Immunity

Dr. K. Jaiganesh, MD
Deputy Registrar - SBV
Professor & Head of Physiology
MGMC & RI
 Immunity

Immunity
Ability of the body to recognize and defend itself
against specific pathogens or antigens.

Immune Response
Involves production of antibodies and generation of
specialized lymphocytes against specific antigens.
The Immune System is the Third Line
of Defense Against Infection
 Neutrophils- Actions

Skin surface Swelling

Pin

Phagocytes
Bacteria
Phagocytes and
Chemical fluid move
signals into area
White
blood cell

1 Tissue injury; release of 2 Dilation and increased leakiness 3 Phagocytes (macrophages and
chemical signals such as of local blood vessels; migration neutrophils) consume bacteria
histamine of phagocytes to the area and cell debris; tissue heals
 Neutrophils at center

1. Margination

2. Diapedesis

3. Chemotaxis
Pathogen

Comp protein 4. Opsonisation by complementary proteins

5. Phagocytosis by neutrophil
 Neutrophils- Actions

1. Margination

2. Diapedesis
3. Chemotaxis
4. Opsonisation
5. Phagocytosis
Classification of immunity

Immunity

Innate Acquired

Natural Artificial

Active Active

Passive Passive
 Innate or Genetic Immunity

Immunity that the body is born with.

 Innate Immunity

■ 1. Skin, mucous membrane

■ 2. Saliva, gastric juice, intestinal juices

■ 3. Reflex mechanisms: cough, sneeze

■ 4. GIT flora

■ 5. WBCs
 Acquired Immunity

Immunity that the body develops during

lifetime after birth.

■ May be acquired naturally or artificially.

 Types of Acquired Immunity

Naturally Acquired Immunity:

Obtained in the course of daily life

Artificially Acquired Immunity:

Obtained by receiving a vaccine or immune serum.
 Types of Naturally Acquired Immunity
NA- Active Immunity

■ Pathogens enter body

naturally
■ Body generates an
immune response to
antigens.
■ Immunity may be
lifelong (chickenpox
or mumps)
or temporary (influenza
or intestinal infections)
 Types of Naturally Acquired Immunity
NA-Passive immunity:

■ Antibodies pass from mother to

fetus via placenta or breast
feeding (colostrum)
■ No immune response to antigens
■ Immunity is usually short-lived
(weeks to months)
■ Protection until child’s immune
system develops
 Types of Artificially Acquired Immunity
Artificially Acquired -Active Immunity:

■ Antigens are introduced in

vaccines (immunization)
■ Body generates an immune
response to antigens
Immunity can be
■ lifelong (oral polio vaccine)
■ temporary (tetanus toxoid)
 Types of Artificially Acquired Immunity
Artificially Acquired -Passive Immunity

▪ Preformed antibodies
(antiserum) are introduced
into body by injection
■ Host immune system does

not respond to antigens

■ Immunity is short lived

(half life three weeks)

■ Snake antivenom injection

from horses or rabbits

 Active & Passive Immunities

Naturally After exposure to Antibody

Active
acquired an infection produced
Naturally Antibody
Passive Breast milk
acquired received
Artificially
Antibody
acquired Active Tetanus Toxoid
produced

Artificially
Anti Tetanus Antibody
acquired Passive
serum received
 Active Immunity

1. Cell Mediated Immunity

T-Lymphocytes – 70%

2. Humoral Immunity
B-Lymphocytes – 30%
 Development of T lymphocytes

■ Thymus

■ T cells develop from

stem cells in the bone
marrow of adults

■ They mature at Thymus

and then migrate to
lymphoid organs (lymph
node or spleen)
 T-Cell- Actions

■ T cells regulate proliferation and activity of other cells of

the immune system:
B cells, macrophages, neutrophils, etc.
Cytokines: Chemical messengers of immune cells.
■ Stimulate and/or regulate immune responses.
■ Interleukins: Communication between WBCs.

■ Interferons: Protect against viral infections.

■ Chemokines: Attract WBCs to infected areas.

