macrophages in lungs to secrete cytokines
Macrophages in lymph nodes, spleen, and 2.)​ Vasodilation and increased vascular
bone marrow permeability allow fluid, protein, and
inflammatory cells to leave blood and
2ND LINE enter tissue
Innate nonspecific 3.)​ The infected tissue becomes inflamed,
-​ When an agent breached the 1st line, causing redness, heat, swelling, and
2nd line encompasses inflammatory pain
factors and interferons (for viruses)
Redness due to vasodilation, increasing blood
3RD LINE pressure and flow in the area.
Adaptive immunity Heat is also due to vasodilation
-​ Crossing beyond third line results to Pain due to chemical mediators received by
disease nosi receptors (prostaglandin)

4TH LINE 1.)​ Initial entry of bacteria/toxin into

-​ When bone marrow is forced to tissue
produce more neutrophils and -​ If agent is confined to a
macrophages on order to fight localised area, then
infections lasting days inflammation is localized
-​ Results from feedback mechanism of -​ If agent crossed to blood and
macrophages and neutrophil responses lymph, inflamm would trigger
if infection had not stopped other tissues/organs reached
-​ Production of newly-formed by the bacteria
granulocyte/monocyte takes 3-4 days 2.)​ Chemical mediators-induced
but amplified production from bone vasodilation and increased protein
marrow can increase quantities of it at permeability of capillaries and venules
rate 20-50x than normal in the infected area
 -​ CHEMICAL MEDIATORS the venules and capillaries of
BASED ON ORIGIN inflamed area
a.​ Peptides 2.)​ Diapedesis
b.​ -​ Intercellular attachment
between endothelial cells of
VASODILATION CAUSE EXCESS BLOOD the capillaries and small
FLOW for red and heat venules loosen and create a
Net filtration of plasma into interstitial fluid space
-​ Space allow neutrophils to
“Walling-off effect”: fibrinogen clot by crawl directly from blood to
reaction to tissue products (e.g. histamines, tissue spaces
prostanglandins, bradykinins, serotonin) -​ Monocyte can also perform
complement system products and blood this movement when they are
clotting system transformed into macrophages
-​ Basophils and eosinophils can
Inflamm cytokines which initiate chemotaxis perform this as well but only
-​ TNF under presence of certain
-​ Interleukin -1 and 6 pathogens

3.) CHEMOTAXIS

Leukocyte exit venules into the interstitial

fluid of the infected area
Migration of large number of granulcytes and
monocytes into the tissue
Stages:
-​ 1.) marginalization
-​ 2.) diapedesis

4.) DESTRUCTION OF BACTERIA OR

AGENT
-​ Phagocytosis - cellular ingestion or the
agent
-​ Complement system pathway
- classical
- Alternative
- MBL

