Antibody

1. IMMUNOGLOBULINS:
Structure and Function
MHC COMPLEX
CYTOKINES

2. 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

3. Immunoglobulin Structure
• Y shaped protein
molecule- flexible
hinge
4 polypeptide
chains:
• 2- Light (L) chains–
kappa/ lambda
• 2- Heavy (H)
chains– alpha, beta,
gamma, mu, epsilon
• Chains held together
by disulphide
bonds
CH1
VL
CL
VH
CH2 CH3
Hinge Region
Carbohydrate
Disulfide bond

4. Antibody Structure

5. 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
• L CHAINS- 214
• H CHAINS- 446
• The stem and lower part of Y
arms are called constant (C)
region
• Fc region—responsible for
immunological reactions.
CH1
VL
CL
VH
CH2 CH3
Hinge Region
Carbohydrate
Disulfide bond

6. Immunoglobulin Fragments:
Structure/Function Relationships
• Cleavage by papain enzyme at
hinge area:
- 2 -Fab (Fragment antigen
binding)
-1 –Fc ( crystallizable
fragment) CH2 __CH3
• Fab --- binds to epitopes
• Fc -- binds to complement,
bonding to macrophage,
participates in allergic
reactions, can cross placental
barrier
• Fab
 Ag binding
 Valence = 1
 Specificty determined by VH and VL
Papain
Fc
Fab
Effector functions

7. Immunoglobulin Fragments:
Structure/Function
Relationships
Ag Binding
Complement Binding Site
Placental Transfer
Binding to Fc
Receptors- M*,
Polymorps
FC REGION
FAB REGION

8. 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

9. Human Immunoglobulin Subclasses
• ON BASIS OF DIFFERENT DISTINCTIVE
HEAVY CHAINS WITHIN CLASS:
• IgG Subclasses
IgG1 - Gamma 1 (1) heavy chains
IgG2 - Gamma 2 (2) heavy chains
IgG3 - Gamma 3 (3) heavy chains
IgG4 - Gamma 4 (4) heavy chains
• IgA subclasses
IgA1 - Alpha 1 (1) heavy chains
IgA2 - Alpha 2 (2) heavy chains

10. Human Immunoglobulin
Light Chain Types
• Kappa ()
• Lambda ()
• Subtypes Lambda light chain:
Lambda 1 (1)
Lambda 2 (2)
Lambda 3 (3)
Lambda 4 (4)

11. IgG
• Structure
Monomer (7S)
Subclasses differ in number of disulfide bonds and
length of hinge region
These give rise to difference in biological behaviour
IgG1, IgG2 and IgG4 IgG3

12. IgG
• Properties
• Most versatile immunoglobulin
Major serum Ig- 75% of serum Ig
Major Ig in extravascular spaces
Placental transfer – Does not require Ag
binding ( IgG2)
Fixes complement ( IgG4)
Binds to Fc receptors ( IgG2, IgG4)
 Phagocytes - opsonization
 K cells – ADCC
 Neutralize bacterial toxins

13. IgG Molecule

14. IgM
• Structure
Pentamer
Macromolecule
mu chains
Extra domain (CH4)
J chain
C4
J Chain

15. IgM
Properties
3rd highest serum Ig
First Ig made by fetus and B
cells
Fixes complement
Agglutinating/ cytolytic
antibody
Binds to Fc receptors

16. IgA• Structure
Serum - monomer
Secretions (sIgA)
 Dimer –
 J chain
 Secretory component-
recruited from serous
epithium.
J
Chai
n
Secretory
Piece
Origin of Secretory Component of sIgA

17. IgA
Properties
2nd highest serum Ig
1ST
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 cells
Neutralizes viruses and toxins

18. IgE
• Structure
Monomer
Extra domain (CH4)
C4

19. IgE
Properties
Least common serum Ig
 Binds to basophils and mast cells (does not require
Ag binding)
Allergic reactions
Parasitic infections (Helminths)
 Binds to Fc receptor on Eosinophils
 Activation of macrophages--- ADCC
Does not fix complement

20. IgD
• Structure
Monomer
Tail piece Tail Piece
Properties
 4th highest serum Ig
 B cell surface Ig
 Does not bind complement
 Increased levels in AIDS

21. Characteristics of Various Classes of Immunoglobins

22. Characteristics of Various Classes of Immunoglobins

23. PROPERTIES OF ANTIBODIES

24. Elimination of foreign agents by antibiotics

25. MHC COMPLEX

26. MAJOR HISTOCOMPATIBLE COMPLE (MHC)
• 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

27. MAJOR HISTOCOMPATIBLE COMPLEX
(MHC)
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

28. MHC COMPLEX
• MHC 1 ANTIGENS MHC II ANTIGENS
1.Present on the surface 1. Present on the B cell,
of all nucleated cells macrophages and
of the body, platelets. activated T cells.
2. Bind Ag/ peptide 2. Bind Ag/ peptides
endogenously produce exogenously produced
eg. viral proteins. then processed within
cell after phagocytosis.
3. Present Ag to CD8 - 3.Present Ag to CD4 cells-
TC cells. TH Cells
CLASS1 AND 11 GENES ENCODE CELL SURFACE GLYCOPROTEINS.
CLASS III GENES ENCODES FOR COMPONENTS OF COMPLEMENT

31. CYTOKINES

32. CYTOKINES
• Defined as a class of non antibody molecules
that are produced by many different cells (both
immune and non immune) in a highly regulated
manner
• Hormone like peptides or glycopeptides with
wide spectrum of effects
• Short acting soluble mediators released during
interaction between lymphocytes, monocytes,
macrophages, inflammatory cells and
endothelial cells
• Concerned with induction and regulation of
immune response
• Control of lymphocyte growth
• Activation of innate immunity mechanism
including inflammation

33. CYTOKINES
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

34. FAMILIES OF CYTOKINES
5 families recognized currently:
INTERLEUKINS (IL I – IL15)
TUMOUR NECROSIS FACTOR (TNF)
INTERFERONS( IFN)
COLONY STIMULATING FACTOR (CSF)
OTHERS (TGB transforming growth factor
LIF- leukaemia inhibitory factor)

35. CYTOKINES

36. EFFECTS OF CYTOKINES

37. EFFECT OF IL-2

39. Important Cytokines