IMMUNITY AND DISEASE II

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1 IMMUNITY AND DISEASE II A. Evolution of the immune system. 1. Figure , p from Raven and Johnson Biology 6 th ed. shows how the immune system evolved. Figure 1. How the immune system evolved. a. All animals possess phagocytic cells. b. They also indicate the ability to recognize self from non-self. c. Invertebrates lack lymphocytes. d. Invertebrates possess lectins, which may be the forerunners of antibodies. e. The Agnatha (lampreys, etc) possess lymphocytes but not those distinguished as B and T cells.

2 2. Chondrichthyes (sharks) are the earliest to show distinct populations of T and B cells. a. They evolved 450 million years ago. b. They possess a thymus that produces T cells and a spleen that is rich in B cells. c. The amino acid sequence in the sharks and mammals is very similar. B. Specific immune response 1. Foreign materials which stimulate the body to produce antibodies are called antigens. a.antigens are usually protein or complex carbohydrate in nature. b. Antigenicity refers to the ability of an antigen to stimulate the immune response (production of antibodies or killer cells). 1) This depends upon the number and type of specific antigenic sites on the foreign material. 2) These sites are called epitopes. c. How does the body recognize its tissues from foreign cells or tissues? 1) Ability is referred to as self versus nonself. 2) Almost every cell carries distinctive molecules on its surface that identify it. 3) These marker molecules are coded for by genes on a specific chromosome and are referred to as MHC, Major Histocompatibility Complex. 2.Acquired immunity a. Non-specific immunity occurs in most people and they are born with it. b. Acquired immunity is not a type that people are born with but some event must occur so that they obtain it. c. Active immunity is one in which the individual produces his/her own antibodies. 1) It can be obtained by having the disease and recovering from it. 2) It can be obtained by being vaccinated with a dead or attenuated form of the bacterium or virus, or with part of the organism. 3) It takes a time to develop but is relatively long lasting. d. Passive immunity is one in which the antibodies against the disease are produced by an outside agent and injected. 1) Can occur by the fetus getting antibodies from the mother s blood or milk.

3 a) IgG is the only antibody that can cross the placental barrier, but it only has a half life of 23 days. b) IgA is passed from mother to baby by nursing. There is a sudden burst due to the baby receiving colostrums (expelled from breasts hours after delivery. And is provided in a lower concentration in the mother s milk. 2) Can be obtained by giving a person an injection of antiserum which contains antibodies. 3) It is fast acting by does not last for a long period of time. 4) Often used after the organism has entered the body. C. Immune system 1. T-cells which originate in the bone marrow but migrate to the thymus where they develop. a. They are responsible for cell mediated immunity. b. Mature Helper T-Cells are necessary to activate cytotoxic T cells which then destroy infected cells. 2. B-cells originate and mature in the bone marrow. a. They move from bone marrow to lymph and blood where they circulate. b. Under the affect of mature Helper T-Cells they become plasma cells, which produce antibodies. 3. Production of plasma cells and memory cells from B-cells (fig. 2) a. B-cells uses receptors to bind to a matching antigen (recognition).

4 Figure 2. Activation of B cells to make antibody

5 b. It engulfs and processes the antigen (processing) c. It then presents a piece of the antigen bound to a class II protein in its surface (presentation) d. It binds with a mature Helper T-cell, which releases interleukins that causes them to divide and become B cells into antibody producing Plasma cells and Memory cells. e. The antibodies mark cells that do not have the proper ID. 1) Complement proteins then attack these cells. 2) Also the makers activate macrophages and natural killer cells. 4. Antibodies are proteins called immunoglobins (Ig) a. Antibodies are soluble proteins that circulate in the fluids of the body and exhibit properties that contribute specifically to immunity and protect the body from foreign materials. b. Immunoglobins are either secreted or membrane-bound. 1) Secreted are produced by plasma cells. 2) Membrane-bound is present on the surface of B cells where it serves as the antigen specific receptor. c. There are five major categories of Ig molecules: IgA, IgD, IgE, IgG, and IgM. d. Table 4.1 taken from Immunology 4 th ed by Benjamini et al., 2000 page 67 presents a summary of the properties of the immunoglobulin classes.

6 Table 4.1. The most important features of immunoglobulin isotopes.

7 e. Figure 3. shows a diagrammatic illustration of an antibody. 1) It has two heavy chains and two light chains. 2) The variable portion of both chains contain the antigen binding site. 3) The variable region composed of amino acids gives the antibody its specificity for binding to the antigen. Figure 3. Diagrammatic representation of an antibody. 5. Maturation of a Helper T-Cell (fig. 4 ) Figure 4. Maturation of a Helper T-cell.

