Microbiology – Chapter 15 The Immune system: Specific defenses – Specific immunity The immune system is a network of cells and organs that extends throughout the body and functions as the third line of defense against invaders. It is a specific response and it generates specific chemicals to counteract invaders. 1. Foreign substances are antigens 2. Proteins made by the body in response are called antibodies Microbiology – Chapter 15 Two types of immunity: 1. Active: the individual own immune system produces the immunity A. Naturally acquired: by disease B. Artificially acquired: vaccination 2. Passive: either have antibodies passed from mother to child or having immune globulin administered medically Microbiology – Chapter 15 Antigens: The body can recognize materials as non-self or foreign material. These materials are called antigens. 1. Generally protein or large polysaccharides, nucleic acids or lipids are antigenic only if combined with protein or polysaccharides 2. Any cell, part of a cell, or chemical that induces an immune response bythe B-cells or Tcells (lymphocytes), is called antigenic. 3. Usually large molecules 10,000 mw, in many cases the antigen is some particular part of a cell – like a cell wall polysaccharide, capsule material, flagella, or fimbriae Microbiology – Chapter 15 Antigens: The body can recognize materials as non-self or foreign material. 4. Viral protein, pollen, other protein (egg or milk protein) can cause an immune response and are antigenic. 5. Antibodies tend to react with specific parts of an antigen – called and antigenic determinant or epitope. Size and shape; lock-key just like in enzyme substrate interactions. 6. Small molecules that are too small to cause an immune response are called haptens. Penicillin is an example. By itself, too small to be antigenic, but it combines with serum proteins and then can become antigenic (penicillin allergy ) Fig. 15.8 Microbiology – Chapter 15 Antibodies are produced by Lymphocytes 1. T or B cell lymphocytes recognize foreign material as antigens. 2. They have receptor sites on their cell surface that bind antigens in order to eliminate them as foreigners. 3. The antibody molecules are large proteins that are specific in size and shape to interact chemically with their particular antigen. Antibody structure: several kinds of antibodies (chart on pg ____) Microbiology – Chapter 15 G M A D E 1. IgG – Monomer, simple antibody, Y shaped, composed of two heavy chains and two light chains, a. The “y” ends have a variable region, amino acid sequence can vary, thus allowing specific interaction with their specific antigen – they have two antigen binding sites b. Constant region, on the molecule’s stem, this c region is called constant, it can be different (actually have 5 different c region types – giving 5 different types of antibodies) c. IgG- most prevalent ab, found in blood and it is called monomer for its simple shape d. When acting on antigen, enhances phagocytosis, neutralizes toxins e. Since it is small, it passes the placenta and provides passive immunity to infants Microbiology – Chapter 15 G M A D E 2. IgM – Pentamer, composed of 5 monomers (5 Y monomer units) a. Large and stays in blood stream or attaches to blood cells b. The first kind of ab to appear after an antigenic challenge c. Involved in clumping (agglutination) reactions, works with complement and clumps antigens and cells, so the can be easily phagocytized d. Kind of reaction seen with ABO blood grouping Microbiology – Chapter 15 G M A D E 3. IgA – Secretory antibody, secreted along epithelium linings a. Found in respiratory tract, GI tract, mother’s milk b. Localized protection 4. IgD – function not well known, found on b cell surfaces, may function in initiation of immune response (B cell activation) 5. IgE – bound antibodies, found on surfaces of mast cells, stimulates inflammatory response, may be a trigger for allergic response Microbiology – Chapter 15 The immune response: B cell immunity (Humoral immunity) **** Know for test **** The B cells are lymphocytes that develop from stem cells located in the red bone marrow. 1. In embryonic development, stem cells differentiate into b cells 2. Some move to thymus gland and become T cells 3. Both B and T cells later migrate to other lymph tissue (lymph nodes, spleen) 4. When B cells are exposed to antigens, they are activated, they start to divide and become a clone of many effector cells called plasma cells Microbiology – Chapter 15 The B cells are lymphocytes that develop from stem cells located in the red bone marrow. 