Adaptive Immunity Chapter 17 Tortora


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Adaptive Immunity Chapter 17 Tortora

  1. 1. Adaptive Immunity: Specific Defenses of the Host Chapter 17 Tortora
  2. 2. Immunity <ul><li>Protection against disease (etc) </li></ul><ul><li>The immune system recognizes foreign substances and develops an immune response against them. </li></ul><ul><li>Innate or nonspecific immunity seems to have an inherited (genetic) component </li></ul><ul><li>Adaptive or specific immunity adapts to a particular invader or foreign substance </li></ul>
  3. 3. Types of acquired immunity <ul><li>Acquired immunity can be acquired passively or actively </li></ul><ul><li>Active or passive can be acquired naturally or artificially </li></ul><ul><li>Naturally acquired active immunity-exposure to antigens (you get sick and recover) </li></ul><ul><li>Naturally acquired passive immunity-natural transfer of antibodies from mom to child (breast feeding and in utero)-this is short lived. </li></ul>
  4. 4. Immunity continued <ul><li>Artificially acquired active -get a vaccination which introduces specially prepared antigens into the body </li></ul><ul><ul><li>Doesn’t cause disease but stimulates your reaction </li></ul></ul><ul><li>Artificially acquired passive -introduce antibodies into the body </li></ul><ul><ul><li>These are derived from serum so are called antisera </li></ul></ul><ul><ul><li>Often inject a horse with antigen and then use the horse antibody (spider and snake antivenom) </li></ul></ul>
  5. 5. Dual nature of the immune system <ul><li>First Nobel prize winner was Emil von Behring who discovered immunity can be passed from one organism to another (now called humoral immunity) </li></ul><ul><li>Scientists later discovered this was due to antibodies (1930’s) </li></ul><ul><li>Cell mediated immunity is governed by lymphocytes </li></ul><ul><li>Humoral immunity (antibody mediated) involves the production of antibody </li></ul>
  6. 6. Humoral immunity <ul><li>B cells or B lymphocytes are responsible for antibody production </li></ul><ul><li>This provides resistance to bacteria and viruses and bacterial toxins </li></ul><ul><li>B stands for the Bursae of Fabricius </li></ul><ul><li>Antibody or immunoglobulins recognize different types of antigen </li></ul>
  7. 7. Cell mediated Immunity <ul><li>Involves T cells (T lymphocytes) that act against foreign cells or tissue </li></ul><ul><li>T cells mature in the thymus gland </li></ul><ul><li>Also regulate the activation and proliferation of other immune system cells </li></ul><ul><li>Cell mediated immune response is directed against bacteria and viruses inside phagocytic cells or infected host cells, fungi, protozoa, and helminths </li></ul><ul><li>This also causes rejection in implanted tissue </li></ul>
  8. 8. Antigens and antibody <ul><li>Antigen is any foreign substance </li></ul><ul><li>We recognize ‘ self’ and don’t attack it ( MHC antigen) </li></ul><ul><li>Antibody is produced by B cells and combines with antigenic determinant or epitopes on the antigen </li></ul><ul><li>Some antigens are small (a molecular weight of less than 10,000) and won’t trigger a response unless attached to a carrier. These small antigens are HAPTENS. </li></ul><ul><li>The antibody reacts with the hapten, not the carrier. </li></ul>
  9. 9. Nature of antibody <ul><li>Antibodies are proteins made in response to antigen that recognize and bind to antigen </li></ul><ul><li>The valence of an antibody is the number of antigen binding sites </li></ul><ul><li>Most humans are bivalent </li></ul><ul><li>Antibodies are members of a group of soluble proteins called immunoglobulins or Igs. </li></ul>
  10. 10. Antibody structure <ul><li>A bivalent is the simplest structure for an antibody so it is referred to as a monomer </li></ul><ul><li>A monomer usually has 4 protein chains </li></ul><ul><li>Two of these are identical light chains (L) and two are identical heavy chains (H) </li></ul><ul><li>Light and heavy refer to molecular weights </li></ul> Citation for picture
  11. 11. Antibody structure continued <ul><li>Variable regions (V) are located at the end of the Y’s arms </li></ul><ul><li>Their structure reflects the specific antigen they recognize, and these are specific to the two antigen binding sites (bind to epitopes) </li></ul><ul><li>The stem and lower portion of the Y are the constant regions (C) </li></ul><ul><li>These are the same for a particular class of Ig </li></ul><ul><li>There are 5 major types of C regions, giving us 5 major classes of immunoglobulin </li></ul><ul><li>The Fc regions (on the stem) are important in immunological reactions </li></ul>