CHEMOTAXIS
1.)​ Marginalization
-​ Increased expression of
adhesion molecules such as
selectins and ICAM-1
-​ These adhesion molecules
react with integrin on
neutrophil surface which
causes neutrophil to stick onto
FINAL DISCUSSION B. LYMPHOCYTE RECEPTORS
(Source of Notes: Yango, 2025) ●​ The ability to distinguish one antigen
08/05/25 from another is determined by the
lymphocyte receptors.
A. The Secondary Lymphoid Organs ●​ The two lymphocyte receptors are the
●​ The Lymph Nodes, Spleen, Tonsils, T-Cell and B-Cell Receptors.
Peyer's Patches, Appendix, Mucosal ●​ The B-Cell Receptors
Associated Lymphoid Tissue (MALT), → Plasma Cells — Secrete antibodies‍​
Gut Associated Lymphoid Tissue -​ After activation, B cells proliferate &
(GALT), Bronchus Associated differentiate to plasma cells
Lymphoid Tissue (BALT). ‍​ - Plasma cells derived from a
-​ Areas where lymphocytes are particular B cell can secrete only particular
activated and participate in antibody
adaptive immune response.
Lymphocytes the secondary lymphoid organs → B-Cell Receptors — Surface proteins that
are not synthesized within them, but rather are copies of particular antibodies that is
originate from the primary lymphoid organs produced by its plasma cell progeny, which is
-​ The “the stand-by areas” of the located on the B-Cell surface
T-cells, B-cells, and Phagocytes
-​ Once in the secondary organ, a mature
lymphocyte coming from the bone → Immunoglobulins are cell surface receptors
marrow or thymus can undergo cell that are found in the B-Cells which act on a
division to produce additional specific antigen
identical lymphocytes
-​ All lymphocytes are descended from ●​ Proteins made of B-Cell Receptors
ancestors that matured in the bone and Antibodies
marrow or thymus but may not ●​ When secreted, they are considered as
themselves have arisen in those organs antibodies
Some lymphocytes may leave the secondary ●​ NOTE: The receptors, although
lymphoid organs to enter the lymphatic vessels identical to the antibodies, are not
to drain into the blood or vice versa, leave the classified as antibodies since only
blood >> enter the interstitial fluid >> secreted immunoglobulins are termed
lymphatic capillaries >> lymphatic vessels >> antibodies.
lymph nodes ●​ Five major classes — determined by
the amino acid sequences in the heavy
This recirculation happens all the time, not just chains and a portion of the light
during an infection, although migration of chains:
lymphocytes to an inflamed area is greatly IgA, IgD, IgE, IgG, and IgM
sped up by CHEMOTAXIS.
Structure of Immunoglobulins Two classes of MHC proteins:
-​ Composed of four interlinked ●​ MHC class I proteins – present on
polypeptide chains every nucleated cell
-​ Two long heavy chains and ●​ MHC class II proteins – found only on
two short light chains antigen presenting cells (macrophages,
-​ Each Ig has: dendritic cells and B cells)
-​ Fc portion – a stem that ●​ Different subsets of T cells do not all
consists of the lower half of have the same MHC requirements:
the heavy chains
-​ Fragment Antigen-binding -​ Cytotoxic T cells – require
(Fab) site – upper half of the class I MHC proteins
heavy chains and their -​ CD8 proteins binds to
associated light class I MHC proteins
-​ Helper T cells – require class
●​ The T-Cell Receptors II MHC proteins
→ Multiple DNA rearrangements occur during -​ CD4 proteins binds to
T-cell maturation class II MHC proteins
→ Millions of different T-cell clones
→ Distinct in that the cells of any given clone Rule 8: 8/MHC Class = CD of Cell
possess receptors of a single specificity
→ Maturation occurs in the thymus Class I MHC: 8/1 = 8 (CD8)
Class II MHC: 8/2 = 4 (CD4)
●​ T-Cell Receptors (CD - Cluster of Differentiation)
→ Unlike the B-Cell Receptors, they do not
produce immunoglobulins
→ T-cell receptors for antigen are not C. ANTIGEN PRESENTATION
immunoglobulins
→ Two-chained proteins that have specific ●​ Antigen-presenting Cells (APCs) –
regions that differ from one T-cell to another cells with antigen complexed with
→ Remain embedded and are not secreted like MHC proteins on their plasma
immunoglobulins membrane
→ Cannot combine with antigen unless the → For the recognition of certain Lymphocytes
antigen is first complexed with the major such as T-Cells
histocompatibility complex (MHC) → Antigens are displayed in the cell surface
such a way it can bind to a T-Cell Receptors
