BENUE STATE

UNIVERSITY MAKURDI
DEPARTMENT OF BIOLOGICAL
SCIENCES

1
 Table of Contents
HOST RESISTANCE AND THE IMMUNE SYSTEM..............................................................................4
TYPE OF IMMUNITY...............................................................................................................................5
Innate Immunity......................................................................................................................................5
Acquired Immunity.................................................................................................................................5
CELLS AND ORGANS OF THE IMMUNE SYSTEM.............................................................................5
HEMATOPOIESIS.....................................................................................................................................6
Cells of Immune System..........................................................................................................................7
Lymphocytes...........................................................................................................................................7
B Cells.................................................................................................................................................8
T Cells.................................................................................................................................................8
Null Cells................................................................................................................................................8
Mononuclear cells...................................................................................................................................8
Mast Cells................................................................................................................................................9
Dendritic Cells.........................................................................................................................................9
ORGANS OF THE IMMUNE SYSTEM....................................................................................................9
Primary Lymphoid Organs......................................................................................................................9
The Thymus.......................................................................................................................................10
Secondary Lymphoid Organs................................................................................................................10
Lymph Node......................................................................................................................................10
Process of Activation.........................................................................................................................11
Spleen................................................................................................................................................11
Mucosal – Associated Lymphoid Tissue (MALT).............................................................................11
IMMUNOLOGY OF INFECTIONS.........................................................................................................12
VIRAL INFECTIONS...........................................................................................................................12
CELL – MEDIATED ANTIVIRAL MECHANISMS...............................................................................12
BACTERIAL INFECTIONS.................................................................................................................13
KILLING BY NK CELLS.....................................................................................................................14
ANTIBODY-DEPENDENT CELL – MEDIATED CYTOTOXICITY (ADCC)..................................14
COMPLEMENT SYSTEM...................................................................................................................15

Page 2 of 20
 COMPLEMENT COMPONENTS........................................................................................................15
ANTIBODIES...........................................................................................................................................16
Structure of Immunoglobulin.................................................................................................................16
HYPERSENSITIVITY..............................................................................................................................17
Type I hypersensitivity..........................................................................................................................17
Type II hypersensitivity.........................................................................................................................18
Type III hypersensitivity.......................................................................................................................19
Type IV hypersensitivity.......................................................................................................................19
BLOOD GROUPING................................................................................................................................19
A and B red cell antigens and the Antibodies in serum.........................................................................20

Page 3 of 20
HOST RESISTANCE AND THE IMMUNE SYSTEM
The natural resistance present in the body can usually confine microorganisms to the surface of
the body and prevent entry into the inner most tissues and organs. Occasionally, however,
microorganisms possess unusual qualities that add to their pathogenicity. Under these conditions,
the human body employs three lines of defense against disease: surface defenses, phagocytic
defenses and specific defenses centered in the immune system. The surface defenses can be
subdivided as mechanical defenses, chemical defenses and microbial defenses.

The most essential mechanical defense mechanism is the intact skin surface and the
mucous membranes that line many of the systems, such as the respiratory tract, gastrointestinal
tract, urogenital tract and conjunctiva of the eyes. The first stage of a disease is to breach these
barriers by means of cuts, puncture wounds or other trauma. Mucous membrane can also be
weakened by tobacco smoke, air pollutants and toxic gases.

There are several factors the augments the mechanical defenses. Among these are the
mucous and cilia present in the respiratory tract. The sticky traps particles that enter the tract and
cilia move the mucus along into the throat where it is swallowed. Coughing and sneezing expel
microorganisms from the respiratory tract. Nasal hairs add to mechanical defenses and body
hairs prevent microorganisms from reaching the skin. Urine flow reduces the microbial
population of the urinary tract and tears flush the eyes constantly.

The body synthesizes chemicals to assist its surface defenses. For instance, lysozyme in
tears and saliva can destroy the cell wall of Gram-positive bacteria. Many fatty acids in the sweat
and ear wax also have antimicrobial activities. The hydrochloric acid in the stomach kills most
bacteria in this organ and the vagina has a high acid content that also protects against microbial
contamination. Bile from the gall bladder kills some microorganisms in the gastrointestinal tract
and enzymes in the intestinal tract kills others.

Microorganisms in the normal flora compete with pathogenic organisms for nutrient in
the environment and available space. The normal flora microorganisms also produce substances
that inhibit pathogens. For example, lactobacilli in the vagina produce acid which inhibits the
growth of many pathogens.

