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Immunity
Dr Meenal Atharkar
Dr Meenal Atharkar
MDS
Dept of Conservative Dentistry & Endodontics
Contents
 Definition
 Classification
 Innate immunity
 Acquired immunity
 Cells & tissues of immune system
 Cell mediated immunity
 Humoral immunity
 Disorders of immunity
 Miscellaneous
 References
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.
Classification
A Summary of Innate and Acquired
Immunity
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.
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.
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.
Difference between active & passive immunity
 By convention, immune system and immune response
refer to acquired immunity
 Two types of acquired immunity
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.
CONTD..
2)Artificial active immunity
 -Produced by vaccination.
 -Produced by vaccination.
 -The vaccines are prepared from
live,attenuated or killed microorganisms
or their toxoids.
VACCINES
A)Live vaccines
 -BCG
 -MMR
B)Killed vaccines
 -TAB
 -Hepatitis B vaccine
C)Bacterial products
 -Tetanus toxoid
Types of passive immunity
A)Natural-Through transplacental
maternal IgG antibodies.
B)Artificial-Through antiserum
injection
Cells & tissues of immune
system
system
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.
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.
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.
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.
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..
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)
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
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
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
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
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
Class III MHC antigens
 Class III MHC genes encode C2, C4 complement
components of the classical pathway & propesdin
factor B of alternate pathway
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
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
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.
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.
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
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
Contd…
Classification of
immunoglobulins
 Human sera contain IgG, IgA, IgM, IgD & IgE in descending order
of concentration
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
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
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
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
IgD:
 Normal concentration is 3 mg/100 ml of serum
 Half life is 3 days
 It resembles IgG structurally
 Function is uncertain
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
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
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
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
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
Cell mediated & humoral immunity
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
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.
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)
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
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
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
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
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
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
Disorders of human immunity
They are of 3 types:
1. immunodeficiency
2. autoimmunity
3. hypersensitivity
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
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
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.
Immunodeficiency Diseases
 An acquired or secondary immunodeficiency results
from exposure to various chemical and biological
agents.
Stress and the Immune
System
 Growing evidence shows that physical and emotional
stress can harm immunity.
Acquired Immunodeficiency
Syndrome (AIDS)
 People with AIDS are highly susceptible to
opportunistic infections and cancers that take
advantage of an immune system in collapse.
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).
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
References
 1)Basic Pathology- Robin.
 2)Essential Pathology-Harsh Mohan.
 3)Textbook of Microbiology-Ananthanarayan & Paniker.
 4)Textbook of Microbiology-C P Baveja.
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Types of Immunity and cells

  • 1. Immunity Dr Meenal Atharkar Dr Meenal Atharkar MDS Dept of Conservative Dentistry & Endodontics
  • 2. Contents  Definition  Classification  Innate immunity  Acquired immunity  Cells & tissues of immune system  Cell mediated immunity  Humoral immunity  Disorders of immunity  Miscellaneous  References
  • 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.
  • 5. A Summary of Innate and Acquired Immunity
  • 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.
  • 9.
  • 10.
  • 11. Difference between active & passive immunity
  • 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.
  • 15. VACCINES A)Live vaccines  -BCG  -MMR B)Killed vaccines  -TAB  -Hepatitis B vaccine C)Bacterial products  -Tetanus toxoid
  • 16. Types of passive immunity A)Natural-Through transplacental maternal IgG antibodies. B)Artificial-Through antiserum injection
  • 17. Cells & tissues of immune system system
  • 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
  • 38. Classification of immunoglobulins  Human sera contain IgG, IgA, IgM, IgD & IgE in descending order of concentration
  • 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
  • 50. Cell mediated & humoral immunity
  • 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.