Immunity

• Capacity to resist organisms or toxins that

tend to damage tissues or organs

• Innate immunity

• Acquired immunity
 Innate immunity Acquired immunity
• Available since birth • Acquired after birth after
• Prior sensitization not exposure to microorganism
required • Prior sensitization required
• Not specific to a micro • Specific for each species of
organism micro organism and shows
immunological memory (2nd
exposure to the same foreign
substance produces a more
rapid and greater response)
• Able to recognise and • More complex mechanism and
respond immediately to requires time to be fully
any foreign cell or particle developed
• Involves NK cells, • Involves T and B lymphocytes
neutrophils, monocytes
and macrophages
 Innate immunity
Mechanisms involved:

• Phagocytosis by WBC and macrophages

• Destruction by acid secretion of stomach and by

digestive enzymes in the intestine

• Resistance offered by skin

• Natural killer lymphocytes

• Presence of certain compounds:
– Lysozyme: a mucopolysaccharide that can
destroy bacteria in tears
– Basic polypeptide that act against gram
+ve bacteria
– Complement complex: 30 proteins which
on activation can destroy bacteria
– C reactive protein an acute phase reactant
is known to increase the complement
response
 Natural killer cells
• Large granular lymphocytes that do not pass
through thymus
• called non T non B lymphocytes
• Forms 10-15% of mononuclear cells in
circulation ,5-10% of peripheral lymphocytes
• They kill cells without any prior sensitisation
and without involvement of MHC antigen
• They destroy virus infected cells and cells that
have undergone malignant transformation
• They have no immunological memory and their
action is not specific for any virus
Mechanism of action of NK Cells
• NK cells target those cells to be killed by
detecting that they do not display MHC1
proteins.
• Because most virus infected cells lose their
ability to synthesise MHC 1 protein
• NK cells release perforins that punch holes
in the cell membrane of target cells
• They also release cytotoxic substances into
the cell leading to cell lysis
• They recognise antibody coated target cells and
kill them by antibody dependent cell
mediated cytotoxicity (ADCC)
• IgG coated target cells are identified by NK
cells
• Fc portion of immunoglobulin is recognized
by Fc receptors in NK cells
• Killing ensues by a mechanism similar to
cytotoxic T cells
• NK cells identify tumour cells via a protein
called MICA (MHC class I chain related
protein A) expressed on tumour cells and kill
them
Action of Natural killer cell
Acquired immunity

• Immunity developed after exposure to a

micro organism or antigen

Types:
• Active immunity
• Passive immunity
 ACQUIRED IMMUNITY

ACTIVE PASSIVE

NATURAL ARTIFICIAL NATURAL ARTIFICIAL

CELL HUMORAL
MEDIATED
Active immunity

• Here body has active involvement in the

immune response
• Types :
• Natural : lymphocytes
• Artificial : vaccines
 Natural active immunity
• Immunity provided by lymphocytes after
exposure to an antigen
• Can be cell mediated or humoral immunity
• T cells are involved in cell mediated immunity
• B cells are involved in humoral immunity which
inturn is mediated through antibodies
Artificial active immunity
• Vaccines : either killed or inactivated micro
organisms
Passive immunity
• Here body has no role in immune
response
• Types: natural and artificial
• Natural: maternal antibodies transferred
through placenta
• Artificial : antibodies given externally
• eg. In snake bite antivenom is given which
is a preformed antibody from horse’s
serum
Antigen

• They are usually proteins or large

polysaccharides which form a part of the
toxins or bacteria which are capable of
initiating an immune response
• Molecular weight of an antigen is usually
>8000
Hapten
• Substances with molecular weight <8000
rarely act as antigens
• But if they combine with a substance eg.
Protein , the combination can elicit an
immune response
• Such a substance is called as hapten
• Egs of haptens are: drugs, chemicals,
constituents of dust , degenerative
products of scaling skin
 Development and organisation
of immune system
• Development of immunity is development of
lymphocytes
• T lymphocytes are involved in cell mediated
response
• B lymphocytes produce antibodies which are
involved in humoral immune response
• Major site of lymphocyte development are the
primary lymphoid organs:bone marrow,
thymus, foetal liver
• Lymphocyte precursors from bone marrow
that populate the thymus become T
lymphocytes
• The lymphocytes that are processed by
foetal liver (in mid foetal life) and bone
marrow (in late foetal life and after
birth) become B lymphocytes
• In birds B lymphocytes mature in the
Bursa of Fabricius located near the cloaca
• The name of the lymphocyte comes from
the bursa
• Most of the preprocessing of T lymphocytes
occur shortly before the birth of the baby
and for few months after birth
• Thymus offers T lymphocytes specificity to
react to an antigen
• Thymus releases only those T cells that are
non reactive to body’s own antigen
• The reactive ones undergo apoptosis
(programmed cell death)
• B and T lymphocytes migrate to peripheral
lymphoid tissue; spleen, lymph node,
Payer’s patches, tonsil etc.
• B cells differentiate into plasma cells and
memory B cells
T cells
Constitute 60-70% of peripheral lymphocytes
4 Types:
1. Helper or inducer T cells

