SZL2111 HIV/AIDs

LESSON 3
The Immune system
Learning outcomes
Upon completing this topic, you should be able to :
ˆ Have an overview of the Human Immune system(IS)
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ˆ Understand various types of immunity

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ˆ Describe various stages of immune response

ˆ What is immunodeciency?
ˆ Various disorders and diseases associated with immune
system
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3.1. Overview of the Immune System
Immune system is a system of biological structures and processes
within an organism that protects against diseases by identifying
and killing pathogens and tumor cells. The immune system
is made up of organs that are involved in ghting invasion by
foreign bodies. They include;
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3.1.1. The bone marrow

The bone marrow is the production site of the white blood
cells(WBC) involved in immunity WBC involved includes the
B-lymphocytes (B cells) and the T lymphocytes (T cells). The
B-lymphocytes mature in the bone marrow and then enter the
JJ II circulation. T lymphocytes move from the bone marrow to the
J I thymus, where they mature into several kinds of cells capable
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of dierent functions Lymphoid organs The Lymphoid tissues
include the thymus gland, the spleen, the lymph nodes, the
tonsils and adenoids, and similar tissues in the gastrointesti-
nal, respiratory, and reproductive systems The lymph nodes are
distributed throughout the body. They are connected by lymph
channels and capillaries, which remove foreign material from the
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lymph before it enters the bloodstream. The lymph nodes also

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serve as centers for immune cell proliferation. The remaining

lymphoid tissues, such as the tonsils and adenoids and other
mucoid lymphatic tissues, contain immune cells that defend the
body against microorganisms

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3.1.2. Types of Immunity
• Innate/ Inborn/Natural/Non-specic immunity;
Present at birth Provide non-specic immunity to any foreign
invador regardless of invadors' composition. Operates under cer-
tain mechanisms or factors
ˆ Physical/mechanical barrier
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 Skin protects from entry of pathogens to our body

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 Respiratory tracts- the hairs /cilia along the tract

leads to coughing & sneezing in presence of microor-
ganism hence act as lters to clear the pathogens from
upper respiratory tract.

JJ II ˆ Biochemical factors Acidic gastric juices e.g. Hydrochloric

J I acid in the stomach. Enzymes present in sweat, saliva and
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breast milk respond by destroying invading microorgan-
isms. Blood protein factors e.g. interferons, compliments,
acute phase proteins destroy by puncturing holes in the
body.
ˆ Genetic - control People may become carriers but not sick
ˆ Cellular factors - WBCs participate both in natural & ac-
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quired immune responses. The cells ght invading for-

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eign bodies by releasing cell mediators. Other cells (non-

granular) e.g. monocytes & macrophages are phagocytic
i.e. engulf, digest &kill microorganism Inammatory re-
sponses. The inammatory response is a major function
of the natural (nonspecic) immune system elicited in re-
JJ II sponse to tissue injury or invading organisms. Chemical
J I mediators assist this response by: Minimizing blood loss
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Walling o the invading organism. Activating phagocytes
and promoting formation of brous scar tissues. Regener-
ation of injured tissue.

• Acquired/ Adaptive / Specic Immunity

Immunologic responses are acquired during life. Are not present
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at birth. They develop as a result of immunization/vaccination.

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Also developed after contracting a disease i.e. weeks or months

after exposure to the disease, the body produces an IR su-
cient to defend against re-infection. The two types of acquired
immunity: active and passive. In active acquired immunity, the
immunologic defenses are developed by the person's own body.
This immunity generally lasts many years or even a lifetime.
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Passive acquired immunity is temporary immunity transmitted
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from another source that has developed immunity through pre-
vious disease or immunization. For example, gamma-globulin
and antiserum, obtained from the blood plasma of people with
acquired immunity, are used in emergencies to provide immu-
nity to diseases when the risk for contracting a specic disease
is great and there is not enough time for a person to develop
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adequate active immunity.

