1. 1 Immune Defenses Against Disease Chapter 15 (innate immunity) Chapter 16 (adaptive/acquired immunity) Chapter 17 (passive vs active immunization – pp 505-512) Health lies in the balance your immune system achieves in its response to different antigens Response vs Tolerance Modulation of response Immune Defenses

2. 2 What are the two main arms of the immune defense system? 1. ‘Innate’ defenses against infection (antigen-nonspecific) ‘Barriers’ to infection Normal microbiota Cellular / enzymatic responses 2. ‘Acquired’ defenses against infection antigen-specific humoral & cell-mediated systems These systems interact in many ways

3. Immune Defenses3 What are the types of Innate Immunity? I. Non-induced mechanisms “Barriers to infection” -- 1 st line of defense Anatomical Mechanical Cilia and mucus Skin wounding

4. Immune Defenses4 Innate Immunity… II. Cellular responses Physiological, e.g., fever Cellular, e.g., phagocytosis Enzymatic, e.g., complement Receptor-mediated Broadly specific -- recognize “danger signals” -- molecules shared by many pathogens “PAMPs” Responses pathogen killing (intra- & extra-cellular) activation of acquired immune responses http://lpi.oregonstate.edu/infocenter/phagocytosis.html

5. Immune Defenses5 What are the cells of the Immune System? Innate granulocytes macrophages Acquired lymphocytes ‘Cytokines’ coordinate activities

6. Immune Defenses6 Organs of the Immune system Primary Lymphoid organs Bone marrow Thymus Secondary lymphoid organs Spleen lymph nodes etc. B-cells and T-cells circulate

7. Immune Defenses7 What are 4 characteristics of the Adaptive Immune system? Specificity Diversity Memory Self/nonself discrimination What are the two branches? Humoral Response: Attack free antigens via antibodies B-cell lymphocytes “B-cell receptors” (BCR) Cell-mediated Response: Hormonal regulation Attack infected cells T-cell lymphocytes “T-cell receptor” (TCR) AG on MHC proteins

8. 8 Acquired Immune system recognizes antigens …What is an antigen? Complex macromolecules (e.g., proteins) -- distinctive to a pathogen (+/-) Perceived as “foreign” -- ‘self ‘ vs ‘non-self’ B-cell antigens (antibodies) -- on pathogen surface T-cell antigens -- from intracellular pathogens Immune Defenses

9. 9 What is an epitope? Actual part of the antigen recognized By antibody or T-cell Receptor

10. Immune Defenses10 What is an antibody? Functional regions antigen binding sites constant region -- triggers response hinge region What are the 5 types of antibodies and their functions? IgG – primary serum Ig IgA – secretory Ig IgM – B-cell receptor IgE – eukaryotic Ags IgD – membrane associated

11. Immune Defenses11 How does the Humoral System respond to an infection? “Clonal Selection” ‘Naïve’ B-cells Activation (AG selection) + T H cell stimulation Plasma cells “Antibody” factories Memory cells create acquired defense (T-cell response is similar)

12. Immune Defenses12 Clinical Manifestation of Immunity Primary vs Secondary responses Differences in: lag time Ab Titer memory cells

13. Immune Defenses13 How do antibodies trigger an immune response? Blocking of receptors Toxin neutralization Antigen clearing Enhanced phagocytosis Activation of complement

14. 14 T-Killer cell activation is carefully regulated “Professional” antigen presenting cells T-Helper cells Tc (T-Killer) cells -- attack infected body cells -- trigger cell death Thus, the need for attenuated pathogen vaccines! Immune Defenses

15. 15 How does the Cell-mediated system respond to infections? MHC proteins -- antigen “presentation” Role of macrophages T-Helper cells -- release cytokines -- interferons, interleukins, etc Cytotoxic-T (T-Killer) cells -- attack infected body cels --trigger cell lysis, apoptosis Killer-T cell activationKiller-T cell video

16. How can our bodies produce millions of different types of B-cells and T-cells? Each B- or T-cell can recognize only a specific antigen Antibody/TCR genes are randomly “rearranged” Why don’t B and T-cells act against “self” antigens? -- Cells “tested” in bone marrow and thymus 16Immune Defenses

17. 17 How is MHC different? -- 100s of different MHC among humans -- We each possess only 12-18 -- inherited from parents Cause predispositions -- Disease susceptibility -- Allergies -- Autoimmune disorders Is basis of Transplant Compatibility Immune Defenses

18. 18 Types of tolerance Central vs Peripheral Types of peripheral tolerance 1. Missing signals, e.g., -- no T H help for B-cells or Tc cells 2. Treg cells -- Immunosuppressive cytokines 3. Tolerogenic DC cells -- induced by missing danger signals

19. Immune Defenses19 Overview of Acquire immune responses Cell meditated T H activated by AG presented on P-APC -- cytokines needed for T C and B-cell activation T C activated by DC cells & AG presented on infected cell -- kill target cells Humoral B-cells activated by free AG Ab bind to pathogens -- induce phagocytosis -- activates “complement” -- etc

20. Immune Defenses20 Immunization Passive Immunotherapy maternal antibodies anti-toxins Active Immunotherapy (i.e., vaccination) Types of vaccines dead cells attenuated cells molecular components Vaccine production

21. Immune Defenses21 Autoimmune disorders Examples Type I diabetes -- B-cells of pancreas Rheumatoid arthritis -- cartilage of joints Myasthenia Gravis -- acetylcholine receptors Multiple sclerosis -- myelin sheath

22. 22 How can microbes trigger Autoimmune disorders? Examples Type I diabetes -- B-cells of pancreas Rheumatoid arthritis -- cartilage of joints Myasthenia Gravis-- acetylcholine receptors Multiple sclerosis -- myelin sheath Possible examples of “Molecular Mimicry” Immune Defenses

23. 23 What causes Allergies Two steps Sensitization B-cells ----> IgE mast cells Triggering mast cell activation histamine inflammation Immune Defenses IgE and Allergy