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Antigen antibody interactions

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Antigen antibody interactions

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Antigen antibody interactions

  1. 1. ANTIGEN-ANTIBODY INTERACTIONS Dr Sufyan Akram
  2. 2. AN OVERVIEW OF THE IMMUNE RESPONSE
  3. 3. 3 Helper T Lymphocytes B Lymphocytes Antibodies Cell-mediated Immunity Humoral Immunity Cytotoxic T Lymphocytes Interleukins Direct killing of Microbes
  4. 4. ACTIVATION OF B LYMPHOCYTES  On entry of a foreign antigen, macrophages in the lymphoid tissue phagocytize the antigen and then present it to adjacent B lymphocytes  In addition, the antigen is presented to T cells at the same time, and activated helper T cells are formed. These helper cells also contribute to extreme activation of the B lymphocytes
  5. 5. WHAT ARE ANTIGENS?
  6. 6.  An antigen is a substance that evokes the production of one or more antibodies  An immunogen is a specific type of antigen. An immunogen is a substance that is able to provoke an adaptive immune response if injected on its own
  7. 7. ANTIGENICITY  Foreignness  Size  The larger the molecule the more immunogenic it is  Chemical Composition  In general, the more complex the substance is chemically the more immunogenic it will be  Physical form  In general particulate antigens are more immunogenic than soluble ones  Degradability  Antigens that are easily phagocytosed are generally more immunogenic. This is because for most antigens the development of an immune response requires that the antigen be phagocytosed, processed and presented to helper T cells by an antigen presenting cell (APC)
  8. 8. ANTIGENICITY  Host Factors:  Genetic Factors  Some substances are immunogenic in one species but not in another. Similarly, some substances are immunogenic in one individual but not in others (i.e. responders and non-responders)  Age  Age can also influence immunogenicity. Usually the very young and the very old have a diminished ability to mount and immune response in response to an immunogen
  9. 9. HAPTENS  Haptens are small molecules which could never induce an immune response when administered by themselves but which can when coupled to a carrier molecule  Free haptens, however, can react with products of the immune response after such products have been elicited  Haptens have the property of antigenicity but not immunogenicity
  10. 10. SUPERANTIGENS  When the immune system encounters a conventional T-dependent antigen, only a small fraction of the T cell population is able to recognize the antigen and become activated  However, there are some antigens which polyclonaly activate a large fraction of the T cells (up to 25%). These antigens are called superantigens…  Examples of superantigens include: Staphylococcal enterotoxins (food poisoning), Staphylococcal toxic shock toxin (toxic shock syndrome) and Streptococcal pyrogenic exotoxins (shock)
  11. 11. ANTIBODIES
  12. 12. FORMATION OF ANTIBODIES  B lymphocytes specific for the antigen immediately enlarge and take on the appearance of lymphoblasts  Lymphoblasts further differentiate to form plasmablasts, which are precursors of plasma cells  The mature plasma cell then produces gamma globulin antibodies at an extremely rapid rate-about 2000 molecules per second  This process continues for several days or weeks until finally exhaustion and death of the plasma cells occur
  13. 13. MEMORY CELLS  A few of the lymphoblasts formed by activation of a clone of B lymphocytes do not go on to form plasma cells but instead form moderate numbers of new B lymphocytes similar to those of the original clone  These lymphocytes are called memory cells  Subsequent exposure to the same antigen will cause a much more rapid and much more potent antibody response this second time around
  14. 14. PRIMARY RESPONSE AND SECONDARY RESPONSE  There is usually a 1-week delay in the appearance of the primary response, its weak potency, and its short life  The secondary response, by contrast, begins rapidly after exposure to the antigen, is far more potent, and forms antibodies for many months…
  15. 15. PRIMARY RESPONSE AND SECONDARY RESPONSE  The increased potency and duration of the secondary response explain why immunization is usually accomplished by injecting antigen in multiple doses with periods of several weeks or several months between injections
