Immunology

M. Deepalakshmi
Lecturer

Department of Pharmacy Practice

JSS College of Pharmacy, Ooty
(A Constituent College of JSS University, Mysore)
 Introduction

• The immune system is a network of cells, tissues, and organs that

work together to defend the body against attacks by “foreign”
invaders.

• These are primarily microbes, tiny-infection-causing organisms

such as bacteria, viruses, parasites, and fungi.

• It is the immune system’s job to keep them out or, failing that, to
seek out and destroy them.
 Introduction
• The immune system is amazingly complex.

• It can recognize and remember millions of

different enemies, and it can produce
secretions and cells to match up with and wipe
out each one of them.
• Although vital to survival, the immune system is
similar to the proverbial two-edged sword. (On
the one hand, immunodeficiency states render humans
easy prey to infections and possibly tumors; on the other
hand, a hyperactive immune system may cause fatal
disease, as in the case of an overwhelming allergic
reaction to the sting of a bee.)
 Introduction
Immunophysiology
(Structure and function Immunopathology
of the normal immune (Study of
system) derangements in
the immune
system)

Immunology
 Introduction
• Antigen: A substance which is usually a
protein, which when introduced into the
tissues stimulates antibody production.

• Hapten: A non-protein substance with no

antigenic properties, but on combining with a
protein can form a new antigen capable of
forming antibodies.

• Antibody: A protein substance produced in

response to antigenic stimulation

• They are also called as immunoglobulin's and

are of 5 types (IgG, IgA, IgM, IgE, IgD)
 Antigen-Antibody Reaction

Primary Reaction

Secondary Reaction
 Types of Immunity

• The physiologic function of the immune

system is to protect individuals from
infectious pathogens.

• The mechanisms that are responsible for this

protection fall into two broad categories, each
with humoral and cellular components.

1. Nonspecific or innate immunity

2. Specific or adaptive immunity

 Innate immunity
• Innate immunity (also called natural, or native,
immunity) refers to defense mechanisms that are
present even before infection and have evolved
to specifically recognize microbes and protect
multicellular organisms against infections.

• It is the first line of defense without antigenic

specificity

• Its major components are

i. Humoral: Comprised by complement

ii. Cellular: consists of neutrophils,

macrophages and natural killer cells.
 Adaptive immunity
• Adaptive immunity (also called acquired, or
specific, immunity) consists of mechanisms
that are stimulated by (adapt to) microbes
and are capable of also recognizing
nonmicrobial substances, called antigens

• The adaptive immune system consists of

lymphocytes and their products, including
antibodies
 Cont.…
• It is characterized by antigenic specificity

• Its main components are

i. Humoral: protects against

extracellular microbes and their
toxins, consisting antibodies formed
by B cells

ii. Cellular: responsible for defense

against intracellular microbes,
mediated by T cells
Cont.…
 Cont.…

• B cells differentiate into plasma cells which

form specific antibodies

• T cells proliferate on coming in contact with

appropriate antigen after which the non-
specific accessory cells (PMNs and
macrophages) play a critical role in
completion of immunopathologic reaction.
 Differences between T and B
lymphocytes
Feature T cells B cells

1. Origin Thymus Bone marrow

2. Life span Small T cells: Small B cells: < 1

months to years month

T cell blasts: B cell blasts:

Several days Several days

3. Location
i. Lymph nodes
Perifollicular Germinal Centres,
ii. Spleen medullary cords

Periarteriolar Germinal Centres,

iii. Peyer’s patches
red pulp

Perifollicular Central follicles

 Differences between T and B lymphocytes
Feature T cells B cells

4. Presence in
80% 20%
i. Blood
ii. Bone marrow Rarely present numerous
iii. Lymph nodes 85% 15%
iv. Spleen 65% 35%
v. Thymus
90% 10%
5. Surface markers

i. Ag receptors P A
ii. Surface Ig A P
iii. Fc receptor A P
iv. Complement
receptor A P
v. CD markers TH CD4, 3,7,2 CD19, 21, 23
TS CD8, 3, 7, 2
 Differences between T and B lymphocytes
Feature T cells B cells

6. Functions
i. CMI via Role in humoral
cytotoxic T immunity by
cells positive synthesis of
for CD3 and specific antibodies
CD4

i. Delayed Precursors of
hypersensitivit plasma cells
y via CD4+ T
cells
i. Immunoregula
tion of other T
cells B cells
and stem cells
via T helper
CD4+ or T
suppressor
CD8+ cells
Human Leucocyte antigen
System
• These antigens were first discovered on
leucocytes and are important in the
regulation of the immune system.