MAJOR HISTOCOMPATIBILITY → Aside from the T-Cells, the other cells
COMPLEX (MHC) involved in antigen presentation are called
→ Are plasma membrane proteins and Antigen-Presenting Cells (APCs)
participate in antigen presentation → APCs involved are usually the
→ MHC Proteins – proteins that are coded by macrophages, dendritic cells, and B-Cells.
genes that can be located in a single
chromosome
→ MHC Proteins – genetic markers of
biological individuality, "Identity Tags"
→ Self vs Non-self Recognition – ability of T
cells to distinguish its own cells from foreign
cells
Presentation to Helper T-Cells -​ The secretion by APCs of
IL-1 and TNF upon binding
●​ Helper T-Cells require MHC Class II with the Helper T-Cell act as
Proteins for antigen presentation Paracrine agents on the
●​ As mentioned for Helper T-Cells, attached Helper T-Cell which
APCs involved are the macrophages, act as a stimulus for the
dendritic cells, and B-Cells activation of Helper T-Cells
●​ Antigen Presentation by Macrophages ●​ Attachment of pairs of Non-specific
Plasma Proteins
Macrophages are the immune cells that form a -​ The attachment of the protein
link between the nonspecific and specific pairs from the surface of the
immunity. Helper T-Cells and APCs
●​ When microbes or foreign antigens are provide a necessary
phagocytized by the Macrophages, costimulator for Helper T-Cell
they are partially broken down by activation
Proteolytic Enzymes into smaller ●​ Antigen Presentation
fragments -​ The presentation of antigen
●​ The MHC II Proteins present in the fragments on the cell surface
macrophage with the resulting will and the Helper T-Cell’s
bind fragments (aka: Antigenic subsequent binding to it
Determinants or Epitopes) -​
●​ The complex of MHC II Protein and → The activation of Helper T-Cells by the
Epitope will be transported to the mentioned methods cause the Helper T-Cells
plasma membrane and displayed on to secrete Interleukin 2 (IL-2) and express the
the cell’s surface. This complex receptor for IL-2, and secrete other cytokines
displayed on the cell surface is where The released IL-2 and other cytokines have a
the Helper T-Cell binds. autocrine effect on the Helper T-Cell and
paracrine effect on the nearby Cytotoxic
Antigen Presentation of B-Cells T-Cells, NK Cells, adjacent B-Cells and other
→ The same process as the antigen cell types
presentation in Macrophages
→ The B-Cells ability to act as an Antigen Presentation to Cytotoxic T-Cells
Presenting Cell is only its secondary function
→ B-Cells primary function is still in the ●​ APCs for the Cytotoxic T-Cells are
secretion of immunoglobulins virtually all cells except the
erythrocytes. Since the MHC Class I
Antigen Presentation and the Activation of proteins that bind with the Cytotoxic
Helper T-Cells T-Cells involve only nucleated cells.
→ Antigen presentation is important for the ●​ The cells involved are those usually
activation of the Helper T-Cells infected by viruses and the cancer
→ The binding of the APCs to the Helper cells.
T-Cells is not enough to activate the Helper ●​ The antigens that form the complex
T-Cell with MHC Class I protein arise from
→ APCs aid in the activating of Helper the cell (Intracellular, Endogenous)
T-Cells by the following ways:
→ Virus-infected cells manufacture viral
●​ Secretion of Interleukin 1 (IL-1) and proteins due to the viral nucleic acids present
Tumor Necrosis Factor (TNF) in the host cell
→ Cancer cells have altered genes such as 5.​ These antibodies combine with the
protein synthesis. The cells reproduce antigen on the surface of the bacteria
uncontrollably, proteins that are not normally anywhere in the body.
found in the cell. 6.​ Presence of antibodies bound to
→ Some of these unusual proteins are antigen facilitates phagocytosis of the
hydrolyzed by cytolytic enzymes into peptide bacteria by neutrophils and
fragments, which are transported to the macrophages. It also activates the
endoplasmic reticulum (ER). complement system, which further
→ In the ER they are complexed with the enhances phagocytosis and can
MHC Class I proteins and by exocytosis directly kill the bacteria by the
placed on the cell’s surface membrane attack complex. It may also
→ Once on the surface the Cytotoxic T-Cells induce antibody-dependent cellular
bind with them and subsequently destroy the cytotoxicity mediated by NK cells that
cell as per the Cytotoxic T-Cell’s function. bind to the antibody's Fc portion.