  16. 16. WHAT ARE ANTIBODIES  The antibodies are gamma globulins called immunoglobulins (Ig), and they have molecular weights between 160,000 and 970,000  All the immunoglobulins are composed of combinations of light and heavy polypeptide chains  Most are a combination of two light and two heavy chains  However, some of the immunoglobulins have combinations of as many as 10 heavy and 10 light chains
  17. 17. STRUCTURE OF ANTIBODIES  A designated end of each light and heavy chain, called the variable portion; the remainder of each chain is called the constant portion  The variable portion is different for each specificity of antibody, and it is this portion that attaches specifically to a particular type of antigen  The constant portion of the antibody determines other properties of the antibody  such as diffusivity of the antibody in the tissues and other biological properties of the antibody
  18. 18. SPECIFICITY OF ANTIBODIES  Each antibody is specific for a particular antigen; this is caused by its unique structural organization of amino acids in the variable portions of both the light and heavy chains  On a bivalent antibody, there are two variable sites for attachment of antigens  A small proportion of the antibodies, which consist of combinations of up to 10 light and 10 heavy chains, have as many as 10 binding sites
  19. 19. TYPES OF ANTIBODIES  There are five general classes of antibodies, respectively named IgM, IgG, IgA, IgD, and IgE  IgG, a bivalent antibody, constitutes about 75 percent of the antibodies of the normal person  The IgM class is also interesting because a large share of the antibodies formed during the primary response are of this type. These antibodies have 10 binding sites that make them exceedingly effective in protecting the body against invaders
  20. 20. ANTIGEN-ANTIBODY INTERACTIONS
  21. 21. ANTIGEN ANTIBODY INTERACTIONS  Lock and Key Concept- The combining site of an antibody is located in the Fab portion of the molecule and is constructed from the hypervariable regions of the heavy and light chains  Non-covalent Bonds- The bonds that hold the antigen to the antibody combining site are all non- covalent in nature. These include hydrogen bonds, electrostatic bonds, Van der Waals forces and hydrophobic bonds  Since antigen-antibody reactions occur via non- covalent bonds, they are by their nature reversible
  22. 22. AFFINITY AND AVIDITY  Affinity- is the strength of the reaction between a single antigenic determinant and a single combining site on the antibody  Affinity is the equilibrium constant that describes the antigen-antibody reaction. Most antibodies have a high affinity for their antigens  Avidity- is a measure of the overall strength of binding of an antigen with many antigenic determinants and multivalent antibodies  Affinity refers to the strength of binding between a single antigenic determinant and an individual antibody combining site whereas avidity refers to the overall strength of binding between multivalent antigens and antibodies
  23. 23. SPECIFICITY AND CROSS REACTIVITY  Specificity- refers to the ability of an individual antibody combining site to react with only one antigenic determinant. In general, there is a high degree of specificity in antigen-antibody reactions. Antibodies can distinguish differences in:  The primary structure of an antigen  Isomeric forms of an antigen  Secondary and tertiary structure of an antigen  Cross reactivity- Cross reactivity refers to the ability of an individual antibody combining site to react with more than one antigenic determinant  Cross reactions arise because the cross reacting antigen shares an epitope in common with the immunizing antigen
  24. 24. TESTS FOR ANTIGEN-ANTIBODY REACTIONS  Agglutination tests  Agglutination/Hemagglutination  Coomb's Test (Antiglobulin Test)  Precipitation tests  Radial Immunodiffusion  Immunoelectrophoresis  ELISA/ RIA  Immunofluorescence  Flow Cytometry  Complement Fixation
  25. 25. TESTS FOR ANTIGEN-ANTIBODY REACTIONS  Some examples…  Blood typing…..  Qualitative Agglutination Test  Bacterial Infections…..  Quantitative Agglutination Test  Detection of Rh antibodies…..  Coomb’s Test  Qualitative analysis of complex mixtures of antigens…..  Immunoelectrophoresis  Quantitative analysis of Antigens/ Antibodies…..  ELISA  Detection of cell-associated antigens…..  Immunofluorescence, Flow Cytometry