• The major importance of human

histocompatibility antigens of HLA system
lies in matching donor and recipient for
organ transplant.
Human Leucocyte antigen
System
• Out of various genes for histocompatibility
antigens, most of the transplantation
antigens are located on a portion of
chromosome 6 of all nucleated cells of the
body and platelets, this is called major
histocompatibility complex or HLA
Complex.
• Depending upon the characteristics of MHC
they are divided into 3 classes

• Class I MHC antigens: these have loci as HLA-

A, HLA-B, HLA-C.

• CD8 lymphocytes carry receptors for class I

MHC and are used to identify the cells having
them.

• Class II MHC: have single locus as HLA-D,

further these 3 loci, DR, DQ and DP.

• Class II MHC is identified by B cells and CD4

or T helper cells.
• Class III MHC: these are components of the
complement system coded on HLA complex
but are not associated with HLA expression
and are not used in antigen identification.
 Role of HLA Complex
1. Organ transplantation: The recipient’s
immune system can recognise the
histocompatibility antigens on the donor
organ and accordingly accept it or reject it.

• Both humoral and cell mediated immune

responses are involved in case of genetically
non-identical transplants.

2. Regulation of the immune system: Class I

and II histocompatibility antigens play a role
in regulating both cellular and humoral
immunity.
 Role of HLA Complex
• Class I Ags regulate the function of cytotoxic
T cells e.g. in virus infections

• Class II Ags regulate the function of helper T

cells.

3. Association of diseases with HLA: increasing

number of diseases has been associated
with specific histocompatibility antigens

• E.g. inflammatory such as ankylosing

spondylitis

• Autoimmune disorders: e.g. rheumatoid

arthritis.
Role of HLA Complex
 Hypersensitivity Reactions

• Hypersensitivity is defined as a state of

exaggerated immune response to an
antigen
• The lesions of hypersensitivity are due to
interaction between antigen and the
antibody produced in response to the
antigen.
Hypersensitivity Reactions
• Two distinct forms of hypersensitivity
reactions are recognized, based upon the
rapidity and duration of the immune
response.

1. Immediate type: the reaction occurs

immediately within seconds to minutes on
administration of antigens.

• The immune response is mediated by

humoral antibodies

• It is further of 3 types, Type I, Type II, Type III

Hypersensitivity Reactions
2. Delayed type: the reaction is slower in onset
and develops within 24-48 hrs and the effect
is prolonged

• It is mediated by cellular response

• Type IV is delayed hypersensitivity reactions.

 Type I Hypersensitivity
Reactions
• These are Anaphylactic, Atopic reactions

• Anaphylaxis is opposite of prophylaxis

• It is defined as a state of rapidly developing

immune response to an antigen to which the
individual is previously sensitised.

• The response is mediated by humoral

antibodies of IgE type
 Type I Hypersensitivity
Reactions

Increased vascular
permeability
Smooth muscle
Release of anaphylactic contraction
IgE antibodies sensitise mediators e.g.
histamine, serotonin, Shock
basophils of the
peripheral blood or chemotactic factors of Early vasoconstriction
mastcells of tissues anaphylaxis for followed by
neutrophils, esonophils, vasodilatation
leukotriens,
prostaglandins, PAF increased gasrtic
secretion
Increased nasal and
lacrimal secretions
 Type I Hypersensitivity
Reactions
• Examples of anaphylaxis can be systemic or
local

• Systemic:

– Administration of antisera: e.g. anti-

tetanus

– Administration of drugs: e.g. penicillin

• The clinical features of systemic anaphylaxis

include itching, erythema, contraction of
respiratory bronchioles, pulmonary edema,
shock and death.
 Type I Hypersensitivity
Reactions
• Local:

– E.g. seasonal allergic rhinitis due to pollen

sensitisation of conjunctiva and nasal
passages.

