3. Definition
Immunity is defined as the resistance exhibited by the
host towards injury caused by microorganisms& their
products.
This resistance plays a major role for the prevention of
infectious diseases.
6. Innate immunity ( Natural or native)
It is the resistance which individual possesses by birth.
It is by virtue of his genetic & constitutional make-up.
It doesn’t depend on prior contact with foreign antigen.
7. Types of innate immunity
1. Species immunity
It refers to resistance to a pathogen shown by all members of a particular
species. E.g. B. anthracis infects human beings but not chickens
2. Racial immunity
Within one species different races may exhibit differences in susceptibility
or resistance to infections. This is known as racial immunity.
In human beings , it is reported that American Negroes are more
susceptible than white race to tuberculosis.
3. Individual Immunity
Resistance to infection varies with different individuals of same race &
species. This is known as individual immunity.
8. Factors influencing innate immunity
1. Age:
The two extremes of life (fetus & old persons) carry
higher susceptibility to various infections.
In fetus, immune system is immature whereas in old
age there is gradual waning of immune responses.
age there is gradual waning of immune responses.
2. Hormones:
Certain hormonal disorders such as diabetes mellitus &
hypothyroidism enhance susceptibility to infections.
3. Nutrition:
Malnutrition predisposes to bacterial infections. Both
humoral & cell mediated immune responses are
reduced in malnutrition.
12. By convention, immune system and immune response
refer to acquired immunity
Two types of acquired immunity
13. Types of Active Immunity
1)Natural active immunity
-Acquired by natural subclinical or clinical infections.
-Such immunity is long lasting.
-Persons recovering from smallpox infection develop
natural active immunity.
14. CONTD..
2)Artificial active immunity
-Produced by vaccination.
-Produced by vaccination.
-The vaccines are prepared from
live,attenuated or killed microorganisms
or their toxoids.
18. The Immune System
Immune cells,
red blood cells,
and other
white blood
cells are
cells are
derived from
multipotential
stem cells in
the bone
marrow.
19. The Immune System
Lymphocytes arise
from stem cells in
the bone marrow.
Newly formed
lymphocytes are all
Newly formed
lymphocytes are all
alike, but they later
develop into B cells
or T cells,
depending on
where they
continue their
maturation.
20. Lymphocytes
Present in circulation & in various lymphoid organs.
Lymphocytes develop from precursors in the generative
lymphoid organs.
T- lymphocytes are so called because they mature in
T- lymphocytes are so called because they mature in
the thymus.
B- lymphocytes mature in bone marrow.
21. Development of Lymphocytes
1)In fetus,lymphocytes develop from bone marrow
2)The pluripotent hemopoietic stem cells give rise to
colony forming units(CFU) and lymphoid stem
cells(LSC).
3)The LSCs give rise to lymhoblasts and then the
lymphocytes.
22. CONTD…
4)Initially all the lymphocytes are released in the
circulation.
5)The lymphocytes designed to develop the cellular
immunity migrate into thymus and are transformed into
T lymphocytes.
T lymphocytes.
6)The lymphocytes designed to develop humoral
immunity are processed in liver during fetal life and
bone marrow after birth are transformed into B
lymphocytes..
23. T- lymphocytes
They are the effector cells of cellular immunity and
helper cells for antibody responses to protein antigens
T-cells constitute 60-70 % of lymphocytes in peripheral
blood
T-cells don’t detect free or circulating antigens
Instead majority (>95%) of T-cells recognize only
peptide fragment of protein antigens bound to proteins
of MHC (Major Histocompatibility Complex)
24. Types of T Lymphocytes
During the processing ,T lymphocytes are transformed
into four types..
