DAB IMMUNOLOGY MODULE THREE CLASS

What’s immunology?
Immunology is the study of the body defence against parasites, microbes and foreign
substances. Or immunology is the study of the processes by which the body defends and
maintains the constancy of its internal milieu against invasion by foreign organisms
(antigens), mutations, development of unwanted cells and cell products within itself.
Brief history of immunology
Origin of immunology is usually attributed to Edward Jenner who discovered in 1796 that
cowpox or vaccinia induced protection against smallpox. He called this procedure
vaccination. In 1979 WHO declared smallpox eradicated.
Robert Koch proved that infectious disease are caused by microorganisms. Each
microorganism was responsible for a particular disease. Four types of disease causing
organisms (pathogens) were identified; bacteria, fungi, parasites and viruses
Louis Pasteur derived a vaccine against cholera in chicken and also developed rabies vaccine.
These practical triumphs led to a search for the mechanism of protection and to the
development of science of immunology. In 1890, Emelvon Behring and Shibababuro Kitsato
discovered that the serum of vaccinated individuals contained substances called antibodies
that are specifically bound to relevant pathogens.
What immune system?
This is the system of the body that offers protection against invasive foreign organisms. The
immune system has evolved to be able to identify self from non self. It has the capability of
recognizing non self and reject it. It consists of two main subdivisions
i. Innate immune system (non-specific)
ii. Adaptive immune system (specific)
Immunity
This is an intrinsic or acquired state of resistance to an infection. Immunity is the resistance
of a host organisms to invasive pathogens or their toxic products. Lack of immunity is called
susceptibility
Types of immunity
Immunity is divided into two main types;
i. Innate immunity/non-specific/natural immunity
ii. Adaptive immunity / specific / acquired

Innate immunity
This is the immunity that is present at birth. It includes general common protective reactions
of the organism against invasion. It is the first line of defence against invading
microorganisms. Innate immunity does not involve specific recognition of foreign agents. It
is most useful in protection against
 Pyogenic organisms eg staphylococcus aureus
 Haemophilus influenza
 Fungi eg Candida albicans
 Multicellular parasites eg A lumbricoides larvae
Characteristics of innate immunity
i. Present at birth
ii. Present for life
iii. Non-specific
iv. No immunological memory
v. Does not change in intensity with exposure
Mechanisms of innate immunity
Innate immunity operates through various factors;
1. Mechanical barriers
a) The intact skin and mucous membranes of the body provide high degree of
protection against pathogens. The skin act as an outer barrier of keratinized
epithelium against microorganisms, chemicals and living agents. The relatively
dry conditions of the skin and high concentration of salts in dry sweat are
inhibitory and lethal to many microorganisms.
b) Mucous membrane prevents entry of microorganisms (pathogens). They act as
trapping mechanisms of inhaled particles. These membranes line the GIT,
respiratory, urinary and reproductive tract. The mucosal secretion continually
washes and cleanse the mucosal surface
c) Cilia help in the removal of debris and foreign matter
2. Surface secretions
 Sebaceous secretions and sweat contain bactericidal and fungicidal fatty
acids that provide protection against many potential pathogens
 Nasal secretions and saliva contain mucopolysaccharides capable of
blocking some viruses.
 Tears and mucous secretions contain lysozyme that is particularly active
against some gram negative bacteria. The washing action of tears and
flushing of urine are effective in stopping invasion of microorganisms.
3. Cellular mechanisms
These are major cellular components involved in natural defense. The main cells
involved in defense against invading organisms are;
i. Phagocytes; - Monocytic macrophages and neutrophils- they carry out
phagocytosis of invading microbes. Phagocytes also interact and cooperate
intricately with complement system and specific immune system to potentiate
their defence action
ii. Natural killer cells (NK-cells) can damage virus infected tissues hence they
are important in controlling viral infections. They are important in
 immunological surveillance against neoplastic (cancer) because they are
cytotoxic to many types of tumor at their first exposure
iii. Eosinophils cells: - These cells have granules that contain an array of enzymes
and toxic molecules that are active against worms. These parasites are killed
extracellularly
iv. Platelets; - They participate in coagulation process, control of bleeding and
defense against infections. These cells express PRRs on their surface and
produce cytokines and chemotactic molecules to recruit leucocytes to
inflammatory site
v. Epithelial and endothelial cells; - In addition to acting as physical barriers, the
epithelial and endothelial cells express PRRs on their surface that recognize
PAMPs from microorganisms; secrete proinflammatory cytokines and release
antimicrobial peptides
4. Inflammation; - This is the nonspecific response of the tissues to injuries often caused
by pathogens such as bacteria or endotoxins (LPS), trauma, damaged cells, toxic
compounds or heat. It is characterized by increased blood flow to the tissues,
increased temperature, swelling, redness and pain. It acts by removing these harmful
elements and initiating healing a process. Inflammation leads to protection against
infection and promotes healing