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Both types of acquired immunity involve humoral and cel-

lular (cell-mediated) immunologic responses. It's divided into 2
forms
1. Humoral immunity (AMI) Involves antibodies produced
by B cells The antibodies recognize & bind specically to
JJ II foreign antigens & may cause one of the following: -Break/
J I splitdown the membrane of Ag (lysis) -Coat the Ag mak-
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ing it easier for phagocytosis (opsonization) -Neutralize ac-
tivities of toxins/ virus/ bacteria (neutralization) -Direct
killing of foreign Ag ( cytotoxicity / cell killing) -Clump
parasites together (agglutination)
2. Cell mediated immunity (CMI) - Two most important T
cell subtypes are involved in CMI T helper and T killer
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cells
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• Cells of the Immune System

1. T-Cells  T lymphocytes are divided into two major sub-
sets that dier in functions and identity (functionally and
phenotypically (identiably) dierent).
JJ II (a) The T helper subset, (CD4+ T cell) - The main func-
J I tion is to augment or potentiate immune responses by
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the secretion of specialized factors that activate other
WBCs to ght o infection. They interact with B
cells or T killer cells & help them respond to foreign
agents. T helper1-controls intracellular pathogens
(CMI)
(b) T helper2 - controls extra cellular pathogens (AMI)
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b)T killer/suppressor subset (CD8+ T cell). These

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cells are important in directly killing certain tumor

cells, viral-infected cells and sometimes parasites. They
directly bind to foreign agents, attack & kill those
cells thus eliminating them from the body. The CD8+
T cells are also important in down-regulation of im-
JJ II mune responses.
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NB: Both types of T cells can be found throughout the
body. They often depend on the secondary lymphoid or-
gans (the lymph nodes and spleen) as sites where activa-
tion occurs, but they are also found in other tissues of
the body, most conspicuously the liver, lung, blood, and
intestinal and reproductive tracts.
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2. Natural Killer Cells (NK) Are similar to the killer T cell

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subset (CD8+ T cells). They directly kill certain tumors

such as melanomas, lymphomas and viral-infected cells,
most notably herpes and cytomegalovirus-infected cells.
NK cells, unlike the CD8+ (killer) T cells, kill their tar-
gets without a prior sensitization. But kill more eectively
JJ II when activated by T h cell.
J I 3. B Cells  The major function of B lymphocytes is the
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production of antibodies in response to foreign proteins of
bacteria, viruses, and tumor cells. Antibodies are special-
ized proteins that specically recognize and bind to one
particular protein that specically recognize and bind to
one particular protein. Antibody production and binding
to a foreign substance or antigen, is critical as a means
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of signaling other cells to engulf, kill or remove that sub-

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stance from the body.

4. Granulocytes or Polymorphonuclear (PMN) Leukocytes -
It is a group of WBCs. Granulocytes are composed of
three cell types identied as neutrophils, eosinophils and
basophils, based on their staining characteristics with cer-
JJ II tain dyes. These cells are important in the removal of
J I bacteria and parasites from the body. They engulf these
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foreign bodies and degrade them using their powerful en-
zymes.
(a) Neutrophils -a/c60% - complete dvpt in the BM -
enter blood & remain incirculation for 10hours - leave
thro capillary wall & enter connective tissue - after
a day or 2 they enter the digestive tract or urinary
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tract & are swept out of the body by waters.

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(b) Eosinophils a/c 3% of circulating WBCs - help con-

trol allergic reactions & helminth infections
(c) Basophils- a/c less than 1% - controls allergic reac-
tions, inammatory reactions, clotting process & fat
metabolism
JJ II 5. Macrophages  They are often referred to as scavengers or
J I antigen-presenting cells (APC). This is because they pick
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up and ingest foreign materials and present these antigens
to other cells of the immune system such as T cells and B
cells. This is one of the important rst steps in the ini-
tiation of an immune response. Stimulated macrophages
exhibit increased levels of phagocytosis and are also secre-
tory. Monocytes - they cross capillary wall, enter tissue &
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dierentiate to macrophages, - destroy bacteria, dead cells

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and other matters - Are CD4+

6. Dendritic Cells  Dendritic cells function as APCs. In fact,
they are more ecient APCs than macrophages. These
cells are usually found in the structural compartment of
the lymphoid organs such as the thymus, lymph nodes and
JJ II spleen. They are also found in the bloodstream and other
J I tissues of the body. It is believed that they capture anti-
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gen or bring it to the lymphoid organs where an immune
response is initiated. They are extremely hard to isolate.
Recent nding is that dendritic cells bind high amount of
HIV, and may be a reservoir of virus that is transmitted
to CD4+ T cells during an activation event. Cells that
possess CD4 markers include:
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ˆ T helper cells
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ˆ Macrophages
ˆ Monocytes
ˆ Colon cells
ˆ Dendritic cells
ˆ Retinal cells
JJ II NB: HIV attaches to any CD4+ cell. Immune response
J I to invasion
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When bacteria, viruses or other pathogens overcome the body's
natural immunity and gain entry into the blood system, three
specic mechanism of acquired immunity are initiated. They
include:
ˆ The phagocytic immune response
ˆ The humoral or antibody immune response
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ˆ The cellular or cell mediated immune response