Summary of Events in Antibody-Mediated Antigen Recognition and Lymphocyte

Immunity Against Bacteria Activation

1.​ In secondary lymphoid organs, ●​ Bacteria that penetrated the first line
bacterial antigen binds to specific of defense, the body’s linings, and
receptors on the plasma membrane of entered the interstitial fluid
B cells. ●​ Bacteria that enter the Lymphatic
2.​ Simultaneously, antigen-presenting System and the bloodstream are
cells (APCs), for example, carried to the lymph nodes or the
macrophages, (a) present to helper T spleen
cells processed antigen complexed to ●​ At the spleen or lymph nodes, the
MHC class II proteins on the APCs, B-Cells for a specific for an antigen on
(b) provide a costly stimulus in the the bacterial surface will bind to the
form of another membrane protein, antigen using their plasma membrane
and (c) secrete IL-1 and TNF, which immunoglobulin receptor
act on the helper T cells. → The antigen binding with the B-Cell may
3.​ In response, the helper T cells secrete result in activation of the B-Cell (Rarely
IL-2, which stimulates the helper T happens)
cells themselves to proliferate and → Usually the binding with the antigen is not
secrete IL-2 and other cytokines. enough to activate the B-Cell. The cytokines
These activate antigen-bound B cells released by the Helper T-Cells in the
to proliferate and differentiate into interstitial fluid are also needed for the
plasma cells. Some of the B cells activation of the antigen-bound T-Cells.
differentiate into memory cells rather → For the Helper T-Cells to secrete cytokines
than plasma cells. they must be first bound to a complex of
4.​ The plasma cells secrete antibodies Antigen-MHC Class II protein on an APC.
specific for the antigen that initiated ●​ When APCs are finally bound to
the response, and the antibodies Helper T-Cells, particularly
circulate all over the body via the Macrophages, the APCs secrete IL-1
blood. and TNF that further stimulate the
Helper T-Cells
 ●​ Further stimulation of the Helper → BEST ACTIVATOR OF THE CLASSICAL
T-Cells via IL-1 and TNF causes it to COMPLEMENT PATHWAY
secrete IL-2 and express its own
immune response. IgA
●​ IL-2 (Interleukin 2) acts as a Paracrine → 2 subclasses: IgA1 (serum IgA; usually
agent and further stimulates and monomer), IgA2 (secretory IgA; usually
activates Helper T-Cells dimer)
●​ Activation of the Helper T-Cells cause → Major antibodies or SECRETIONS (tears,
the cells to proliferate /divide, mucus, milk, etc.)
beginning the mitotic cycles → Blocks attachment of pathogens to host
●​ The formation of clones of activated cells in mucous membranes
Helper T-cells that release both IL2
and other cytokines IgD
→ Primarily a cell membrane surface
→ CYTOKINES - additional signals required component of B cells
by antigen-bound B-cells to differentiate into → Functions in Immunoregulation, although
plasma cells in order to secrete antibodies unclear
→ NOT all B-cells differentiates into Plasma → Probably help initiate B cell differentiation
Cells, some differentiate into Memory Cells into plasma cells and memory B cells

IgE
Antibody Secretion → Participate in defenses against multicellular
parasites and mediate ALLERGIC
IgG RESPONSES
→ Mainly produced in ANAMNESTIC
responses (second exposure to the same
antigen)
→ Indicates a REINFECTION or near
recovery
→ Predominant serum antibody
→ Only IgG that crosses the placenta, thereby
conferring maternal immunity
→ Incapable of agglutination alone (needs
Anti-Human globulin or AHG)
→ Subclasses IgG1, IgG2, and IgG3 can
Activation of the Complement System
activate the classical complement pathway
→ The presence of the antibody of the IgG or
(subclass IgG4 cannot)
IgM class bound to the antigen activates the
→ Usually exists as a monomer
classical complement pathway (in contrast
with nonspecific immune responses that
IgM
activate the alternative complement pathway)
→ First circulating antibody to appear in
→ C1 molecule binds to Fc portion of the
response to an INITIAL EXPOSURE to an
antibody combined with the antigen
antigen; concentration then declines rapidly
→ Enzymatic portions of the C1 molecule is
→ Indicates a CURRENT infection
activated, thereby initiating the entire classical
→ Has a pentameric structure, which means
pathway
more antigen-binding sites, making it very
→ The end product of the cascade, the
efficient in agglutinating antigens
membrane attack complex (MAC), can kill the
→ Too large to cross the placenta
cells to which the antibody is bound by ●​ Subsequent infection by the same
making their membranes leaky invader elicits an quicker response
→ The C3b complement molecule is also ●​ Active Immunity – resistance built up
activated, functioning as an opsonin that as a result of body’s contact with
enhances the phagocytosis of the microbe by microorganisms and their toxins
neutrophils and macrophages ●​ Passive immunity – direct transfer of
antibodies from one person to another.
→ IgG transferred from mother to fetus.
→ IgA from breastmilk