8 a. Macrophage engulfs and processes antigen b. It presents piece of antigen complexed with class II protein (MHC) c. Immature Helper T-cell recognizes and complexes with the antigen. d. Interleukin secreted which results in a mature Helper T-cell. 6. Maturation of mature cytotoxic T cell and T memory cells (fig. 5 ) a. Macrophage engulfs and processes antigen. b. Presents antigen complexed with class I protein (HMC) c. Complexes with a immature Cytotoxic T-Cell d. Mature Helper T-cell secrete interleukin 2 which stimulates Cytotoxic T-Cell to mature and proliferate. Figure 5. Activation of Cytotoxic T-cells

9 e. Mature Cytotoxic T-Cells produce chemicals (perforin, granzymes, hydrolytic enzymes which produce apoptosis). These destroy cells that bear antigens bound to MHC; they can t interact with free floating antigens. 7. Primary response (fig. 6) (Taken from Immunology 4 th ed. Page 75 by Benjamini et al., 2000) Figure 6. The kinetics of an antibody response a. B-cells have IgM and IgD receptors on their membrane b. They can bind to free antigens which initiates the primary response; and IgM antibodies are secreted. c. Also get stimulation of cell division and clonal expansion 8. Secondary response (figure 6) a. Upon a second exposure to the antigen, the plasma cells secrete large amts of IgG. b. Production peaks after about 3 weeks. c. The antibodies cause aggregation of complement proteins which cause pores in the cells and rupture of the cells. d. IgG binding to antigens marks them for phagocytosis by macrophages.

10 D. Allergies 1. Reaction to a normally harmless environmental substance dust, pollen, food, drug, etc.. The substance is called an allergen. 2. Subsequent reexposure of a sensitized individual to some allergen elicits an immune attack, which may vary from a mild reaction to a server body damaging reaction that may cause death. 3. Immediate hypersensitivity results from B-cells producing IgE type of antibody. a. These antibodies attach to mast cells and basophils which have receptors for these antibodies. b. Second exposure, and the allergen binds to the antibodies attached to these receptors. c. These cells secrete chemicals including histamine, heparin and WBC activators. d. Symptoms are wheezing, sneezing, runny eyes, itching. e. May result in anaphylactic shock which is life threatening. 1) Swelling of body tissues (throat) 2) Sudden fall in blood pressure due to increased permeability of capillaries. 4. Slow hypersensitivity response a. T cells migrate to the tissues. b. Usually occurs about 48 hours after exposure. c. Induces prolonged and profound contraction of smooth muscle. d. Increased permeability of capillaries. e. Example is response to poison ivy 1) caused by secretion of lymphokines 2) antihistamines have no affect on the symptoms. 3) use corticosteroids. E. Tissue Transplants 1. MHC proteins (HLA-human leukocyte antigens) mainly used for typing 2. # of possible HLA types about 10,000

11 3. Histocompatibility testing is done. Best match identical twins, close relative. 4. Immunosuppression a. Steroids suppress lymphocyte function b. Cyclosporine holds down production of lymphokine, interleukin, which is necessary for T-cell growth. c. If these fail, KOT3 is a monoclonal antibody that seeks out the T3 marker carried on mature T-cells. It either destroys T cell or incapacitates them. KO can bring an acute rejection to a halt. DISCUSSION QUESTIONS OVER IMMUNITY AND DISEASE 1. What was the time span between appearance of general lymphocytes and differentiated T and B lymphocytes? 2. What is the major difference in the roles of B lymphocytes and T lymphocytes? 3. What is the difference in the place of maturity for the B and T lymphocytes? 4. Which Ig are produced during the primary and secondary response to an antigen? 5. List three phenomena that suggest an adverse reaction of the immune system. 6. What is the action of perforin? 7. What is the definition of an antigen? 8. What are the symptoms and causes of anaphylactic shock? 9. What does MHC represent? 10. How does the monoclonal antibody KOT3 produce its effect in halting a rejection reaction?

12 CRITICAL THINKING QUESTIONS 1. What is the reason(s) that some individuals take a lesser dose of immunosuppressiondrugs than others when all have received the same organ. 2. Rheumatoid arthritis is an autoimmune disease. What happens and how is it treated? 3. Some athletes take steroids to build up muscle mass. On the basis of this unit what advice would you give them?

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