Resistance of the Body to Infection:
Immunity
The human body has the ability to resist almost all types of
organisms or toxins that tend to damage the tissues and
organs. This capability is called
immunity
.
Much of immunity is acquired immunity that does not develop
until after the body is first attacked by a bacterium, virus, or toxin,
often requiring weeks or months to develop the immunity.
An additional portion of immunity results from general
processes, rather than from processes directed at specific
disease organisms. This is called innate immunity.
Immunity is of two types:
I. Innate immunity.
INNATE IMMUNITY OR NON-SPECIFIC IMMUNITY
Innate immunity is the inborn capacity of the body to resist
pathogens. By chance, if the organisms enter the body, innate
immunity eliminates them before the development of any
disease. It is otherwise called the natural or non-specific immunity.
Innate immunity (Natural, Nonspecific)
1. Skin: This is an effective physical barrier
2. Stomach acid: This destroys the protein membrane of any
invading micoorganism.
3. Phagocytosis: Some types of WBCs engulf invading
bacterial cells and digest them using enzymes enclosed in
lysosomes
4. Presence in the blood of certain chemical compounds that
attach to foreign organisms or toxins and destroy them. Some of
these compounds are (1) lysozyme, (mucolytic polysaccaride)
found in tears, saliva and nasal secretions which digests
bacterial cell walls; (2) basic polypeptides, which react with and
inactivate certain types of gram positive bacteria; (3) the
complement complex, a system of about 20 proteins that can be
activated in various ways to destroy bacteria; and (4) natural
killer lymphocytes that can recognize and destroy foreign cells,
tumor cells, and even some infected cells
Acquired (Adaptive) Immunity
• Acquired immunity is the resistance developed in the body
against any specific foreign body like bacteria, viruses, toxins,
vaccines or transplanted tissues
• This type of immunity is acquired throughout a lifetime, and
depends on the production of special protein molecules
called antibodies. These antibodies are produced in response
to specific foreign molecules called antigens
• An antigen is a polysaccharide or protein which is recognised as
foreign by special white blood cells, lymphocytes. These
lymphocytes respond by producing specific antibodies for that
antigen.
• It is the most powerful immune mechanism that protects the
body from the invading organisms or toxic substances.
Types of lymphocytes:
1. B- lymphocytes comprise 20% of total lymphocytes. They
are processed in bone marrow & are responsible for humoral
immunity
2. T- lymphocytes. Comprise 80% of total lymphocytes. They
are processed in thymus gland & are responsible for cellular
immunity
T-lymphocytes & B-lymphocytes are morphologically
Lymphocytes Are Responsible for Acquired Immunity
• Acquired immunity is the product of the body’s lymphocytes.
• The lymphocytes are located most extensively in the lymph
nodes, but they are also found in special lymphoid tissues
such as the spleen, submucosal areas of the GIT, thymus,
and bone marrow.
• In most instances, the invading agent first enters the tissue
fluids and then is carried by lymph vessels to the lymph
Two Types of Lymphocytes Promote “Cell Mediated” Immunity or “Humoral” Immunity—the T and B Lymphocytes
The lymphoid progenitor cells that are destined to eventually form activated T
lymphocytes first migrate to and are preprocessed in the thymus gland, and thus they are called “T” lymphocytes to designate
the role of the thymus.
B lymphocytes that are destined to form antibodies—are preprocessed in the liver
during mid–fetal life and in the bone marrow in late fetal life and after birth. This
population of cells was first discovered in birds, which have a special preprocessing organ called the bursa of Fabricius. These lymphocytes are called “B” lymphocytes to designate the role of the bursa, and they
Thymus Gland Preprocesses the T Lymphocytes.
• The T lymphocytes, after origination in the bone marrow, first migrate to the thymus gland.
• In thymus, they divide rapidly and at the same time develop extreme diversity for reacting against different specific antigens. That is, one thymic lymphocyte develops specific reactivity against one antigen. Then the next lymphocyte develops specificity against another antigen. This continues until there are thousands of different types of thymic lymphocytes with specific reactivities against many thousands of different antigens.
• These different types of preprocessed T lymphocytes now leave the thymus and spread by way of the blood throughout the body to lodge in lymphoid tissue everywhere.
• The thymus also makes certain that any T lymphocytes leaving the
thymus will not react against proteins or other antigens that are present in the body’s own tissues; otherwise, the T lymphocytes would be lethal to the person’s own body in only a few days. The thymus selects which T lymphocytes will be released by first mixing them with virtually all the specific “self-antigens” from the body’s own tissues. If a T lymphocyte reacts, it is destroyed and phagocytized instead of being released.