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1. Phagocytic immune response

ˆ The rst line of defense, the phagocytic immune re-
sponse, involves the WBCs (granulocytes and macrophages
which have the ability to ingest foreign particles. These
JJ II cells move to the point of attack, where they engulf
J I and destroy the invading agents.
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2. Humoral or Antibody immune response
ˆ The humoral response is characterized by production
of antibodies by the B-lymphocytes in response to a
specic antigen. Although the B-lymphocyte is ulti-
mately responsible for the production of antibodies,
both the macrophages of natural immunity and the
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special T-cell lymphocytes of cellular immunity are

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involved in recognizing the foreign substance and in

producing antibodies.
3. Antigen recognition
ˆ The part of the invading or attacking organism that
is responsible for stimulating antibody production is
JJ II called an antigen (or an immunogen). For example,
J I an antigen can be a small patch of proteins on the
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outer surface of the microorganism. A single bac-
terium, even a single large molecule, such as a toxin
(diphtheria or tetanus toxin), may have several such
antigens, or markers, on its surface, thus inducing
the body to produce a number of dierent antibod-
ies. Once produced, an antibody is released into the
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bloodstream and carried to the attacking organism.

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There it combines with the antigen, binding with it

like an interlocking piece of a jigsaw puzzle .

3.1.3. Stages in an immune response

• Recognition stage
JJ II ˆ The immune system's ability to recognize antigens as for-
J I eign, or non-self, is the initiating event in any immune
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response (g 2.2). The body must rst recognize invaders
as foreign before it can react to them. The body accom-
plishes recognition using lymph nodes and lymphocytes
for surveillance. Lymph nodes are widely distributed in-
ternally and externally near the body's surfaces. They
continuously discharge small lymphocytes into the blood-
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stream. These lymphocytes patrol the tissues and vessels

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that drain the areas served by that node.

ˆ Lymphocytes are found in the lymph nodes and in the cir-
culating blood. The volume of lymphocytes in the body is
impressive. These lymphocytes recirculate from the blood
to lymph nodes and from the lymph nodes back into the
JJ II bloodstream, in a never-ending series of patrols. Some cir-
J I culating lymphocytes can survive for decades. Some of
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these small, hardy cells maintain their solitary circuits for
the lifetime of the person.
ˆ The exact way in which circulating lymphocytes recognize
antigens on foreign surfaces is not known; however, the-
orists think that recognition depends on specic receptor
sites on the surface of the lymphocytes. Macrophages play
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an important role in helping the circulating lymphocytes

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process the antigens. When foreign materials enter the

body, a circulating lymphocyte comes into physical con-
tact with the surfaces of these materials. Upon contact,
the lymphocyte, with the help of macrophages, either re-
moves the antigen from the surface or in some way picks
JJ II up an imprint of its structure, which comes into play with
J I subsequent re-exposure to the antigen.
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ˆ In a streptococcal throat infection, for example, the strep-
tococcal organism gains access to the mucous membranes
of the throat. A circulating lymphocyte moving through
the tissues of the neck comes in contact with the organ-
ism. The lymphocyte, familiar with the surface markers
on the cells of its own body, recognizes the antigens on
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the microbe as dierent (non-self) and the streptococcal

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organism as antigenic (foreign). This triggers the second

stage of the immune responseproliferation.

• Proliferation stage
ˆ The circulating lymphocyte containing the antigenic mes-
sage returns to the nearest lymph node. Once in the node,
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the sensitized lymphocyte stimulates some of the resident
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dormant T and-lymphocytes to enlarge, divide, and pro-
liferate. T lymphocytes dierentiate into cytotoxic (or
killer) T cells, whereas-lymphocytes produce and release
antibodies. Enlargement of the lymph nodes in the neck
in conjunction with a sore throat is one example of the
immune response.
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• Response stage
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ˆ In the response stage, the changed lymphocytes function

either in a humoral or a cellular fashion. The production
of antibodies by the-lymphocytes in response to a specic
antigen begins the humoral response. Humoral refers to
the fact that the antibodies are released into the blood-
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stream and so reside in the plasma (uid fraction of the
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blood).
ˆ With the initial cellular response, the returning sensitized
lymphocytes migrate to areas of the lymph node (other
than those areas containing lymphocytes programmed to
become plasma cells). Here, they stimulate the residing
lymphocytes to become cells that will attack microbes di-
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rectly rather than through the action of antibodies. These

