2. Immunology
Immunology is a branch of biomedical science that
covers the study of all aspects of the immune system in
all organisms.
It deals with:
the physiological functioning of the immune system in
states of both health and diseases;
malfunctions of the immune system in immunological
disorder (autoimmune diseases, hypersensitivities,
immune deficiency, transplant rejection);
the physical, chemical and physiological characteristics
of the components of the immune system in vitro, in situ,
and in vivo.
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The Immune System
The immune system is the body's defense against infectious
organisms and other invaders.
Each exposure (to the same pathogen) increases the effectivity of
the response
Primary Lymphoid organs of the immune system
I. Thymus
II. bone marrow
Secondary lymphoid organs
I. Lymph nodes
II. Spleen
III. Skin
IV. liver
V. Tonsils
VI. Small intestine
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Basic Immunology
Depends on the ability of the immune system to
distinguish between self and non-self molecules
Self molecules are those components of an
organism's body that can be distinguished from
foreign substances by the immune system
Autoimmunity is an immune reaction against self
molecules (causes various diseases)
Non-self molecules are those recognized as
foreign molecules
One class of non-self molecules are called antigens (
antibody generators) and are defined as substances
that bind to specific immune receptors and elicit an
immune response
5. Immunity
Immunity is the state of having sufficient biological
defences to avoid infection, disease, or other unwanted
biological invasion. It is the capability of the body to resist
harmful microbes from entering it.
Components of the Immune system
Immunity involves both specific and non-specific
components.
1.The non-specific components act either as barriers or as
eliminators of wide range of pathogens irrespective of
antigenic specificity.
2.Specific components of the immune system adapt
themselves to each new disease encountered and are
able to generate pathogen-specific immunity.
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7. Components of the immune system
Innate immune system
Response is non-specific
Exposure leads to
immediate maximal
response
Cell-mediated and
humoral components
No immunological
memory
Found in nearly all forms
of life (plants & animals)
Adaptive immune system
Pathogen and antigen
specific response
Lag time between
exposure and maximal
response
Cell-mediated and
humoral components
Exposure leads to
immunologic memory
Found only in jawed
vertebrates
8. Innate immunity, or nonspecific immunity is the natural resistances
with which a person is born.
It provides resistances through several physical, chemical and
cellular approaches.
Microbes first encounter the epithelial layers, physical barriers that
line skin and mucous membranes.
Subsequent general defences include secreted chemical signals
(cytokines), antimicrobial substances, fever, and phagocytic activity
associated with the inflammatory responses.
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9. Adaptive immunity
This is inducible and develops slowly than the innate
response. This is specific kind of immunity and has
memory, therefore providing long term protection. This
occurs with contact of foreign particle
Adaptive immunity is often sub-divided into two major
types depending on how the immunity was introduced.
I. Naturally acquired immunity occurs through contact
with a disease causing agent, when the contact was not
deliberate
II. Artificially acquired immunity develops only
through deliberate actions such as vaccination
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10. Types of Adaptive immunity
a. Naturally acquired active immunity occurs when the
person is exposed to a live pathogen, develops the
disease, and becomes immune as a result of the
primary immune response.
b. Artificially acquired active immunity can be induced
by a vaccine, a substance that contains the antigen. A
vaccine stimulates a primary response against the
antigen without causing symptoms of the disease.
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11. c. Artificially acquired passive immunity is a short-term
immunization by the injection of antibodies, such as
gamma globulin, that are not produced by the recipient's
cells.
d. Naturally acquired passive immunity occurs during
pregnancy, in which certain antibodies are passed from the
maternal into the fetal bloodstream
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12. Antigen
an antigen is a molecule that induces an
immune response in the body.
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13. Origin of antigen
Exogenous antigens
are antigens that have entered the body from the
outside, for example by inhalation, ingestion,
or injection.
Endogenous antigens
are antigens that have been generated within previously
normal cells as a result of normal cell metabolism, or
because of viral or intracellular bacterial infection
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14. An autoantigen is usually a normal protein or complex of
proteins (and sometimes DNA or RNA) that is
recognized by the immune system of patients suffering
from a specific autoimmune disease.
These antigens should, under normal conditions, not be
the target of the immune system, but, due to mainly
genetic and environmental factors, the
normal immunological tolerance for such an antigen has
been lost in these patients.