Effects of Antibodies F. IMMUNE CELL & THEIR ROLE IN

●​ Direct Enhancement of Phagocytosis VIRAL INFECTION/CANCER
→ The antibodies can directly act as opsonins
Acting as opsonins, the antibodies links the Cytotoxic T-Cells
phagocyte to the antigen ●​ The virus is presented, then helper
Attachment of Phagocytes to the Fc portion of T-cells help cytotoxic T-cells to
antibodies trigger the phagocytosis of the produce more T-cells
bacterium ●​ Once stimulated, Cytotoxic T-cells
releases Perforin (perforate)
●​ Antibody-Dependent Cellular
Cytotoxicity (ADCC) Macrophages and NK Cells
→ Antibodies can link target cells to NK cells, ●​ NK cells are involved in
which can kill the targets by secreting toxic antibody-dependent cellular
chemicals cytotoxicity
→ It is the antibodies that confer specificity in ●​ Activated helper T cell secretes
this process interferon gamma (IFN-γ) and IL-2
●​ → Activates macrophages and NK
●​ Direct Neutralization of Bacterial cells
Toxins and Viruses ●​ Activated macrophages and NK cells
→ Toxins secreted by bacteria can act as secrete chemicals that kill cells
antigens ●​ NK cells can release IFN-γ, resulting
→ antigens combine with the free toxins, in a positive feedback loop
preventing the interaction of the toxins with
susceptible cells
→ Due to 2 binding sites on each antibody,
clump-like chains of antibody-antigen
complexes are formed, then phagocytized.
→ similar process for viruses
→ antibodies bind to viral surface proteins

E. ACTIVE AND PASSIVE HUMORAL

IMMUNITY

●​ After first contact with antigen,

antibody production occurs slowly
over several weeks
 -​ Occurs as the result of binding of
IV. HYPERSENSITIVITY REACTIONS antibodies to the red cell membrane
that fail to activate complement but
●​ Altered and exaggerated responses of promote macrophage uptake as in
the immune system HDN caused by Rh incompatibility
●​ Caused by allergens → Antibody-dependent cell-mediated
●​ Allergic tendency is genetically passed cytotoxicity (ADCC)
from parent to child and is -​ Occurs as a result of cytotoxic
characterized by the presence of large antibodies deposed fixed on the
amounts of IgE antibodies. surface of effector cells and
●​ Defect in mechanisms underlying subsequent antigen binding,
self-recognition performin-dependent or
●​ May be classified depending on granzym-dependent cell lyses of the
mechanisms involved cell bearing the antigen.
→ Types I, II, III
→ Type IV
C. TYPE III Hypersensitivity (Immune
Complex)
A. TYPE I Hypersensitivity
(Immediate-Type/Anaphylactic) ●​ Caused by antibody-antigen
●​ Antigens causing this type of complexes
hypersensitivity are defined as ●​ Antibody-antigen complexes deposit
allergens in tissues and lead to a tissue reaction
●​ → e.g., asthma which is initiated by complement
●​ Antigen stimulates B cells to produce activation and leads to mast cell
IgE with the help of T cells degranulation, leukocyte chemotaxis
●​ The portion of IgE antibodies bind to (predominantly neutrophil), and an
high affinity receptors on the inflammatory reaction caused by the
membrane of mast cells and basophils activation of these cells
●​ Upon contact with Ag >> receptor → e.g., Arthus reaction
cross-linking and degranulation
(release of vasoactive amines such as
histamine and serotonin) D. TYPE IV Hypersensitivity (Delayed
Type)
●​ Sensitization phase
B. TYPE II Hypersensitivity → Helper T cells (TH1) are activated by
(Antibody-Dependent Cytotoxicity) intracellular pathogens, leading to clonal
expansion and differentiation of
●​ Caused by direct antibody-mediated antigen-specific cells into TH1 clones
cell damage or lysis → e.g., Rh
incompatibility ●​ Effector phase
●​ Types: → Upon reencounter with antigen, TH1 clones
→ Complement-dependent red blood cell lysis undergo further clonal expansion and secretion
-​ Occurs in hemolytic transfusion of cytokines and chemokines that lead to
reactions (HTR) caused by ABO macrophage activation and to the development
incompatibility of a local tissue inflammation.
→ Antibody-body dependent red blood cell e.g., Skin rash after contact with
degradation poison ivy
 → When activated: A goes
V. AUTOIMMUNE DISEASES away (fluid form), B binds (solid
form)
●​ Autoimmune Disease – an
inappropriate immune attack triggered ●​ Brief overview:
by the body’s own proteins acting as → Bacteria present in tissue
antigens → Macrophages present
→ Mediated by autoantibodies and antigen to helper T cells
self-reactive T cells → Helper T cells convert B
●​ Examples: cell to Plasma cell
→ Multiple sclerosis – myelin sheath is → Plasma cells produce
attacked antibodies that bind to antigen
→ Myasthenia gravis – receptors for → Antibody-Antigen complex
acetylcholine on skeletal muscle cells are is formed (triggers
targeted complement system)
→ Rheumatoid arthritis – joints are damaged → In Fc portion of antibodies,
→ Type I diabetes mellitus - conformational change occurs,
insulin-producing cells of the pancreas are exposing loops where proteins
destroyed of the complement system will
first bind