Types of T Lymphocytes
During the processing, T lymphocytes are transformed into
four types:
1.
Helper T cells or inducer T cells
. These cells are
also called CD4 cells because of the presence of
molecules called CD4 on their surface.
2.
Cytotoxic T cells or killer T cells
. These cells are
also called CD8 cells because of the presence of
molecules called CD8 on their surface.
3.
Suppressor T cells
.
Liver and Bone Marrow Preprocess the B Lymphocytes
• In the human being, B lymphocytes are known to be
preprocessed in the liver during mid–fetal life and in the
bone marrow during late fetal life and after birth
• B lymphocytes are different from T lymphocytes in
two ways
:
First
, instead of the whole cell developing
reactivity against the antigen, as occurs for the T
lymphocytes, the B lymphocytes actively secrete antibodies
that are the reactive agents.
Second
, the B lymphocytes
have even greater diversity than the T lymphocytes, thus
forming many millions of types of B-lymphocyte antibodies
with different specific reactivities.
• After preprocessing, the B lymphocytes, like the T
Types of B Lymphocytes
After processing, the B lymphocytes are transformed into two
types:
1. Plasma cells
.
Both Types of Acquired Immunity Are Initiated by Antigens
Because acquired immunity does not develop until after invasion by a foreign organism or toxin, it is clear that 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 makeup that are different from all other compounds.
In general, these are proteins or large polysaccharides, and it is they that initiate the acquired immunity. These substances are called antigens (antibody generations)
For a substance to be antigenic:
• High molecular weight, 8000 or greater
ANTIGENS „
DEFINITION AND TYPES
Antigens are the substances which induce specific immune reactions in the body.
Antigens are of two types:
1. Autoantigens or self antigens present on the body’s own cells such as ‘A’ antigen and ‘B’ antigen in RBCs.
NON-SELF ANTIGENS
Following are non-self antigens:
1. Receptors on the cell membrane of microbial organisms such as bacteria, viruses and fungi.
2. Toxins from microbial organisms.
3. Materials from transplanted organs or incompatible blood cells.
4. Allergens or allergic substances like pollen grains
CHEMICAL NATURE OF THE ANTIGENS
DEVELOPMENT OF CELL-MEDIATED IMMUNITY „
INTRODUCTION
• Cell-mediated immunity is offered by T lymphocytes and it starts
developing when T cells come in contact with the antigens.
Usually, the invading microbial or non-microbial organisms carry
the antigenic materials.
ANTIGEN-PRESENTING CELLS„
• Antigen-presenting cells are the special type of cells in the
body, which induce the release of antigenic materials from
invading organisms and later present these materials to the helper
T cells.
Types of Antigen-Presenting Cells
Antigen-presenting cells are of two types:
1. Macrophages: Macrophages are the large phagocytic cells,
which digest the invading organisms to release the antigen.
The macrophages are present along with lymphocytes in almost all the
lymphoid tissues.
2. Dendritic cells: Dendritic cells are nonphagocytic in nature.
Based on the location, dendritic cells are classified into three
categories:
i. Dendritic cells of spleen, which trap the antigen in blood.
ii. Follicular dendritic cells in lymph nodes, which trap the antigen in the
lymph.
Role of Antigen-presenting Cells
• Invading foreign organisms are either engulfed by macrophages
through phagocytosis or trapped by dendritic cells. Later, the
antigen from these organisms is digested into small peptide
products. These antigenic peptide products move towards the
surface of the antigen-presenting cells and bind with human
leukocyte antigen (HLA). HLA is a genetic matter present in the
molecule of class II major histocompatiblility complex (MHC),
which is situated on the surface of the antigen presenting cells.
• MHC molecules in human beings are divided into two types:
1. Class I MHC molecule
: It is found on every cell in human
body. It is specifically responsible for presentation of endogenous
antigens (antigens produced intracellularly such as viral proteins
and tumor antigens) to cytotoxic T cells.
Presentation of Antigen
• Antigen-presenting cells present their class II MHC molecules
together with antigen-bound HLA to the helper T cells. This activates
the helper T cells through series of events
Sequence of Events during Activation of Helper T cells
1. Helper T cell recognizes the antigen displayed on the surface of the antigen-presenting cell with
the help of its own surface receptor protein called T cell receptor.