5. Biochemical factors
a) HCL of gastric secretions has antibacterial activity
b) Human milk provides antibacterial substances against E. coli and Staphylococci
(called lactoferritin and neuraminic acid).
c) Interferons; -
 This is a family of glycoproteins that are produced by nucleated
human cells. They inhibit viral replication and cell proliferation of
certain tumor cells. They bind to receptors of uninfected neighboring
cells to induce antiviral state- this state result in the production of
enzymes that inhibit translation and destroy MRNA, therefore
progeny virus cannot be produced. The viral infected cell is thus
isolated from health cells that would permit viral replication.
Interferons ideally inhibit host cell function as well as virus
production.
 Act as anti-cancer agents eg Type 1 interferons (β and).
 Interferons also act on cells of the immune system in both
stimulatory and inhibitory fashion, cells such as NK- cells,
macrophages etc
d) Lysozyme are proteolytic enzymes exo-secreted by macrophages and are found in
most tissue fluids such as saliva, tears and human milk except in cerebral spinal fluid,
sweat and urine. They provide protection against gram negative bacteria. These
enzymes hydrolyze the peptidoglycan of the cell wall of G- bacteria
e) Defensins;- These are cationic peptides that produce pores in the membrane of the
bacteria and their by killing them. They are present mainly in lower respiratory tract
and GIT. Respitaory contain ß- defensins and GIT contain α-defensins
 6. Normal bacterial flora/ biological barrier
The normal bacterial flora of the skin may produce various antibacterial substances
such as bacteriocines or acids. The flora plays a role in excluding other
microorganisms; for example;
a) They compete with the potential pathogens for essential nutrients
b) The lactobacilli of the vagina produce acids during normal metabolic processes
which increase the Ph to Ph. 4. This prevents growth of pathogenic bacteria, yeast
and parasites. If this flora is disturbed by antibiotic, the pathogenic bacteria, yeast
and parasites will establish.

