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  1. 1. Chapter 17: Adaptive Immunity <ul><li>Adaptive = acquired = specific immunity </li></ul><ul><ul><li>Defense against a particular microbe </li></ul></ul><ul><ul><li>Response has a memory which is enhanced upon re-exposure </li></ul></ul><ul><ul><li>Immunity based on Ab production </li></ul></ul><ul><ul><li>Begins at birth </li></ul></ul>
  2. 2. Adaptive Immunity: Antigens <ul><li>Antigen (Ag) stands for Anti body Gen erator = any chemical substance capable of stimulating the immune system and provoking an immune response </li></ul><ul><ul><li>Recognized as non self by the immune system </li></ul></ul><ul><ul><li>Are large macromolecules and are easily phagocytized by macrophages </li></ul></ul><ul><ul><li>Most common Ags – proteins, polysaccharides, rare – nucleic acids, lipids </li></ul></ul>
  3. 3. Adaptive Immunity: Antigens <ul><li>Antigen </li></ul><ul><ul><li>The immune system recognizes a small part of the Ag called an antigenic determinate or epitope which is the part that binds with a specific Ab or T-cell receptor </li></ul></ul><ul><ul><li>May be part of microbe, pollen, egg whites , blood cell, transplanted tissue or organs </li></ul></ul><ul><ul><li>Haptens are Ags that are too small to stimulate Ab formation unless they are attached to a larger carrier molecule – now can stimulate Ab formation pg 505 </li></ul></ul>
  4. 4. Antibodies, Antigens, “Epitopes”
  5. 5. Adaptive Immunity: Antibodies <ul><li>Antibody (Ab) or immunoglobulins = a protein produced by lymphocytes in response to the presence of an antigen and is capable of combining specifically with the antigen </li></ul><ul><ul><li>Each Antibody has 2 identical antigen binding sites </li></ul></ul>
  6. 6. Adaptive Immunity: Ab structure <ul><li>Each Ab consists of 4 polypeptide chains </li></ul><ul><ul><li>2 identical heavy chains and 2 identical light chains joined together by disulfide (S-S) linkages to form a Y shaped structure </li></ul></ul><ul><li>Each chain (light or heavy) consists of: </li></ul><ul><ul><li>Constant region wh/ is identical among different types of Abs </li></ul></ul><ul><ul><li>Variable region wh/ is uniquely shaped to combine w/ a specific Ag – binds to epitopes on the antigen </li></ul></ul>
  7. 7. Adaptive Immunity: Ab type <ul><li>5 types of Ab (Ig = immunoglobulin ) pg.507 for pix and table </li></ul><ul><li>IgM – largest Ab (M stands for macromolecule), 5 – 10% of Ab in serum (fluid portion of blood), pentimer </li></ul><ul><ul><li>First to appear after B cell stimulation, they decline rapidly </li></ul></ul><ul><ul><li>Principal component of primary Ab response </li></ul></ul><ul><ul><ul><li>1) If found in serum indicates recent infection </li></ul></ul></ul>
  8. 8. Adaptive Immunity: Ab type <ul><ul><li>c. It is one of the Abs bound to the B lymphocyte as a cell surface receptor </li></ul></ul><ul><ul><li>d. IgM generally stays in the blood vessels and does not enter surrounding tissue because of its size </li></ul></ul><ul><ul><li>e. Predominant Ab in ABO blood group Ag rxs, agglutination and complement rxs </li></ul></ul>
  9. 9. Adaptive Immunity: Ab type <ul><li>2. IgG = gamma globulin – monomer </li></ul><ul><li>a. 80 % of total Ab content in normal serum </li></ul><ul><li>b. appears 24 - 48 hours after antigenic stimulation </li></ul><ul><li>c. booster vaccines raise the level of this Ab </li></ul><ul><li>d. provides long term resistance to disease as a product of a memory B cell </li></ul><ul><li>e. crosses blood vessel walls to enter tissue fluids </li></ul>
  10. 10. Adaptive Immunity: Ab type <ul><li>f. maternal IgG crosses the placenta – passive immunity to fetus and for approximately 6 months after birth </li></ul><ul><li>g. protects against circulating bacteria and viruses, neutralizes toxins, triggers complement system, binds to Ag to enhance phagocytic action </li></ul>
  11. 11. Adaptive Immunity: Ab type <ul><li>3. IgA is 10–15% of total Ab in normal serum </li></ul><ul><li>a. 2 types – prevent attachment of pathogens to mucosal surfaces – this is important because mucosal surfaces are portals of entry </li></ul><ul><li>1) serum IgA – monomer </li></ul><ul><li>2) secretory IgA </li></ul><ul><li>a) 2 monomers (dimer) joined by a J chain </li></ul><ul><li>b) predominant in GI fluids, nasal secretions, saliva, tears, colostrum - 1 st milk (passive immunity) </li></ul>
  12. 12. Adaptive Immunity: Ab type <ul><li>4. IgE – 0.002% total serum Abs, monomer </li></ul><ul><li>a. plays a major role in allergic rxs by sensitizing cells to certain Ags by binding the Fc stem to basophils and mast cells which release chemical mediators such as histamine </li></ul><ul><li>b. these inflammatory rxs attract IgG and phagocytic cells </li></ul><ul><li>c. binds to parasitic worms (Helminths) </li></ul>
  13. 13. Adaptive Immunity: Ab type <ul><li>5. IgD – 0.2 % total serum Ab, monomer </li></ul><ul><li>a. it is a cell surface receptor on the B lymphocytes together with IgM </li></ul>
  14. 14. Immunoglobulin Classes Longest lived Ab & present in colostrum. Associated with allergies. Most abundant class (except in serum).