1)Helper T cells
2)Cytotoxic T cells
2)Cytotoxic T cells
3)Suppressor T cells
4)Memory T cells
25. Major Histocompatibility
Complex
Transplants from one individual to another member of
same species (allografts) are recognized as foreign &
rejected
Gorer (1930) identified the antigens responsible for
allograft rejection in inbred mice that led to the
allograft rejection in inbred mice that led to the
discovery of MHC
MHC in human is known as Human Leucocyte Antigen
(HLA) complex
26. The HLA Complex
Histocompatibility antigens mean cell surface antigens that evoke
immune response to an incompatible host resulting in allograft
rejection
These alloantigens are present on the surface of leucocytes in
man and are called Human Leukocyte Antigens (HLA) and the
set of genes coding for them is called the HLA complex
The HLA complex of genes is located on short arm of chromosome
6 & is grouped into 3 classes
Class I: HLA-A, HLA-B & HLA-C
Class II: HLA-DR, HLA-DQ & HLA-DP
Class III: Complement foci encode for C2, C4 & factor B of
complement system & tumor necrosis factor (TNF) alfa & beta
27. Class I MHC Antigens (A,B,C)
Present on the surface of all nucleated cells , so all
virus infected cells can be detected and eliminated by
the CD8+ CTLs
The cytotoxic T cells (CD8) recognize MHC class I
antigens for their action
28.
29. Class II MHC Antigens
(DR,DQ & DP)
They have a very limited distribution & are principally
found on surface of macrophages, monocytes,
activated T-lypmhocytes & B-lymphocytes.
Primarily responsible for the graft- versus host
response & mixed leukocyte reaction
30. Class III MHC antigens
Class III MHC genes encode C2, C4 complement
components of the classical pathway & propesdin
factor B of alternate pathway
31. B- lypmhocytes
Bone marrow derived B-lyphocytes are the cells that
produce antibodies & thus the effector cells of humoral
immunity
B cells make upto 10-20 % of circulating peripheral
lymphocyte population
lymphocyte population
They are also present in the follicles of peripheral
lymphoid tissues ( lymph nodes, spleen, tonsils & other
mucosal tissues )
After stimulation B cells differentiate into plasma cells
which secrete large amount of antibodies
32. Antigens
An antigen is defined as any substance which when
introduced parenterally into the body stimulates the
production of an antibody
Based on the ability to carry out these two functions,
antigens may be classified into different types:
antigens may be classified into different types:
Complete antigen: It is able to induce antibody
formation & produce a specific & observable reaction
with the antibody so produced
Haptens: these are substances which are incapable of
inducing antibody formation by themselves but can
react specifically with antibodies
33. Contd…
Antigens are of two types..
A)Those present on the body’s own cells are called the
auto-antigens or self antigens.
B)The antigens entering the body from outside are
B)The antigens entering the body from outside are
known as foreign or nonself antigens.
34. Contd…
Following are the nonself antigens:
1. The receptors on the cell membraof microbial
organisms like bacteria,viruses and fungi.
2.Toxins from microbial organisms.
2.Toxins from microbial organisms.
3.Materials from transplanted organs.
4.allergens like pollen grains.
35. Antibodies
Antibodies are substances which are formed in the
serum & tissue fluids in response to an antigen & react
with that antigen specifically & in some observable
manner
The chemical nature of antibodies is globulin & they are
The chemical nature of antibodies is globulin & they are
named as immunoglobulins
Immunoglobulins are glycoproteins
All antibodies are immunoglobulins but all
immunoglobulins may not be antibodies
36. Contd…
A molecule of immunoglobulin may have either kappa
or lambda chains but never both
The antigen combining site of the molecule is at its
amino terminus. It is composed of both L & H chains
Of the 214 amino acid residues that make up the L-
chains , 107 constitute the carboxy terminal half, occur
only in a constant sequence
This part of the chain is therefore called the constant
region
On the other hand, the amino acid sequence in the
amino terminal half of the chain is highly variable
39. IgG:
Major serum immunoglobulin
80% of total
Half life of approximately 2-3 days
Normal serum concentration is 8-16 mg/ml
It is the only maternal immunoglobulin that is normally
transported across the placenta & provides natural
passive immunity in newborn
40. Contd…
Passively administered IgG suppresses the
homologous antibody synthesis by a feedback process.