2. Recognition of the antigen by the helper T cell initiates a complex interaction between the helper T cell receptor and the antigen. This reaction activates
helper T cells.
3. At the same time, macrophages (the antigen presenting cells) release interleukin-1, which facilitates the activation and proliferation of helper T cells.
4. Activated helper T cells proliferate and the proliferated cells enter the circulation for further actions.
Role of Helper T Cells
• Helper T cells (CD4 cells) which enter the circulation activate all
the other T cells and B cells. Normal, CD4 count in healthy adults
varies between 500 and 1500 per cubic millimeter of blood.
Helper T cells are of two types:
1. Helper-1 (TH1) cells
2. Helper-2 (TH2) cells.
Role of TH1 Cells
TH1 cells are concerned with cellular immunity and secrete two
substances:
i. Interleukin-2
, which activates the other T cells.
ii. Gamma interferon
, which stimulates the phagocytic activity of
cytotoxic cells, macrophages and natural killer (NK) cells.
Role of TH2 Cells
TH2 cells are concerned with humoral immunity and secrete
interleukin-4 and interleukin-5, which are concerned with:
i. Activation of B cells.
ii. Proliferation of plasma cells.
Role of Cytotoxic T Cells Are “Killer” Cells
• The cytotoxic T cell is a direct-attack cell that is capable of killing microorganisms and, at times, even some of the body’s own cells.
• The receptor proteins on the surfaces of the cytotoxic cells cause them to bind tightly to those organism or cells that contain the appropriate
binding- specific antigen
• After binding, the cytotoxic T cell secretes hole-forming proteins, called perforins, that literally punch round holes in the membrane of the
attacked cell. Then fluid flows rapidly into the cell from the interstitial space.
• The cytotoxic T cell releases cytotoxic substances directly into the attacked cell.
• Some of the cytotoxic T cells are especially lethal to tissue cells that have been invaded by viruses because many virus particles become entrapped in the membranes of the tissue cells and attract T cells in response to the viral antigenicity
Role of Suppressor T Cells
• Much less is known about the suppressor T cells than about the
others, but they are capable of suppressing the functions of
both cytotoxic and helper T cells.
• It is believed that these suppressor functions serve the purpose of
preventing the cytotoxic cells from causing excessive immune
reactions that might be damaging to the body’s own tissues. For this
reason, the suppressor cells are classified, along with the helper T
cells, as regulatory T cells.
Role of Memory T Cells
• Some of the T cells activated by an antigen do not enter the
circulation but remain in lymphoid tissue. These T cells are called
memory T cells. In later periods, the memory cells migrate to
DEVELOPMENT OF HUMORAL IMMUNITY
„
INTRODUCTION
• Humoral immunity is defined as the immunity mediated by antibodies,
which are secreted by B lymphocytes.
• B lymphocytes secrete the antibodies into the blood and lymph.
The blood and lymph are the body fluids (humours or humors in
Latin). Since the B lymphocytes provide immunity through humors,
this type of immunity is called humoral immunity or B cell immunity.
• Antibodies are the gamma globulins produced by B lymphocytes.
These antibodies fight against the invading organisms. The humoral
immunity is the major defense mechanism against the bacterial
infection.
• As in the case of cell-mediated immunity, the macrophages and
other antigen-presenting cells play an important role in the
ROLE OF ANTIGEN-PRESENTING CELLS
• The ingestion of foreign organisms and digestion of their antigen
by the antigen-presenting cells are already explained.
Presentation of Antigen
Antigen-presenting cells present the antigenic products bound with
HLA (which is present in class II MHC molecule) to B cells. This
activates the B cells through series of events.
Sequence of Events during Activation of B Cells
1. B cell recognizes the antigen displayed on the surface of the antigen-presenting cell, with the help of its own surface receptor protein called B cell receptor.
2. Recognition of the antigen by the B cell initiates a complex interaction
between the B cell receptor and the antigen. This reaction activates B cells. 3. At the same time, macrophages (the antigen-presenting cells) release
interleukin-1, which facilitates the activation and proliferation of B cells.
4. Activated B cells proliferate and the proliferated cells carry out the further actions.
Transformation B Cells
Proliferated B cells are transformed into two types of cells:
1. Plasma cells
2. Memory cells.
„
ROLE OF PLASMA CELLS
• Plasma cells destroy the foreign organisms by producing the
antibodies. Antibodies are globulin in nature.