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transformed lymphocytes are known as cytotoxic (killer)

T cells. The T stands for thymus, signifying that dur-
ing embryologic development of the immune system, these
T lymphocytes spent time in the thymus of the develop-
ing fetus, where they were genetically programmed to be-
JJ II come T lymphocytes rather than the antibody-producing-
J I lymphocytes. Viral rather than bacterial antigens induce
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a cellular response. This response is manifested by the in-
creasing number of T lymphocytes (lymphocytosis) seen
in the blood smears of people with viral illnesses, such as
infectious mononucleosis.
ˆ Most immune responses to antigens involve both humoral
and cellular responses, although one usually predominates.
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For example, during transplantation rejection, the cellular

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response predominates, whereas in the bacterial pneumo-

nias and sepsis, the humoral response plays the dominant
protective role.

• Eector stage
JJ II ˆ In the eector stage, either the antibody of the humoral
J I response or the cytotoxic (killer) T cell of the cellular re-
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sponse reaches and couples with the antigen on the surface
of the foreign invader. The coupling initiates a series of
events that in most instances results in the total destruc-
tion of the invading microbes or the complete neutraliza-
tion of the toxin. The events involve interplay of antibod-
ies (humoral immunity), complement, and action by the
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cytotoxic T cells (cellular immunity).

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Production of B-Lymphocytes
ˆ B-lymphocytes stored in the lymph nodes are subdivided
into thousands of clones, each responsive to a single group
of antigens having almost identical characteristics. When
the antigenic message is carried back to the lymph node,
JJ II specic clones of the-lymphocyte are stimulated to enlarge,
J I divide, proliferate, and dierentiate into plasma cells capa-
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ble of producing specic antibodies to the antigen. Other-
lymphocytes dierentiate into-lymphocyte clones with a
memory for the antigen. These memory cells are responsi-
ble for the more exaggerated and rapid immune response
in a person who is repeatedly exposed to the same antigen.

3.1.4. Role of antibodies in Humoral Immune Responses

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ˆ Antibodies are large proteins called immunoglobulins be-

cause they are found in the globulin fraction of the plasma
proteins. Each antibody molecule consists of two subunits,
each of which contains a light and a heavy peptide chain.
The sub-units are held together by a chemical link com-
JJ II posed of disulde bonds. Each subunit has a portion that
J I serves as a binding site for a specic antigen referred to
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as the Fab fragment. This site provides the "lock" por-
tion that is highly specic for an antigen. An additional
portion, known as the Fc fragment, allows the antibody
molecule to take part in the complement system.
ˆ Antibodies defend against foreign invaders in several ways,
and the type of defense employed depends on the structure
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and composition of both the antigen and the immunoglob-

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ulin. The antibody molecule has at least two combining

sites, or Fab fragments. One antibody can act as a cross-
link between two antigens, causing them to bind or clump
together. This clumping eect, referred to as agglutina-
tion, helps clear the body of the invading organism by
JJ II facilitating phagocytosis. Some antibodies assist in re-
J I moving oending organisms through opsonization. In this
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process, the antigenantibody molecule is coated with a
sticky substance that also facilitates phagocytosis.
ˆ Antibodies also promote the release of vasoactive substances,
such as histamine and slow-reacting substance, two of the
chemical mediators of the inammatory response. In addi-
tion, antibodies are involved in activating the complement
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system.
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3.1.5. Types of Immunoglobulins

The body can produce ve dierent types of immunoglobulins.
(Immunoglobulins are commonly designated by the abbreviation
Ig.) Each of the ve types, or classes, is identied by a specic
JJ II letter of the alphabet (IgA, IgD, IgE, IgG, and IgM). Classica-
J I tion is based on the chemical structure and biologic role of the
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individual immunoglobulin. The following list summarizes some
outstanding characteristics of the immunoglobulins: 
ˆ IgG (75% of Total Immunoglobulin) ˆ Appears in serum
and tissues (interstitial uid) ˆ Assumes major role in
blood borne and tissue infections ˆ Activates complement
system ˆ Enhances phagocytosis ˆ Crosses placenta
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ˆ IgA (15% of Total Immunoglobulin) ˆ Appears in body

