IMMUNITY

immunity 1
 Mechanism of cell mediated
immunity
• Mediated by activated T lymphocytes

• T cells respond to Ag only if the Ag is bound to

MHC protein on Ag presenting cells

immunity 2
• Antigen presenting cells:
1. Dendritic cells in LN, spleen & skin
2. Macrophages
3. B cells

• MHC protein - 2 types

– MHC-I --- bound to CD8 T cells
– MHC- II --- bound to CD4 T cells

immunity 3
• When Ag first enters the body, it is taken up by
an Ag presenting cells & partially digested
↓
They present peptide fragment of Ag to T Cell
Receptor on T cells.
↓
T cells are stimulated to multiply forming a clone

immunity 4
immunity 5
 MHC
• Major histocompatibility complex /Human
Leukocyte Antigen
• Function : display peptides for recognition by
CD4+ & CD8+ T lymphocytes
• MHC is encoded by a cluster of genes on
chromosome 6
• On the basis of chemical structure ,2 types of
MHC molecules
– Class I MHC
– Class II MHC immunity 6
Class I MHC
• Expressed on all nucleated cells
• Encoded by HLA-A,HLA-B,HLA-C
• Consists of α & β chains
• α chain contains a cleft where foreign peptide
can bind to MHC for presentation to T cell
• α chain also contains a conserved region that
binds CD8 ensuring only CD8+ cells can respond
to peptides displayed by MHC class I
immunity 7
Class II MHC
• Encoded by genes in HLA-D region
• Expressed only on dendritic cells,macrophages
& B cells
• α chain has a cleft for binding antigenic
peptide & region that binds CD4+

immunity 8
immunity 9
immunity 10
immunity 11
T cell

immunity 12
 Cell mediated immunity
• Responsible for
– Delayed allergic reactions & rejection of
transplants

• Major defense against infections by viruses,

fungi & a few intracellular bacteria like tubercle
bacillus, Mycobacterium leprae etc

– Defense against tumors

immunity 13
 Humoral immunity
• When Ag enters the body, it directly binds to
receptors on B cells

• Simultaneously there is helper T cell activation.

• Helper T cells are necessary for full activation of B

cells & Ab formation

• Some of the activated B cell transform into Plasma

cells & some into Memory B cells

immunity 14
• B cells can recognize freely circulating antigens
• It doesn’t require MHC
• B cells recognize antigens by means of
membrane bound antibody

immunity 15
IMMUNOGLOBULINS

• Plasma cells secrete antibodies also called as

immunoglobulins( γ globulins) – 5 Types

immunity 16
Antibody -structure
• 2 identical heavy chains
• 2 identical light chains
• Each heavy chain & light
chain has a constant & a
variable region
• Antigen binding fragment –
Fab (variable region)
• Fc fragment (constant
region) – binding site for
particular mediators of
immunityantibody induced activities17
immunity 18
 Immune response
• Primary immune response • Secondary immune
• Response of body’s immune response
system to an antigen • response of body’s
introduced to body for the immune system to an
1st time antigen introduced to
• Latent period of 4 days -4 body on a 2nd occasion
weeks • Quick response
• Immunoglobulin is mostly Ig • Immunoglobulin is mostly
M IgG
• Titre of antibody less & • Titre is more present for a
present for a short durationimmunity long duration 19
immunity 20
TYPES OF IMMUNOGLOBULINS

immunity 21
 IgG
• Major serum Ig

• Only maternal Ig that can cross placenta

• Produced mainly during secondary immune

response (Response to an Ag introduced into
the body on a 2nd occasion)

immunity 22
IgM
• Only Ig produced before birth
• Produced mainly during primary immune
response (Response that occur when an Ag is
introduced into the body for the 1st time).

immunity 23
• Ig A
• Secretory Immunoglobulin
• Function :
– localized protection in external secretions like
tears,saliva ,intestinal secretions
– Present in colostrum,accounts for immune
protection conferred by breastfeeding of infants

immunity 24
 IgD
• Present on B cells as a receptor & helps in Ag
recognition by B cells

IgE
• Binds to basophils & mast cells cause release
of mediators resulting in allergic reactions

immunity 25
• Antibodies (immunoglobulins) act mainly
in 2 ways
Attack
Direct through
action complement
activation

immunity 26
immunity 27
 Direct action
 Abs inactivate invading agents in one of the
ways
• Agglutination – Ag Ab complex bound to form a
clump
• Precipitation- Ag Ab complex made insoluble
• Neutralisation - Ab cover toxic sites on Ag
• Lysis - Ab directly attack cell membrane 
rupture

immunity 28
 Complement system
• Consists of a group of > 30 proteins found in
plasma, complements the effects of antibodies
& eliminate invading pathogens.
• Produced in liver
• Present in circulation as inactive molecules

ACTIVATED BY 3 PATHWAYS -
immunity 29
 Classical pathway

 When an Ab binds with an Ag Ab gets

‘activated’.

 This binds with C1 molecule  resulting in a

cascade of reactions

immunity 30
immunity 31
 Effects of compliment system
• Chemotaxis (C5a)

• Opsonisation (C3b) & phagocytosis

• Formation of a membrane attack

complex(C5b6789)destruction of target cell

• Agglutination

• Neutralisation

• Activation of mast cells, basophils

immunity & platelets (C3a,C4a,C5a)
32
Alternative or properdin pathway

 It does not involve the immune complex.

 Triggered by contact with bacteria, viruses,

fungi, tumour cells etc.