– Food allergy due to ingested allergens like

fish

– Cutaneous anaphylaxis due to contact of

antigen with skin characterised by
urticaria.
 Type I Hypersensitivity
Reactions
• Local anaphylaxis is common with genetic
predisposition and therefore also called as
atopic reactions.
Type II Hypersensitivity Reaction
• Cytotoxic Reactions, these cause cell injury by
combining humoral antibodies with cell
surface antigens.

• Blood cells are affected more commonly

• Three types of mechanisms are involved in

mediating cytotoxic reactions

1. Cytotoxic antibodies to blood cells

2. Cytotoxic antibodies to tissue

components

3. Antibody-dependent cell mediated

cytotoxicity (ADCC)
 Type II Hypersensitivity Reaction
• Cytotoxic antibodies to blood cells
Blood cells with
cell surface Combining with
antigens (RBC’s, IgG or IgM class Direct cytolysis
leucocytes, antibodies
platelets)

In the process, complement system is

activated resulting in injury to the cell
membrane.
The cell surface is made susceptible to
phagocytosis due to coating or
opsonisation from serum factors or
opsonins.
Type II Hypersensitivity Reaction
• Examples of cytotoxicity by this mechanism
are

a) Autoimmune haemolytic anemia:

autoantibodies reacting with the
antigens present on the red cell surface.

b) Transfusion reactions

c) Erythroblastosis foetalis: foetal red cells

are destroyed by materbal antibodies
crossing the placenta

d) Idiopathic thrombocytopenic purpurea

Type II Hypersensitivity Reaction
e. Drug induced cytotoxic antibodies:
antibodies are formed on administration
of drugs like penicillin
 Type II Hypersensitivity Reaction
2. Cytotoxic antibodies to tissue components:

• Autoantibodies react with some components

of tissue cells in certain diseases

• Examples include:

a) Grave’s disease: thyroid antibody is formed

which reacts with the TSH receptor to cause
hyperfunction or proliferation

b) Myasthenia gravis: antibody to

acetylcholine receptors of skeletal muscle,
this blocks the neuromuscular transmission
at the motor end plate, resulting in muscle
weakness.
 Type II Hypersensitivity Reaction

c) Male fertility: antisperm antibody is formed

which reacts with spermatozoa and causes
impaired motility and cell injury.

3. Antibody-dependent cell mediated

cytotoxicity: this is mediated by leucocytes
like monocytes, neutrophils,

• The antibodies involved are IgG

• The cell injury occurs by lysis of antibody

target cells

• The examples of target cells killed by this

mechanism are tumor cells.
Type III Hypersensitivity Reaction
• These are immune complex recations

Antigen
Activation of
combines Ag-Ab
complement Cell injury
with an complex
system
antibody
 Type III Hypersensitivity Reaction

• Two types of antigens can cause immune

complex mediated cell injury

• Exogenous antigens: infectious agents

(bacteria, virus, fungi), certain drugs and
chemicals.

• Endogenous antigens: blood components

(tumor antigens), antigens in cells and tissues
(nuclear antigens in SLE)
 Type III Hypersensitivity Reaction

• Type III reactions are of two types, they are

classified based on the distribution and
location of the antigens.

1. Local: Arthus reaction

2. Systemic: Circulating immune complex

disease or serum sickness
 Type III Hypersensitivity Reaction

1. Local: Arthus reaction: It is a localised

inflammatory reaction, usually an immune
complex vasculitis of skin in an individual
with circulating antibodies. Large immune
complexes are formed due to circulating
antibodies.

• These antibodies precipitate locally in the

vessel wall causing fibrinoid necrosis.