This property is utilized in the isoimmunization of
women by the administration of anti-Rh IgG during
delivery
delivery
4 subclasses of IgG have been recognized
IgG1, IgG2, IgG3 & IgG4
41. IgA:
2nd most aboudant class
10-13% of serum immunoglobulin
Normal serum level is 0.6-4.2 mg/ml
Half life is 6-8 days
Major immunoglobulin in colostrums, saliva & tears
2 subclasses of IgA has been recognized: IgA1 & IgA2
42. IgM:
Consists of 5-8 % of immunoglobulin
Normal level is 0.5-2 mg/ml
Half life is 5 days
It is the earliest immunoglobulin to be synthesized by
fetus
Responsible for protection against blood invasion by
micro-organisms
2 subclasses of IgM have been recognized
43. IgD:
Normal concentration is 3 mg/100 ml of serum
Half life is 3 days
It resembles IgG structurally
Function is uncertain
44. IgE:
Normal concentration in blood is 20-500 ng/ml
Half life is 2 days
Doesn’t pass the placenta barrier
It is chiefly produced in the linings of respiratory &
intestinal tracts
It is responsible for anaphylactic type of hypersensitivity
45.
46. Natural killer cells (NK)
NK cells are lymphocytes that arise from common lymphoid
progenitor that gives rise to T & B lymphocytes
They are cells of innate immunity
They have two types of receptors : inhibitory & activating
The inhibitory receptors recognize self class I MHC molecules
which are expressed on all healthy cells, where as the activating
receptors recognize molecules that are expressed on infected cells
with DNA damage
Normally, the effects of the inhibitory receptors dominate over
those of activating receptors, thereby preventing activation of NK
cells
47. Antigen presenting cells:
The immune system contains several cell types that are
specialized to capture microbial antigens & display
these4 to lymphocytes. These are called antigen
presenting cells
presenting cells
48. Dendritic cells:
Cells with dendritic morphology occur as two functionally distinct
types
Also called as interdigitating DCs
They reside in & under epithelia
They are also present in T cells of lymphoid tissues & in the
interstitium many nonlymphoid organs such as heart & lungs
2 types of DCs
1. Plasmacytoid DCs- present in blood & lymphoid organs
produced in response to many viruses
2. Follicular DCs- located in the germinal centers of lymphoid
follicles in the spleen & lymph nodes
49. Macrophages
They ingest microbes & other particulate antigens&
display peptides for recognition by T- lymphocytes
These T cells in turn activate macrophages to kill the
microbes
51. Cell mediated immunity
Activation of T lymphocytes & elimination of cell
associated microbes
T lymphocytes are activated by antigen & proliferate &
differentiate into effector cells, most of which migrate to
any site where the antigen is present
any site where the antigen is present
Upon activation, T lymphocytes secrete soluble
proteins called cytokines which function as growth &
differentiation factors for lymphocytes & mediate
communication between leukocytes
52. Cytokines
Messenger molecules of immune system
They are polypeptide product of many cell types that
function as mediators of immune responses
function as mediators of immune responses
They are synthesized & secreted in response to
external stimuli which may be microbial products,
antigen recognition or other cytokines.
