Lecture 9 : Immunity, Disease, and Vaccines

1. Lecture 9: Immunity, Disease, and Vaccines • Objectives: • Understand how the body fights infections • Defense strategies • Components of the defense • Understand how pathogens fight the defense • Understand how a vaccine works Background Reading: Chapter 35

2. Three Lines of Defense Barriers at Body Surfaces • Physical barriers • Chemical barriers • Normal flora • Disposable surfaces Nonspecific Responses (Innate Immunity) • Inflammation • Fast acting cell types (self vs. non-self) • Cells that remove debris • Proteins: hole plugging, hole making, and cutting tools Specific Immune Responses (Cellular Immunity) • B and T cells • Communication • Antibodies and perforins

3. Barriers at Body Surface • Intact skin and mucous membranes • Lysozyme • Normal bacterial flora • Flushing and Sheading

4. Three Lines of Defense Barriers at Body Surfaces Nonspecific Responses (Innate Immunity) • Inflammation • Fast acting cell types (self vs. non-self) • Cells that remove debris • Proteins: hole plugging, hole making, and cutting tools Specific Immune Responses (Cellular Immunity)

5. Nonspecific Responses • Lymph nodes trap and kill pathogens • Natural killer cells attack a range of targets • Inflammation • Inflammation • Fast acting cell types (self vs. non-self) • Cells that remove debris • Proteins: hole plugging, hole making, and cutting tools

6. Complement System • Plasma proteins that take part in both specific and nonspecific response • Activation of one triggers cascade of reactions that activate others LYSIS OF TARGET CASCADE REACTION FORMATION OF ATTACK COMPLEXES

7. Acute Inflammation • Nonspecific response to foreign invasion, tissue damage, or both • Destroys invaders, removes debris, and prepares area for healing • Characterized by redness, swelling, warmth, and pain

8. Inflammation • Mast cells release histamine • Capillaries dilate and leak • Complement proteins attack bacteria • White cells attack invaders and clean up

9. Inflammation • Redness- vessel dilation • Warmth- increased blood flow • Swelling- edema, leaking • Pain- pressure on free nerve endings

10. Three Lines of Defense Barriers at Body Surfaces Nonspecific Responses (Innate Immunity) Specific Immune Responses (Cellular Immunity) • B and T cells • Communication • Antibodies and perforins

11. Immune Responses • Directed against specific invaders • Carried out by T cells, B cells, and macrophages • Communication signals such as interleukins play a vital role

12. Definitions: B cells, T Cells, and Macrophage • B cell • Covered with antibody (one type) • Don’t recognize MHC presented antibody, only free antigens • T Cell (Thymus) • Ignore free antigen • recognize only antigen presented by MHC • Macrophage • Clears particles • Presents MHC antigens

13. Definitions Antibody Structure • Antibody consists of four polypeptide chains • Certain parts of each chain are variable; impart antigen specificity variable region of heavy chain antigen-binding site antigen-binding site hinge region (flexible) variable region of light chain constant region of light chain

14. Definitions Antigen: Any substance that stimulates the production of antibodies Usually a protein or large molecule Little 3-D shapes that antibodies can recognize.

15. Recognition Self and Non-self

16. Recognition MHC Displaying non-self antigen framents MHC molecule antigen-MHC complex

17. Features of Immune System • Immunological specificity • B and T cells zero in on certain kinds of pathogens; response is pathogen specific • Immunological memory • Immune system recognizes and reacts swiftly to a pathogen it has “seen”

18. Memory and Effector Cells • When a B or T cell is stimulated to divide, it produces more than one cell type • Memory cells are set aside for future use; they are the basis for immune memory • Effector cells engage and destroy the current threat

19. Key Component of Immune Response Key Component of Immune Response • MHC markers • Antigen-presenting cells • Helper T cells • Effector cytoxic T cells • Natural killer cells • B cells

20. Overview of an Immune Response Antibody - mediated response Cell - mediated response Antigen-presenting cell Naive helper T cell Naive B cell Naive cytotoxic T cell Effector B cell Activated helper T cell Effector cytotoxic T cell Key Components of Immune Response • MHC markers • Antigen-presenting cells • Helper T cells • Effector cytoxic T cells • Natural killer cells • B cells

21. Lymphocyte Battlegrounds • Lymph nodes filter antigens from body fluids • Macrophages, dendritic cells, B cell and T cells in nodes and spleen mount a defense

22. Antibody-Mediated Response • Carried out by B cells • Targets are intracellular pathogens and toxins • Antibodies bind to target and mark it for destruction by phagocytes and complement

23. Antibody- Mediated Response • Virgin B cell becomes antigen-presenting B cell • Helper T cell binds to antigen-MHC complex on the B cell • Interleukins stimulate B cell division and differentiation • Effector cells secrete antibodies Naive B cell Antigen-presenting B cell Helper T cell Interleukins Effector B cell secretes antibodies Memory B cell

24. 5 Classes of Immunoglobulins • IgM are secreted first; trigger complement reactions, agglutination • IgD function is not understood • IgG activates complement; can cross placenta • IgA associates with mucus-coated surfaces • IgE triggers inflammation

25. Cell-Mediated Response Another macrophage One macrophage • Carried out by T cells • Stimulated by antigen-presenting macrophages • Main target is antigen-presenting body cells (cells with intracellular pathogens) or tumor cells interleukins Cytotoxic T cell Helper T cell interleukins Infected body cell

26. Organ Rejection • Cytotoxic T cells can contribute to rejection of transplanted tissue • They recognize a portion of the donor cell’s MHC complex as self, view a portion as foreign • Treat the combination as an antigen-MHC complex and attack donor cells

27. Allergies • Immune reaction to a harmless substance • Genetic predisposition • IgE responds to antigen by binding to mast cells and basophils • These cells secrete the substances that cause symptoms

28. Anaphylactic Shock • A life-threatening allergic reaction • Caused by the release of histamine by many mast cells and basophils • Airways constrict and blood pressure drops as capillary permeability soars

29. Autoimmune Disorders • Immune system makes antibodies against self antigens • Grave’s disease • Myasthenia gravis • Rheumatoid arthritis

30. Bacterial Pathogen Category A Threats: • Defined by the CDC as high-priority agents include organisms that pose a risk to national security because they: • Can be easily disseminated or transmitted from person to person • Result in high mortality rates and have the potential for major public health impact • Might cause public panic and social disruption • Require special action for public health preparedness.

31. Bacillus anthracis Infection type Mortality (untreated) Cutaneous 20% Intestinal 80-90% Inhalation 90*-99% *with treatment

32. Major Symptoms • Skin- • characteristic sores • Intestinal- • fever, intestinal discomfort, intestinal ulceration. • Inhalation- • fever, cough, malaise (flu-like) • Sever respiratory distress, chills, edema

33. Pathophysiology

36. Immunization • Process that promotes immunity • Active immunization - • Antigen-containing material is injected • Confers long lasting immunity • Passive - • Purified antibody is injected • Protection is short lived

37. Immunization first exposure to antigen subsequent exposure to the same antigen

38. HIV Picture

39. All you need to know • Chapter 35 • Table 35.1 • Table 35.1 figure 35.5 • Figure 35.6 • Figure 35.7