7. Humoral defence mechanisms

A number of microbicidal substances are present in tissues and body fluids others are
produced in response to an infection such as ;
 Acute phase proteins: - These are proteins present in the serum in low
concentration but their concentrations rise during an infection. For
example, Interleukin-I (IL-1) and other cytokines stimulate the liver during
infection to produce acute phase proteins to high concentrations such as C-
reactive protein which bind to the cell wall of certain microorganisms and
help to activate the complement.
 Basic proteins derived from tissues and blood cells have some antibacterial
properties such as spermine and spermidine can kill tubercle bacilli and
staphylococci. These basic proteins act non-specifically with acid
polysaccharides at the bacterial cell surface
 Complement system; - It comprises of about 20 distinct proteins factors
present in low concentration in normal serum and contributes to normal
body defense. These proteins are in inactive form but can be activated to
form an enzyme cascade- where the product of the first reaction is the
catalyst of the next and so on. Complement potentiates phagocytosis,
destruction of various microorganisms and parasites. It also stimulates
inflammatory reactions.
8. High temperature or fever
a) Cytokines 1L-1, IL-6 and TNF generated in response to bacterial infection cause
hypothalamic thermostat to reset higher (high temp/fever). Growth of some
bacteria is normally optimized to normal body temperature 37 0C and therefore
higher temperature results in partial inhibition of their growth eg Gonococci are
readily killed at temperature of over 400C
b) Phagocytosis and respiratory burst are more efficient at high temperature.
Therefore, pyrexia (increased temperature) that follows so many different types of
infections can function as protective response against the invading
microorganisms
Determinants of innate immunity/ factors influencing innate immunity
1. Environment; - In human the habit and environment of a community affects the
ability to resist a particular infection. eg Caucasians are more resistant to TB than
certain other racial groups
 2. Genetic factor; - Genetic makeup of an individual may influence susceptibility to
infection eg hereditary of abnormality of RBC (sickling)- the RBC cannot be
parasitized by Plasmodium falciparum thus conferring a degree of resistance to
malaria in affected individuals
3. Age;--Infections are more severe in young ones and elderly. The young ones is due to
immaturity of immunological mechanisms that affect the ability of the lymphoid
system to deal with and react with foreign agents. In elderly, the waning of activities
of the immune system, physical abnormalities, and long term exposure to
environmental factors eg smoking lead to susceptibility to infection
4. Sex/hormonal influence-; - There is a marked difference in susceptibility to infection
between sexes. However, the overall incidence of death rate from infectious diseases
is greater in males than females. For example; Autoimmune diseases are more
common in females than males such as Thyroid autoimmune diseases, type 1 diabetes
etc
5. Natural factors; - Poor nutrition or inadequate diet may lead to increased
susceptibility to a variety of bacterial diseases because of decreased phagocytic
activity or low leukocyte number
ADAPTIVE /ACQUIRED IMMUNITY/ SPECIFIC IMMUNITY
Adaptive immunity is a specific reaction of the body to non-self-agents in which the body
immune products react specifically with the stimulating agent. The body reacts to the
organism that induces the response. It is the second line of defence and it is antigen specific.
The immune also provided protection against re-exposure to same organism (immunological
memory). It is most useful in protection against bacteria, intracellular influenza, viruses and
protozoa.
Characteristic of adaptive immunity
1. Not present at birth. It is gained as part of the body development
2. Is specific and diverse in response. Immune responses are directed against selected
parts of the antigen known as antigenic determinants (epitopes)
3. Immunological memory: - memory cells are formed during the primary response to a
particular antigen. Subsequent re-exposure to this particular antigen result in a more
effective and rapid response than the primary response
4. Regulation: - all normal immune responses decline with time as the stimulus (antigen)
is removed.
5. Self – tolerance: - the immune system is able to respond and destroy foreign material
but yet remain unresponsive to self- molecules.
6. The immune responses intensity increase with continue exposure
Types of acquired immunity
Acquired immunity is divided into passive ot active immunity both of which may be either
natural or artificial
a) Acquired passive immunity
It involves either the transfer of antibodies or sensitized white blood cells from an
immune person to non-immune person. This can natural or artificial
 i. Natural passive acquired immunity- This is the transfer of immunity from
mother to infant across the placenta (placental transfer). This transfer can also
occur from mother to child through breast milk (colostrum) in sub primate
species. For example, transfer of IgG from mother to foetus.
ii. Artificial passive acquired immunity: - This refers to therapeutic use of
various antitoxins or antibodies (gammaglobulins). Eg in treatment of tetanus,
diphtheria, gas gangrene, snake bite and immunodeficiency. Artificial passive
immunity can also be transferred by use of sensitized WBC from immune
person to non-immune person eg treatment of TB, Leprosy etc
NB: passive immunity is short lived. It depends on the life span of antibodies
or transferred immune cells in the recipient, when they disappear, the host
again becomes susceptible to the disease
b) Acquired active immunity
This occurs when the body encounters a foreign substance (antigen) that induces an
immune response. This immune response involves either production of antibodies or
production of sensitized lymphocytes. Active immunity is divided into;
i. Natural active acquired immunity: - This is acquired when a person is
exposed to an antigen in the course of daily life and the immune system
responds by producing antibodies and sensitized lymphocytes. For some
diseases the immunity acquired is lifelong eg in measles, chicken pox etc and
in other diseases it short lived.
ii. Artificial active acquired immunity: - this is the resistance or immunity
induced by vaccines. Previously prepared antigens are injected into the
susceptible individual whose immune system responds by producing
antibodies or sensitized lymphocytes. This is achieved through vaccination or
immunization.
Stages of acquired/ adaptive immunity
1. Recognition
The lymphocytes receptors recognize fragments of foreign agents grooved in MHC
(Major histocompatibility complex) of APC. This antigen stimulation leads to an
immune response that result in production of antibodies or sensitized lymphocytes.
The capacity of an antigen to stimulate an immune response is determined by the
degree of foreignness of the molecule to the host