53. Contd…
Action of cytokines may be
Autocrine (on the cell that produces cytokines)
Paracrine (on adjacent cells)
Endocrine (at a distance from the site of production)
54. Contd…
Cytokines may be grouped into several classes on the
basis of their biologic activities & functions:
Cytokines involved in innate immunity:
Earliest host response to microbes & dead cells
Earliest host response to microbes & dead cells
Major cytokines in this group are TNF & interleukin 1 &
a group of chemo attractant cytokines called
chemokines
55. Contd…
Cytokines that regulate lymphocyte responses &
effector functions in adaptive immunity
Different cytokines are involved in proliferation &
differentiation of lymphocytes ( eg. IL-2 & IL-4) & in the
activation of various effector cells (IFN 1) which
activation of various effector cells (IFN 1) which
activates macrophages . IF-5 which activates
eosinophils
56. Contd…
Cytokines that stimulate hematopoesis
Many of these are called colony stimulating factors
They function to increase output of leucocytes from
bone marrow & to thus replenish leucocytes tha are
consumed during immune & inflammatory reactions
57. Effector function of T
lymphocytes
One of the earliest responses of CD4+ helper T cells is
secretion cytokine IL-2
IL-2 is a growth factor that acts on these T lymphocytes
& stimulate their proliferation leading to an increase in
number of antigen specific lymphocytes
number of antigen specific lymphocytes
These effector cells migrate to sites of infections and
accompanying tissue damage
Activated CD8+ lymphocytes differentiate into CTLs
which kills viruses that infect many cell types or
bacteria that are ingested by macrophages
58. Humoral immunity
Activated B lymphocytes
Upon activation, B lymphocytes proliferate & then differentiate into
plasma cells that secrete different classes of antibodies with distinct
functions.
There are two major mechanisms of B cell activation
T cell independent
T cell dependent
59.
60. Contd…
A. T cell independent:
Many polysaccharide & lipid antigens have multiple
identical antigenic determinants (epitopes) that are able
to engageseveral antigen receptor molecules on each
B cells and initiate process of B cell activation
B cells and initiate process of B cell activation
B. T cell dependent:
Globular protein antigens are not able to bind to
many antigen receptors & response of B cells to protein
antigens require help from CD4+ T cells
61. Disorders of human immunity
They are of 3 types:
1. immunodeficiency
2. autoimmunity
3. hypersensitivity
62. Immunodeficiency
It occurs when one or more components of immune systems are
inactive
The ability of immune system to respond to pathogens is
diminished in both young & elderly
diminished in both young & elderly
Diets lacking sufficient proteins are associated with impaired cell
mediated immunity, phagocyte function, IgA concentration &
cytokine production
63. Contd…
The loss of thymus at an early age through genetic
mutation or surgical removal results in severe
immunodeficiency & high susceptibility to infections
It can be inherited or acquired
Chronic granulomatous disease where phagocytes
have a reduced ablility to destroy pathogens is an
example of inherited or congenital immunodeficiency
64. Immunodeficiency Diseases
An inborn or primary immunodeficiency results from
hereditary or congenital defects that prevent proper
functioning of innate, humoral, and/or cell-mediated
defenses.
65. Immunodeficiency Diseases
An acquired or secondary immunodeficiency results
from exposure to various chemical and biological
agents.
66. Stress and the Immune
System
Growing evidence shows that physical and emotional
stress can harm immunity.
67. Acquired Immunodeficiency
Syndrome (AIDS)
People with AIDS are highly susceptible to
opportunistic infections and cancers that take
advantage of an immune system in collapse.
68. Acquired Immunodeficiency
Syndrome (AIDS)
Because AIDS arises from the loss of helper T
cells, both humoral and cell-mediated immune
responses are impaired.
The loss of helper T cells results from infection
by the human immunodeficiency virus
by the human immunodeficiency virus
(HIV).
