ANTIGENSan antigen (the generator) when introduced into a host induces

the formation of specific antibodies and

sensitize T lymphocytes that are reactive against that specific

antigen

DefinitionsTWO IMPORTANT CHARACTERISTICS 0F AN

ANTIGEN1) IMMUNOGENICITY: The ability of a

substance to stimulate a specific immune response

2) ANTIGENICITY : The ability of a substance to react specifically with antibodies/ sensitized T cells

• HAPTEN: are small molecules that cannot induce an immune response by themselves unless complexed with a large carrier molecule like protein/ polysaccharide

• EPITOPE or Antigenic Determinant: that portion of an antigen that combines with the product of a specific Immune response

• ANTIBODY (Ab): a specific protein produced in response to an immunogen

Factors Influencing Immunogenicity

• Foreignness• Size- Macromolcule• Chemical Composition Complexity of structure • Physical Form

Particulate / SolubleDenatured / NativeBiodegradabilityAg processing by Ag Presenting Cells (APC)

CLASSIFICATION OF ANTIGEN• FOREIGN (OUTSIDE THE HOST)

MICROBE COMPONENTS/ PRODUCTS, DRUGS ENVIRONMENTAL ANTIGENS• AUTOANTIGENS THYROGLOBULIN, NUCLEIC ACID, CORNEA COMPONENTS• ISOANTIGENS HISTCOMPATIBILITY TISSUE ANTIGENS BLOOD GROUP ANTIGENS• HETROANTIGENS HETROPHILE ANTIGENS CROSS REACTING MICROBIAL ANTIGENS eg. Streptococcal cell wall antigen cross react with human cardiac and glomerular tissue

ANTIGEN EPITOPES ON BACTERIAL CELL

EPITOPES /

ANTIGENIC DETERMINANTS:

Chemical groups on

the antigenic molecule

against which antibodies

are produced.

Eg: bacterial cell–

have 100 or more epitopes

Chemical Nature of Immunogens

• Proteins– pure or glycoproteins or lipoproteins

• Polysaccharides– pure or lipopolysac• Nucleic Acids- poor immunogens or

become immunogen when single stranded or complexed with proteins

• Lipids– generally non immunogensSome glycolipids and phosopholipids

can be immunogenic for T cells and illicit a cell mediated immune response

Types of Antigens 1)T-independent Antigens

(directly stimulates B cells to produce antibodies without

help of T cells) • POLYSACCHARIDES

• ExamplesPneumococcal

polysaccharide lipopolysaccharideFlagella

Types of Antigens2) T-dependent antigens

(do not directly stimulate Ab formation without the help of T cells)

• PROTEINS

• ExamplesMicrobial

proteinsNon-self or

Altered-self proteins

ANTIGENSHEPTENS--- small molecules that

cannot induce an immune response unless complexed with a large carrier molecule like protein/ polysac

then the hepten alone can react specifically with the antibodies or immune cells produced in response to the hepten-carrier complex.

Two types: simple- one antigenic determinant complex- many antigenic determinants

Native determinants

Haptenic determinants

Are immunogenic molecules to which heptans become attachedHapten-carrier conjugates:

Hapten-carrier conjugatesDefinition:

Are immunogenic molecules to which heptans become attached

Native determinants

Haptenic determinants• Structure

native determinants

haptenic determinants

(created by Heptans)

SUPER ANTIGENS• Definition: T-dependent antigens

cause massive activation of large fraction (25%) of T cells (polyclonal response) ---uncontrolled release of cytokines

• Examples Staphylococcal enterotoxins Staphylococcal toxic shock

toxin Staphylococcal exfoliating

toxin Streptococcal pyrogenic

exotoxins

IMMUNOGLOBULINS:Structure and Function

Immunoglobulins:Structure and Function

• DEFINITION: Glycoprotein molecules that are produced by plasma cells in response to an immunogen and which function as antibodies

• FUNCTIONS:• Recognizing and binding to foreign

substances and facilitating their removal• Binding to various cells– phagocytic,

lymphocytes mast cells, basophils, placental trophoblast

• Increase phagocytosis• Neutralizing toxins and viruses• Activating complement

Immunoglobulin Structure

• Identical : 2-Heavy(H) & 2 Light Chains-L

• Disulfide bondsInter-chainIntra-chain

CH1

VL

CL

VH

CH2 CH3

Hinge Region

Carbohydrate

Disulfide bond

Immunoglobulin Structure: on basis of their A. acid

sequence.• DOMAINS• Variable (V) • Constant (C)

Regions VL & CL VH & CH

• Hinge Region• CL 110 A.Acid• VL 110• VH 11O• CH 33O—44O

CH1

VL

CL

VH

CH2 CH3

Hinge Region

Carbohydrate

Disulfide bond

Immunoglobulin Fragments: Structure/Function

Relationships• FabAg bindingValence = 1Specificty

determined by VH and VL

Papain

Fc

Fab

• FcCH2 __CH3

Effector functions

Immunoglobulin Fragments:

