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Review of literature
Chapter (1)IMMUNITY
Immunity is the ability of human body to resist almost all types of
organisms or toxins that tend to damage the tissues and organs(Guyton
and Hall, 2006).
The immune system is a complex network of cells, proteins,
tissues, and organs that work together to protect the body against
infectiousdiseases or other insults. The immune system is composed of a
number of cell types that function in different ways, and other blood-
borne factors to provide a large variety of defense
mechanisms(Moazzamet al,2013).
Structure of immune system :
The organs of the immune system are positioned throughout the
body. They are called lymphoid organs because they are home to
lymphocytes, a type of white bloodcells (WBCs) that are the key players
in the immune system.
There are two groups of immune system organs:
A) Primary (central) organs:where immature lymphocytes develop,
these organs are:
1-Bone marrow:It is the soft tissue in the hollow center of bones which is
the ultimate source of all blood cells, including lymphocytes.
2-The thymus:It is a lymphoid organ that lies behind the sternum.
Lymphocytes known as T lymphocytes or T cells (“T” stands for
“thymus”) mature in the thymus and then migrate to other tissues. B
lymphocytes, also known as B cells (“B” stands for “bone marrow”),
become activated and mature in the liver during the fetal life and in the
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bone marrow after birth into plasma cells, which make and release
antibodies(Janeway et al,2005).
B) Secondary (peripheral) tissues:Where antigen (an agent or substance
that can trigger an immune response) is localized so that it can be
effectively exposed to mature lymphocytes, these tissue are :
1-Lymph nodes: They are Small bean-shaped structures ,which are
located in many parts of the body along the lymphatic vessels, with
clusters in the neck, axilla, abdomen, and groin. They are lymphoid
tissues that contain numerous specialized structures.
Each lymph node contains specialized compartments where the
immune cells congregate , and where they can encounter antigens. As
regard structure of lymph node, it is divided into 3 compartments; the
outer cortex, the inner medulla and the paracortex inbetween. The cortex
consists mainly of the B cells arranged as follicles, which may develop a
germinal center when challenged with an antigen, while T cells from the
thymus concentrate in the paracortex and plasma cells located in the
medulla (Tomoya et al, 2004).
Immune cells, microbes, and foreign antigens enter the lymph
nodes via incoming lymphatic vessels or the lymph nodes’ tiny blood
vessels. All lymphocytes exit lymph nodes through outgoing lymphatic
vessels. Once enter in the bloodstream, lymphocytes are transported to
tissues throughout the body. They circulate everywhere for foreign
antigens, then gradually drift back into the lymphatic system to begin the
cycle all over again.
Cells and fluids are exchanged between blood and lymphatic
vessels, enabling the lymphatic system to monitor the body for invading
microbes(Tomoya et al,2004).
2-The spleen: It is a flattened organ at the upper left of the abdomen.
Like the lymph nodes, the spleen contains specialized compartments
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where immune cells gather and work. The spleen serves as a meeting
ground where immune defenses confront antigens (Mebius and Kraal,
2005).
3- Mucosal-Associated Lymphoid Tissue (MALT): They are clumps of
lymphoid tissue which are found in many parts of the body, especially in
the linings of the digestive tract, airways, and lungs that serve as
gateways to the body. These tissues include:
GALT (Gut-Associated Lymphoid Tissue): Include the tonsils,
adenoids, appendix, and peyer's patches.
BALT (Bronchial/Tracheal-Associated Lymphoid Tissue).
LALT (larynx-associated lymphoid tissue).
NALT (Nose-Associated Lymphoid Tissue).
VALT (Vulvovaginal-Associated Lymphoid Tissue).
CALT (conjunctival-associated lymphoid tissue).
LDALT (lacrimal duct-associated lymphoid tissue).
SALT (skin-associated lymphoid tissue)(Cesta,2006).
Types of cells of immune system:The cells associated with the immune system are generally termed
leukocytes, or WBCs. Leukocytes are divided into two main categories:
phagocytes (granulocytes, monocytes, and macrophages) and
lymphocytes (T-lymphocytes, B-lymphocytes, and natural killer cells)
which are the major players in the immune response.