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uids (blood, saliva, tears, breast milk, and pulmonary,

gastrointestinal, prostatic, and vaginal secretions) ˆ Pro-
tects against respiratory, gastrointestinal, and genitouri-
nary infections ˆ Prevents absorption of antigens from food
ˆ Passes to neonate in breast milk for protection
JJ II ˆ IgM (10% of Total Immunoglobulin) ˆ Appears mostly in
J I intravascular serum ˆ Appears as the rst immunoglobulin
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produced in response to bacterial and viral infections ˆ
Activates complement system
ˆ IgD (0.2% of Total Immunoglobulin) ˆ Appears in small
amounts in serum ˆ Possibly inuences B-lymphocyte dif-
ferentiation, but plays unclear role
ˆ IgE (0.004% of Total Immunoglobulin) ˆ Appears in serum
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ˆ Takes part in allergic and some hypersensitivity reactions

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ˆ Combats parasitic infections

3.1.6. Cellular (or cell mediated) immune response

ˆ It is called cellular because it involves production of special
cells T lymphocytes (or T cells) that are primarily respon-
JJ II sible for cellular immunity. These lymphocytes spend time
J I in the thymus, where they are programmed to become T
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cells rather than antibody-producinglymphocytes (Figure
2.3). Several types of T cells exist, each with designated
roles in the defense against bacteria, viruses, fungi, para-
sites, and malignant cells. T cells attack foreign invaders
directly rather than by producing antibodies.
ˆ Cellular reactions are initiated by the binding of an anti-
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gen with an antigen receptor located on the surface of a

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T cell. This may occur with or without the assistance of

macrophages. The T cells then carry the antigenic mes-
sage, or blueprint, to the lymph nodes, where the produc-
tion of other T cells is stimulated. Some T cells remain
in the lymph nodes and retain a memory for the antigen.
JJ II Other T cells migrate from the lymph nodes into the gen-
J I eral circulatory system and ultimately to the tissues, where
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Figure 3.1: Cellular (or cell mediated) immune response

they remain until they either come in contact with their

respective antigens or die.
JJ II
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• Role of T lymphocytes
Two major categories of eector T cells are helper T cells and
cytotoxic T cells. These cells participate in destroying foreign
organisms. Other T cells include suppressor T cells and mem-
ory T cells. T cells interact closely with-cells, indicating that
humoral and cellular immune responses are not separate, unre-
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lated processes but rather branches of the immune response that

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can and do aect each other.

1. Helper T cells (helper CD4 cells) are activated upon recog-
nition of antigens and stimulate the rest of the immune
system. When activated, helper T cells secrete cytokines
that attract and activate-cells, cytotoxic T cells, natu-
JJ II ral killer cells, macrophages, and other cells of the im-
J I mune system (Laurence J. 1995). Separate subpopula-
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tions of helper T cells produce dierent types of cytokines
and determine whether the immune response will be the
production of antibodies or a cell-mediated immune re-
sponse. Helper T cells produce lymphokines, one cate-
gory of cytokines. These lymphokines activate other T
cells (interleukin-2, or IL-2), natural and cytotoxic T cells
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(interferon-gamma), and other inammatory cells (tumor

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necrosis factor). Helper T2 cells produce IL-4 and IL-5,

lymphokines that activate-cells to grow and dierentiate
(Laurence J. 1995, Roit I; et al 1989)).
2. Cytotoxic T cells (killer T cells) attack the antigen di-
rectly by altering the cell membrane and causing cell lysis
JJ II (disintegration) and releasing cytolytic enzymes and cy-
J I tokines. Lymphokines can recruit, activate, and regulate
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other lymphocytes and WBCs. These cells then assist in
destroying the invading organism.
3. Suppressor T cells, has the ability to decrease B-cell pro-
duction, thereby keeping the immune response at a level
that is compatible with health (e.g. sucient to ght in-
fection adequately without attacking the body's healthy
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tissues). Memory T cells are responsible for recognizing

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antigens from previous exposure and mounting an immune

response.