Phagocytic defenses of the body are centered in phagocytosis, a process performed by

certain white blood cells. These cells engulf microorganisms while enzymes from lysosomes of
the phagocyte digest the microbe. Such enzymes as proteases, lipases and peptidoglycanases are
active in phagocyte. Cells involved in phagocytosis are the neutrophils which have multilobed
nucleus; monocytes which have a single horseshoe-shaped nucleus and macrophages.

Page 4 of 20
TYPE OF IMMUNITY
The human body has two basic types of immunity innate immunity and acquired immunity. Each
yields specific host resistance when the body is confronted with infectious microorganisms.

Innate Immunity

Innate immunity results from the anatomical, physiological, biochemical and genetic makeup of
an individual. This immunity develops independent of any previous experiences with a specific
pathogen. For example, humans are innately immune to the virus that cause canine distemper in
dogs because the virus cannot attach to human cells, since human cells lack the appropriate
receptor sites. Similarly, dogs do not suffer from AIDS because dog cells do not possess the
receptor sites for HIV.

Acquired Immunity

Acquire immunity is that type of immunity resulting from exposure to pathogen or other foreign
substances. In general acquired immunity develops as a result of a highly specific response to the
invading organism or substance.
Acquired immunity can be natural acquired immunity or artificial acquired immunity.
Natural acquired immunity occurs during the natural course of infection, while artificial acquired
immunity results from deliberate introduction of some foreign substances such as vaccine to
stimulate an immune response.

Natural acquired immunity can be active or passive. Natural acquired active immunity comes
about after a person is exposed to a pathogen and responds by forming antibodies that attack and
neutralize the pathogens. Natural acquired passive immunity comes about when antibodies are
transmitted from mother to child via the placenta and umbilical cord. The antibodies that pass to
the developing foetus remain within the child for about six months after it is born.

Artificially acquired immunity can also be active or passive. Artificially acquired active
immunity occurs after a person has been injected with a vaccine or other immune-stimulating
agents and has produced antibodies. The ability to produce antibodies remains with the
individual and those antibodies neutralize the pathogens. Vaccines are composed inactive or
dead microbes, fragments of viruses or bacteria, or genetically engineered chemical components
of microorganisms.

Artificially acquired passive immunity comes about from the injection of antibodies into an
individual. These antibodies provide immediate defense against disease, but the antibodies do not
remain in the system for more than several days or weeks.

CELLS AND ORGANS OF THE IMMUNE SYSTEM

The immune system consists of many structurally and functionally diverse organs and tissues
that are widely dispersed throughout the body. These organs can be classified on the basis of
Page 5 of 20
functional differences into two main groups. The primary lymphoid organs provide appropriate
microenvironment for lymphocytes maturation.

The secondary lymphoid organs trap antigens from defined tissues or vascular spaces and
provide sites where mature lymphocytes can interact effectively with antigen.

The blood vasculature and lymphatic system interconnect these organs, uniting them into a
functional whole.

The white blood cells or leukocytes populate the blood and lymph and the various lymphoid
organs.

Of these cells, only the lymphocytes posses the attributes of diversity, specificity, memory, and
self/non self recognition, the hall mark of an immune system. All the other cells play necessary
roles, serving to activate lymphocytes to increase the effectiveness of antigen clearance by
phagocytosis or to secrete various immune effector molecules

HEMATOPOIESIS
Hematopoiesis refers to the formation and development of red and white blood cells from stem
cells.

This begins in the yolk sac in the first week of embryonic development

Yolk sac differentiate into primitive erythroid cells containing embryonic hemoglobin

In the third month, stem cells immigrate from yolk sac to the foetal liver and spleen

These two organs have major roles in hematopoiesis from 3rd – 7th month of gestation.

But the bone marrow takes over and hematopoiesis completely cease in the liver and spleen at
birth.

A hematopoietic stem cell is pluripotent (able to differentiate along a number of pathways) and
thereby generate a number of cells.

In adult bone marrow, the hematopoietic cells grow and mature on a meshwork of stromal cells.

e.g fat cells, endothelial cells, fibroblast and macrophages.

The stromal cells influence hematopoietic stem-cell differentiation by providing a hematopoietic-

inducing microenvironment consisting of a cellular matrix comprising of either membrane-bound
or diffusible growth factors

Page 6 of 20
Cells of Immune System
Normal adult blood cell count shows;

Cell type cells/mm3

Red Blood Cells (RBC) 50x106

Platelets (Thrombocytes) 2.5x105

Leucocytes 7.3x103

Leucocytes or White Blood cells (WBC) count shows

Neutrophil 50-70%

Lymphocyte 20-40%

Monocyte 1-6%

Eosinophil 1-3%

Basophil <1%

Lymphocytes
They are the cells of the immune system, responsible for acquires immunity and posses the
immunologic attributes of diversity, specificity, memory and self and non self recognition.