• The rate of the antibody production is very high, i.e. each
plasma cell produces about 2000 molecules of antibodies per
second. The antibodies are also called immunoglobulins.
• Antibodies are released into lymph and then transported into the
circulation.
ROLE OF MEMORY B CELLS
• Memory B cells occupy the lymphoid tissues throughout the body.
The memory cells are in inactive condition until the body is
exposed to the same organism for the second time.
• During the second exposure, the memory cells are stimulated by the
antigen and produce more quantity of antibodies at a faster rate,
than in the first exposure.
• The antibodies produced during the second exposure to the
foreign antigen are also more potent than those produced during first
exposure. This phenomenon forms the basic principle of vaccination
against the infections.
„
ROLE OF HELPER T CELLS
Helper T cells are simultaneously activated by antigen.
Activated helper T cells secrete two substances called interleukin-2 and
B cell growth factor, which promote:
1. Activation of more number of B lymphocytes.
2. Proliferation of plasma cells.
Formation of Antibodies by Plasma Cells
• B lymphocytes specific for the antigen immediately enlarge and
take on the appearance of lymphoblasts.
• Some of the lymphoblasts further differentiate to form
plasmablasts, which are precursors of plasma cells.
• In the plasmablasts, the cytoplasm expands and the rough
endoplasmic reticulum vastly proliferates. The plasmablasts then
begin to divide at a rate of about once every 10 hours for about nine
divisions, giving in 4 days a total population of about 500 cells for
each original plasmablast.
• The mature plasma cell then produces gamma globulin antibodies at
an extremely rapid rate—about 2000 molecules per second for each
plasma cell.
ANTIBODIES OR IMMUNOGLOBULINS
• An antibody is defined as a protein that is produced by B lymphocytes
in response to the presence of an antigen.
• Antibody is gamma globulin in nature and it is also called
immunoglobulin (Ig).
Structure of Antibodies
• Antibodies are gamma globulins with a molecular weight of 1,50,000 to
9,00,000.
• The antibodies are formed by two pairs of chains, namely one pair of heavy or long chains and one pair of light or
short chains. Each heavy chain
consists of about 400 amino acids and each light chain consists of about 200 amino acids.
• In each antibody, the light chain is
parallel to one end of the heavy chain. The light chain and the part of heavy chain parallel to it form one arm. The remaining part of the heavy chain forms another arm.
• Each chain of the antibody includes two regions:
• The variable portion is different for each specificity of antibody, and it is this portion that attaches specifically to a particular type of antigen.
• The constant portion of the antibody determines other properties of the antibody,
establishing such factors as 1) diffusivity of the antibody in the tissues, 2) adherence of the antibody to specific structures within the tissues, 3) attachment to the
complement complex, 4) the ease with which the
antibodies pass through membranes, and other
biological properties of the antibody.
There are five general classes of antibodies, respectively named IgM, IgG, IgA, IgD,and IgE.
Ig stands for immunoglobulin, and the other five respective letters designate the respective classes.
two of these classes of antibodies are of particular importance:
IgG, which is a bivalent antibody and constitutes about 75 percent of the antibodies of the normal person
IgE, which constitutes only a small percentage of the antibodies but is especially involved in allergy.
IgM class is also interesting because a large share of the antibodies formed during the primary response are of this type. These antibodies have 10 binding sites that make them exceedingly effective in protecting the body against invaders, even though there are not many IgM antibodies.
IgA; is an antibody that plays a critical role in immune function in the mucous membranes
IgD, is an antibody isotype that makes up about 1% of proteins in the plasma membranes of immature B-lymphocytes where it is usually co-expressed with another cell surface antibody called IgM
Formation of “Memory” Cells—Difference Between
Primary Response and Secondary Response
After invasion by a micro-organism the individual will suffer the disease until there are sufficient antibodies produced. This is the primary
response. If the individual is infected by the same micro-organism, memory B cells in the body will quickly produce many antibodies, and
memory killer T cells will attack the infected cells, so the response is much faster preventing the disease. This is the secondary response
The 1-week delay in the appearance of the primary response, its weak
potency, and its short life. The secondary response, by contrast,
begins rapidly after exposure to the antigen (often within hours), is far more potent, and forms antibodies for
Mechanisms of Action of Antibodies
Antibodies act mainly in two ways to protect the body against
invading agents:
(1) by direct attack on the invader
Direct Action of Antibodies on Invading Agents
Antibodies can inactivate the invading agent in one of
several ways, as follows:
1. Agglutination, in this, the foreign bodies like RBCs or bacteria with antigens on their surfaces are held together in a clump by the antibodies
2. Precipitation, in which the molecular complex of soluble antigen (such as tetanus toxin) and antibody becomes so large that it is rendered
insoluble and precipitates
3. Neutralization, in which the antibodies cover the toxic sites of the antigenic agent
4. Lysis, it is done by the most potent antibodies. These antibodies rupture the cell membrane of the organisms and then destroy them
These direct actions of antibodies attacking the antigenic invaders often are not strong enough to play a major role in protecting the body against the invader. Most of the protection comes through the amplifying effects of the
• “Complement” is a collective term that describes a system of
about 20 proteins, many of which are enzyme precursors. The
principal actors in this system are 11 proteins designated C1
through C9, B, and D.