• E.g. injection of antitetenus serum

 Type III Hypersensitivity Reaction

• Systemic: serum sickness

Antigen introduced into Antigen stimulates the

the circulation formation of antibodies

The complex deposit at

different tissue sites
formation of Ag-Ab
containing basement
complexes
membrane exposed to
circulating blood

Acute inflammation and

activation of the Phagocytosis of the
complement with the immune complexes and
release of biologically destruction
active compounds
 Type III Hypersensitivity Reaction

• Examples of circulating immune complex

diseases are

• SLE, Rheumatoid arthritis

 Type IV Hypersensitivity Reactions

• These are cell mediated reactions

• It is mediated by specifically sensitised T

lymphocytes produced in the cell-mediated
immune response.

• They are classified into two types

1. Classical delayed hypersensitivity

2. T cell-mediated cytotoxicity
 Type IV Hypersensitivity Reactions

• Classical delayed hypersensitivity: the CD4+ T

cell subpopulation cells posses surface
receptors which bind to the antigen, resulting
in cell injury characterised by slowly
developing inflammatory response.

• E.g. the tuberculin reaction.

• T-cell mediated cytotoxicity: CD8+

subpopulation of T lymphocytes are the
cytotoxic T cells and are generated in
response to antigens like virus-infected cells
and incompatible transplanted tissue.
 Autoimmunity
• It is a state in which the body's immune
system fails to distinguish between self and
non-self and reacts by formation of
autoantibodies against one’s own tissue
antigens.

• In autoimmunity there is loss of immune

tolerance
 Autoimmunity
• Immune tolerance is a normal phenomenon
present since foetal life and is defined as the
ability of an individual to recognise self tissue
and antigens.

• The immune tolerance occurs by the

following mechanisms.

1. Clonal elimination

2. Concept of clonal anergy

3. Suppressor T cells
 Autoimmunity
• Clonal elimination: during embryonic
development, T cell maturing in the thymus
acquire the ability to distinguish self from
non self.

• These T cells are then eliminated by

apoptosis for the tolerant individual.

• Concept of clonal anergy: according to this

theory the t cells which have acquired the
ability to distinguish self and non self
antigens are not eliminated but instead
become non-responsive and inactive
 Autoimmunity
• Suppressor T cells: according to this
mechanism, the tolerance is achieved by a
population of specific suppressor T cells
which do not allow the antigen-responsive
cells to proliferate and differentiate.
Criteria for Autoimmunity
• Direct evidence: Direct evidence that a
human disease is caused by autoimmunity
can be obtained in those instances where the
pathological injury is due to an autoantibody.

• Direct evidence requires transmissibility of

the characteristic lesions of the disease from
human to human, or human to animal.

• Graves' disease and myasthenia gravis (in

which there are temporary signs of disease in
the infant due to transplacental transfer)
Criteria for Autoimmunity
• Indirect evidence:

• Indirect evidence requires re-creation of the

human disease in an animal model. The
majority of autoimmune diseases fit in this
category.

• E.g. Hashimoto's thyroiditis and multiple

sclerosis can be reproduced by immunizing
the animal with an antigen analogous to the
putative autoantigen of the human disease.
Criteria for Autoimmunity
• When direct and indirect evidence to define
an autoimmune disease are not available,
investigators are left with circumstantial
evidence, that is, with listing "markers"
descriptive of autoimmune disease.
Criteria for Autoimmunity
• Examples of these

• positive family history for the same disease,

or for other diseases known to be
autoimmune
presence of infiltrating mononuclear cells in
the affected organ or tissue

• deposition of antigen-antibody complexes in

the affected organ or tissue
 Pathogenesis of
Autoimmunity
• The mechanisms by which the immune
tolerance of the body is broken causes
autoimmunity.

• These mechanism may be

1. Immunological

2. Genetic

3. Microbial
 Pathogenesis of
Autoimmunity
• Immunological factors: failure of immunological
mechanisms of tolerance initiates autoimmunity,
these mechanisms are

• Polyclonal activation of B cells: these cells may

be directly activated by stimuli such as infection
with micro-organisms and their products leading
to bypassing of T cell tolerance.