They constitute 20%-40% of the body’s white blood cells (WBC) and 99% of the cells in lymph.

Lymphocytes continuously circulate in the blood and lymph and are capable of migrating into
the tissues spaces and lymphoid organs thereby providing a high degree of cellular integration to
the immune system as a whole.

The lymphocytes can be broadly subdivided on the basis of the function and cell-membrane
components into three populations.

(i) B cells
(ii) T- cells
(iii) Null cell

All these three are small, motile, non phagocytic cells, which cannot be distinguished
morphologically. B and T cells that have not interacted with antigens are referred to as naïve
or unprimed and are resting cells. They may be called small lymphocytes (6µm). As they
progress through the cell cycle and interact with antigens, enlarges into 15µm diameter blast

Page 7 of 20
 cells called lymphoblast. Lymphoblast proliferates and eventually differentiates into effectors
cells or into memory cells.

B Cells
B-Lymphocyte- derived its name from its site of maturation in the bursa of fabricus in birds
or bone marrow in mammals.

B Lymphocytes possess membrane - bound immunoglobulin (antibody) molecules, Class II

MHC molecules and acts as Antigen presenting cells (APC)

T Cells
T-Lymphocyte- derived from thymus site of maturation have membrane receptors for
antigen. T cells also express distinctive membrane molecule, either CD4 or CD8. These
define the two major sub-populations of T lymphocyte.

(i) T helper (TH) CD4+, are MHC class II restricted

(ii) T cytotoxic (TC) CD8 +, are MHC class I restricted

Null Cells
These are a group of peripheral blood lymphocytes that fail to express the membrane
molecules that distinguished T and B all lineage.

They also lack antigen – binding receptors of T and B lymphocytes.

Hence they lack immunogenic attribute of specificity and memory.

They are called killer cells (NK cells).

They are large granulated lymphocytes and constitute 5%-10% of the peripheral blood
lymphocytes in humans

Mononuclear cells
The mononuclear phagocytic system consists of circulating monocytes in the blood and
macrophages in the tissues. During hematopoiesis in the bone marrow, granulocyte-
monocyte progenitor cells differentiate into promonocyte which leaves the bone marrow and
enter the blood, where they further differentiate into mature monocyte. Monocytes circulate
in the blood stream for about 8 hours during which time they enlarge, migrate into the tissue
and differentiate into specific tissue macrophages. Hence we have;

i. Alveolar macrophages - lungs

ii. Histiocytes - connective tissue

iii. Kupffers cells - liver

Page 8 of 20
 iv. Mesangial cells - kidney

v. Microglial cells - brain

Mast Cells
These are cells of allergy that differentiate only when they enter the tissues. They are found
in skin, connective tissues, and mucosal epithelial tissues of the genitourinary and digestive
tract. Mast cells together with basophils play an important role in the development of
allergies.

Dendritic Cells
These cells got their name from long membrane processes resembling dendrites of nerve
cells. Most dendritic cells process and presents antigen to T helper cells. These cells can be
classified based on location. Hence we have;

i. Langerhan cells - in the epidermis and mucous membranes

ii. Interstitial dendritic cells - Most organs (e.g. heart, lungs, liver, kidney, gastrointestinal
tract)

iii. Interdigitating dendritic cells-In T – cell areas of lymphoid tissue

iv. Circulating dendritic cells - blood and lymph.

ORGANS OF THE IMMUNE SYSTEM

A number of morphologically and functionally diverse organs and tissues have various
functions in the development of immune responses. These can be divided on the basis of
function into the primary and secondary lymphoid organs.

i. Primary or central lymphoid organ consist of the thymus and bone marrow, sites for
maturation of lymphocytes.

ii. Secondary lymphoid organs consist of lymph nodes, spleen and various mucosal
associated lymphoid tissues (MALT) which traps antigen and provides sites for mature
lymphocytes to interact with the antigen.

iii. The tertiary lymphoid tissues may also exist, which normally contain few lymphoid cells
and can import lymphoid cells during an inflammatory response.