• All these are present normally among the plasma proteins in the
blood, as well as among the proteins that leak out of the
capillaries into the tissue spaces. The enzyme precursors are
normally inactive, but they can be activated mainly by the
so-called classic pathway.
• The indirect actions of antibodies are stronger than the direct
actions and play more important role in defense mechanism of the
body than the direct actions.
• Complement system is the one that enhances or accelerates
various activities during the fight against the invading
organisms. Normally, these enzymes are in inactive form and are
activated in two ways:
a.
Classical pathway
b.
Alternate pathway.
The classic pathway is initiated by an antigen-antibody reaction. That is, when an antibody binds with an antigen, a specific reactive site on the “constant” portion of the antibody becomes uncovered, or “activated,” and this in turn binds directly with the C1 molecule of the complement system, setting into motion a “cascade” of sequential reactions, beginning with activation of the proenzyme C1 itself.
a. C1 binds to antigen – antibody
complexes.
b. C2 and C4 associate and this acts
as C3 convertase.
c. C3 is cleaved to C3a and C3b
d. C3a stimulates inflammation
e. C3b opsonizes and cleaves C5 to
produce C5a and C5b
f. C5a stimulates inflammation
g. C6, C7, C8, and C9 associate to
1. Opsonization and phagocytosis. One of the products of the
complement cascade, C3b, strongly activates phagocytosis by both neutrophils and macrophages, causing these cells to engulf the bacteria to which the antigen-antibody complexes are attached. This process is called opsonization. It often enhances the number of bacteria that can be destroyed by many hundredfold.
2. Lysis. One of the most important of all the products of the
complement cascade is the lytic complex, which is a combination of multiple complement factors and designated C5b6789. This has a direct effect of rupturing the cell membranes of bacteria or other invading organisms.
3. Agglutination .The complement products also change the surfaces of the invading organisms, causing them to adhere to one another, thus promoting agglutination.
4. Neutralization of viruses. The complement enzymes and other
complement products can attack the structures of some viruses and thereby render them nonvirulent
5. Chemotaxis. Fragment C5a initiates chemotaxis of neutrophils and macrophages, thus causing large numbers of these phagocytes to migrate into the tissue area adjacent to the antigenic agent.
6. Activation of mast cells and basophils. Fragments C3a, C4a, and C5a
activate mast cells and basophils, causing them to release histamine, heparin, and several other substances into the local fluids. These substances in turn cause increased local blood flow, increased leakage of fluid and
plasma protein into the tissue, and other local tissue reactions that help inactivate or immobilize the antigenic agent. The same factors play a major role in inflammation and in allergy.
7. Inflammatory effects. In addition to inflammatory effects caused by activation of the mast cells and basophils, several other complement products contribute to local inflammation.
These products cause (1) the already increased blood flow to increase still further, (2) the capillary leakage of proteins to be increased,
and (3) the interstitial fluid proteins to coagulate in the tissue spaces, thus preventing movement of the invading organism through the tissues.
Complementary system is also activated by another way, which is called alternate pathway. It is due to a protein in circulation called factor I. It binds with polysaccharides present in the cell membrane of the invading organisms. This binding activates C3 and C5, which ultimately attack the antigenic
products of invading organism
IMMUNIZATION Or vaccination
Active immunization
: develops after contracting a disease or
taking a vaccine which could be a toxoid or killed or attenuated
microorganism
Passive immunization
: is done by infusing antibodies ,
activated T cells or both to a person at danger, the antibodies
last for 2-3 weeks, during this period it gives protection to the