  15. 15. Adaptive Immunity: Lymphatic System <ul><li>The lymphatic system is anatomically intertwined with the cardiovascular system – both systems circulate body fluids </li></ul><ul><li>Cardiovascular system circulates blood w/in the BVs </li></ul><ul><ul><li>Certain components of the blood move into tissue spaces and now the fluid is called interstitial fluid </li></ul></ul><ul><ul><li>Interstitial fluid is picked up by the lymph system and is now called lymph </li></ul></ul><ul><ul><li>Lymph is drained back into the blood </li></ul></ul>
  16. 16. Adaptive Immunity: Lymphatic System <ul><li>3. Lymph nodes contribute to both innate and adaptive immunity and are situated along the path of lymphatic vessels </li></ul><ul><li>a. Swollen lymph nodes in the armpits, groin, or neck indicate an active immune response to infection </li></ul><ul><li>b. these nodes contain both B cell and T cell lymphocytes and are the site of antibody production </li></ul><ul><li>c. they also contain phagocytes which destroy microbes and stimulate the adaptive immunity response </li></ul>
  17. 17. Primary Lymphoid Organs The primary lymphoid organs , are bone marrow and the thymus, where lymphocytes originate and/or mature (depending on type).
  18. 18. Secondary Lymphoid Organs The secondary lymphoid organs , such as Lymph Nodes, are the sites of interaction among immune system cells including with antigens presented by Antigen Presenting Cells.
  19. 19. Adaptive Immunity: Lymphocytes <ul><li>Lymphocytes = small WBCs with a large </li></ul><ul><li>nucleus that develop from stem cells in the fetal liver or in the red bone marrow </li></ul><ul><li>of adults </li></ul><ul><li>B lymphocytes (B cells) – mature in the bone marrow and then migrate to lymphoid tissue – lymph nodes, tonsils, adenoids </li></ul><ul><ul><li>a. responsible for Ab mediated immunity that reacts with microbes, Ags, and non self cells </li></ul></ul>
  20. 20. Adaptive Immunity: Lymphocytes <ul><li>2. T lymphocytes (T cells) – mature in the thymus gland then migrate to lymphoid tissue via the blood and lymph </li></ul><ul><li>a. the thymus is a flat, bi-lobed organ that lies behind the sternum and above the heart </li></ul><ul><li>b. have surface cell receptors called T cell receptors </li></ul><ul><li>c. responsible for cell mediated immunity that reacts w/ eukaryotic pathogens, antigen marked cells (virus infected cells, transplant cells) </li></ul><ul><li>d. recognize and destroy non self cells (esp. Ca) </li></ul>
  21. 21. Adaptive Immunity <ul><li>The specific immune system is divided into two categories: humoral and cell mediated </li></ul><ul><li>Humoral (Ab mediated) immunity – B cell </li></ul><ul><li>a. most Ags are large protein molecules associated w/ microbes, tumor cells, damaged cells, pollens, dust, food </li></ul><ul><li>b. they trigger the production of Abs specific for that Ag </li></ul>
  22. 22. Adaptive Immunity <ul><li>2. Cell mediated immunity (CMI), T-cell </li></ul><ul><li>a. Ags trigger the production of T lymphocytes directed against that Ag </li></ul><ul><li>b. T lymphocytes have a role in both humoral and cell mediated immunity </li></ul><ul><li>c. there are several T cell types and each has a specific role and is identifiable by the cluster of differentiation (CD) molecules acquired in the thymus during the T cell maturation process. </li></ul>
  23. 23. T cells and Cell Mediated Immunity <ul><li>Directed against intracellular Ags not exposed to circulating Abs (viruses, some bacteria, protozoans) </li></ul><ul><li>Before an inactive T cell can attack Ags, the T cell must become sensitized to recognize the Ag </li></ul><ul><li>Sensitization involves macrophages wh/ phagocytize and present the partially digested Ag on the macrophage surface to the T cells </li></ul><ul><ul><li>a. macrophages secrete interleukin–1 and interferons wh/ stimulate T cell growth and division </li></ul></ul><ul><ul><li>b. most of the time T cells are inactive </li></ul></ul>
  24. 24. T cells and Cell Mediated Immunity <ul><li>4. Once T cells are sensitized they increase in size and # to produce a clone = a group of identical cells which then differentiate into various cell types </li></ul>
  25. 25. Each T lymphocyte has a specific role Id by the cluster of differentiation Cell Type CD (receptors) Fx T helper cell CD4 Activates B cell to produce Abs and activates cytotoxic T cells Cytotoxic T-cell – killer cell that works against cells w/ foreign intracellular Ags CD8 Goes to invasions site and secretes perforin – causes cell lysis T suppressor cell (regulatory) CD8 stops immune rx w/otherTcells