Primary Lymphoid Organs

Immature lymphocytes generated during hematopoiesis mature and become committed to a
particular antigenic specificity within the lymphoid organ. Only after a lymphocyte has matured
within a primary lymphoid organ is the cell immunocompetent (i.e capable of mounting an

Page 9 of 20
immune response). In mammals, B – cell maturation occurs in the bone marrow and T – cell
maturation occurs in the thymus.

The Thymus
The thymus is a flat, bilobed, organ situated above the heart. Each lobe is surrounded by a
capsule and is divided into lobules, which are separated from each other by strands of connective
tissues called trabeculae. Each lobe is organized into two compartments the outer called the
cortex which is densely packed with immature T – cells called thymocytes, the inner
compartment or medulla is sparely populated with thymocutes.

After progenitor T – cells formed during hematopioesis enters the thymus, they are
thought to multiply rapidly within the cortex; the rapid proliferation of thymocytes is coupled
with enormous cell death. A small subset of thymocytes is thought to migrate from cortex to
medulla where they continue to mature until they finally leave the thymus.

Cortex and medulla are crisis – crossed by a three – dimensional strand – cell network
composed of epithelial cells and interdigitating dendritic cells which physically interact with the
thymocytes, so that the antigenic diversity of the T – cell receptor is generated. After developing
thymocytes begins to express antigen – binding receptors, they are subjected to a two – step
selection process, so that only T – cells recognizing antigenic peptides in the context of self –
MHC molecules are released from the thymus.

Secondary Lymphoid Organs

Lymph nodes and the spleen are the most highly organized of the secondary lymphoid organs.
They possess distinct regions of T cell and B cell activity and are surrounded by a fibrous
capsule.

Lymph Node
These are encapsulated bean – shaped structure containing a reticular network packed with
lymphocytes, macrophages and dendritic cells. Cluster at the junctions of the lymphatic vessels,
lymph nodes are the first organized lymphoid structures to encounter antigen. As the lymph
percolates through a node, any particulate antigen that is brought in with the lymph is be trapped
by the cellular network of phagocytic cells and dendritic cells.

Lymph node be divided into 3 roughly concentric region; the cortex, paracortex and
medulla.

The cortex (outer layer) contains lymphocytes mostly B – cells macrophages and follicular
dendritic cells arranged in primary follicles. Following antigenic challenge, the primary follicles
enlarges into secondary follicles, each containing a germinal center. Intense B – cell activation
and differentiation into plasma and memory B – cells takes place in the germinal center.

Page 10 of 20
 The paracortex is dominated with T – lymphocytes and also contains interdigitating
dendritic cells thought to have migrated from tissues to the node. They express high level of
MHC class II for antigen presentation to TH cells.

The medulla is sparely populated with lymphocytes but many of these are plasma cells
actively secreting antibody molecules.

Process of Activation
- Antigens are trapped, processed and presented together with MHC class II molecules by
interdigitating dendritic cells in the paracortex resulting in TH- cell activation.

- B – cells are also activated in the paracortex. B cells and T cells form small foci
consisting largely of proliferating B – cells at the edge of the paracortex. Some B – cells
differentiate into plasma cells secreting IgM and IgG. Foci reach maximum size in 3 – 4 days
of antigenic challenge.

- in 4 – 7 days, few B – cells and T H cells migrate to primary follicles in the cortex where
the interaction between follicular dendritic cells, B – cells and T – cells takes place, leading
to development of secondary follicles, with a central germinal centre.

Germinal centre made up of follicular dendritic meshwork trap antigen-antibody complex

for long period of time. Also produce B cell growth factor. The activated B – cells in the
germinal center divide rapidly and either differentiates into plasma and memory cell or die a
programmed death.

Following infection or introduction of other antigen into the body the lymph leaving a
node through its single efferent lymphatic vessel is enriched with antibodies newly secreted
by medullary plasma cells and also has a 50 – fold higher concentration of lymphocytes than
the afferent lymph.

Spleen
Large ovoid lymphoid organ situated high in the left abdominal cavity, adapted to filtering
blood and trapping blood – borne antigens. The spleen is divided into compartments. These
are of two types, the red pulp and white pulp. The red pulps are populated with macrophages
and numerous red blood cells (erythrocytes) it is the site where old and defective red blood
cells are destroyed and remove. Many macrophages in the red pulp contain red blood cells or
iron pigments from degraded hemoglobin. The white pulp contains mainly T – lymphocytes.
The marginal zone which is peripheral to the white pulp is rich in B cells organized into
primary lymphoid follicles.