• Roles of null lymphocytes and natural killer cells in

cellular immune responses
JJ II Null lymphocytes and natural killer (NK) cells are other lym-
J I phocytes that assist in combating organisms. These are distinct
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from-cells and T cells and lack the usual characteristics of-cells
and T cells.
1. Null lymphocytes, a subpopulation of lymphocytes, de-
stroy antigens already coated with antibody. These cells
have special Fc receptor sites on their surfaces that allow
them to couple with the Fc end of antibodies (antibody-
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dependent, cell-mediated cytotoxicity, Beattie, T et al 2002).

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2. Natural killer cells, another subpopulation of lymphocytes,

defend against microorganisms and some types of malig-
nant cells. NK cells are capable of directly killing invading
organisms and producing cytokines. The helper T cells
contribute to the dierentiation of null and NK cells (Lau-
JJ II rence J. 1995).
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3.1.7. Complement System
ˆ Circulating plasma proteins, which are made in the liver
and activated when an antibody couples with its antigen,
are known as complement. These proteins interact sequen-
tially with one another in a cascade or "falling domino"
eect. This complement cascade alters the cell membranes
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on which antigen and antibody complex form, permitting

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uid to enter the cell and leading eventually to cell lysis

and death. In addition, activated complement molecules
attract macrophages and granulocytes to areas of antigen
antibody reactions. These cells continue the body's de-
fense by devouring the antibody-coated microbes and by
JJ II releasing bacterial agents.
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ˆ Complement plays an important role in the immune re-
sponse. Destruction of an invading or attacking organ-
ism or toxin is not achieved merely by the binding of the
antibody and antigens; it also requires activation of com-
plement, the arrival of killer T cells, or the attraction of
macrophages.
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3.2. Immunodeciency
ˆ When some or one of the components of the immune sys-
tem is lacking, disorders or abnormalities arises and this is
referred to as an immunodeciency. These abnormalities
or disorders are either as a result of genetic abnormally
JJ II (congenital) or are acquired within the course of life due
J I to a number of factors
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 Old age
 Nutrition
 Autoimmune disorder
 Neoplastic disease
 Chronic illness and surgery
 Medication
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 Lifestyle and other factors

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 Stress
1. Age - People at the extremes of the lifespan are more likely
to develop problems related to immune system functioning
than are those in their middle years. Frequency and sever-
ity of infections are increased in elderly people, possibly
JJ II from a decreased ability to respond adequately to invad-
J I ing organisms. Both the production and the function of
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T and B -lymphocytes may be impaired. The incidence
of autoimmune diseases also increases with aging, possibly
from a decreased ability of antibodies to dierentiate be-
tween self and non-self. Failure of the surveillance system
to recognize mutant, or abnormal, cells may be responsible
for the high incidence of cancer associated with increasing
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age.
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2. Declining function of various organ systems associated with

increasing age also contributes to impaired immunity. De-
creased gastric secretions and motility allow normal in-
testinal ora to proliferate and produce infection, caus-
ing gastroenteritis and diarrhea. Decreased renal circula-
JJ II tion, ltration, absorption, and excretion contribute to risk
J I for urinary tract infections. Moreover, prostatic enlarge-
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ment and neurogenic bladder can impede urine passage
and subsequently bacterial clearance through the urinary
system. Urinary stasis, common in elderly people, per-
mits the growth of organisms. Exposure to tobacco and
environmental toxins impairs pulmonary function. Pro-
longed exposure to these agents decreases the elasticity of
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lung tissue, the eectiveness of cilia, and the ability to

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cough eectively. These impairments hinder the removal

of infectious organisms and toxins, increasing the elderly
person's susceptibility to pulmonary infections and can-
cers. Finally, with aging, the skin becomes thinner and
less elastic. Peripheral neuropathy and the accompanying
JJ II decreased sensation and circulation may lead to stasis ul-
J I cers, pressure ulcers, abrasions, and burns. Impaired skin
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 SZL2111 HIV/AIDs
integrity predisposes the aging person to infection from
organisms that are part of normal skin ora.
3. Nutrition - Adequate nutrition is essential for optimal func-
tioning of the immune system. Vitamin intake, essential
for DNA and protein synthesis, if inadequate, may lead
to protein-calorie deciency and subsequently to impaired
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immune function. Vitamins also help in the regulation of

