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Antibodies done


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Antibodies done

  2. 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. 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. 4. Antibody Structure
  5. 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. 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. 7. Immunoglobulin Fragments: Structure/Function Relationships Ag Binding Complement Binding Site Placental Transfer Binding to Fc Receptors- M*, Polymorps FC REGION FAB REGION
  8. 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. 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. 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. 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. 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. 13. IgG Molecule
  14. 14. IgM • Structure Pentamer Macromolecule mu chains Extra domain (CH4) J chain C4 J Chain
  15. 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. 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. 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. 18. IgE • Structure Monomer Extra domain (CH4) C4
  19. 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. 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. 21. Characteristics of Various Classes of Immunoglobins
  22. 22. Characteristics of Various Classes of Immunoglobins
  24. 24. Elimination of foreign agents by antibiotics
  25. 25. MHC COMPLEX
  26. 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. 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. 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
  29. 29. CYTOKINES
  30. 30. 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
  31. 31. 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
  32. 32. 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)
  33. 33. CYTOKINES
  35. 35. EFFECT OF IL-2
  36. 36. Important Cytokines