Mucosal – Associated Lymphoid Tissue (MALT)

This is a collective name for a group of organized lymphoid tissues. These tissues range from
loose clusters of lymphoid cells with little organization like the intestinal villi to structures

Page 11 of 20
 such as tonsils, appendix and peyers patches. They defend the mucous membrane lining the
digestive tract and urogenital system. The functional importance of MALT in the body’s
defense is attested to by its large population of antibody producing plasma cells whose
number far exceeds that of the plasma cells in the spleen, lymph nodes and bone marrow
combined.

IMMUNOLOGY OF INFECTIONS

VIRAL INFECTIONS
A number of specific immune effectors mechanisms together with non – specific defense
mechanisms, are called into play to eliminate an infecting virus

1. Viral neutralization by antibodies.

Antibodies specific for viral surface antigen are often crucial in containing the spread of a
virus during acute infection and in protecting against molecules that enable them to initiate
infection by binding specifically to host cell membrane molecules e.g.

i. Influenza binds to sialic acid residue or cell – membrane glyco-proteins.

ii. Rhinovirus binds to intercellular adhesion molecules (ICAMs)

iii. Epstein Bar binds to type 2 complement receptors on B – Cells.

Antibody to the viral receptor can block infection altogether.

Non specific defense against virus are interferon α and β which are produced by various cells in
response to a viral infection.

Secretary 1gA in mucous secretions plays an important role in host defense against viruses by
blocking viral attachment to mucosal epithelial cells. Polio vaccine induces production of 1gA
which block attachment of wild polio virus to cells of the gastrointestinal tract.

Antibodies may sometimes block viral penetration by binding to epitopes that are necessary to
mediate fusion of the whole envelope with the plasma membrane (e.g 1gG, 1gM, and 1gA).

Antibody may induce complement activation resulting to antibody – complement lyses.

Antibody or complement can agglutinate viral particles and function as opsonizing agent to
facilitate phagocytosis.

CELL – MEDIATED ANTIVIRAL MECHANISMS

Antibodies may contain the spread of a virus in acute phase of infection but once the infection is
established they are unable to eliminate the virus. In such instances, cell mediated immune

Page 12 of 20
 mechanisms are important in host defense. In general CD8+ Tc cells and CD4+ TH cells are the
main component of cell mediated antiviral defense.

Activated TH cells release cytokines (1L-2, IFN-ɣ and TNF) that act either directly or indirectly
against viruses. IFN-ɣ induces an antiviral state in cells. IL-2 activates cytotoxic T –
lymphocytes (CTL).

IL-2 , IFN-ɣ and activate Nk cells at initial stage until CTL response develops. CTL- eliminate
virus infected self cells

* Cell-mediated- IFN-ɣ secreted by TH or TC cells direct antiviral activity on surrounding

cells. Cytotoxic T lymphocytes (CTLs) kill virus-infected self cells

NK cells and macrophages – kill virus infected cell by antibody – dependent cell –
mediated cytotoxicity (ADCC)

BACTERIAL INFECTIONS
Immunity to bacterial infections is achieved by means of antibody unless the bacterium is
capable of intracellular growth in which case delayed hypersensitivity plays an important
role.

Bacterial enter the body either through a number of natural entry routes (e.g
respiratory trait, gastrointestinal tract (GIT) and the genitourinary tract) or through breaks
in mucous membrane or skin. The level of immune response is dependent on, the
virulence of the organisms and inoculums size.

If the inoculums size and virulence are both low, then localized tissue phagocytes
may be able to mount a non-specific defense and eliminate the bacteria. Larger inoculums
of organisms with increased virulence tend to induce an immune response.

Immune Response to Extracellular and Intracellular Bacteria

Extracellular bacteria induce production of human antibodies which are ordinarily secreted by
plasma cells in regional lymph nodes and the sub mucosa of the respiratory and gastrointestinal
tracts.

Antibody that binds to antigen on the surface of bacterium can together with complement
components act as opsonin that increases phagocytosis.

Antibody mediated activation of the complement system can induced localized production of
immune effectors that help to develop an amplified and more effective inflammatory response.

If the bacterium secrets an exotoxin or endotoxin, antibody may bind to the toxin and neutralize it.
The antibody-toxin complexes are then cleared by phagocytic cells. There could also be ADCC

Page 13 of 20
Antibody-mediate mechanisms for combating infection in extracellular bacterium

1. Antibody neutralizes bacteria toxins

2. Complement activation on bacterium surface leads to complement-mediated lyses of
bacterial
3. Antibody and the complement split products C3b bind to bacteria, serving as opsonin to
increase phagocytosis.
4. C3a and C5a, generated by Antibody- mediated complement activation, induce local
mast cell degranulation, releasing substances that mediate vasodilation and
extravasations of lymphocytes and neutrophils.
5. Other complement split products are chemotactic to neutrophilis.