69. Autoimmunity
Overactive immune responses comprise the other end
of immune dysfunction, particularly the autoimmune
disorders
Here the immune system fails to properly distinguish
between self & non-self and attacks parts of the body
between self & non-self and attacks parts of the body
Autoimmune diseases result from a hyperactive
response as if they are foreign organisms
Eg. Rheumatoid arthritis,
SLE
70. Hypersensitivity
(immunologic tissue injury)
It is defined as a state of exaggerated immune
response to antigen
The lesions of hypersensitivity are produced due to
interaction between antigen and product of immune
response
71. Contd…
Depending upon the rapidity and duration of the
immune responses 2 distinct forms are recognized
1. Immediate type:
1. Immediate type:
On administration of antigen, the reaction occurs
immidiately (within seconds to min)
Immune response in this type is mediated largely by
humoral antibodies
Eg. Type I, II & III
72. Contd…
2. Delayed type:
Reaction is slower in onset & develops within 24-48
hours & effect is prolonged
Mainly mediated by cellular response
Mainly mediated by cellular response
Eg. Type IV
There are 4 types of hypersensitivity reactions
73. Type I (Anaphylactic, Atopic)
It is defined as a state of rapidly developing immune
response immune response to an antigen to which the
individual is previously sensitized
Response is mediated by humoral antibodies of IgE
IgE antibodies sensitize basophils of peripheral blood
or mast cells of tissues leading to release of
anaphylactic mediators
74. Contd…
Clinical examples of
anaphylaxis may be of 2 types
Examples of systemic anaphylaxis
Systemic
local
Examples of local anaphylaxis
Examples of systemic anaphylaxis
1. administration of antisera
2. administration of drugs
3. bee sting
Examples of local anaphylaxis
1. hay fever
2. bronchial asthma
3. urticaria
4. angioedema
75. Type II (cytotoxic)
Cytotoxic reactions are defined as those reactions which cause
injury to the cells by combining humoral antibodies with cell
surface antigens
3 types of mechanisms are involved in mediating cytotoxic
reactions
1. Cytotoxic antibody to blood cells
Autoimmune hemolytic anemia
Transfusion reactions
Hemolytic disease of the newborn
76. Contd…
2. Cytotoxic antibodies to tissue components
Grave’s disease
Myasthenia gravis
3. Antibody dependent cell mediated cytotoxicity (ADCC)
Cytotoxicity by this mechanism is mediated by
monocytes, neutrophils etc.
Eg. Target cells are killed by this mechanisms are
tumor cells, parasites
77. Type III (immune complex)
It results from formation of immune complexes by direct
antigen-antibody combination as a result of which the
complement system gets activated causing cell injury
Depending upon the distribution & location of antigens
it is of two types
it is of two types
1. Local: Arthus reaction:
Eg. Farmer’s lung
2. Systemic: Circulating immune complex disease or
serum sickness
Eg. Various forms of glomerulonephritis
78. Type IV (cell mediated)
It is mediated by specifically sensitized T lymphocytes
produced in the cell mediated immune response
It is of 2 types
Classical delayed hypersensitivity
T cell mediated cytotoxicity
79. Contd…
Classical delayed hypersensitivity
This is mediated by specifically sensitized CD4+ T cells
subpopulation on contact with antigen
Eg. Tuberculin reaction, typhoid fever, contact
Eg. Tuberculin reaction, typhoid fever, contact
dermatitis
T cell mediated cytotoxicity
CD8+ subpopulation of T lymphocytes are the cytotoxic
T cells & are generated in response to antigen like virus
infected cells, tumor cells and incompatible
transplanted cells
80. Miscellaneous
Combined immunization
A combination of active & passive immunization is
employed simultaneously which is known as combined
employed simultaneously which is known as combined
immunization.
Passive immunity provides the protection necessary till
the active immunity becomes effective
81. Adaptive immunity
Injection of immunologically competent lymphocytes is
known as adaptive immunity
Instead of whole lymphocytes, an extract of
Instead of whole lymphocytes, an extract of
immunologically competent lymphocytes can be used
such lymphocytes are collectively known as transfer
factor
82. Contd…
Local immunity
Natural infection or the live viral vaccine administered
orally or intranasally provides local immunity at the site
orally or intranasally provides local immunity at the site
of entry such as gut mucosa & nasal mucosa
respectively
83. Herd immunity
It refers to overall resistance in a community
When herd immunity is low, chances of epidemics
increase on introduction of a suitable antigen
increase on introduction of a suitable antigen
Eradication of any communicable disease depends on
development of a high level of herd immunity rather
than of immunity in individuals
84. References
1)Basic Pathology- Robin.
2)Essential Pathology-Harsh Mohan.
3)Textbook of Microbiology-Ananthanarayan & Paniker.
4)Textbook of Microbiology-C P Baveja.