2. Specificity and activation stage

The immune response apart from the activated microphages is specific. The activation
result in generation of antibodies and cells that specifically target the inducing
organism or foreign molecule (antigen). The specificity of the antibodies and T-cells
produced is generally determined by the epitope of the antigen

3. Activation
The lymphocytes that have bound antigen on their surface receptors are triggered into
action. There is a phase of cell proliferation leading to increased number of antigen
specific cells which then differentiate and mature into cells that can aid in elimination
of the antigen. The B-cells develop into plasma cells.
4. Effector stage
The final stage of the immune response is when the activated lymphocytes produce
molecules that eliminate the antigen. The plasma cells produce antibodies and
activated cytotoxic T-cells destroy target cells or secrete lymphokines. Many of the
molecules produced by activated lymphocytes act on or in conjunction with
components of innate immunity to aid in the elimination of the antigen. After
elimination some activated lymphocytes become memory cells. In subsequent
exposure, it will be these cells that are stimulated

Comparison between innate and adaptive immunity

Innate immunity Acquired/adaptive immunity
1 None antigen specific and reacts Antigen specific and only reacts to
equally well to a variety of organisms the organism that induce the
response
2 The response is immediate, the The response is slow and takes
defences are present and ready to about 3-5 days to react to invading
mobilize against the infection organism
3. It does not demonstrate immunological It demonstrate immunological
memory memory
4 Present at birth Not present at birth
5 Immune responses do not change with Immune responses increase with
intensity or repeated exposure exposure
6 Cell mediated reactions are Cell mediated reactions are
characterized by NK-cells and characterized by lymphocytes
 phagocytes
7 In humoral reactions there is acute In humoral reactions there are
phase proteins, lysozyme and antibodies and complement system
complement
8. Pattern recognition receptors (PRR) Receptors are specific for a
possess a broad specificity for various particular epitope. B-cell receptors
Pathogens Associated Molecules (BCR) and T-cell receptors (TCR)
Pattern (PAMP)

Immunological memory
Immunological memory is an important part of active immunity. It is a function of
memory cells formed during active immune response in a host. In case of B-cell
humoral response, the response is illustrated by measuring antibodies level produced
over a period of time in response to repeated antigen stimulus. The following stages
are involved;

1. Specific recognition
Before the development of acquired immune response the immune system is in a
state of ignorance and naivety toward the invading antigen. During the first
encounter between host and amicable antigen (Ag). The immune system begins to
identify and learn distinctive features of the microorganism

2. Primary immune response

On the first exposure (primary) to an antigen, the lag phase occurs in which no
antibody is produced. The immune response takes some time to get going since
the B- cells have to proliferate before differentiating to effector cells (plasma
cells). This may take 2-3 days. Plasma cells produce antibodies; this leads to
development of immunity against the particular antigen. At the same time a bank
of memory cells is generated. During this period;
 The amount of antibodies produced is relatively low
 Antibody level declines to a point where it is undetectable
 The first antibody produced is IgM and small amount of IgG

3. Secondary immune response

If repeat exposure to the same antigen (organism) occurs, the lag phase is very
short, second immune response occurs that’s is;
 more rapid and more strong and will be more lasting.
 The antibodies will appear within 24-36 hours and rise to a much higher
level and persist for longer than in primary response. More IgG antibodies
produced than IgM
 The IgG antibody level tends to remain higher for longer
 The quantity of antibodies is more specific and they are less likely to close
react with other antigens.
 The antigen binding force (avidity) is much stronger than in primary.
NB: A similar memory phenomenon occurs in cell mediated response (T-cell).
Effector T- cells kill target cells or produce lymphokines. Formation of memory
 cells in an immune response allows clonal expansion by 10-100 fold in response
to a particular epitope