KILLING BY NK CELLS
NK cells help in the host’s defense by recognizing and destroying tumor cells, virus infected
cells, fungi, bacteria, protozoa and helminthes parasites. This process is immune surveillance.
This is done through cell mediated lyses.

1. The Nk cell is activated by interferon produced by virus infected cells and/or interleukin -
2 from TH cells.

2. The Nk cells recognize MHC class I on the target cell and binds to it.

3. The Nk cell inserts a pore-forming protein, perforin into, the target cells plasma
membrane

4. Lysosomal secretions are also produced by the NK cells.

5. The attacked cell undergoes cytolysis

ANTIBODY-DEPENDENT CELL – MEDIATED CYTOTOXICITY (ADCC)

- When antibody is specifically bound to a target cell, these receptor-bearing cells can bind
to the antibody FC region, and thus to the target cells and cause lyses of target cells

- The cytotoxic cells involved are non-specific but the specificity of the antibody directs
them to specific target cells.

- Cells that can mediate ADCC include Nk cells, Macrophages, Monocytes, neutrophils
and eosinophil

- When these cells bind to a target cell by way of the Fc receptor, they became more active
metabolically; as a result the lytic components in their cytoplasmic lysosomes or granules
increase and release of these lytic components at the site of the FC-mediated contact may
result in damage to the target cell. Also activated monocytes, macrophage and Nk cells
may secrete tumor necrosis factor (TNF) which may have cytotoxic effect on the bound
target cells.
Page 14 of 20
 Since NK cells and Eosinophil contain perforin in cytoplasmic granules, their target cell killing
may also involve perforin-mediated membrane damage.

COMPLEMENT SYSTEM
Complement system composed of a group of plasma protein that plays a major role in defense.

- Complement proteins can lysed antibody coated eukaryotic cells and bacteria.

- Can mediate inflammation and attract and activate phagocytic cells.

- They generally amplify the effect of antibodies

There are 11 complement proteins designated C1 through C9 in addition to factor B, D, H, I and

properdin.

The component system acts in a cascade fashion, the activation of one component resulting in
the activation of the next.

Complement components make up the major portion of the globulin fraction of serum but are in
an inactive state.

They are activated after the binding of antibodies to antigens and are specifically directed against
the molecules that have been identified by the antibodies.

There are 2 pathways of complement activation, the classical and alternate or properdin
pathways.

 Activation of classical pathway requires initiation by the interaction of 1gG1,

1gG3d or 1gG antibodies with antigens that is usually cell bound.
 Alternate pathway does not require binding of antibodies to antigens for its
activation. It plays an important role in innate (non specific) immune defense
agent intravascular invasion by bacteria and some fungi that occur before the
development of specific antibodies.

COMPLEMENT COMPONENTS
C4a Anaphylatoxin (contraction of smooth muscles, increased vascular

permeability and histamine release)

C4b Causes viral neutralization

C3a Anaphylatoxin, immunoregulatory

C3b Key component of alternate pathway and major opsonin in serum (Opsonin means
prepare for eating)

Page 15 of 20
C5a Anaphylatoxin, principal chemotactic factor in serum; induces neutrophil attachment to
blood vessel wall

C5b Initates membrane attack

C5b6789 Membrane attack complex (MAC)

ANTIBODIES
Antibodies also known as Immunoglobulin (Ig) are group of glycoproteins present in serum and
tissue fluid of all mammals. There production is induced by host lymphoid system coming in
contact with immunogenic foreign molecule (antigen) and binds specifically to the antigen which
induce their formation. The different classes of Ig are; IgG, IgM, IgA, IgD and IgE. They are
associated with different physiological properties of antigen. They differ from each other in size,
charge, amino acid composition and carbohydrate content.

Electrophoretically, immunoglobulins show unique range of heterogeneity which extends from

gamma to alpha fraction of normal serum. But the basic structure of immunoglobulin consists of
two identical light polypeptide chains (200 amino acid each), and identical heavy polypeptide
chains (450 amino acid each). Both the light and heavy chains are linked together by disulphide
bonds

Each antibody molecule has a constant region and a variable region. The variable region is the
place where an antibody molecule unites specifically with the antigen that stimulates its
production. The epitope of the antigen fits perfectly with antibody combining site.