A)Phagocytes:
1) Macrophages: Its function is mediated through phagocytosis; it is
initiated by Chemotaxis; the process by which phagocytes are attracted
and adhere to microorganisms. Macrophages have cell-surface receptors
that recognize certain molecules on the surface of various pathogens.
Then the pseudopods of phagocytes engulf the microorganism and
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enclose it in a phagocytic vesicle (phagosome) to complete ingestion by
lysosomal enzymes and oxidizing agents(Aderem and Underhill, 1999).
Also, macrophages can Processes and presents antigens to T
cellswhich named antigen-presenting cells (APCs).They cansecret
cytokines, interleukin-1 (IL-1) to induceproliferation of B cells and also,
secret interferon that stimulates T cell growth(Joke MM den Haan et al,
2014).
2)Monocytes:can develop into two types of cell:
a) Dendritic cells (DCs):which are APCs able to mark out foreign
bodies to be destroyed by lymphocytes.
b) Macrophages:they are phagocyte cells able to act as
APCs(Ziegler-Heitbrock et al, 2010).
3)Granulocytes: (Microphages) :
a) Neutrophils:They may be subdivided into segmented neutrophils
and banded neutrophils. They form part of the polymorphonuclear
cell family (PMNs) together with basophils and eosinophils. They
are phagocytes, capable of ingesting bacteria and other
microorganisms or particles(Nathan, 2006).
b) Eosinophils: They are involved in allergic reactions and attack
multicellular parasites such as worms(Rothenberg & Hogan,
2006).
c) Basophils: They are involved in allergic reactions. They can
release histamine, which helps to trigger inflammation and release
heparin, which prevents blood from clotting(Nakanishi, 2010).
B)Lymphocytes:
1)T-Lymphocytes:They are classified into :
a) Cytotoxic T (killer T) (CD8)cells:They carry the CD8 protein
surface cell marker. They can kill foreign cells through chemical
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lysis. Also They release cytokines, interferon-gamma (IFN-γ) that
attractmacrophages and increases their phagocytic activity. They
also prevent macrophage migration from site of action.
b) Helper T (CD4) cells:Theycarry the CD4 protein surface cell
marker. They Cooperate with B cells to amplify antibody
production by plasma cells. They Secrete interleukin-2 (IL-2) to
help to stimulate proliferation of T and B cells and also secrete
IFN-γ and tumor necrosis factor (TNF), which stimulate the
inflammatory response.
c) Suppressor T (regulatory T)(Tregs)cells:They regulate the actions
of T cells and B cells and help to prevent the immune system from
overreacting. They may directly destroy activated lymphocytes.
d) Memory T cells:They remainin lymphoid tissue and recognize
original invading antigens, even years after exposure(Janeway et
al,2001).
2) B lymphocytes:They differentiated into :
a) Plasma cells:They produce antibodiesor immunoglobulins, which
are Y shaped proteins that bind to infected microbes or cells of our
body that have become infected. Antibodies can either neutralize
the target microbe or can mark it out for attack by T lymphocytes.
b) Memory B cells: They can respond more rapidly and forcefully if
the same antigen enter the body in the future(Janeway et al,2001).
3) Natural killer (NK) cells: They are non-T, non-B lymphocytes.They
can destroy cells with malignant transformation or infected with
viruses(Janeway et al,2001).
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Immunoglobulins (Antibodies)Immunoglobulins (Igs) or antibodies (Abs) are glycoprotein
molecules produced inresponse to antigens (Ags) which are foreign
substances entering the living body. Theybinding to them and forming
antigen-antibody complexes resulting in Ag elimination andprotection of
the body of the host. Igs are produced by B-lymphocytes(plasma cells)
and are found in fraction of blood called gamma globulin.Igs are
synthesized with a molecular arrangement that fits the shape of molecules
on the antigens, in order to allow effective binding of the Igs. Igs binding
to Ags basically help toinactivate, weaken or enhance phagocytosis of
Ags(Schroeder and Cavacini, 2010).