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cell proliferation and maturation of immune cells. Excess

or deciency of trace elements (i.e., copper, iron, man-
ganese, selenium, or zinc) in the diet generally suppresses
immune function. Fatty acids are the building blocks that
make up the structural components of cell membranes.
JJ II Lipids are precursors of vitamins A, D, E, and K as well
J I as cholesterol. Both excess and deciency of fatty acids
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 SZL2111 HIV/AIDs
have been found to suppress immune function.
4. Depletion of protein reserves results in atrophy of lym-
phoid tissues, depression of antibody response, reduction
in the number of circulating T cells, and impaired phago-
cytic function. As a result, susceptibility to infection is
greatly increased. During periods of infection and serious
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illness, nutritional requirements may be exaggerated fur-

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ther, potentially contributing to depletion of protein, fatty

acid, vitamin, and trace elements and an even greater risk
of impaired immune response and sepsis.

3.2.1. Autoimmune disorders

JJ II In general, autoimmune disorders are more common in females
J I than in males. This is believed to be the result of the activ-
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 SZL2111 HIV/AIDs
ity of the sex hormones. The ability of sex hormones to mod-
ulate immunity has been well established. There is evidence
that estrogen modulates the activity of T lymphocytes (espe-
cially suppressor cells), whereas androgens act to preserve IL-
2 production and suppressor cell activity. The eects of sex
hormones on B -cells are less pronounced. Estrogen activates
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the autoimmune-associated B-cell population that expresses the

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CD5 marker (an antigenic marker on the-cell). Estrogen tends

to enhance immunity, whereas androgen tends to be immuno-
suppressive.Autoimmune disorders include lupus erythematosus,
rheumatoid arthritis, or psoriasis

JJ II
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 SZL2111 HIV/AIDs
3.2.2. Neoplastic disease
Immunosuppression contributes to the development of cancers;
however, cancer itself is immunosuppressive. Large tumors can
release antigens into the blood, and these antigens combine with
circulating antibodies and prevent them from attacking the tu-
mor cells. Furthermore, tumor cells may possess special blocking
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factors that coat tumor cells and prevent destruction by killer

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T lymphocytes. During the early development of tumors, the

body may fail to recognize the tumor antigens as foreign and
subsequently fail to initiate destruction of the malignant cells.
Hematologic cancers, such as leukemia and lymphoma, are as-
sociated with altered production and function of WBCs and
JJ II lymphocytes. All treatments that an individual has received or
J I is currently receiving, such as radiation or chemotherapy, are
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 SZL2111 HIV/AIDs
vital. Radiation destroys lymphocytes and decreases the pop-
ulation of cells required to replace them. The size or extent
of the irradiated area determines he extent of Immunosuppres-
sion. Whole-body irradiation may leave the patient totally im-
munosuppressed. Chemotherapy also destroys immune cells and
causes Immunosuppression.
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3.2.3. Chronic illness and surgery

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ˆ Chronic illness may contribute to immune system impair-

ments in various ways. Renal failure is associated with
a deciency in circulating lymphocytes. In addition, im-
mune defenses may be altered by acidosis and uremic tox-
JJ II ins. In diabetes, an increased incidence of infection has
J I been associated with vascular insuciency, neuropathy,
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 SZL2111 HIV/AIDs
and poor control of serum glucose levels. Recurrent respi-
ratory tract infections are associated with chronic obstruc-
tive pulmonary disease as a result of altered inspiratory
and expiratory function and ineective airway clearance.
Additionally, surgical removal of the spleen, lymph nodes,
or thymus or organ transplantation may place an individ-
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ual at risk for impaired immune function.

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3.2.4. Special problems

ˆ Conditions such as burns and other forms of injury and
infection may contribute to altered immune system func-
tion. Major Burns or other factors cause impaired skin
JJ II integrity and compromise the body's rst line of defense.
J I Loss of large amounts of serum with burn injuries depletes
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 SZL2111 HIV/AIDs
the body of essential proteins, including immunoglobu-
lins. The physiologic and psychological stressors asso-
ciated with surgery or injury stimulates cortisol release
from the adrenal cortex; increased serum cortisol also con-
tributes to suppression of normal immune responses.
1. Medications
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 In large doses, antibiotics, corticosteroids, cyto-

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toxic agents, salicylates, nonsteroidal anti-inammator

drugs, and anesthetics can cause immune sup-
pression.
2. Lifestyle and Other Factors
 Like any other body system, the immune sys-
JJ II tem functions depend on the function of other
J I body systems. Poor nutritional status, smoking,
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 SZL2111 HIV/AIDs
excessive consumption of alcohol and exposure
to environmental radiation and pollutants have
been associated with impaired immune function.

