Presented by Vasudha Singh Moderated by Dr.

Niti Singhal

IMMUNITY
Resistance of host to pathogen & their toxic products Types Innate (Native) Acquired (Adaptive)

Resistance by virtue of genetic & constitutional make up

Resistance individual acquired during life

Innate immunity
Natural/native/inborn First line of defence Always in response to microbes No memory

Acquired immunity
Adaptive Appears after innate immunity Against diverse spectrum Memory

Not able to differentiate b/w Able to differentiate b/w microbes and molecules microbes and molecules

Specific reactivity induced in host by an antigenic stimulus Two types Humoral

or Antibody mediated immune

response
Cell

mediated immune response

 Discovered

by Von Behring & Kitasato in Berlin in 19th century Observation Serum of appropriately immunized animal contain neutralizing sub. or antitoxins antibodies

Sera having high Ab levels following infection called immune sera

Tiselius (1937) seperated serum proteins based on electrophoretic mobilities intoalbumin globulin globulin globulin

With this fraction Ab activity associated

All antibodies are immunoglobulin but all immunoglobulin can not be antibodies

Immunoglobulins are
Glycoprotein

molecule produced by plasma cell in response to immunogen Present in serum & body fluid Constitues 20-25% total plasma protein Called as globulin

By combining with bacterial surface By activating complement By neutralizing toxins By coating virus particle

a)

Antigen binding Effector functions - Fixation of complement - Binding to various cell types

b)

Glycoprotein made up of1. Heavy & light chain -Y shaped tetramer(H 2 L 2) -2 Light & 2 heavy chains
Chain Molecular weight (daltons) Amino acid

Heavy

50,000-75,000

450

Light

23,000

220

2. Disulfide bond
INTER CHAIN DISULFIDE BOND Present between Heavy & Light chains & two heavy chains
INTRA CHAIN DISULFIDE BOND Present within each of polypeptide chain

Both heavy & light chains have these regionsChains Light chain Variable region Half Amino Terminal (VL) One quarter of amino terminal region (VH) Constant region Half carboxy region (CL) 3 quarter of carboxy terminal (CHI, CH2, CH3)

Heavy chain

STRUCTURE OF ANTIBODY SHOWING VARIABLE & CONSTANT REGION

H

CH
CL CH

VL

CH

4.Hinge region
Point where arms of antibody forms Y shaped structure Flexibility in molecule at this point

Hinge region

3D image reflects that immunoglobulin is not a straight structure rather folded into globular region called as domains.
Chain Light chain
Heavy chain

Domains VL & CL
VH , CH1-CH3

Structure of domains

STRUCTURE OF IMMUNOGLOBULIN

Antibody(Ig)
Cystine
Proteolytic enzyme Papain

Peptide bonds in hinge region broken

2 Fab(Fragment Ag binding) +1Fc(fragment crystallizable) Ag binding site

PROTEOLYTIC CLEAVAGE OF IMMUNOGLOBULIN

Functions of Fc
Binds

to complement leading to CF Binds to cell receptors Determines passage of IgG across placenta Determines skin fixation & catabolic rate

Antibody
Pepsin Mercaptoethanoal

F(ab) + pFc Disulfide bond reduced 2 + Small peptide releasing 4 peptide chains

Based on difference in amino acid sequence in constant region of heavy chain IgG ( heavy chain) IgA ( heavy chain) IgM ( heavy chain) IgD ( Heavy chain) IgE ( heavy chain)

Based on difference in amino acid sequence in constant region of light chain light chain light chain

IgG
Most abundant class of immunoglobulin 75% of total immunoglobulin Distributed equally in intravascular & extravascular pools Produced during secondary response

 All

immunoglobulins are monomers Occasionally exist in Polymerized form

IgG - (Gamma 1 heavy chain)

IgG - (Gamma 2 heavy chain) IgG - (Gamma 3 heavy chain) IgG - (Gamma 4 heavy chain)

 Second

most abundant class of immunoglobulin 10-13% of serum immunoglobulin Present in colostrum, tears, saliva, mucous Provides local immunity Secretory immunoglobulin Promotes phagocytosis & intracellular killing of microrganism

Monomer but in secretion exist as dimeric form J chain found in Dimeric form Secretory IgA contains secretory component

IgA1 (Alpha 1 heavy chain)

IgA2 (Alpha 2 heavy chain)

 Oldest

class of immunoglobulin Third most common serum immunoglobulin 5-8% serum immunoglobulin Largest immunoglobulin among all Produced in primary response Present intravascularly First Ab produced in early stages of infection

Exist as pentamer, can exist as monomer Have 5HL units & one molecule of Jchain All chains are identical

 Another

important class of immunoglobulin Present on surface of B lymphocyte Binds with specific Ag leads to stimulation of B - cells Constitutes small part of immunoglobulin Distributed intravascularly

 Exist

as monomer Structurally resembles to IgG Y shaped in structure

 Discovered

in 1966 by Ishizaka Least common serum immunoglobulin Susceptible to mercaptoethanol Present extravascularly Heat labile Involved in anaphylactic type of hypersensitivity

 Resemble

structurally with IgG Y Shaped in structure Have an extra domain in constant region

Igs IgG

FUNCTIONS Responsible for humoral immunity

IgA

Protect body surfaces

IgM

Provide immunity against primary infections

IgD

Function as Ag receptors on B - lymphocytes

IgE

Involved in anaphylactic reactions

PROPERTIES
HEAVY CHAIN LIGHT CHAIN MOL.WT.(Da) SERUM CONC.

IgG
,,,chain / 150,000 8-16 mg/ml

IgA
, chain / 160,000 0.6-4.2mg/ml

HALF LIFE
PLACENTAL TRANSPORT COMPLEMENT FIXATION

23 DAYS
+ +

6 DAYS
_ +

PROPERTIES HEAVY CHAIN LIGHT CHAIN MOL.WT.(da)

IgM CHAIN / 900,000

IgD CHAIN / 180,000

IgE CHAIN / 190,000

SERUM CONC.
HALF LIFE PLACENTAL TRANSPORT COMPLEMENT FIXATION

0.5-2 mg/ml
5 DAYS +

0.03 mg/ml
2-8 DAYS -

0.00004 mg/ml
1-5 DAYS

IMMUNOGLOBULINS

INCREASE IN

DECREASE IN

IgG

Granulamatous infections Agammaglobulinemia Liver diseases Lymphoid aplasia Malnutrition , RA IgA Myeloma Malaria Trypanosomiasis Actinomycosis, RA Cirrhosis of liver IgA Myeloma LE & RA Chronic infections IgD Myeloma Asthma Hay fever Anaphylactic shock Agammaglobulinemia Lymphoid aplasia IgA & IgG Myeloma IgG Myeloma Malabsorption syndrome Leukemia -

IgM IgA

IgD

IgE

Congenital agammaglobulinemia hypogammaglobulinemia

Thank you