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Transcript
MICROBIOLOGY – ALCAMO LECTURE: Specific Immune System B Cells & T Cells Specific Immune System • Late 1800’s: – not sure how body responded to disease – knew there were certain proteins in blood involved (Bence Jones proteins) • 1922: – these proteins were unlike other serum proteins Specific Immune System • 1950’s: – post-war explosion in biological research – realized that specific resistance applied to disease, organ transplant, allergies, resistance to cancer • 1960’s: – structure of antibodies deciphered – maturing of immunology as a key scientific discipline Specific Immune System • Last defense mechanism of the body – failure to beat the invader means death • “Man to Man” defense against invaders • Specific immune system cells: – Only Lymphocytes – type of WBC Antigens • Substances capable of mobilizing the immune system and provoking immune responses • Large complex molecules not normally present in the body • They are anything non-self: Mo’s, Cells, Cells containing MO’s, or chemicals • Epitope – small area of antigen that stimulates the immune response Antigens • Exhibit 2 important properties: – Immunogenicity – ability to stimulate the proliferation of the immune system cells – Reactivity – ability to react with the products of the immune system cells or the immune system cells themselves Antigens • Specific Immunologic Tolerance – before birth, the proteins and polysaccharides of the body contact and inactivate immune system cells • These substances are now seen as “self” and will be tolerated by immune system Origins of Immune System • General term for a complex series of cells, factors, and processes that provide a specific response to antigens • Lymphocytes – the cornerstone of the immune system: – Spread throughout the body – Small cells (10-20 um) with a large nucleus – Can be B-lymphocytes or T-lymphocytes Origins of Immune System • Immune system arises in a fetus ~ 2 months after conception • Lymphocytes arise from precursor cells in the bone marrow (stem cells) • Stem cells can be: – Erythropoietic – become RBC’s – Lymphopoietic – become WBC’s T Lymphocytes Original cells from bone marrow • Memory programmed in thymus gland • Circulate in blood, colonize lymph tissue • Interact directly with antigen marked cells and destroy them • Antigens: Infected body cells, fungi, protozoa, cancer, transplants T Lymphocytes 2 “T” cell types (total 4 “T” Cells) – Effector “T” Cells: • Killer T - worker • Delayed Sensitivity T allergies – Regulator “T” Cells: • • Helper T – don’t kill • Suppressor T – lower immune response Active chemical: Lymphokines ( a group of glycoproteins) T Lymphocytes Process • Phagocytic cell finds antigen in tissue (cell’s surface looks different if infected) • Brings it to lymph tissue containing memory cells (spleen or lymph node) • May remember antigen • If “Yes” • If “No” • Cell mediated Immunity (CMI) T Lymphocytes If “Yes” • Clones 2 Cell Types • Memory T Cells and • Killer T which makes lymphokines • Lymphokines kill or inactivate antigens and stimulate phagocytosis Back T Lymphocytes If “NO” • In thymus, program blank T cells for antigen memory • To lymph tissue in nearest war zone • Now: Clone Memory T and Killer T Back B Lymphocytes Profile • Original cells from bone marrow • Memory programmed in bone marrow • Circulate in blood and colonize lymph tissue • Antigens: Bacteria, Viruses, Chemicals • Active chemical: Antibody B Lymphocytes Process • Phagocytic cell finds antigen in blood • Brings it to lymph tissue containing memory B cells • May remember antigen from before – We all have 1,000s of memory B cells • If “YES” • IF “NO” B Lymphocytes • If “Yes”: – Clones 2 cell types – Memory B cell (so it won’t forget) and plasma cell to make antibodies (2,000 molecules/sec/cell 4-5 days) – Antibodies kill or inactivate antigen and stimulate phagocytosis Back B Lymphocytes • If “No”: – Blank B cells in bone marrow program for antigen memory to lymph tissue nearest “war zone” – Now clone memory and plasma cells Back B Lymphocytes Process (continued) • Antibodies: Stimulate complement proteins to attack • Monocytes and macrophages clean up • Antibody Mediated Immunity (AMI) Antibodies • Edelman and Porter described the structure of antibodies (1972) • Basic Antibody Protein: • Has 4 polypeptide chains – 2 identical heavy chains (400 AA) – 2 identical light chains (200 AA) – Joined together by disulfide bonds to form a “Y” shaped structure • Is called a monomer and has 2 identical halves (1 heavy and 1 light chain each) Antibodies • Have constant and variable regions • Constant regions – identical in all antibodies (AB) • Variable regions – differ among 100’s of thousands of different AB – Form a very specific, 3-D structure – Uniquely shaped to “fit” a specific antigen – Each arm can bind an antigen Types of antibodies • Five Types – based on differences in heavy chain: – 1. IgM – five monomers joined to form a pentamer, First AB to appear after stimulation of B-cells – 2. IgG – monomer, the major AB in the blood that appears 24-48 hrs after antigen appears, provides long-term resistance, crosses placenta to give immunity to fetus Types of antibodies • Five Types – based on differences in heavy chain: – 3. IgA – dimer shaped AB that accumulates in body secretions in respiratory and GI tracts, in tears and saliva, and in the 1st milk secreted by a nursing mother – 4. IgE – monomer that is involved in allergic reactions – 5. IgD – monomer – function unknown Antigen antibody Interaction • Neutralizing AB’s – react with viral capsids and prevent entry into cells • Antitoxins – alter toxin molecules released by antigen • Agglutinins – cause clumping of antigens and enhances phagocytosis • Precipitins – react with dissolved antigens and convert them to solids