NB
IgM is the first antibody to be produced, and declines as the antigen is eliminated. IgG takes
time to be synthesized during first exposure to antigen. during second exposure, there rapid
production and take time to clear from body long after antigen is eliminated

The antibody production graph takes the following phases

Lag phase; - Time when antibodies are not detected in serum. The B-cells are proliferating
and differentiating to become effector cells (plasma cells)
Log phase / exponential phase; -High production of antibodies in serum. More
differentiated B-cells (plasma cells)
Constant phase/ steady phase; - The amount of antibodies produced is equal to amount
degraded
Decline phase; - The immune response begins to shut down, antibody production declines,
more antibodies degraded. memory are cells produced and immunity established
Phagocytosis
This is the ability of certain cells of the immune system (phagocytes) to ingest and kill
microorganisms. Phagocytosis is a component in the host defence, it involves recognition and
binding, ingestion, and digestion of microorganisms. It is achieved using pseudopodia the
pseudopodium extends to surround the organism or a particle that gets attached to the cell
membrane of the phagocyte. Ingestion of microorganisms by phagocytes is enhanced by
presence of Fc receptors and opsonization. The membrane fuse to form an enclosed vacuole
termed phagosome/endosome. This phagosome fuses with lysosome to form a
phagolysosome. The lysosome contains hydrolytic enzymes and other bactericidal
substances. The hydrolytic enzymes digest and solubilize the bacteria. The degradation
products are then released to the exterior
In neutrophils: - intracellular phagosome fuse with the granules which release digestive and
toxic contents to attack the phagosome contents. Occasionally the granules content may be
discharged to the exterior milieu of the particle/organism if it is too large to be engulfed
leading to tissue damage termed reverse phagocytosis
Process of phagocytosis

Inflammation and tissue healing

This is the nonspecific response of the tissues to injuries often caused by pathogens such as
bacteria or endotoxins (LPS) or trauma or heat. It is characterized by increased blood flow to
the tissues, increased temperature, swelling, redness and pain. The following cellular events
occur during inflammation reaction; vasodilation, increased vascular permeability and
cellular infiltration. These changes are brought about mainly by chemical mediators
generated by immune cells such as mast cells, macrophages and neutrophils.
Tissue damage causes the degranulation of mast cells and subsequent liberation chemical
mediators such as histamine, 5-hydroxytrypta, prostaglandins, etc. The action of these
mediators cause vasodilation which leads to increased blood supply to the affected area,
giving rise to redness and heat. Therefore, there is increased supply of molecules and immune
cells that can combat the agent. The leaking of fluid will cause swelling (edema) that will in
turn lead to increased tissue tension and pain
The plasma proteins including, a cute phase protein such as inflammatory C-reactive proteins,
molecules of clotting and complement proteins, activate the complement system.
Chemotactic factors produced at the site of tissue injury attracts phagocytes (neutrophils,
MO, eosinophils and dendritic cells and lymphocytes. Reactive oxygen and nitric oxide
(respiratory burst) produced by activated phagocytes are toxic to microorganisms and may
lead to tissue damage. Inflammatory process continues until the conditions responsible for its
initiation are resolved. However, if the causative agent is not removed, then chronic
inflammation will occur which may result in tissue destruction and complete loss of function.
Or the damaged cells can clump together over the agent at the site of infection to form a tiny
nodule (granuloma). The granuloma is formed to contain the agent and prevent its spread.
Inflammatory responses lead to protection against infection and promote healing. In
appropriate trigger of inflammation can lead to allergic diseases such as asthma or
autoimmune disorders.

