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Antibodies done

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Antibody

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Antibodies done

  1. 1. IMMUNOGLOBULINS: Structure and Function MHC COMPLEX CYTOKINES
  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
  23. 23. PROPERTIES OF ANTIBODIES
  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
  34. 34. EFFECTS OF CYTOKINES
  35. 35. EFFECT OF IL-2
  36. 36. Important Cytokines

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