Basic structure of immunoglobulins:All Igs have the same basic structural units of 2 identical light
chains and 2 identical heavy chains, theheavy and light chains are joined
together by interchain disulphide bonds and non-covalent
interactions.The number of interchain disulphide bonds varies among
different Igs. Amino acid sequence ofboth heavy and light chains of an Ig
characterizes two distinct regions known as variable (V) and constant (C)
regions (Janeway et al,2001).
Light and heavy chainsare composed of both a variable and
constant region designated as VL and CL (light chains) and VH and
CH(heavy chains).The amino acid sequence of the variable region
determine antigenic specificity of the Igs. Constant regions are the same
for each specific class of Igand carry the effector sites(Schroeder and
Cavacini, 2010).
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Fig.(I):Basic structure of Immunoglobulin(Janeway et al, 2001).
There are two types of light chains,kappa (κ) and lambda (λ).No
functional difference has been found between Igs having λ or κ light
chains. The ratio of the two types of light chain varies from species to
species. In mice, the average κ to λ ratio is 20:1, whereas in humans it is
2:1. The reason for this variation is unknown. Differences in the type of
light chains also form a basis for grouping of Igs into various
types(Redegeld and Nijkamp, 2003).
There are 5 types of heavy chains whichdefines the class of Igs,
namely, Alpha (α), Gamma (γ), Miu (μ), Delta (δ) and Epsilon (ε). The
hinge region is the area of the Ig where the arms of the Abs form a ‘Y’,it
is a flexible region(Janeway et al,2001).
Fragmentation of Ig using reducing & denaturing agents produce
subunits of Ig, two heavy (H) chain and two light (L) chain which are
found in equimolar amounts with 2 H and 2 L chains. While proteolytic
digestion by proteasesproduce fragments. Papain enzyme cleaves the
immunoglobulin molecule into three pieces, two Fab fragmentsand one
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Fc fragment. So, molar ratio of Fab/Fc is 2:1. While pepsin enzyme
cleaves immunoglobulin to yield one F(ab')2 fragment and many small
pieces of the Fc fragment, the largest of which is called the pFc' fragment.
These fragments are:
1-Fab (fragment for antigen binding):It is the region of Ig that bind
to Ag. It is gotten upon digestion of Ig with papain and its cleavage at the
hinge region. It is composed of one constant and one variable
domainfrom each heavy and light chains of the Ig (the antigen binding
site) which is particular to the kind of antigenic determinant the Ig will
bind(Janeway et al,2001).
2-Fc(fragment crystallizable):It is the region of Ig which mediate
effector functions of an Ig to Ag.It is called fragment crystallizable
because it is readily crystallized. It is gotten upon digestion of Ig with
papain and its cleavage at the hinge region. It is composed of two heavy
chains that contribute two or three constant domains depending on the
class of the antibody.Variations in the Fc determines the different classes
of Igs.The hinge region is between the Fab and the Fc portion and
controls interactions between these portions(Janeway et al,2001).
3- F(ab')2 : Treatment of Igs with pepsin results in cleavage of the
heavy chain, resulting in a fragment that contains both antigen binding
sites held together by disulfide bonds, it is called F(ab')2 because it is
divalent. Fc portion is digested into small peptides by pepsin, the largest
of which is called the pFc′ fragment. The F(ab')2 binds to Ag but does not
mediate effector functions. F(ab')2 is written with a prime because it
contains a few more amino acids than Fab, including the cysteines that
form the disulfide bonds(Janeway et al,2001).
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Fig.(II):The Y-shaped immunoglobulin molecule can be dissected by partial
digestion with proteases(Janeway et al,2001).
General functions of immunoglobulins:
1) Antigens binding: Igs bind to specific Antigenic determinants (ADs)
on the antigen surface. They bind to at least 2 or in a few cases more
ADs. The number of ADs to which an Ig can bind is referred to as its
valency. Ag binding result in formation of antigen-antibody complexes,
resulting in Ag elimination and protection of the body of the host.
Different Igs molecules can have different Ag binding properties
because of different variable region of heavy chain (VH) and variable
region of light chain (VL)(Janeway et al,2001).