  26. 26. B cells and Ab mediated Immunity (humoral immunity) <ul><li>Humoral immunity is mediated by Abs </li></ul><ul><ul><li>a. Abs are products of B cells in response to Ags </li></ul></ul><ul><ul><li>b. the binding of Abs to Ags facilitate the destruction of the Ag bearing microbe </li></ul></ul><ul><li>Ab secreting cells are called plasma cells </li></ul><ul><li>T helper cells are required to help B cells produce Abs by releasing cytokines that causes clonal expansions of the B cells </li></ul>
  27. 27. B cells and Ab mediated Immunity (humoral immunity) <ul><li>4. Some B cells develop into long lived memory B cells which frequently provide life-long immunity to a microbe or vaccine-Ag encountered earlier in life </li></ul><ul><li>a. they respond more rapidly and forcefully to a future encounter with the Ag </li></ul><ul><li>5. B cells don’t leave the lymphoid tissue </li></ul><ul><li>a. a macrophage processes and presents an Ag to the B cell in the lymphoid tissue </li></ul>
  28. 28. B cells and Ab mediated Immunity (humoral immunity) <ul><li>6. B cells are specific for the Ag they are sensitized to </li></ul><ul><li>a. some of them enlarge, divide and develop into plasma cells which secrete Abs into your circulation </li></ul>
  29. 29. Clonal Selection Theory Applies to both B and T cells. B cells are associated with Ab (Ig) production. T cells are associated with cell-mediated immunity. Takes place in 2° lyphoid organs.
  30. 30. Antigen Presentation by B Cell Results in production of Abs against T-Dependent Antigens (no T-helper binding, then no Ab). Note binding by only one-half of the “Y”.
  31. 31. Antigen-Antibody Interaction (forms complex) <ul><li>1. Neutralization = Abs that alter toxin molecules and inactivate viruses by blocking their attachment to host cells </li></ul><ul><li>a. neutralizing of toxins increase their size making them more susceptible to phagocytosis and they are less likely to be able to diffuse through the cell </li></ul><ul><li>2. Opsonization = Abs coat bacteria preventing them form attaching to cells and enhancing phagocytosis </li></ul>
  32. 32. Antigen-Antibody Interaction <ul><li>3. Agglutination = Abs react with Ag on surface of bacteria causing them to clump together making them easier to phagocytize </li></ul><ul><li>a. IgM is the main Ab because it has more binding sites (lg. molecule) </li></ul><ul><li>4. Precipitins = Ab that react w/ dissolved Ag and convert them to solid precipitates wh/ inactivates them and makes them more easily phagocytized </li></ul>
  33. 33. Antigen-Antibody Interaction <ul><li>5. Activation of complement system – triggered by IgG or IgM Abs </li></ul><ul><li>a. Abs attach the complement to the bacteria resulting in cell lysis, also causes inflammation </li></ul>
  34. 34. Immunoglobulin Actions These are now available for phago-cytosis. This is a host cell, covered with foreign antigens and therefore with antibody. Pilus as well as flagellum binding. Recall that C3b can bind directly to cell. Prevents binding to host tissues.
  35. 35. Pos & Neg T Cell Selection <ul><li>Both T cells and B cells are derived from hematopoietic stem cells found in bone marrow. </li></ul><ul><li>T cells migrate to the thymus for further development (and hence the “T” in T cells, though the “B” in B cells stands for Bursa). </li></ul><ul><li>T cells, during their development in the thymus, are subject to two round of selection. </li></ul><ul><li>The first round is Positive Selection where only T cells that can bind MHC are retained. </li></ul><ul><li>The second round is Negative Selection where T cells that recognize self antigens in association with MHC are deleted. </li></ul><ul><li>The resulting T cells, both helper and cytotoxic, consequently can bind MHC (II or I, respectively), but only if complexed with non-self antigens. </li></ul>
  36. 36. Antigen Recognition by T Cells Recognition by Cytotoxic T cell (CD8 receptor) Recognition by Helper T cell (CD4 receptor)
  37. 37. Cytotoxic Consequences Apoptosis is cellular suicide which here is induced by the CTL. I.e., they tell their “friends” (other cytotoxic T cells).
  38. 38. Stimulating T-Helper Cells Macrophages and Dendritic cells present antigens to, and thereby stimulate, T-helper cells.
  39. 39. Adaptive Immunity Good summary of Adaptive Immunity!