• Generation of self-reacting B cell clones: it also

causes bypassing of T cell tolerance.
 Pathogenesis of
Autoimmunity
• Decreased T suppressor and increased T helper
cell activity: this causes high levels of auto-
antibody production by B cells contributing to
autoimmunity.

• Sequestered antigen released from tissues: self

antigen which is completely sequestered may act
as foreign antigen when introduced to the
circulation later.
 Pathogenesis of
Autoimmunity
• Genetic factors: increased expression of class II
HLA antigens on tissues involved in
autoimmunity

• Increased familial incidence of some of the

autoimmune disorders

• Microbial factors: infection with micro-organisms

particularly virus.
 Types of Autoimmune
diseases
• Depending upon the type of autoantibody, the
diseases are classified into 2 types

1. Organ specific diseases

2. Non-organ specific diseases

 Types of Autoimmune
diseases
• Organ specific diseases: the autoantibodies
formed react specifically against an organ or
target tissue component and cause its chronic
inflammatory destruction.

• The tissues affected are endocrine glands, blood

cells.

• Non-organ specific diseases: these are the

diseases in which a number of autoantibodies
are formed which react with antigens in many
tissues and thus cause systemic lesions.
 Types of Autoimmune
diseases
• ENDOCRINE DISEASE: Autoimmune thyroiditis

• HEMATOLOGIC DISEASE: Acquired hemolytic

anemia

• Skin diseases: systemic lupus erythematosus

• NERVOUS SYSTEM DISEASE: Myasthenia gravis

• Rheumatological diseases: Rheumatoid arthritis

 Transplant rejection
• It is classified into 4 types based upon the
relationship between the donor and the
recipient.

• Autografts: these are grafts in which the donor

and the recipient is the same individual.

• Isografts: these are the grafts between the donor

and the recipient of the same genotype.

• Allografts: donor is of same species but of

different genotype

• Xenografts: donor is of different species from

that of the recipient.
 Transplant rejection
• For a successful tissue transplant without
immunological rejection matching of major
histocompatibility locus antigens between the
donor and the recipient is of vital importance.

• The greater the disparity between donor and the

recipient in HLA system, the stronger and more
rapid will be the rejection.
 Mechanisms of graft
rejections
• Except for autografts and isografts, an
immune response against allografts is
inevitable.

• Allograft rejection involves both cell-

mediated and humoral immunity.

1. Cell-mediated immune reactions:

• Mediated by T cells

• Play major role in graft rejection

 Mechanisms of graft
rejections

T cells of the Sensitization in cytotoxic T cells

recipient come case of as well as
in contact with incompitability hypersensitivity
the HLA reactions
antigens of the initiated by T
donor helper cells
attack the graft
and destroy it.
 Mechanisms of graft
rejections
2. Humoral immune reactions:

• Humoral antibodies play a role in

rejection of a graft.

• These include

• Preformed circulating antibodies due to

pre-sensitization of the recipient before
transplantation e.g. by blood transfusions
and previous pregnancies
 Mechanisms of graft
rejections
• Non-sensitized individuals by
complement dependent cytotoxicity,
ADCC, Ag-Ab complexes.
 Types of rejection
reactions
• They are classified into 3 types

• Hyperacute rejection

• Acute rejection

• Chronic rejection
 Types of rejection
reactions
• Hyperacute rejection:

• Occurs within minutes to hours of placing

the transplant and destroys it.

• It is mediated by preformed humoral

antibody against donor-antigen.
 Types of rejection
reactions
• Acute rejection:

• Occurs within few days to few months of

transplantation

• It is more common and is characterised

by extensive infiltration of lymphocytes,
a few plasma cells, monocytes and a few
polymorphs
 Types of rejection
reactions
• Chronic rejection:

• It may follow repeated attacks of acute

rejection or may develop slowly over a
period of months to year or so.

• The underlying mechanisms may be

immunologic or ischemic