2) Most Igs mediate several effector functions which include:
a-Activation (fixation) of complement:It is an important means
of clearance of opsonized pathogens that results into lysis of cells and
release of biologically active molecules.
b-Binding to various cells: It is donethrough Fc receptors on these
cells to facilitate specific functions by bound cells e.g. phagocytic cells,
lymphocytes, platelets etc.
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Most effector functions of Igs are carried out after the Ig binds to
Ags (Janeway et al,2001).
** Fc receptor(FcR):It is a protein found on the surface of most of
immune system cells including B lymphocytes, follicular dendritic cells,
natural killer cells, macrophages, neutrophils, eosinophils, basophils,
human platelets, and mast cells that contribute to the protective functions
of the immune system. Its name is derived from its binding specificity to
Fc (Fragment, crystallizable) region of the antibody. Fc receptors bind to
antibodies that are attached to infected cells or invading pathogens. Their
activity stimulates phagocytic or cytotoxic cells to destroy microbes, or
infected cells by antibody-mediated phagocytosis or antibody-dependent
cell-mediated cytotoxicity, so they are considered a key immune
regulatory receptors connecting the antibody mediated (humoral) immune
response to cellular effector functions(Owen etal, 2009).
Immunoglobulins types and classes : Based on differences in the amino acid sequences in the constant
region of the heavy chains. There are five classes of Igs:
1-IgG -Gamma (γ) heavy chains.
2-IgM -Mu (μ) heavy chains.
3-IgA -Alpha (α) heavy chains.
4-IgD -Delta (δ) heavy chains.
5-IgE -Epsilon (ε) heavy chains.
In each class of Ig small differences in the constant regions of the
heavy chain still occur, leading to subclasses of the Igs e.g. : IgG and IgA
Subclasses(Janeway et al,2001).
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1- IgG :
It is the predominant isotype found in the body so, It is the major Ig
in serum (systemic immunity) and It is also the major Ig found in
extravascular spaces. It has the longest serum half-life of all Igs.
All IgGs are monomers, subtypes and subclasses differ in number
of disulphide bonds and lengths of hinge region. Based on structural,
antigenic and functional differences in the constant region of the heavy
chain, IgG classified into 4 subclasses (IgG1, IgG2, IgG3 and IgG4), they
are IgG1 -Gamma 1 (γ1) heavy chains, IgG2 -Gamma 2 (γ2) heavy
chains, IgG3 -Gamma 3 (γ3) heavy chains and IgG4 -Gamma 4 (γ4)
heavy chains (Scharf et al,2001).
It is the most versatile Ig and can carry out all functions of Ig
molecules. IgG subclasses exhibit different functional activities.As regard
activation of the complement cascade, IgG4 is the only subclass that fails
to fix complement. All IgG subclasses have similarity in transplacental
transport and participation in the secondary immune response. It is
considered the only Ig that crosses the placenta.
IgG antibodies also contribute directly to an immune response
including neutralization of toxins and viruses which then destroyed by
phagocytosis(Cavacini et al,2003).
2- IgM :
It is the 3rd most abundant Ig in serum and the first Ig made by
fetus in most species.It normally exists as a pentamer in serum but also
occur as a monomer. It has an extra domain on the mui chain (CH4) and
another protein covalently bound via disulfide bond called J-chain. This
chain helps it to polymerize to the pentamer form.
Its function include that it is a good complement fixing Ig and a
good agglutinating Ig.IgM can bind to some cells via Fc receptors. One of
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the important functions ofIgM is to diagnose acute exposure to pathogen
as it is associated with a primary immune response (Boes, 2000).
3- IgA:
It is the second most abundant Ig in serum after IgG, but has higher
levels at mucosal surfaces and in secretions so, it is the major class of Ig
in secretions (tears, saliva, colostrums, mucus, gastric and pulmonary
secretions) and is important in mucosal (local) immunity.
Serum IgA is monomeric, but IgA found in secretions (secretory
IgA) is a dimer. Secretory IgA also contains a protein called secretory
piece or tail piece (T- piece) which help the IgA to move across mucosa
without degradation in secretions.