TERMINOLOGIES
Antigen – This is a macromolecule that induces specific immune responses in the body. they
can be proteins, polysaccharides or conjugates of lipids. Or an antigen is any molecule that is
recognized by adaptive elements of the immune system.
Immunogen: - these are substances that illicit immune responses. All immunogens are
antigens but not all antigens are immunogens
Hapten :- these are small molecules that are immunogenic and which would never induce an
immune response when administered alone but which can when coupled by a carrier
molecules.
Antibodies: - This is a specific glycoprotein that is produced by B-cells (plasma cells) in
response to an antigen and reacts with that antigen
Epitopes/ antigenic determinants: - this is portion of the antigen that combines with the
products of the specific immune responses such as the antibodies, MO, and sensitized T-cell
Paratope: - this is part of the antibody or T-cell receptor that interacts or binds with the
epitope
Interferons: - this is a family of anti-viral agents. They are of two types; Type 1 interferons
(ϓ and β) and are part of the innate immunity. Type 2 interferons (Υ) is produced by T-cells
as part of acquired immune response
Memory cells: - these are experienced (primed) lymphocytes that have returned to and
remained in quiescent state. They respond during re-exposure to similar antigen giving rise to
secondary immune response. Or memory cells are programmed lymphocytes that are ready to
respond upon future encounter with an antigen that caused them to form
Effector cells: - These are lymphocytes that have differentiated; B-cells into plasma cells
(antigen secreting cells) and T-cells into subsets such as CD8 + cytotoxic T- cells, CD4+ cells
etc
T-Independent antigens: - These are antigens which can directly stimulate B-cells to
produce antibodies without the requirement of T-helper cells
T-dependent antigens: antigens that do not directly stimulate the production of antibodies
without the help of T-cells eg proteins
Super antigens: - These are antigens which polyclonally activate a large fraction of T-cells
up to 25% e.g. staphylococcus pyogenes exotoxins
Isoimmunity/ alloimmunity :- This is immune response to non-self-antigens from members
of the same species which are called alloantigens or isoantigens or
Isoimmunity is an immune disease in which the antibodies are produced as a result of
antigens from another person
Cytokines: - These are small molecular weight soluble factors released by cells to
communicate with and influence function of other cells through specific surface receptors eg
MAF (macrophage activating factor), cytokine factors produced by lymphocytes are called
lymphokines eg IL-2, IFN-Υ etc. those produced by monocytes and macrophages are called
monokines eg IL-1
Chemotaxis: - This is the movement of a cell or organism in response to a chemical stimulus

IMMUNOGENICITY
Immunogenicity is the ability of a foreign substance (antigen) to provoke an immune
response in the body of a human or other animals
Factors influencing immunogenicity/ properties of an immunogen
1. Foreignness: - An antigen must be foreign (non-self) to animal body so as to illicit an
immune response.
2. Molecular size: - Active immunogens should be of suitable size with a molecular
mass greater than 100,000 Da. Eg tetanus toxoid, whereas substances with small
molecular mass of less than 5,000 to 10,000 Da are poor immunogens eg insulin is
non immunogenic
3. Chemical nature; - Substances that are chemically more complex are more
immunogenic than simple substances eg most antigens are proteins or polysaccharides
4. Heterogeneity: - Synthetic homopolymers are weak immunogens, whereas
hereropolymers are more immunogenic
5. Physical form; - Particulate antigens are more immunogenic than soluble ones.
denatured antigens are more antigenic than the native forms. large insoluble or
aggregates are more immunogenic than small soluble ones
6. Antigen processing and presentation: - antigens that cannot be processed and
presented in MHC molecules are poor immunogens, whereas antigens that are easily
phagocytosed are generally more immunogenic
Host factors that influence immunogenicity
7 The genotype of the host animal: - This a major factor that determine development
of immune response, some substances are immunogenic in one species or individual
but not in the other
8 Dosage: -insufficient dosage of immunogen will not illicit immune response (either it
will fail to illicit immune response or lead to a state of tolerance), conversely high
dosage will lead to unresponsiveness or tolerance. A single experimental dosage is not
sufficient to develop immune response, however, a booster dose over a period of time
enhances immunogenicity
9 Route of administration/ portal of entry: -Administration route strongly influences
immune response. eg subcutaneous route is better than the intravenous or intragastric
routes
10 Adjuvants: - Adjuvants are substances that when mixed and injected with an antigen,
enhance immunogenicity of the antigen eg Aluminium potassium sulphate (Alum