Immunity

1. Immunity Anatomy & Physiology Tony Serino, Ph.D.

2. Immunity: Topic Objectives • Be able to describe the multilevel defenses of the body. • Be able to describe the symptoms and triggers for inflammation. • Be able to define adaptive immunity, antibodies, antigens and haptens. • Be able to explain how haptens can be immunoreactive but not immunogenic. • Be able to explain how T and B cells become immunocompetent and activated. • Be able to identify the different cell types produced in monoclonal expansion of lymphocyte cell lines and their functions. • Be able to identify and explain antibody structure, characteristics of different antibody types and their actions. • Be able to explain how APCs activate lymphocytes. • Be able to explain how vaccines work and how they are made. • Understand the difference between naturally and artificially acquired active and passive immunity

3. Immune System • Provide defense of the body against infectious agents, toxins, foreign bodies, and cancers • Two types of defenses: • General (Non-specific or Innate) Defense • Barriers • Normal Flora and Fauna • Fever • Surveillance • Inflammation • Non-specific Phagocytic WBCs and NK cells • Protective Chemicals • Specific (Adaptive) Defense --Lymphocytes

4. Barriers • Prevent infectious agents from penetrating internal environment • Epithelium ( thickness, tight junctions, keratin)-especially the skin • Cilia and mucus • Watery secretions (tears, saliva) • Acidity (stomach, urine, vaginal secretions) • Normal Flora and Fauna –resident bacteria prevent infectious agents from growing on body surfaces

5. Surveillance • Number of cells and organs to detect invading agents • Langerhans cells of skin, Mast cells, Dendritic cells, and organs like: Tonsils, GALT cells • Gather antigens and present them to lymphocytes

6. Fever • Rise in Body Temperature • Inhibits invading cell growth; increase body metabolism to increase defense/repair cell activity • Produced by release of pyrogens from leukocytes • Low grade fever is beneficial in fighting infection, high sustained fever may be life threatening

7. Inflammation • Allows more blood defenses into damaged areas • Triggered by release of paracrines from damaged tissues (PG), attacking WBCs (cytokines), mast cells (heparin and histamine), and activation of blood protective chemicals (complement and bradykinins) • Increases: • blood flow through vasodilation (hyperemia) • capillary permeability • Both lead to local edema • If prolonged or systemic, can become life threatening

8. Inflammatory Response

9. Phagocytic WBC and NK cells • WBCs can distinguish the sugars in mammalian cells and those found on bacteria or other parasites • PMNs, macrophage, and mast cells can injure or destroy cells that do not display normal sugars • NK cells –related to T-cells but attack any cell not displaying MHC I proteins • Kill by secreting perforins and other chemicals

10. Phagocytosis

13. Protective Chemicals • Chemicals that aid in destroying or retarding infectious agents • Interferon –cytokine released when cell attacked by virus; warns other cells in area • Lysozyme –antibacterial enzyme present in tears and saliva • Complement –blood proteins which can detect and destroy bacteria

14. Interferon

15. Complement MAC –membrane attack complex (C3-C9)

16. Specific (Adaptive) Immunity • Individual targets are selected for attack by the lymphocytes that can bind that target (antigen) • Antigens (Ag) – any large substance not normally found in the body; these illicit an immune response (immunogenic and immuno-reactive) • Haptens are small molecules that can trigger an immune response only if bound to larger molecules (like: pollen, some cosmetics, detergent fragrances, poison ivy animal dander and drugs); they are immuno-reactive but not immunogenic by themselves

17. Antigenic Determinants Large macromolecules illicit immune response because they have many sites to which immune molecules will attach; proteins have the most of any molecule

18. Identifying “Self” from “Non-self” • T-cells migrate to thymus, B-cells remain in bone marrow (the primary lymphoid tissues) • Become immunocompetent -selected for their ability to produce a surface receptor against an antigen and to tolerate self antigens • Those that bind weakly to self-antigens are selected, the others are eliminated • The strongest self-antigens are the MHC proteins • Once competent, the cells are released to move through the blood and aggregate in the secondary lymphoid tissues

19. Thymic Selection

20. Movement of Lymphocytes

21. Cells Involved in Specific Immunity • Lymphocytes (B and T cells) -attack antigen bearing agents either chemically (humoral immunity –the B-cells) or physically (cellular immunity –the T-cells) • T and B-cell activation to an antigen works best when they are presented with the antigen by another cell • APCs (Antigen Presenting Cells) (macrophage, surveillance cells, B-cells, infected cells) display foreign antigenic determinants on their MHC II cell surface proteins to activate the lymphocytes

22. Memory T cell

23. B-cell Clonal Expansion

24. Antibody Structure

27. Antibody Actions Opsonization –Ag-Ab complex makes ID for phagocytosis easier

28. Humoral Response

29. Control of Lymphocyte Response • B-cells can be activated by the antigen alone, but it is more effective if they are presented the antigen by APCs or stimulated by T-helper cells • Activation of T-helper cells stimulates complete lymphocyte response

30. MHC I –found on all body’s cells except RBCs Surface proteins usually bound to pieces of intracellular proteins, but when infected they present fragments of the infectious agent

31. MHC II –found on APCs -bound to phagocytized outer coat molecules of immuno-agent

32. T-cell Types

34. Helper T-cells

35. Clonal Selection of T-cell

36. Cytotoxic T-cell Attack

37. Primary Immune Response

38. Vaccine Production

39. Types of Acquired Immunity

40. Immediate Allergic Reaction

41. Hypersensitivity -like in TB test - Some drug allergies where the drug is precipitated and Ag-Ab is being destroyed 4. Cytotoxic hypersensitivity –mediated by antibodies that leadto damage or destruction of cells –like in ABO test and hemolyticfetal diseases

42. Pathologies: AIDS • AIDS –HIV invades T-helper cells, diminishing effectiveness of immune response; may have as long as 8 year incubation time, 100% fatal

43. Pathologies • Autoimmune Diseases –Immune system targets naturally occurring compounds of the body (usually sequestered proteins) MS, rheumatoid arthritis, Diabetes mellitus (I), etc. • Cancer –cancers cells spontaneously form during life, but the immune system keeps them in check; failure results in tumors and metastasis