  12. 12. Classes of Ig <ul><li>IgG -80% of all serum antibody, cross blood vessel walls and enter tissue fluids </li></ul><ul><ul><li>Cross placenta to protect fetus </li></ul></ul><ul><ul><li>Protect against circulating bacteria, viruses, neutralize toxin, trigger complement, and enhance phagocytic cells </li></ul></ul><ul><li>IgM 5-10% of serum antibody and is shaped like a pentamer </li></ul><ul><ul><li>First to respond to initial antigen exposure. Subsequent exposure results in increased IgG </li></ul></ul><ul><ul><li>Valuable in diagnosis because it is early to respond. </li></ul></ul>
  13. 13. Classes continued <ul><li>IgA -5-10% of serum antibody, but most common in fluids like saliva and breast milk (helps keep baby safe while it develops its own immune system) </li></ul><ul><ul><li>Prevent attachment of viruses and/or bacteria to mucosal surfaces </li></ul></ul><ul><li>IgD -0.2%, found on surface of B cells and act as antigen receptors (no known function in serum) </li></ul><ul><li>IgE -0.002% of serum antibody, Fc portion binds to mast cells and basophils (allergic reactions), </li></ul><ul><ul><li>Increases during parasite or allergy </li></ul></ul>
  14. 14. B cells and Humoral immunity <ul><li>This antibody mediated immunity is carried out by B cells </li></ul><ul><li>HOW? </li></ul><ul><li>B cell exposed to antigen and become activated </li></ul><ul><li>B cells divide and produce clones called plasma cells </li></ul><ul><li>Plasma cells produce antibody to that specific antigen (say you have measles for instance, it won’t work against chicken pox) </li></ul><ul><li>Some turn into memory cells so that you can have long term immunity to that disease. </li></ul>
  15. 15. More on B cells <ul><li>B cells come from stem cells in bone marrow (adult) and liver (fetus) </li></ul><ul><li>Mature B cells are found in spleen and lymph nodes </li></ul><ul><li>Recognize antigen by antigen receptors on cell surface </li></ul><ul><li>Apoptosis -programmed cell death </li></ul><ul><li>We make 100 million lymphocytes a day, so equal number must die. Any that don’t encounter antigen quickly go through apoptosis </li></ul>
  16. 16. Activation of antibody producing clones <ul><li>Each B cell can only produce an antibody against a particular antigen </li></ul><ul><li>A mature B cell can have 100,000 IgM or IgD antibody bound to it’s surface </li></ul><ul><li>When antigen binds to antigen receptor, the B cell proliferates into clones that will recognize this one antigen (clonal selection) </li></ul><ul><li>Each B cell has the ability to respond to 100 million antigens thanks to the variable region, but once it has responded it can only make clones for ONE type. </li></ul>
  17. 17. Antigen/antibody complex <ul><li>B cells usually require the help of a helper T cell </li></ul><ul><li>An antigen that requires the helper T cells for antibody production is called a T-dependent antigen </li></ul><ul><li>B cell contacts the antigen and is processed inside the B cell </li></ul><ul><li>Fragments of the antigen combine with MHC and are displayed on the B cell surface. </li></ul><ul><li>The T cell comes in contact with the antigenic fragment/MHC presented on the B cell and activates the T cell </li></ul><ul><li>The T cell produces cytokines that in turn activate the B cell to produce clones, some of which become the plasma cell. </li></ul>
  18. 18. Antigen-antibody binding and results <ul><li>Antigen/antibody complex is formed quickly </li></ul><ul><li>Binding targets the antigen for phagocytosis or complement </li></ul><ul><li>Agglutination is clumping of antigens to make them easier for phagocytes to digest </li></ul><ul><li>Neutralization-IgG antibodies inactivate viruses by blocking their attachment to a host </li></ul><ul><li>Opsonization-antigen is covered by antibody to aid in ingestion/digestion by phagocytic cells </li></ul><ul><li>IgG and IgM trigger complement </li></ul>
  19. 19. T cells and Cell mediated Immunity <ul><li>The chemical messengers of immune cells are called cytokines </li></ul><ul><li>These chemical messengers allow the cells to communicate with each other </li></ul><ul><li>There are 60 different cytokines identified to date </li></ul><ul><li>Some cytokines help the communication between leukocytes and are called interleukins </li></ul><ul><li>There are 18 of these (IL-1, IL-2 etc) (see table 17.3) </li></ul><ul><li>Another group is called chemokines that help induce leukocytes to migrate into infected areas. </li></ul>
  20. 20. Cellular components of immunity <ul><li>T cells are the key component </li></ul><ul><li>They develop from stem cells in bone marrow and mature in the thymus gland </li></ul><ul><li>After maturation they migrate to lymphoid organs </li></ul><ul><li>T cells respond to specific antigen, multiply as clones into effector T cells, and destroy the invader </li></ul>