  26. 26. HOW DO ANTIBODIES WORK?  Antibodies act mainly in two ways to protect the body against invading agents:  (1) by direct attack on the invader (Antigen- Antibody Interaction), and  (2) by activation of the "complement system" that then has multiple means of its own for destroying the invader
  27. 27. DIRECT ACTION OF ANTIBODIES ON INVADING AGENTS  Agglutination: multiple large particles with antigens on their surfaces, such as bacteria or red cells, are bound together into a clump  Precipitation: the molecular complex of soluble antigen and antibody becomes so large that it is rendered insoluble and precipitates  Neutralization: the antibodies cover the toxic sites of the antigenic agent  Lysis: some potent antibodies attack membranes of cellular agents and cause their rupture
  28. 28. COMPLEMENT SYSTEM FOR ANTIBODY ACTION  "Complement" is a collective term that describes a system of about 20 proteins, many of which are enzyme precursors  All these are present normally in the blood  When an antibody binds with an antigen, a specific reactive site on the "constant" portion of the antibody becomes "activated," and this in turn binds directly with the C1 molecule of the complement system…
  29. 29. COMPLIMENT CASCADE  Activation of C1 molecule of the complement system, sets into motion a "cascade" of sequential reactions  There is successively increasing quantities of enzymes in the complement cascade  Multiple end products are formed, and several of these cause important effects that help to prevent damage to the body's tissues caused by the invading organism or toxin…
  30. 30. FUNCTIONS OF COMPLEMENT  Opsonization and phagocytosis: One of the products of the complement cascade, C3b, strongly activates phagocytosis by both neutrophils and macrophages  Lysis: One of the most important of all the products of the complement cascade is the lytic complex, C5b6789. This has a direct effect of rupturing the cell membranes of bacteria or other invading organisms  Agglutination: The complement products also change the surfaces of the invading organisms, causing them to adhere to one another, thus promoting agglutination
  31. 31. FUNCTIONS OF COMPLEMENT  Neutralization of viruses: The complement enzymes and other complement products can attack the structures of some viruses  Chemotaxis: Fragment C5a initiates chemotaxis of neutrophils and macrophages, thus causing large numbers of these phagocytes to migrate into the tissue area adjacent to the antigenic agent  Activation of mast cells and basophils: Fragments C3a, C4a, and C5a activate mast cells and basophils, causing them to release histamine, heparin, and several other substances into the local fluids. This causes local Inflammatory effects
  32. 32. CLINICAL APPLICATIONS
  33. 33. IMMUNIZATION BY INJECTION OF ANTIGENS  Immunization has been used for many years to produce acquired immunity against specific diseases  A person can be immunized by  Injecting dead organisms that are no longer capable of causing disease but that still have some of their chemical antigens  Immunity can be achieved against toxins that have been treated with chemicals so that their toxic nature has been destroyed even though their antigens for causing immunity are still intact  And, finally, a person can be immunized by being infected with live organisms that have been "attenuated"
  34. 34. PASSIVE IMMUNITY  Temporary immunity can be achieved in a person by infusing antibodies obtained from the blood of someone else or from some other animal that has been actively immunized against the antigen  Antibodies last in the body of the recipient for 2 to 3 weeks, and during that time, the person is protected against the invading disease
  35. 35. SOME DRUGS MAY ACT AS HAPTENS !!  Hydralazine, a blood pressure-lowering drug occasionally can produce drug-induced lupus erythematosus in certain individuals  The anaesthetic gas halothane can cause a life- threatening hepatitis  Some penicillin-class drugs may cause autoimmune hemolytic anemia
  36. 36. REFERENCES Guyton and Hall Textbook of Medical Physiology, 12th edition, 2011 Naish Medical Sciences, 1st edition, 2011

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