There are two subclasses of IgA, IgA1 and IgA2, whose structures
differ mainly in their hinge regions. They are IgA1 -Alpha 1 (α1) heavy
chains and IgA2 -Alpha 2 (α2) heavy chains.
IgA has a critical role in protection of mucosal surfaces from
toxins, virus and bacteria by direct neutralization or by prevention of
binding to the mucosal surface. Intracellular IgA may also be important in
preventing bacterial or viral infection and/or pathogenesis. It can bind to
Fc receptors on some cells as PMN cells and lymphocytes. It does not
normally fix complement (unless aggregated)(Woof andMestecky, 2005).
4- IgD:
It is found in low levels in serum (4th highest serum Ig) with a
short plasma half-life due to sensitivity of the molecule. It exists as
monomers and have a tail piece.IgD is expressed on the membranes of B
cells when they leave the bone marrow and populate secondary lymphoid
organs (Geisberger et al,2006).
Its function is unclear, as it is not known to participate in themajor
antibody effector mechanisms.However membrane-bound form of IgD is
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found primarily on B cells surface and serves as a receptor for Ag and
also regulates B cell fate. As regard complement fixation, it does not fix
complement(Riesbeck and Nordstrom,2006).
5- IgE :
It is the lowest serum Ig with the shortest half-life, however IgE is
a very potent Ig. It occurs as a monomer and has an extra domain (CH4)
in the constant region.
It binds very tightly to Fc receptors on basophils and mast cells
even before interacting with Ags cells (Does not require Ag binding) , so,
it is involved in allergic reactions. Also it plays a role in parasitic
diseases. Eosinophils have Fc receptors for IgEs and when eosinophoils
bind to IgEs coated helminthes death of the parasite results. As regard
complement fixation, it does not fix complement. The development of
anti-IgE antibodies has been used as therapy for allergy andasthma
(Chang et al,2007).
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Types of immunity The immunity can be divided into two major components:
I- Non-specific (innate) (natural) immunity :
It is the immunity that present at birth and comprises defense
mechanisms that provide a general response against invasion by a wide
range of antigens(Medzhitov, 2007).
It includes the following:
A) Mechanical and chemical barriers:
1) Theepithelium that covers the skin and the mucous membrane that
lines the gastrointestinal, genitourinary and respiratory tracts.
2) Destruction of swallowed organisms by the acid secretions of the
stomach and the digestive enzymes.
3) Other physiological properties of the body, such as temperature,
pH (acid/base), and oxygen levels, also act to destroy or keep out
potential antigens(Janeway et al, 2005)
B) Non-specific cellular defense mechanisms:
1. Phagocytosis of bacteria and other invaders by WBCs and cells of
the tissue macrophage system.
2. Natural killer (NK) cells, which are non-T, non-B lymphocytes
and can recognize and destroy foreign cells, tumor cells, and even
some infected cells(Janeway et al, 2005).
C) Non-specific humoral defense mechanisms:
Due to the presence of certain chemical compounds in the blood
that attach to foreign organisms or toxins and destroy them, as:
1) lysozyme, a mucolytic polysaccharide that attacks bacteria.
2) basic polypeptides, which react with and inactivate certain types
of gram-positive bacteria.
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3) thecomplement complex, a system of about 20 proteins that can be
activated in various ways to destroy bacteria and promote
clearance of dead cells and antibody complexes(Rus et al, 2005).
II- Specific (acquired) immunity:
It is the ability of the body to develop an extremely powerful
immunity against individual invading agents such as lethal bacteria,
viruses and toxins(Guyton and Hall, 2006).
Acquired immunity does not develop until after invasion by a
foreign organism or toxin and the body must have some mechanism for
recognizing this invasion. Each toxin or each type of organism almost
always contains one or more specific chemical compounds in its
membrane. In general, these are proteins or large polysaccharides, and
initiate the acquired immunity. These substances are called antigens
(antibody generations). For a substance to be antigenic, it usually must
have a high molecular weight, 8000 or greater. Furthermore, the process
of antigenicity usually depends on regularly recurring molecular groups,
called epitopes, on the surface of the large molecule. This also explains
why proteins and large polysaccharides are almost always antigenic,
because both of these have this stereochemical characteristicand so, Both
types of acquired immunity are initiated by antigens(Guyton and Hall,
2006).