Structure/Function Relationships

Ag Binding

Complement Binding Site

Placental Transfer

Binding to Fc Receptors- M*,

Polymorps

Human Immunoglobulin Classes

• ON BASIS OF DIFFERENCE IN A.ACID SEQUENCE IN CONSTANT REGION OF HEAVY CHAINS:

• IgG - Gamma () heavy chains• IgM - Mu () heavy chains• IgA - Alpha () heavy chains• IgD - Delta () heavy chains• IgE - Epsilon () heavy chains

Human Immunoglobulin Subclasses

• IgG SubclassesIgG1 - Gamma 1 (1) heavy chainsIgG2 - Gamma 2 (2) heavy chainsIgG3 - Gamma 3 (3) heavy chainsIgG4 - Gamma 4 (4) heavy chains

• IgA subclassesIgA1 - Alpha 1 (1) heavy chainsIgA2 - Alpha 2 (2) heavy chains

Human ImmunoglobulinLight Chain Types

• Kappa ()• Lambda () • Subtypes Lambda light chain:

Lambda 1 (1)Lambda 2 (2)Lambda 3 (3) Lambda 4 (4)

IgG• Structure

Monomer (7S)Subclasses differ in number of disulfide

bonds and length of hinge region

IgG1, IgG2 and IgG4 IgG3

IgG• Properties• Most versatile immunoglobulin

Major serum Ig- 75% of serum IgMajor Ig in extravascular spacesPlacental transfer – Does not require

Ag binding ( IgG2)Fixes complement ( IgG4)Binds to Fc receptors ( IgG2, IgG4)

Phagocytes - opsonization K cells - ADCC

IgM

• StructurePentamer mu chainsExtra domain

(CH4)J chain

C4

J Chain

IgMProperties

3rd highest serum Ig

First Ig made by fetus and B cells

Fixes complementAgglutinating

antibodyBinds to Fc

receptors

IgA• Structure

Serum - monomerSecretions (sIgA)

Dimer – J chain Secretory

component- recruited from serous epith.

J ChainSecretory Piece

Origin of Secretory Component of sIgA

IgAProperties

2nd highest serum Ig1ST line of defense in mucous membrane

pathogen Major secretory Ig (Mucosal or Local Immunity)

Tears, saliva, gastric and pulmonary secretions Does not fix complement (unless

aggregated)Binds to Fc receptors on some cellsNeutralizes viruses and toxins

IgD

• StructureMonomerTail piece

Tail Piece

IgDProperties

4th highest serum IgB cell surface IgDoes not bind complementIncreased levels in AIDS

IgE

• StructureMonomerExtra domain

(CH4)

C4

IgEProperties

Least common serum Ig Binds to basophils and mast cells (does not

require Ag binding)Allergic reactionsParasitic infections (Helminths)

Binds to Fc receptor on Eosinophils Activation of macrophages--- ADCC

Does not fix complement

Antibodies eliminate foreign agents in 3 ways

Characteristics of Various Classes of Immunoglobins

Properties of Antibiotics

MHC COMPLEX

MAJOR HISTOCOMPATIBLE -MHC COMPLEX

• MHC complex defines uniqueness of the individual• Part of the genome encoding for MHC antigens–

clustered on a small segment of chromosome 6– CONSTITUTE HLA COMPLEX

• At least 20 different genes encode for MHC PROTEINS

• Variety of MHC proteins exist in humans• Identical twins have same MHC molecules• All family members have a mixture of similar and

different MHC molecules• Functions:• The principle function is to bind peptide

fragments of foreign proteins and present it to antigen specific T cell.

• Immune recognition• Interaction between B and T and other cells• Rejection of allograft

MHC COMPLEX• MHC 1 ANTIGENS MHC II ANTIGENS1.Present on the surface Present on the B cell, of all nucleated cells Macrophages and of the body, platelets activated T cells2. Bind Ag/ peptide Bind Ag/ peptides endogenously produce exogenously produced eg. viral proteins then processed

within cell after

phagocytosis3. Present Ag to CD8 - Present Ag to CD4 cells-

TC cells TH CellsCLASS1 AND 11 GENES ENCODE CELL SURFACE GLYCOPROTEINS AND

CLASS III GENES FOR COMPONENTS OF COMPLEMENT SYSTEM

CYTOKINES

CYTOKINES• Short acting soluble mediators released during interaction

between lymphocytes, monocytes, macrophages, inflammatory cells and endothelial cells

• Concerned with induction and regulation of immune response

• Hormone like peptides or glycopeptides with wide spectrum of effects

• PROPERTIES• Individual cytokines produced by different cell types eg.

IL-I,TNF -- PRODUCED BY VIRTUALLY ALL CELLS• Cytokines have PLEOTROPIC effect– act on many cell

types—IL2 ---T cells, B, NK CELLS• Cytokines produce their effect by combining with high

affinity receptors on the target cell eg:IL2 activate T cells by binding to IL2 receptor

• They can act on the same cell that produces it eg IL 2 produced by activated T cell promote T cell growth

Important Cytokines