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15. Immunogen
An immunogen is in analogy to the antigen a substance (or a
mixture of substances) that is able to provoke an immune
response if injected to the body. An immunogen is able
to initiate an innate immune response first, later leading to
the activation of the adaptive immune response, whereas an
antigen is able to bind the highly variable immunoreceptor
products (B-cell receptor or T-cell receptor) once these have
been produced.
Immunogenicity is the ability to induce a humoral and/or cell-mediated
immune response
Antigenicity is the ability to combine specifically with the final
products of the immune response (i.e. secreted antibodies
and/or surface receptors on T-cells). Although all molecules that
have the property of immunogenicity also have the property of
antigenicity, the reverse is not true
16. Epitope – The portion of an antigen that is
recognized and bound by an antibody or TCR-MHC
combination; also called antigenic determinant.
Antigen(ic) specificity
is the ability of the host cells to recognize an antigen
specifically as a unique molecular entity and distinguish it from another
with exquisite precision. Antigen specificity is due primarily to the side-chain
conformations of the antigen.
Hapten
is a small molecule that can elicit an immune response only when
attached to a large carrier such as a protein; the carrier may be one
that also does not elicit an immune response by itself.
Epitope:
The portion of an antigen that recognize and bound by antibody also
called antigenic determinant.
.
17. An antigen-presenting cell (APC) or accessory cell is
a cell that displays foreign antigens complexed
with major histocompatibility complexes (MHC's) on their
surfaces; this process is known as antigen
presentation. T-cells may recognize these complexes
using their T-cell receptors (TCRs). These
cells process antigens and present them to T-cells.
Eg.
Dendritic cell,
macrophages,
B cell,
epithelial cells,
fibroblast
18. Antibody
An antibody (Ab), also known as an immunoglobulin (Ig), is a large
Y-shape protein produced by B cells that is used by the immune
system to identify and neutralize foreign objects such
as bacteria and viruses.
The antibody recognizes a unique part of the foreign target, called an
antigen.
Each tip of the "Y" of an antibody contains a paratope (a structure
analogous to a lock) that is specific for one
particular epitope(similarly analogous to a key) on an antigen,
allowing these two structures to bind together with precision.
Using this binding mechanism, an antibody can tag a microbe or an
infected cell for attack by other parts of the immune system, or can
neutralize its target directly (for example, by blocking a part of a
microbe that is essential for its invasion and survival).
The production of antibodies is the main function of the humoral
immune system.
19. Antibodies are secreted by a type of white blood
cell called a plasma cell.
Antibodies can occur in two physical forms
1. a soluble form that is secreted from the cell,
2. a membrane-bound form that is attached to the
surface of a B cell and is referred to as the B cell
receptor (BCR). The BCR is only found on the surface
of B cells and facilitates the activation of these cells
and their subsequent differentiation into either
antibody factories called plasma cells or memory B
cells that will survive in the body and remember that
same antigen so the B cells can respond faster upon
future exposure.
21. Mechanism of Actions of Antibodies
Antibodies protect the body from invading organisms in two ways (Fig.b):
1. By direct actions
2. Through complement system
Direct Actions of Antibodies
Antibodies directly inactivate the invading organism by any one of the
following methods:
i. Agglutination: In this, the foreign bodies like bacteria with antigens on
their surfaces are held together in a clump by the antibodies.
ii. Precipitation: In this, the soluble antigens like tetanus toxin are
converted into insoluble forms and then precipitated.
iii. Neutralization: During this, the antibodies cover the toxic sites of
antigenic products.
iv. Lysis: It is done by the most potent antibodies.These antibodies rupture
the cell membrane of the organisms and then destroy them.
22. Complement System
The complement system is a biochemical cascade of the innate immune
system that helps clear pathogens from an organism.
It is derived from many small plasma proteins that work together to disrupt
the target cell's plasma membrane leading to cytolysis of the cell.
The complement system consists of 9 proteins from c1 to c9,
The complement system is involved in the activities of both innate
immunity and acquired immunity.
Two biochemical pathways activate the complement system:
classical complement pathway,
alternate complement pathway,
The classical complement pathway typically requires antibodies for
activation and is a specific immune response,
while the alternate pathway can be activated without the presence of
antibodies and is considered a non-specific immune response.
A.Classical complement pathway
In this the C1 binds with the antibodies and triggers a series of events.