This part of the immune system develops based on the exposure to
antigens and involves:
A)Humoral immunity or B-cell immunity:
It is mediated by production of specific
antibodies(immunoglobulins) (Igs) by B-lymphocytes into the body’s
fluids. Antibodies recognize antigens circulating in the bloodstream. They
are powerless, however, to penetrate cells. Each B cell is programmed to
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make one specific antibody. When a B cell encounters its triggering
antigen, it gives rise to many large cells known as plasma cells. Every
plasma cell is essentially a factory for producing an antibody(Guyton and
Hall, 2006).
Whenever antigen and antibody interlock, they form an antigen-
antibody (immune) complex. Antibodies themselves do not destroy
antigen; they inactivate and mark it for destruction by the following
mechanisms:
1- Neutralization:in which neutralizing antibodies bind to and block
specific sites on surface of antigens (viruses and bacteria), thus
preventing these antigens from binding to receptors on tissue cells and
render its attack ineffective,later destroyed by phagocytes.
2-Agglutination:in which antibodies bind the same determinant on more
than one antigen and make antigen-antibody complexes that are clumped
into large clumps (agglutination)that are attractive targets for
phagocytosis.IgMs are good at this with mismatched blood.
3-Precipitation:in which antibodies glue together withserum-soluble
antigens and form soluble molecules which are clumped into large
insoluble complexes, forcing them to precipitate out of solution in clumps
that are attractive targets for phagocytosis.
4-Complement activation (fixation):in which antibodies bound to cells
change their shape and exposecomplement binding sites.This triggers
complement fixation on the antigenic cell surfaceand thus activate the
classical complement pathway (known as complement dependent
cytotoxicity or CDC) resulting in cell lysis(Rus et al, 2005).
5-phagocytosis:it is initiated by Chemotaxis; the process by which
phagocytes are attracted and adhere to microorganisms. Macrophages
have cell-surface receptors that recognize certain molecules on the
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surface of various pathogens. Then the pseudopods of phagocytes engulf
the microorganism and enclose it in a phagocytic vesicle (phagosome) to
complete ingestion by lysosomal enzymes and oxidizing agents
(Aderem and Underhill, 1999) .
Activation of effector cells: Critically antibodies also act as a link
between the antibody-mediated and cell-mediated immune responses
through interaction with Fc receptors on effector cells to engage antibody
dependent cellular cytotoxicity (Powelland Hogarth, 2008).
In order to combat pathogens that replicate outside cells, antibodies
bind to pathogens to link them together, causing them to agglutinate.
Since an antibody has at least two paratopes, it can bind more than one
antigen by binding identical epitopes carried on the surfaces of these
antigens. By coating the pathogen, antibodies stimulate effector functions
against the pathogen in cells that recognize their Fc region(Pier et al,
2004).
Those cells that recognize coated pathogens have Fc receptors,
which, as the name suggests, interact with the Fc region of IgA, IgG, and
IgE antibodies. The engagement of a particular antibody with the Fc
receptor on a particular cell triggers an effector function of that cell;
phagocytes will phagocytose, mast cells and neutrophils will degranulate,
natural killer cells will release cytokines and cytotoxic molecules; that
will ultimately result in destruction of the invading microbe. The
activation of natural killer cells by antibodies initiates a cytotoxic
mechanism known as antibody-dependent cell-mediated cytotoxicity
(ADCC) – this process may explain the efficacy of monoclonal antibodies
used in biological therapies against cancer(Janeway et al,2001).
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Formation of memory B cells:After exposure to an antigen, some of
activated B-lymphocytes do not differentiate into plasma cells but forms
memory B cells that can respond more readily on second exposure to the
same antigen (the secondary response) (Janeway et al,2001).