5. The plasma cells produce the antibodies that counteract the specific antigen that activated the original B cells 6. Theory of antibody production – Clonal selection a. During development the B cells undergo tremendous genetic recombination that results in literally millions of different receptor sites on their surfaces. These receptor sites are able to bind with the specific shape of specific antigens. b. Because of the tremendous number of potential genetic combinations on the gene regions that code for these antigen recognition sites – millions of possibilities – result – millions of genetically different B cells Microbiology – Chapter 15 The B cells are lymphocytes that develop from stem cells located in the red bone marrow c. Recognition – an antigen enters the host, only one or a few b cells have a site on its surface that fits that antigen (better the fit, the betterthe immune response) – antigenic selection – antigen selects its B cell d. The specific matching b cell is now activated and undergoes cell division into many cells (a clone) – *****Clonal selection***** e. See pg ___ -know this for the test – be able to diagram andexplain Microbiology – Chapter 15 i. Recognition ii. Activation iii. Proliferation iv. Differentiation (plasma cells, memory cells) v. Production of antibodies (secreted into plasma) vi. Memory cells – long lived cells, survive and can respond very quickly if encounter antigen again (immunological memory) Microbiology – Chapter 15 The first reaction – recognition - activation –proliferation - etc. Takes time - This is the primary response – 1 to 2 weeks (pg____) Secondary response is very quick – memory B cells can respond quickly to produce more b cells and antibodies, just a few days How does the body know the difference between self and non-self material?? Still a mystery – self tolerance, the forbidden clone?? Maybe the B and T cells that are exposed to self antigens are destroyed in fetal development when they pass through the thymus gland (clonal deletion) Microbiology – Chapter 15 T cell response T cells – T lymphocytes, cell mediated immunity – just touch on it a little 1. T cell activation is different than that of B cells 2. The antigen that is presented to the T cell is first processed by antigen presenting cells – usually a macrophage a. Macrophage encounters antigen – ingests it, digests it and then seperates it into antgenic determinants b. Antigenic determinants migrate to the phagocyte cell surface c. Antigens are held on surface of the phagocyte Microbiology – Chapter 15 3. The correct T cell encounters the antigen on the phagocyte and is activated 4. T cells then can divide and differentiate into different types of T cells (be able to list and give a function) a. T-helper cells (Th) – most prevalent, secrete lymphokines (interleukins – chemical messengers between cells of the immune system) see pg ____ b. Cytotoxic T cells (Tc) – destroy target cell when in contact (virus infected cell killed before virus can replicate) c. T suppressor cells (Ts) – may regulate the immune response, turns it off when not needed d. Td – delayed hypersensitive cells – cause inflammation reaction associated with hypersensitivity, and some of the problems with tissue rejection Microbiology – Chapter 15 Diagnostic Immunlogy Many diagnostic tests in microbiology are based on immunology 1. Ag – Ab reactions can b used to determine presence of infection or an exposure to an antigen 2. Hiv test, Hep C are used to determine exposure to these viruses 3. Clinical immunology (serology) is the branch of immunology involved with identifying cause of diseases based on the presence of antigens or antibodies in serum of patients 4. a good diagnostic immunological test should meet two criteria a. Specificity – test will indicate the presence of only one particular antibody or antigen , won’t react with even closely related Ag or Ab b. Sensitivity – can detect even tiny amounts of antibodies or antigens in serum Microbiology – Chapter 15 c. Titer – the serum, with antibodies, is diluted and the dilutions are tested for antigens. The highest dilution that still tests positive (a visible reaction) with the antigen is the titer 5. Agglutination test: easy to see and read, type of test for blood types. a. Whole cells are tested for presence of antigens on their surfaces b. Antiserum is added, if positive (specific ag –ab reaction), clumping or aggregation of cells occurs ( blood typing pg – ___) c. A,B,O blood groups, rh factor testing ( Photo atlas, in lab, page 108-109) i. A – a ag, antib ab ii. B- b ag, anti a ab iii. AB – both a and b ag and no anti a or b ab iv. O – neither a or a antigen, both anti a and anti b ab Microbiology – Chapter 15 6. Elisa test (EIA test) – enzyme linked immunosorbent assay (pg 532) a. Widely used in clinical labs, adaptable for direct assay to detect presence of antigen or indirect assay by testing for the presence of antibody b. These tests can be easily automated and results determined by a computer Direct ELISA (photo atlas pg 110 –111) handout 1. Ab for a specific Ag attached to the plastic microtiter well 2. Test Ag is added, if it binds, then add enzme-linked ab specific for the test ag 3. Then a substrate that is specific for that enzyme is added. This will produce a specific color change 4. The enzyme and substrate are selected so that a specific color is produced that can be detected in the computer – using optical density reader Microbiology – Chapter 15 ii. Indirect – like the HIV test. Known antigen is attached to the well. Test antiserum is added. If it is complementary to the antigen, it binds. p.532 Other tests: Complement fixation test – pg 529 Fluorescent AB pg 530, Precipitin, Western blot test (confirmatory for HIV after ELISA)