●​ Sequence of proteins according to

their appearance in the pathway
→ C1 > C4 > C2 > C3 > C5 > C6 >
VI. COMPLEMENT SYSTEM C7 > C8 > C9

●​ Complex system composed of many ●​ Form the membrane attack complex

proteins that act in a sequential (MAC) that will ultimately kill the
cascade and links the innate and pathogen byboring holes into its
adaptive immune system membrane, allowing salts, ions, and
●​ Complement proteins are synthesized water to pass through, disrupting its
by the liver and enter the circulatory intracellular integrity
system (exception: some are from
macrophages; C1 is from GIT) Three Pathways of the Complementary
●​ Most are proenzymes (inactive forms) System
that require selective proteolysis for
activation 1.​ Classical Pathway
●​ Antibodies that specifically activate 2.​ Lectin Pathway
complement system: IgG, IgM 3.​ Alternative Pathway
●​ Most of complement proteins have A
and B parts (except C1, which has
subcomponents q, r, and s, with q
binding to Fc loop of antibody)
→ When the A and B
components are together, the proteins
are inactive
The Classical Pathway
1.​ C1 q binds to Fc of antibody
2.​ C1 activated
3.​ C1 activates C4 (C4a goes away, C4b
binds)
4.​ C4 activates C2 (C2a goes away, C2b
binds)
5.​ C4b-C2b make a very active complex
that activates C3 (that is why it is also
called C3 convertase)
6.​ C3 activated (C3a goes away, C3b
binds)
7.​ C4b-C2b-C3b activates C5 (that's why
it is called C5 convertase)
8.​ C5 activated (C5a goes away, C5b
binds)
9.​ C6, C7 binds to C5b
10.​ C8, C9 binds to C5b-C6-C7
11.​ C5b-C6-C7-C8-C9 complex forms
MEMBRANE ATTACK COMPLEX
(MAC)

YOU HAVE MADE IT TO THE FINISH LINE,

CLASSMATE. I WISH YOU GOOD LUCK TO
WHOEVER READ THIS MESSAGE

END
ALL CREDITS OF THE NOTES GOES
TO MA’AM HAZEL
Ctto…
 Following their development and initial
selection, mature yet antigen-inexperienced
(naïve) lymphocytes exit the primary
lymphoid organs and enter the circulation.
Migration through the bloodstream ensures
that these cells continuously access and patrol
peripheral sites for potential antigens.
Importantly, they home to secondary lymphoid
organs such as lymph nodes, spleen, Peyer’s
patches, tonsils, and mucosal-associated
lymphoid tissues, which are specially
structured environments designed to optimize
interactions between antigens,
antigen-presenting cells (APCs), and
lymphocytes.