Structure of Immunoglobulin
Because of their classification as globulin proteins, and due to the fact that they function in the
immune response, antibodies are known as Immunoglobulins (designated as Ig).

Immunoglobulin Gamma (IgG) represents 80% of the antibody in the body at any one time.
This antibody is the most important long-acting antibody in the specific immune response. It
consists of a single monomer of four amino acids chains, and it is able to pass across the placenta
from mother to child in natural passive immunity.

The second important kind of antibody molecule is IgM. This antibody is huge and consists of
five monomer units, and because of its size, it cannot leave the bloodstream, nor can it cross the
placenta. IgM represents about 5 – 10% of the antibody total in the blood. It is the first antibody
to arrive at the scene to neutralize the antigen and is the principal component of the primary
antibody response.

Immunoglobulin Alpha (IgA) is known as the secretory antibody. It is secreted into the
cavities of the body such as the gastrointestinal tract and the respiratory tract and onto the body

Page 16 of 20
surface. The antibody consists of two monomer units connected by a secretory piece known as
the J chain. IgA is secreted in mother’s milk and is passed to the child who nurses.

Immunoglobulin Delta (IgD) represents only 1 – 3% of the antibody in the serum. This
antibody serves as a receptor site at the surface of B cells. The epitope displayed by the
macrophage arriving in the lymphoid tissue unites with the antibody to stimulate the immune
response. IgD consist of single monomer unit.

Immunoglobulin Epsilon (IgE) represents less than one percent of the antibody in the blood; it
function in many allergic reactions. The molecule attaches to granulated cells such as basophils
and induces the cells to lose their granules when a succeeding antibody – antigen reaction occurs.
This release leads to the release of histamine and the allergic response.

HYPERSENSITIVITY
Hypersensitivities are immune reactions traced to dysfunction of the immune system.
Hypersensitivity implies an overly aggressive sensitivity to an antigen entering the body. The
immune response ordinarily would neutralize the antigen but in the case of hypersensitivity, the
immune reaction results in damage to the body. There are four types of hypersensitivity reaction:
type I, type II, type III and type IV.

Type I hypersensitivity
Type I hypersensitivity is also known as immediate hypersensitivity because the reaction because
the reaction takes place almost immediately in the body. It is known as anaphylaxis if it
involves the entire body; it is known as allergy if it involves a limited area of the body.

The antibody that functions in type hypersensitivity reaction is IgE. This antibody is produced by
plama cells and B cells on stimulation by antigens such as penicillin molecules, mold spores,
certain foods, pollen grains and dust particles.

Once IgE is release in the blood stream, it circulates and fixes itself to the surface of mast cells
and basophils. The body usually experiences no reaction from the attachment of IgE to basophils
and mast cells as long as it is for the first time. The more the antibody build up, the more
sensitive the person becomes. However, at a later date, as this antigen reenters the body and
reacts with IgE molecules on the cell surfaces, the cell undergoes degranulation and releases
various kinds of mediators (Histamines, serotonin, bradykinin, leukotrienes e.t.c). These
mediators induce the contraction of smooth muscles and bring about many of the symptoms of
allergy reaction (localized) or anaphylaxis (whole body).

When mediators like histamines are released throughout the body, the result is life threatening.
E.g closure of the bronchial tubes, could lead to suffocation and death within minutes.

Notwithstanding, several things can be done for the person in the mist of anaphylaxis or allergy.

Page 17 of 20
 i. Injections of Epinephrine (adrenaline) will stabilize the basophils and mast cells to
prevent release of granules.
ii. Antihistamines can be administered to neutralized the histamine been release
iii. A smooth muscles relaxer can be used to offset the contractions of the smooth
muscles.
iv. Cortisone can be used to reduce swelling.

Type II hypersensitivity
Type II hypersensitivity is also known as cytotoxic hypersensitivity. This is because the
hypersensitivity involves an attack on the body cells by antibodies. The attack results in
activation of the complement system, and elements of the complement system bring about
destruction of the cells.

An example of a cytotoxic hypersensitivity is a condition known as thrombocytopenia. In this

condition, antigens such as drug molecules enter the body and the body responds with antibodies.
The antibodies attack the thrombocytes (platelets) of the body and as the complement system is
activated, complement is fixed on the surface of the cells and the thrombocytes are destroyed.
With the destruction of thrombocytes, the body’s ability to form a blood clot is reduced, the
clotting time is extended and hemorrhaging can occur in the body tissues.