 This does not involve C1, C2 or C4.

 Directly C3 is activated.
immunity 33
 Mannose binding lectin pathway

 lectin is a plasma protein which binds with

mannose on bacteria.

 activated in the absence of Ab.

 The rest of pathway is same as that of

classical pathway.
immunity 34
immunity 35
ABNORMALITIES OF IMMUNE
SYSTEM

immunity 36
1. Over reaction of system  allergy &
hypersensitivity reaction

2. Attack against body’s own tissue 

autoimmune disease

3. Immunodeficiency diseases
4. Transplantation & rejection
immunity 37
 Hypersensitivity reactions
• Abnormal hyperimmune reaction

• 4 types of hypersensitivity reactions

Type I /immediate hypersensitivity reactions
Type II/Antibody mediated hypersensitivity
Type III/ Immune complex mediated
hypersensitivity
Type IV/Cell mediated/delayed hypersensitivity

immunity 38
 Allergy
• Inappropriate immune attacks against harmless
environmental substances
• Mediated by Ig E antibodies
• Occurs due to mast cell degranulation  release
of histamine & other vasoactive substances
• Individuals susceptible to type I
hypersensitivityatopic individuals
immunity 39
immunity 40
 Autoimmune diseases
• Body produce Ab / T cells against self Ags
Eg -
• Type 1 diabetes mellitus - Abs against
pancreatic islet cells

• Myasthenia gravis – against nicotinic

cholinergic receptors

• Graves disease - TSH receptors

immunity 41
• Production of antibodies against invading
organisms may cross react with normal body
constituents  molecular mimicry
• Eg. Rheumatic fever following streptococcal
infection
• Antibodies formed against streptococcal M
protein cross react with cardiac myosin &
damages the heart

immunity 42
 Disorders of immune def

• Defense mechanism of the body is impaired

 leads to repeated microbial infection &
even malignancy

immunity 43
• Primary Immunodeficiency
Abnormalities in the development of immune
mechanisms
• Secondary immune deficiencies
Consequence of disease ,drugs ,nutritional
inadequacies & other processes that interfere
with proper functioning of mature immune
system

immunity 44
 Primary immunodeficiencies
• Humoral immunodeficiencies
 Eg.X –linked agammaglobulinemia- all classes of Ig s
are grossly depleted in the serum
• Cellular immunodeficiencies
 Eg.Digeorge syndrome- aplasia /hypoplasia of
thymus  defective cell mediated immunity
• Combined immunodeficiencies
 SCID /Severe combined immunodeficiency
 Severe deficiency of both CMI & humoral immunity
immunity 45
 Secondary immunodeficiencies
• Acquired Immunodeficiency Syndrome
• AIDS
• Infection by human immunodeficiency virus
(HIV)

immunity 46
• Transmission
• Parenteral route –through blood
• Unscreened blood transfusion
• Tattoing
• Use of infected razors
• Sexual route –multiple sex partners,sex workers
• Transplacental route –from infected mother to
fetus

immunity 47
AIDS

• HIV binds to CD4 protein on helper T cells &

↓the no. of T4 cells  ↓ response to Ag 
defective CMI

• This leads to abnormal B cell fn defective

humoral immunity

immunity 48
• Signs & symptoms
- Are mostly of opportunistic infections
- Repeated episodes of diarrhoea
- Unexplained weight loss
- Continous fever for > 1 month
- TB,Candidiasis
- Ulcers,Kaposi sarcoma (cancer of skin &
lymphnodes)
immunity 49
 Transplantation
• Act of transferring cells ,tissues or organs from
a donor to a recipient
• Done when an organ or tissue becomes
irreversibly damaged or organ is congenitally
defective/absent

immunity 50
 Transplant rejection
• Occurs when recipient’s immune system
recognize donor tissue as foreign
• MHC-I & MHC-II play a role in transplant
rejection
• HLA s expressed in transplanted tissue is
identified as non –self by host’s dendritic cells
• Dendritic cells presents foreign HLA s to Host’s
helper T cell & cytotoxic T cells destruction of
graft cells
immunity 51
• Antigenically similar tissue  histocompatible
no immunological response
• Antigenically different tissue
histoincompatible Tissue rejection
• Due to inherited nature of HLA –genes family
members are more likely histocompatible
• Parent or a sibling may be best donor in many
situations
• Identical twins –little concern of rejection
immunity 52
immunity 53
 Immunosuppressive agents
• To overcome rejection of transplanted organs
• Corticosteroids
Inhibit cytotoxic T cell proliferation by inhibiting
production of IL-2
• Cyclosporine or tacrolimus
Inhibit T cell mediated immune responses
May cause kidney damage & cancer

immunity 54
• Specific immunosuppression
• Monoclonal anti T cell antibodies

immunity 55
• Summary of Acquired
Immunity

immunity 56
ACQUIRED IMMUNITY
• 1.APC ingest,partially digest antigens &
presents it along with MHC
• 2.Immune synapse is formed between
APC & a naïve CD4 T cell which is
activated to produce IL-2
• 3.IL-2 acts in an autocrine fashion
causing cell proliferation forming a clone
• 4.Activated CD4 cell may activate a
cytotoxic CD8 cell
(CD8 cell can also be activated forming a
synapse with MHC-I antigen presenting cell)
Activated CD4 may promote B cell
activation & proliferation of plasma cells
that produce antibodies
immunity 57
T cell

immunity 58