 T- Cells: Mechanism of Action

T cells are key cellular component of immunity

■ T cells have an antigen receptor (T cell receptor) that
recognizes & reacts to a specific antigen
■ Antigens that stimulate this response are mainly
intracellular & requires constant presence of antigen to
remain effective
■ T cell receptor only recognize antigens combined with
Major Histo Compatability (MHC) proteins on the
surface of cells.
■ MHC Class I: Found on all nucleated cells.
■ MHC Class II: Found on phagocytes.
T Cells Only Recognize Antigen Associated
with MHC Molecules on Cell Surfaces
T Lymphocytes - Active Against

Defense against
Bacteria & viruses that are inside host cells
& are inaccessible to antibodies.
Cancer cells
Transplanted tissues
 T Lymphocytes -Types

1. T Helper (TH) Cells

2. T Cytotoxic cells

3. Supressor T cells

4. Memory T cells
 1.T Helper (TH) Cells

Central role in immune response.

■ Most are CD4+
■ Recognize antigen on the surface of antigen
presenting cells (e.g: macrophage)
■ Activate macrophages
■ Induce formation of cytotoxic T cells
■ Stimulate B cells to produce antibodies.
Central Role of Helper T Cells
 2.Cytotoxic T (Tc) Cells

Destroy target cells.

■ Most are CD8
■ Recognize antigens on the surface of all cells:
■ Kill host cells that are infected with viruses or bacteria.
■ Recognize and kill cancer cells.
■ Recognize and destroy transplanted tissue.
■ Release protein called Perforin which forms a pore in
target cell, causing lysis of infected cells.
■ Undergo apoptosis when stimulating antigen is gone.
Cytotoxic T Cells Lyse Infected Cells
3.T Suppressor (Ts) Cells:
May shut down immune response.

4. MemoryT Cells:
Keep in Memory
Thank you
Humoral Immunity
 Development of B lymphocytes

■ Bursa of Fabricius
■ B cells develop from
stem cells in the bone
marrow of adults

■ After maturation B cells

migrate to lymphoid
organs (lymph node or
spleen)
 Humoral Immunity

Antibody-Mediated Immunity
■ Involves production of antibodies against
foreign antigens
■ Antibodies are produced by a subset of
lymphocytes called B cells which when
stimulated become plasma cells to secrete
antibodies
 Antibodies

● Belong to a group of serum proteins called

immunoglobulins (Igs)
● Proteins that recognize and bind to a particular
antigen with very high specificity

● Made in response to exposure to the antigen

● One virus or microbe may have several antigenic
determinant sites, to which different antibodies may
bind
 Antibody Structure
■ Y shaped proteins
■ 2 heavy chains, 2 light chains
■ Fab: antigen-binding fragment
■ Fc: constant fragment, determines “class”
 Antibody Types

■ IgG - 75%, Secondary response-Gestation-II

■ IgA - Secretory: saliva, tears-Alimentary
■ IgM - Primary antibody response- I
■ IgE - Allergic responses-Eosinophilia

■ IgD - Cell-surface receptor on B lymphocytes

Consequences of Antigen-Antibody Binding
Actions of Antibodies

Antigen-Antibody Complex:
Formed when an antibody binds to
an antigen it recognizes.

1.Agglutination: ↑ phagocytosis &

↓ the no. of infectious units
Antibodies cause antigens to
clump together.
2.Opsonization:
Antigen is covered with
antibodies that enhances its
ingestion and lysis by phagocytic
cells.
Coating Ag with Ab ↑ phagocytosis
 Consequences of Antigen-Antibody Binding

3.Neutralization: Binding to the

surface and neutralize toxins by
blocking their active sites.

4.Complement Activation: Both IgG

and IgM trigger the complement
system which results in cell lysis and
inflammation.
5.Antibody-dependent
cell-mediated cytotoxicity:
Target organism is coated with
antibodies and bombarded with
chemicals from nonspecific
immune cells.[Used to destroy
large organisms (e.g.: worms)]
Consequences of Antibody Binding
Consequences of Antibody Binding
 Relationship Between Cell-Mediated and
Humoral Immunity- (B to T)

Antibody Dependent Cell Mediated Cytotoxicity

■ Target cell is covered with antibodies, leaving Fc portion
sticking outwards.
■ Natural killer and other nonspecific cells that have
receptors for Fc region are stimulated to kill targeted
cells.
■ Target organism is lysed by substances secreted by
attacking cells.
 Relationship Between CMI & HI-T to B

Antibody Production
T-Dependent Antigens:
Antibody production requires
assistance from T helper cells.