Byproducts formed during these events produce the following activities:
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23. 1.Opsonization:
Activation of neutrophils and macrophages to engulf the bacteria, which
are bound with a protein in the plasma called opsonin.
ii. Lysis:
Destruction of bacteria by rupturing the cell membrane.
iii. Chemotaxis:
Attraction of leukocytes to the site of antigen-antibody reaction.
iv. Agglutination:
Clumping of foreign bodies like RBCs or bacteria.
v. Neutralization:
Covering the toxic sites of antigenic products.
vi. Activation of mast cells and basophils, which liberate histamine: Histamine
dilates the blood vessels and increases capillary permeability.So, plasma
proteins from blood enter the tissues and inactivate the antigenic products.
B. Alternate pathway:
Activation of Complementary system 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
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the antigenic products of invading organism.
25. Functions of Different Antibodies
1. IgA plays a role in localized defense mechanism in
external secretions like tear
2. IgD is involved in recognition of the antigen by B
lymphocytes
3. IgE is involved in allergic reactions
4. IgG is responsible for complement fixation
5. IgM is also responsible for complement fixation.
26. Dual nature of specific immunity
Immunization occurs when an individual naturally or artificially
exposed to an antigen and the immune system is activated to produce
humoral immunity and cellular immunity.
This means that the effectors of specific immunity are found in both
the humoral phase of the body fluids(eg.blood serum)and among the
white blood cells in the blood and lymphoid organs.
These two effectors of immunity are different physically and
functionally eg they resist different types of pathogens
I. Antibodies(soluble mediators in body fluids)are more effective
against pathogen found outside cells
II. Immune cells(cellular elements especially T
lymphocytes,macrophages and natural killer cells)are more effective
against pathogen found inside cells.
Thus humoral immunity defends the body primarily against
bacteria,bacterial toxins and viruses in body fluids.
Cellular immunity defends the host from bacteria and viruses located
within infected cells or phagocytic cells as well as from fungi,protozoa
and other parasites
27. Humoral immunity or B cell immunity
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). Antibodies are produced by B lymphocytes. These
antibodies fight against the invading organisms. The humoral immunity is the
major defense mechanism against the bacterial infection. The macrophages
and other antigen-presenting cells play an important role in the development
of humoral immunity
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.
28. 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.
5.Simultaneously, the antigen bound to class II MHC molecules
activates the helper T cells, also resulting in development of cell-mediated
immunity.
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.
3. Production of antibodies.
29. Cellular immunity or T cell immunity
Cell-mediated immunity is defined as the immunity developed by cell-mediated
response. Cellular immunity is the major defense mechanism
against infections by viruses, fungi and few bacteria like tubercle
bacillus. It is also responsible for delayed allergic reactions and the
rejection of transplanted tissues.
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.
These antigenic materials are released from invading
organisms and are presented to the helper T cells by
antigen-presenting 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 (Fig.a).
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.
30. 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.
Fig a., Antigen presentation. The antigen-presenting cells present their class II MHC
molecules together with antigen-bound HLA to the helper T cells.
31. Cytotoxic T cells
Cytotoxic T cells that are activated by helper T cells,circulate through
blood, lymph and lymphatic tissues and destroy the invading organisms by
attacking them directly.
Mechanism of Action of Cytotoxic T Cells
1. Receptors situated on the outer membrane of cytotoxic T cells bind the
antigens or organisms tightly with cytotoxic T cells.
2. Then, the cytotoxic T cells enlarge and release cytotoxic substances like
the lysosomal enzymes.
3. These substances destroy the invading organisms.
4. Like this, each cytotoxic T cell can destroy a large number of
microorganisms one after another.
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33.
34. WBC(leukocytes) in circulating blood
Types of leucocyte %age in a normal
leukocyte differential
account
Functions
Granulocytes
Neutrophils
Basophils
Eosinophils
Agranulocytes
Monocytes
Lymphocytes
60-70
0.5-1
2-4
3-8
20-25
Phagocytosis
Production of heparin and
histamine
Phagocytosis
Phagocytosis
Specific immunity
35. Lymphocytes
Lymphocytes are competent to initiat an immune respose
A lymphocyte is any of 3 types of white blood cell in
a vertebrate's immune system. All 3 are agranulocytes.
Mammalian stem cells differentiate into several kinds of
blood cell within the bone marrow. This process is
called haematopoiesis.
All lymphocytes originate, during this process, from a
common lymphoid progenitor before differentiating into
their distinct lymphocyte types.
The formation of lymphocytes is know as lymphopoiesis.
Following maturation,the lymphocytes enter the
circulation and peripheral lymphoid organs (e.g.
spleen and lymph nodes) where they survey for
invading pathogens and/or tumor cells.