  21. 21. Types of T cells <ul><li>Helper T- have central role in immune response, these activate macrophages and help form cytotoxic T cells </li></ul><ul><li>Cytotoxic T destroy target cells on contact by producing perforin that lysis a bacterial or viral infected cells </li></ul><ul><li>Delayed hypersensitivity T involved in allergic reactions and tissue rejection, </li></ul><ul><li>Suppressor T are involved in stopping the reaction once the danger is passed. (Now called regulatory T cells). </li></ul><ul><li>Another way to classify T cells is by the type of surface receptor called CD (clusters of differentiation) </li></ul><ul><li>Two are CD4 and CD8. </li></ul>
  22. 22. Nonspecific cellular components <ul><li>Natural killer cells or NK cells -lymphocytes that can destroy other cells, especially tumor cells and other viral infected cells </li></ul><ul><li>Activated macrophages are stimulated macrophages that have been activated by the cytokines produced by helper T cells </li></ul><ul><li>These macrophages can be activated by digesting antigen too. </li></ul><ul><li>Macrophages often act as antigen presenting cells (APC’s) </li></ul><ul><li>This is identified by the T cells </li></ul>
  23. 23. Interrelationship between cell mediated and humoral immunity <ul><li>Antibody production depends on macrophages and T cells (T dependent antigen) </li></ul><ul><li>1. antigen is ingested and presented by the APC </li></ul><ul><li>2. The helper T cells reacts with this MHC-antigen complex </li></ul><ul><li>3. This activates the T cell and it begins to proliferate and produce cytokines. </li></ul><ul><li>4. The cytokines activate macrophages, CD8 cells, and natural killer cells </li></ul>
  24. 24. continued <ul><li>5. IL-2 influences a B cell to differentiate into a plasma cell that produces antibody </li></ul><ul><li>Sometimes antigen can stimulate B cells directly without the help of T cells. This is called T independent antigen </li></ul><ul><li>In this case the antigen reacts directly with the B cell receptors. </li></ul><ul><li>This is usually weaker </li></ul>
  25. 25. Immunological memory <ul><li>Intensity of the antibody mediated humoral response is reflected by antibody titer </li></ul><ul><li>This is the amount of antibody in the serum after infection has been cleared </li></ul><ul><li>There is no detectable titer in the serum for 4-7 days (initial infection) </li></ul><ul><li>IgG peaks in 10-17 days, and titer increases </li></ul><ul><li>This is the primary response </li></ul><ul><li>If you are exposed again, the memory response peaks in 2-7 days and is much greater! </li></ul>
  26. 26. When the immune system goes haywire! <ul><li>Hypersensitivity -antigenic response beyond the normal response due to previous exposure (sensitization) by an allergen </li></ul><ul><li>4 types: </li></ul><ul><ul><li>Type I-anaphylatic reactions </li></ul></ul><ul><ul><li>Type II cytotoxic reactions </li></ul></ul><ul><ul><li>Type III-Immune complex reactions </li></ul></ul><ul><ul><li>Type IV-delayed cell mediated (delayed hypersensitivity) </li></ul></ul><ul><ul><li> </li></ul></ul>
  27. 27. Type I <ul><li>Occur quickly (2-30 minutes) after exposure </li></ul><ul><li>May be localized or systemic </li></ul><ul><li>Localized reactions include hives, hay fever, asthma </li></ul><ul><li>Systemic includes shock and breathing difficulty (death can result) </li></ul><ul><li>Over reactive IgE ( you inherit the sensitivity but may have a completely different allergy) </li></ul>
  28. 28. Type II <ul><li>Involve activation of complement by IgG or IgM antibodies within an antigenic cell </li></ul><ul><li>This causes lysis of the cell </li></ul><ul><li>Common type II reactions are transfusion reactions (ABO blood group) </li></ul><ul><li>Erthryoblastosis fetalis or hemolytic disease of the newborn (Rh negative mom has a second Rh positive baby, the second baby is likely to develop this) </li></ul>
  29. 29. Type III <ul><li>Form when certain ratios of antigen and antibody occur </li></ul><ul><li>Usually involves IgG </li></ul><ul><li>IF there is a slight excess of antigen, the soluble complex that forms is small and escape phagocytosis </li></ul><ul><li>It this happens the complex may become trapped in the basement membrane beneath cells, activating complement and inflammation </li></ul><ul><li>Neutrophils enter and release enzymes that can damage the cells within 2-8 hours. </li></ul><ul><li>An example is glomerulonephritis which damages kidney glomeruli causing kidney failure </li></ul><ul><li>Another is serum sickness following injection of antitoxin produced by an animal </li></ul>
  30. 30. Type IV <ul><li>Caused by T cells </li></ul><ul><li>Delay may be a day or more </li></ul><ul><li>Include allergic contact dermatitis (allergic to latex) </li></ul><ul><li>T B tine test </li></ul>