2. Suppressor T cells

3. Cytotoxic T cells

4. Memory T cells
Helper T cells
• Form ¾ of total lymphocytes
• Regulator cells
• Have CD4 (Cluster differentiation 4)
glycoprotein on cell surface
• Produce lymphokines- IL-2(interleukin-
2),IL-3, IL4, IL-5, IL-6, GM CSF &
interferon γ
• TH1→IL-2 & interferon γ
• IL-2 stimulate suppressor and cytotoxic T
cells & interferon γ activate macrophages
(cellular immunity)
• TH2→IL-4, IL-5, IL-6 stimulate B cells →
plasma cells→ increase antibody
production (humoral immunity)
• Lymphokines slow & stop migration of
macrophages after they have reached the
tissue by chemotaxis
• This results in accumulation of
macrophages and effective phagocytosis
• Direct positive feedback effect especially
mediated by IL-2 causes amplified T cell
response
stimulates
 Cytotoxic T cells
• CD8 glycoprotein on cell surface
• Called killer cells as they directly attack and kill
micro organisms
• They bind to the organism via T cell receptors
• Secrete perforins that punch holes in cell
membrane of attacked cell
• Release cytotoxic substances into attacked cell
• Destroy cancer cells, transplant cells and virus
infected cells
Suppressor T cells

• Suppress activity of cytotoxic and helper

cells
• Prevent excessive immune reaction that
may be severely damaging to body’s own
tissues
• Role in self tolerance ie, limiting the ability
of immune system to attack a person’s
own body tissues
 Memory T cells
• Readily convert to effector cells on later
encounter with same antigen
• Survive for months and years
• Similar antigenic exposure at any time during
the life of a person induces prompt and
focussed cell mediated immune response
Acquired immune responses

Cell mediated immune response

Humoral immune response

 Cell mediated immune
response
• Specific immune responses that do not involve
antibodies
• Responsible for
– Delayed allergic reactions and rejection of
transplants
– Major defence against infections by viruses,
fungi and a few bacteria (eg. mycobacterium
tuberculosis)
– Defence against tumors
Steps involved in cell mediated
immune response
• Antigen processing and presentation
• Antigen recognition
• Activation of T cells
• Proliferation and differentiation of T cells
• Elimination of the invader
1.Antigen processing and
presentation
• B cells directly bind antigen
• Antigen presenting cells (Eg. Macrophage)
take up and digest antigen and present
peptide fragment to T cell receptor (TCR)
• In APCs peptide fragment of antigen is
coupled to major histocompatibility
(MHC) antigens and presented on cell
surface
Antigen processing & presentation
Antigen presentation
Antigen presenting cells:
1. Dentritic cells in lymph nodes and spleen

2. Langerhans dendritic cells of skin

3. Macrophages

4. B cells
 Major histocompatibility complex
(MHC)
• MHC molecules are important regulators of
immune response.
• The principal function of these cell surface
molecules is to bind peptide fragments of
foreign proteins for presentation to appropriate
antigen specific T cells
• MHC genes are located on short arm of
chromosome 6
• The products of MHC genes are called
human leukocyte antigen (HLA)
• MHC genes code for 3 types of glycoproteins
which differ in their structure and function
• They are class I, class II and class
III MHC antigens
Class I antigens
• Found on all nucleated cells and platelets
• Activate T8 cells
• CD 8 glycoprotein on T8 cells act as
coreceptor for MHC class I molecules
• MHC class I molecules are coupled to
intracellular antigens (eg.from virus) to
activate T8 cells
Class II antigens
• Found on antigen presenting cells , some
T cells and B cells
• Activate T4 cells
• CD4 glycoprotein on T4 cells act as
coreceptor for MHC class II molecules
• MHC class II molecules should be coupled
to extracellular antigen (eg. From
bacteria) to activate T4 cells
 APC APC

T4 CELL
T8 CELL
2.Antigen recognition
• T cells are the major cells involved in cell
mediated immune response
• All T cells have receptors on their cell
surface called T cell receptors (TCR) that
project from the cell membrane
• TCR has a cleft on it for antigen binding
• Fine differences exist between TCR of one
lymphocyte from that of the other
• So a particular antigen alone can bind to a
particular TCR
• Most TCR have 2 sub units
– 90% have α and β sub unit called αβ T cells
– 10% have γ and δ sub unit called γδ T cells
• TCR has 2 regions-variable and constant
• Variable region is encoded by 1 of 50
genes
• Variable region permits development of
1015 different TCR
3.T cell activation
2 signals are required for activation of T
cells
• Binding of digested antigen with TCR
• Binding of adhesion molecules and proteins
adjacent to TCR to complementary proteins
in antigen presenting cell to form an
immunological synapse
• If 1st signal occurs and second does not T
cell is inactivated and becomes unresponsive
Immunlogical synapse

cell

cell
• T cell before it contacts an antigen is
called naïve T cell
• When an immune synapse forms with the
naïve T cell it is activated to produce IL-2
(INTERLEUKIN -2)
 4.Proliferation and differentiation
of T cells
• IL2 acts in an autocrine fashion to cause the
cell to multiply
• A large group of T cells that respond to the
particular antigen are produced forming a
clone.
• IL2 stimulates and activates both suppressor
and cytotoxic T cells
• Activated CD4 cell especially T helper 2 via
IL4,IL5 and IL6 promotes B cell activation
and production of plasma cells
• Cytotoxic T cells can also be activated by
forming a synapse with MHC I antigen
presenting cell
Elimination of the invader
• Cytotoxic T cells destroy the invading
microbes by following mechanisms:
i.T cells after binding with target cell secrete
hole forming proteins called perforins that
punch holes in membrane of target cell
• Pores cause cell death by disrupting
homeostasis
• ii. T cells enlarge and release cytotoxic
substances
• T cells secrete enzymes that cause
apoptosis