The Role of Secondary Lymphoid Organs in

EXPANDED ANTIGEN PRESENTATION Immune Activation
PATHWAY:​
​ Secondary lymphoid organs (SLOs) develop
Lymphocyte Growth and Maturation: during embryogenesis or in the first weeks
Locations and Sequential Development after birth via tightly regulated interactions
among hematopoietic, stromal, and
Lymphocyte development is a foundational mesenchymal cells. These tissues include
process for adaptive immunity, beginning in lymph nodes, spleen, Peyer's patches, and
specialized anatomical structures known as mucosal-associated lymphoid structures, and
primary lymphoid organs and progressing provide a unique anatomical context for the
through stages that culminate in activation efficient initiation of immune responses. SLOs
within secondary lymphoid organs. Primary serve three critical functions: they concentrate
lymphoid organs include the bone marrow and antigens from peripheral sites, provide
the thymus. In the bone marrow, hematopoietic platforms for interaction between naïve
stem cells (HSCs)—which possess the lymphocytes and APCs, and create
capacity to give rise to all blood cell microenvironments for lymphocyte activation,
types—differentiate into lymphoid proliferation, and differentiation. Their
progenitors. B lymphocytes (B cells) mature in architecture is meticulously
the bone marrow, undergoing processes such organized—distinct zones are populated by B
as clonal selection to eliminate self-reactive cells (follicles) and T cells (paracortex or
clones while generating a diverse array of periarteriolar lymphoid sheaths), and networks
antigen receptors. The thymus is the site of T of stromal cells coordinate cellular movement
lymphocyte (T cell) maturation, where bone via chemokine signaling.
marrow-derived progenitors undergo rigorous
selection events—positive and negative
selection—to establish a functional, Migration Patterns: Lymphocyte Homing
self-tolerant T cell repertoire. and Surveillance
Naïve lymphocytes must circulate through presented. Broadly, there are two primary
various SLOs to maximize the chance of MHC antigen presentation pathways:
encountering their specific antigen.
Lymphocyte migration into SLOs is initiated 1. MHC Class II Presentation (Exogenous
as they exit the bloodstream and enter these Pathway):
organs via specialized blood vessels called
high endothelial venules (HEVs). The homing Exogenous antigens—such as those derived
process is governed by a complex interplay of from extracellular pathogens—are internalized
adhesion molecules (e.g., L-selectin) on into endocytic compartments, processed into
lymphocytes and their respective ligands peptide fragments, and loaded onto MHC class
(vascular addressins) on HEVs, as well as II molecules. MHC class II molecules,
chemokine gradients generated by stromal and synthesized in the ER with the invariant chain
hematopoietic cells within the lymphoid (Ii) to prevent premature peptide binding,
tissues. Once within SLOs, directed travel to endosomal/lysosomal compartments
migration—regulated by chemokines acting on where the Ii is removed and antigenic peptides
CCR7, CXCR4, and other receptors—delivers are loaded with the help of HLA-DM (or
lymphocytes to appropriate H-2DM in mice). These peptide-MHC II
microenvironmental niches, such as B-cell complexes are then transported to the cell
follicles or T-cell zones, thereby orchestrating surface for recognition by CD4+ T cells.
precise interactions required for immune
activation.
2. MHC Class I Presentation (Endogenous
Antigen Uptake: Initial Steps Toward Pathway):
Presentation
Endogenous antigens, typically derived from
Antigen uptake is performed primarily by proteins synthesized within the cell—such as
professional APCs, which include dendritic viral or tumor antigens—are degraded by the
cells (DCs), macrophages, and B cells. These proteasome into short peptides. These peptides
cells continuously sample their environments are translocated into the ER by the transporter
for pathogens, abnormal self-components, or associated with antigen processing (TAP) and
foreign molecules. They acquire antigens via loaded onto MHC class I molecules with the
endocytosis, phagocytosis, or assistance of chaperone proteins and the
macropinocytosis, depending on their peptide-loading complex. The stable