Another example is a condition called hemolytic disease of the new born also known as
erythroblatosis fetalis. The rhesus antigen (or Rhesus factor) is an antigen present on the red
blood cells of the great majority of individuals. Those possessing this antigen are said to have
positive blood such as type-A positive or type O positive. Cytotoxic hypersensitivities due to this
antigen are considered not important in adults, but during fetal development and in new borns,
the hypersensitivities can result in a condition known as hemolytic disease of the new born. For
example, when an Rh-positive male (e.g blood type A +) mates with an Rh-negative (A-), there is
a 75% probability or 3:1 chance, that the offspring will be Rh-positive. During the pregnancy the
danger is minimal, but at birth some of the child’s blood might enter the blood of the mother.
Should this happen, the mother’s immune system will respond to the Rh antigens and produce
anti-Rh antibodies. If a succeeding conception results in another Rh-positive feotus, then the RH
antibodies may pass across the placenta (along with other antibodies of the mother) and enter the
blood of the foetus and attack the Rh- positive antigen on the surface of the red blood cells of the
feotus. This attack will result in a destruction of the red blood cells, a cytotoxic hypersensitivity
and death of the new born.

To prevent hemolytic disease of the new born, it is important that the mother’s immune system
be prevented from forming anti-Rh antibodies. This can be achieved by giving the woman an
injection of RhoGAM shortly after the birth of the first child. RhoGAM contains Rh antibodies.
These antibodies neutralize Rh antigens coming from the child’s blood.

Page 18 of 20
Type III hypersensitivity
Type III hypersensitivity reactions involve the formation of immune complexes. Immune
complexes develop when dissolved antibody molecules react with dissolved antigen molecules.
The antibody and antigen molecules combine in such a fashion that a large lattice forms. This
lattice is composed of interlocking antigen and antibody molecules that form as a mass so large
that it is visible. This elicits the complement system, and the complement system brings about
destruction of the local tissue.

Formation of these immune complexes occurs in various regions of the body including the skin,
joints and kidneys. When the complexes form in the skin a condition called systemic lupus
erythematosus can result. This condition is characterized by a butterfly-shaped rash on the skin
and tissue damage in blood rich organs such as the kidneys and spleen. In the joints, the immune
complexes can lead to a condition called rheumatoid arthritis.

Type IV hypersensitivity
Type IV hypersensitivity is also known delayed hypersensitivity. This is because the
hypersensitivity reaction occurs some hours or days after union between antigens and immune
system products. In the case of type IV hypersensitivity, there are no antibodies. Instead, the
reaction involves cell mediated immunity. T cells are involved in this reaction.

For example, the tuberculin skin test is an example of a type IV delayed hypersensitivity. When a
person has been exposed to tubercule bacilli or has a tuberculosis immunization, the body
responds with sensitized T cells that distribute themselves throughout the body including the
skin. .In the tuberculin skin test, a preparation of tuberculosis known as PPD (purified protein
derivatives) is injected superficially into the skin. The sensitized T cells react with the antigens
and the site of injection becomes reddened and thickened within several hours. In two to three
days the reaction reaches its peak implying that the person has been exposed to tuberculosis
antigens at some time in the past.

BLOOD GROUPING
A person’s ABO blood grouping depends on the A, B or O gene (located on chromosome 9)
inherited from each parent as follows:

Genes inherited (Genotype) Blood group (Phenotype)

A and A Group A
A and O*
B and B Group B
B and O*
A and B Group AB
O and O Group O

Page 19 of 20
A and B genes are dominant. The recessive O gene is expressed only when A and B dominant
genes are absent. A person who is group O must be of the genotype OO.

A and B red cell antigens and the Antibodies in serum

Genotype Blood group (Phenotype) Antigen Serum Antibody
A and A Group A A Anti B
A and O*
B and B Group B B Anti A
B and O*
A and B Group AB A and B Nil
O and O Group O Nil Anti A and Anti B

The transfusion reaction typifies a cytotoxic hypersensitivity because antibodies attack human
cells, activate the complement system and destroy cells. For example, if type B blood were to be
donated to the person with type A blood, then the red blood cells entering the recipient would
have B antigen on their surface. The recipient has anti B antibodies in the serum. These
antibodies would react with the incoming antigens of the donor blood and the reaction would be
elicited the complement system, leading to destruction of red blood cells and clumping reactions
probably leading to death.

Page 20 of 20