B) Cell-mediated immunity or T-cell immunity:
It is mediated by activation of specific cells(activated T-
lymphocytes) against a particular pathogen or other foreign substance. T
cells recognize antigen infected cells through proteins, termed major
histocompatibility complex(MHC), displayed on the surface of an infected
cell. These cells include:
1) Cytotoxic (killer) T cells: They can recognize and destroy the
infected cells by secretion of hole forming proteins called
perforinsand then extracellular pathogens stimulate a response from
helper T cells(Guyton and Hall, 2006).
2) Helper T cells: They coordinate immune responses by
communicating with other cells of the immune system that can
destroy the infected cell by exchanging chemical messengers called
cytokines. Some cytokines function as chemical “switches” that turn
certain immune cell types on and off. Examples of cytokines include
interleukins (IL), tumor necrosis factor α (TNF-α), and interferon γ
(IFN-γ)(Janeway et al,2001).
3) Suppressor (regulatory) T cells (Tregs): Theymodulate the immune
system, maintain tolerance to self-antigens, and abolish autoimmune
disease. These cells generally suppress or downregulate induction and
proliferation of effector T cells and thus cause shutting down immune
responses after they have successfully eliminated invading organisms.
This is an important "self-check" built into the immune system to
prevent excessive reactions(Shevach,2000).
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The immune system must be able to discriminate between self and
non-self. When self/non-self discrimination fails, the immune system
destroys cells and tissues of the body and as a result causes autoimmune
diseases. Regulatory T cells actively suppress activation of the immune
system and prevent pathological self-reactivity, i.e. autoimmune disease
(Shevach,2000).
4) Memory T cells: After exposure to an antigen, some immune cells
become memory T cells and can respond more readily when the
immune system encounters that antigen again(Janeway et al,2001).
5) Antigen-Presenting Cells (APCs): These are another type of cells of
acquired immunity. They do not respond to specific antigens and Play
essential roles in immunity. They engulf foreign particles and present
fragments of antigens on their own surfaces to be recognized by T
cells.The major APCs are dendritic cells (DCs), macrophages, and
activated B cells. They are the major initiators of acquired immunity,
as they migrate to the lymph nodes and secondary lymphoid organs,
and present antigens to T and B cells(Janeway et al,2001).
Acquired immunity can be classified into:
1-Passive immunity:
It is the transfer of active immunity, in the form of readymade
antibodies, from one individual to another. Passive immunity can occur
naturally, when maternal antibodies are transferred to the fetus through
the placenta, and can also be induced artificially, when high levels of
human (or horse) antibodies specific for a pathogen or toxin are
transferred to non-immune individuals.Passive immunity provides
immediate protection, but the body does not develop memory, therefore
the patient is at risk of being infected by the same pathogen
later(Janeway et al,2001).
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2-Active immunity:
When Band T cells are activated by a pathogen, memory cells
develop, and the primary immune response results. Throughout the
lifetime of an animal these memory cells will "remember" each specific
pathogen encountered, and are able to mount a strong secondary
response, if the pathogen is detected again(Janeway et al, 2001).
Active immunity can occur naturally, when a person is exposed to
a live pathogen, and develops a primary immune response, which leads to
immunological memory. This type of immunity is "natural" because it is
not induced by intentional exposure. Also it can be induced artificially by
a vaccine, a substance that contains antigen. A vaccine stimulates a
primary response against the antigen without causing symptoms of the
disease. There are four types of traditional vaccines: Inactivated (killed)
vaccines, Liveattenuated vaccines,Toxoids (inactivated toxins) and
Subunit (conjugate)vaccines(Plotkin et al,2013).
Factors that can affect immune system:Our immune system is only as strong and healthy as we help itto
be. So, we can influence the health of our immune system.There are
many factors that can contribute to the general weakening of theimmune
system and also there are many factors within your control that can affect
the strengthof your immune system and help you live a healthier life
(Coico etal,2003).These factors include:
1) Stress : The successful management of stress is very important to the
health of your immune system. Studies have shown that high levels of
stress cause a decrease in the activity of the white blood cells,
depressing your entire immune system. Although people who
experience chronic stress or on-going stress have the poorest immune
function, even acute or temporary stress causes marked changes in the
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optimal functioning of the immune system. This relation will
discussed later in details(Salleh, 2008).
