MICROBIOLOGY – ALCAMO

1. MICROBIOLOGY – ALCAMO LECTURE: Specific Immune System B Cells & T Cells

2. 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

3. 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

4. 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

5. 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

6. 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

7. 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

8. 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

9. 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

12. 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

13. 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)

14. 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)

15. 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

16. 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

17. 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

18. 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”

19. 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

20. 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

21. B Lymphocytes Process (continued) • Antibodies: Stimulate complement proteins to attack • Monocytes and macrophages clean up • Antibody Mediated Immunity (AMI)

25. 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)

26. 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

28. 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

29. 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

32. 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