3.2.5. Role of immune system in HIV pathogenesis

ˆ The immune system is responsible for body defense against
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attack from pathogenesis

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ˆ It is made up of white blood cells which include granulo-

cytes such as neutrophils and basophils, and agranulocytes
such as monocytes and lymphocytes.
ˆ T-helper lymphocytes have a CD4+ marker that the HIV
use for entry into the cell and replicates
JJ II ˆ T-helper lymphocytes are important in immune regula-
J I tion because when they are activated they recruit other
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 SZL2111 HIV/AIDs
immune cell involved in immune responses.
ˆ HIV uses the CD4+ cells to replicate and produce more
viral particles.
ˆ CD4 are killed and destroyed as viral production progresses
ˆ Cytotoxic T-lymphocytes with CD8+ marker target any
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virally infected CD4+ cells and kills them

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ˆ Macrophages which have a CD4+ marker too act as reser-

voir and are also killed by cytotoxic
ˆ As virtually infected cells are killed by cytotoxic T-lymphocytes
and more of the CD4+ cells destroyed as a result of viral
replication, their numbers goes down.
JJ II ˆ The immune system is depleted of these crucial cells in-
J I volved in body defense and becomes vulnerable to attack
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 SZL2111 HIV/AIDs
by opportunistic pathogens.

Example . Briey describe the sexual transmission of HIV/AIDS

Solution : The risk of transmission through unprotected vaginal
sex is thought to be lower than anal sex, though still highly
signicant. However, where there is a risk of vaginal tears or
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sores e.g. in the presence of sexually transmitted infection, the

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risk of transmission is increased signicantly. HIV transmission

through oral sex is a much debated subjected. However, the
virus is present in blood and semen, which means that in theory,
this is a possible transmission route. There may be an increased
risk if there is ejaculation, bleeding gums, lips, or inammation
caused by common throat infections. The sharing of sex toys
JJ II
also carries a risk of HIV transmission. If more than one person
J I
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 SZL2111 HIV/AIDs
is going to use a vibrator or dildo, is essential that it is cleaned
thoroughly between uses or covered with afresh condom before
each use. . 
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JJ II
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 SZL2111 HIV/AIDs
Exercise 1.  Revision Questions
Discuss the role of immune system in HIV pathogenesis
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JJ II
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 SZL2111 HIV/AIDs
References and Additional Reading Materials
1. Maranga R. O, Muya S. M and Ogila K. O (2008) Funda-
mentals of HIV/AIDS Education. Signon Publishers.
2. Barry D. S. (1999) AIDS and HIV in Perspectives. CPU.
ISBN-13: 9780521627665
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3. Ellison G. Parker M., Camphpbell C (2003) Learning from

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HIV and AIDS. Cambridge CPU.ISBN-13: 9780521709286.

4. Shavitri Ramaiah (2008) HIV/AIDS; Health solutions. Ster-
ling Publishers Ltd. ISBN-9788120733305.

JJ II
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 SZL2111 HIV/AIDs
Solutions to Exercises
Exercise 1. The immune system is responsible for body de-
fense against attack from pathogens. It is made up of white
blood cells which include granulocytes such as neutrophils and
basophils, and agranulocytes such as monocytes and lympho-
cytes. T-helper lymphocytes have a CD4+ marker that the HIV
JKUAT

uses for entry into the cell and replicates. T-helper lymphocytes
SODeL

are important in immune regulation because when they are ac-

tivated they recruit other immune cell involved in immune re-
sponses. HIV uses the CD4+ cells to replicate and produce more
viral particles. CD4 are killed and destroyed as viral production
progresses. Cytotoxic T-lymphocytes with CD8+ marker target
JJ II any virally infected CD4+ cells and kills them. Macrophages
J I which have a CD4+ marker too act as reservoir and are also
J DocDoc I 54
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 SZL2111 HIV/AIDs
killed by cytotoxic. As virtually infected cells are killed by cy-
totoxic T-lymphocytes and more of the CD4+ cells destroyed
as a result of viral replication, their numbers goes down. The
immune system is depleted of these crucial cells involved in
body defense and becomes vulnerable to attack by opportunistic
pathogens. Exercise 1
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JJ II
J I
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