specialized capacities. Dendritic cells are peptide-MHC I complex is then transported
particularly adept at capturing and transporting via the Golgi to the cell surface, ready for
antigens from peripheral tissues to SLOs, recognition by CD8+ cytotoxic T
where they undergo maturation, upregulate lymphocytes.
costimulatory molecules, and vastly improve
their ability to stimulate naïve T cells.
Cross-Presentation:
Antigen Processing and MHC Pathway
Specification Some DC subsets can process extracellular
antigens and present them via MHC class I
The nature of the antigen and its cellular molecules, a mechanism termed
location determine its route of processing and cross-presentation, which is essential for
the type of major histocompatibility complex initiating CD8+ T cell responses to
(MHC) molecule on which it will be extracellular pathogens and tumors.
 costimulatory molecules, enhancing APC
Antigen-Presenting Cells and Delivery to immunogenicity. A lack of costimulatory
Secondary Lymphoid Organs signaling results in T cell anergy or tolerance,
preventing autoimmunity.
Upon processing antigens and upregulating
costimulatory molecules, mature APCs Additionally, APCs deliver cytokine signals
(particularly DCs) migrate from peripheral (Signal 3) that direct T cell
tissues to SLOs, following chemokine cues differentiation—such as IL-12 for Th1
such as CCL19 and CCL21. Within SLOs, polarization or IL-4 for Th2 responses—thus
APCs strategically position themselves at tailoring the adaptive immune response to the
T-cell zones, increasing the efficiency of context of infection or inflammation.
contact with rare, antigen-specific naïve T
cells. B cells primarily recognize unprocessed Lymphocyte Activation: Molecular Events
antigens directly via their surface and Signal Transduction
immunoglobulins in SLO follicles, but they
also act as APCs for T helper cell activation. The union of TCR:MHC-peptide (Signal 1)
with costimulation (Signal 2) triggers a
cascade of intracellular signaling within
lymphocytes. This includes the activation of
T Cell Scanning and the Immunological tyrosine kinases (e.g., Lck, ZAP-70), second
Synapse messenger systems, and adapter proteins that
bridge antigen receptor signaling to nuclear
Within the microenvironments of SLOs, naïve transcription factors. Key pathways such as the
lymphocytes dynamically scan APC surfaces MAPK/ERK, PI3K/Akt, and canonical NF-κB
for their cognate peptide-MHC complexes. signaling are engaged, orchestrated in part by
Productive interaction occurs when a T cell’s the CBM complex
antigen receptor (TCR) specifically recognizes (CARMA1-BCL10-MALT1), which is central
an antigenic peptide presented on an to T and B cell activation. These molecular
appropriate MHC molecule by an APC. This events culminate in gene transcription required
interaction forms the immunological for cytokine production (e.g., IL-2),
synapse—a specialized junction through which proliferation, survival, and differentiation of
critical signals are exchanged. lymphocytes.

Co-stimulatory Molecules and Signal Cytokine feedback loops and signals from the
Integration local microenvironment further direct the
lineage commitment of activated lymphocytes
For full T cell activation, recognition of the toward distinct helper (Th1, Th2, Th17, Tfh),
peptide-MHC complex (Signal 1) must be cytotoxic, or regulatory T cell fates, and the
accompanied by additional costimulatory maturation of B cells into plasma cells or
signals (Signal 2), predominantly provided by memory B cells.
interactions between B7 molecules
(CD80/CD86) on APCs and CD28 on T cells. Effector Differentiation and Migration
Dendritic cells, which constitutively express
high levels of B7, are especially effective at Following clonal expansion, activated
priming naïve T cells. Inflammatory stimuli lymphocytes upregulate specific adhesion and
and pathogen-associated molecular patterns chemokine receptors that facilitate their exit
(PAMPs) detected by pattern recognition from SLOs and migration to peripheral tissues
receptors on APCs upregulate these where their effector functions are needed.
Effector T cells and plasma cells thus provide
targeted immune responses—eliminating
pathogens, infected cells, or tumors—and
establish long-lived immunological memory.