2) Environmental pollution and Radiation : They lead to weakening of
the immune system. Heavy metals as mercury, lead, cadmium,
arsenic, nickel, and aluminum are poisonous which can result from
environmental contamination due to industrial pollution. Mercury
causes a neurological side effect which decrease production of WBCs,
including T cells. While Cadmium creates retarded immune responses
due to effect on the kidneys, liver, and T cell production (Janeway
and Travers, 2004).
3) Nutrition :Eating a healthy well-balanced diet helps to receive the
protective effects of vitamins and minerals. Many vitamins
andminerals are being studied for their beneficial effect on the
immune system. Studies have shown that Vitamins A, C, and
E(antioxidants) may protect cell damage from free radicals - the
electrons that can damage healthy cells and lead to tumors.Vitamins
B6 and B12 may help boost the immune system, and zinc and
selenium are being studied for their ability toimprove white blood cell
activity. So, malnutrition (unbalanced diet/poor eating habits that
cause a lack of vitamins and minerals) lead to weakening of
theimmune system(Roitt and Delves, 2001).
4) Exercise : Studies have shown that regular exercise improves blood
circulation in the body and boosts immune systemresponse time. So,
lack of exercise as well as excessive exercise resulting in
physiological stress that lead to weakening of theimmune system
(Roitt and Delves, 2001).
5) Sleep : Good quality sleep aids your immune system while sleep
deprivation leads to impairedimmune cell function.A lot of studies
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Review of literature
have showedthat sleep deprivation cause decreased T-cells and
increased inflammatory cytokines(Born etal, 1997).
6) Age: Ability of the immune system to respond is decreased at early
and old age.The gradual deterioration of the immune system occurred
with natural age advancement is called immunosenescence. It involves
both the host’s capacity to respond to infections and the development
of long-term immune memory, especially by vaccination. It is
considered a major contributory factor to the increased frequency of
morbidity and mortality among the elderly (Muszkat etal, 2003).
Immunosenescence is a multifactorial condition leading to many
pathologically significant health problems in the aged population. Some
of the age-dependent biological changes that contribute to the onset of
immunosenescence are:
a. Reduction in the self-renewal capacity of hematopoietic stem
cells (HSC), which provide the regulated lifelong supply
of leukocyte progenitors that are in turn able to differentiate into a
diversity of specialised immune cells
(including lymphocytes, antigen-presenting dendritic
cells and phagocytes). This is due to the accumulation
of oxidative damage to DNA by aging and cellular metabolic
activity and the shortening of telomeric terminals of chromosomes
(Ito etal, 2004).
b. Decline in the total number of phagocytes in aged hosts with an
intrinsic reduction of their bactericidal activity(Strout and Suttles,
2005).
c. Reduction in the cytotoxicity of NK-cells and the antigen-
presenting function of dendritic cells with old age(Mocchegiani
and Malavolta, 2004).
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Review of literature
d. Decline in humoral immunity caused by a reduction in the number
of antibody producing B-cells along with a
smaller immunoglobulin diversity and affinity(Gibsonetal, 2009).
7) Alcohol, drugs and tobacco :Alcohol and drugs such as heroin and
cocaine have shown a markedsuppression of immune system
functions. Smoking is one of the major causes of lung cancer and heart
disease and amajor contributor ofcell-damaging free radicals. Studies
have shown that cigarette smoke might contain radioactive particles
and when tobacco is inhaled, two dangerous alpha-emitting
radioisotopes enter the body and affect the lymph nodes(Coico
etal,2003).
8) Medications : Anti-cancer drugs, corticosteroids, immune suppressant
drugs, and antibiotics lead to weakening of the immune system.
9) Diseases : either infectious diseases or others causing more depression
on the immune system like:Cancer, and hematological malignancy
(such as leukemia, lymphoma and myeloma), Diabetes Mellitus,
Cystic fibrosis, Lupus Erythematosus, Nephrotic syndrome, Viral
infections, HIV, Ulcerative colitis, Sickle-cell disease, Liver
disease/cirrhosis, and Cushing's syndrome(Roitt and Delves, 2001).
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