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37. Types of Lymphocytes
1. T lymphocytes or T cells, which are responsible for the development of
cellular immunity
2. B lymphocytes or B cells, which are responsible for humoral immunity
T cells (thymus cells) and B cells (bursa-derived cells]) are the major cellular
components of the adaptive immune response.
Types of B Lymphocytes
After processing, the B lymphocytes are transformed into two types:
a. Plasma cells. destroy the foreign organisms by producing the antibodies
b. Memory Bcells. 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 potent
antibodies at a faster rate than in the first exposure eg immunity to chicken
pox after you’ve had it
Storage of B Lymphocytes After transformation, the B lymphocytes are
stored in the lymphoid tissues of lymph nodes, spleen, bone marrow and
the GI tract.
The function of T cells and B cells is to recognize specific “non-self”
antigens, Once they have identified an invader, the cells generate specific
responses that are tailored to maximally eliminate specific pathogens or
pathogen-infected cells.
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38. 38
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. Helper T cells (CD4 cells) which enter the circulation activate
all the other T cells and B cells
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. Cytotoxic T cells that are activated by helper T
cells,circulate through blood, lymph and lymphatic tissues and
destroy the invading organisms by attacking them directly.
3.Suppressor T cells are also called regulatory T cells.These T
cells suppress the activities of the killer T cells.Thus, the suppressor
T cells play an important role in preventing the killer T cells from
destroying the body’s own tissues along with invaded organisms.
Suppressor cells suppress the activities of helper T cells also.
39. 4.Memory T Cells: the memory cells migrate to various lymphoid
tissues throughout the body. When the body is exposed to the same
organism for the second time,the memory cells identify the organism
and immediately activate the other T cells. So, the invading
organism is destroyed very quickly. The response of the T cells is
also more powerful this time.
Storage of T Lymphocytes
After the transformation, all the types of T lymphocytes leave the
thymus and are stored in lymphoid tissues of lymph nodes, spleen,
bone marrow and GI tract.
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40. 3.Natural killer cells
NK cells are a part of the innate immune system and play a major
role in defending the host from both tumors and virally infected cells.
NK cells distinguish infected cells and tumors from normal and
uninfected cells by recognizing changes of a surface molecule
called MHC (major histocompatibility complex) class I.
NK cells are activated in response to a family of cytokines called
interferons. Activated NK cells release cytotoxic (cell-killing)
granules which then destroy the altered cells.They were
named "natural killer cells" because of the initial notion that they do
not require prior activation in order to kill cells.
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41. Major histocompatibility complex
The MHC is a set of cell surface molecules encoded by
a large gene family in all vertebrates. MHC molecules
mediate interactions of leukocytes, which are immune
cells, with other leukocytes or body cells. MHC
determines compatibility of donors for organ
transplant as well as one's susceptibility to
an autoimmune disease via cross reacting immunization.
In humans, MHC is also called human leukocyte
antigen (HLA).
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42. ….. 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.
2. Class II MHC molecule: It is found on B cells,macrophages and
other antigen-presenting cells. It is responsible for presenting the
exogenous antigens(antigens of bacteria or viruses which are
engulfed by antigen-presenting cells) to helper T cells.
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CD8+ = proteins associated with Tc
(cytotoxic or killer T cells)
CD4+ = proteins associated with Th
(helper T cells)
43. Cytokines
Cytokines are a broad category of small proteins (~5–20
kDa) that are important in cell signaling - they are
released by cells and affect the behavior of other cells,
and sometimes the releasing cell itself.
Cytokines include
chemokines, interferons, interleukins, lymphokines, tumo
ur necrosis factor but not hormones or growth factors.
Cytokines are produced by broad range of cells,
including immune cells like macrophages, B
lymphocytes and T lymphocytes, mast cells, as well
as endothelial cells, fibroblasts,
a given cytokine may be produced by more than one
type of cell 43
44. Chemokines (Greek -kinos, movement) are a family of
small cytokines, or signaling proteins secreted by cells.
Their name is derived from their ability to induce
directed chemotaxis in nearby responsive cells; they
are chemotactic cytokines.
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46. Vaccine
A vaccine is a biological preparation that improves
immunity to a particular disease. A vaccine typically
contains an agent that resembles a disease-causing
microorganism and is often made from weakened or
killed forms of the microbe, its toxins or one of its surface
proteins. The agent stimulates the body'simmune
system to recognize the agent as foreign, destroy it, and
keep a record of it, so that the immune system can more
easily recognize and destroy any of these
microorganisms that it later encounters.
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