A macrophage cells ingest antigen and

presents it to TH cell.

TH cell stimulates B cells specific for

antigen to become plasma cells
 NATURAL KILLER CELLS

•Large granular Non T, Non B

lymphocyte cells.

•NK cells releases lethal

substances into the infected
target cell and leads to death of
the cell

•Prevents multiplication of virus in

the cell

•Don’t require antigen stimulation

 Complement system

■ A group of sequentially reacting proteins, which upon

activation, mediate a no. of biological reactions important to
host defense.

■ ‘C’ designation for 11 of the complement proteins (C1,C2 etc)

B,D,P,H,I & Others

■ Synthesised by hepatocytes, monocytes, fibroblasts etc

■ Works in 2 pathways
Classical (Ag Ab complexes) & Alternate
 Complement system-Units

■ C1q, C1r, C1s – Recognition unit

■ C2,C3,C4 – Activation unit

■ C5,6,7,8,9 – Membrane Attacking Complex

 Classical pathway

C1 (recognition unit) + Ag + Ab
C2,C3,C4
C5 C5a,C5b
C6,7,8,9

C5b,C6,7,8,9 (Membrane Attacking Complex)

 Alternate pathway

C3 + polysaccharide C3b

C5 C5a,C5b
C6,7,8,9

C5b,C6,7,8,9 (membrane attacking complex)

Functions of Complement system

C – Chemo taxis
O – Opsonisation
M – Mobility impairment
P – Phagocytosis
 Immunological Memory

Antibody Titre: The amount of antibody in the serum.

Pattern of Antibody Levels During Infection
Primary Response:
■ After initial exposure to antigen, no antibodies are found

in serum for several days.

■ A gradual increase in titre, first of IgM and then of IgG is

observed.
■ Most B cells become plasma cells, but some B cells

become long living memory cells.

■ Gradual decline of antibodies follows.
 Antibody Response After Exposure to Antigen

Secondary Response
Subsequent exposure to the
same antigen displays a faster &
more intense antibody response.
Increased antibody response is
due to the existence of memory
cells, which rapidly produce
plasma cells upon antigen
stimulation.
Overview of the Immune Response
Pathogen

IL-I

IL-II IL-II
 Pathogen
Tumor
SKIN cell
TNF
Pathogen entered

NK Macro
IL-1 IL-1 Cell phage
Pathogen in Macrophage-APC

B-L IL-2 T-L IL-2 IL-2

IL
-2
Plasma Cell
Suppressor- Memory-
T T
Immmunoglobuli
ns
G-A-M-D-E
Cytotoxic-
T
Perforin /Lymphotoxin
Pathogen
 Broad Mechanisms of Immunosuppression

■ Inhibition of T cell activation.

■ Block antigen binding.
■ Block accessory molecules.
■ Inhibition of IL-2 production.
■ Inhibition of T cell proliferation.
■ T cell depletion.
■ Inhibition of B cell proliferation.
■ Major Immunosuppressants
Cyclosporine A
Steroids
Azathioprine
 Auto Immune Diseases

Diseases Auto Antibodies

Formed Against
Type I Diabetes Mellitus Pancreatic B Cells
Myasthenia Gravis Ach Receptors
Multiple Sclerosis Myelin Basic Protein
Hashimoto’s Thyroid Cells
Thyroiditis
Grave’s Disease TSH Receptors
Rheumatoid Arthritis Collagen Tissue
 Immuno-deficiency Disorders

■ Agammaglobinemia -(B lymphocyte deficiency)

Congenital, Radiation therapy
▪ Multiple myeloma - ( B lymphocyte prolieration)

■ Digeorge Syndrome – (T lymphocyte deficiency)

Congenital Thymic Aplasia
■ Acquired Immuno Deficiency Syndrome (AIDS)