Chapter 43: The Body’s Defenses

1. Chapter 43:The Body’s Defenses • How does your body protect you from invaders?

2. Immune System Review • Microorganism/Microbe • Pathogen • Antibiotic • Antibody • Antigen

3. Key Concepts • 3 Lines of Defense • Innate vs. Acquired immunity • Phagocytes, Lymphocytes, Antibodies, etc… • Humoral vs. Cell-Mediated immunity • Distinguishing self from non-self • Tissue transplantation • Immune Diseases/Disorders

4. Using HIV to treat Cancer?? http://abcnews.go.com/WNT/video/doctors-hiv-treat-cancer-17929437

5. What do you think? • How does your body INITIALLY defend itself from invasion? (1st line – specific or non?) • What happens if the invader gets past the 1st line? (2nd line – specific or nonspecific?) • What about more serious infections? (3rd line)

6. 1st line Defense!! • Skin, mucus, cilia, saliva, acids, tears, oils, bacteria, coughing, sneezing, vomiting • Antimicrobial proteins & Lysozymes

7. Innate vs. Acquired Immunity • Innate Immunity: • Present before exposure; since birth • Includes natural bodily defenses, mother’s milk, or casual exposure • Broad-range capabilities, non-specific • External defenses: • skin, mucus membranes, tears • Internal Phagocytic cells • A.K.A.: “macrophages”; engulf invaders

8. Innate vs. Acquired Immunity • Acquired Immunity: • Develops only after exposure • Highly microbe-specific… how? • Employ lymphocytes & antibodies • Involves both Humoral & Cell-Mediated responses

9. Innate Immunity:Your first line of defense

10. Phagocytic White Blood Cells • Recognize & bind to carbohydrate markers on foreign cell membranes • Triggersreceptor-mediated endocytosis • Engulf & digest pathogens via Phagocytosis

11. Eosinophils: 1.5% of WBCs; destroy large parasites extracellularly Natural killer (NK) cells: trigger apoptosis in virus-infected cells & cancer cells Neutrophils: 60-70% of WBCs; engulf and destroy microbes at infected tissue; short lived Monocytes: 5% of WBCs; develop into…. Macrophages: “big eaters” enzymatically destroy microbes; can be found in spleen, lymph nodes, and other organs Types of White Blood Cells

12. Leukocyte vs. Lymphocyte • Leukocyte = • White blood cells (WBC’s) • Lymphocyte = • Specific type of WBC that mature and migrate through the lymphatic system and target specific antigens via antibodies, receptors and toxin release

13. The Inflammatory Response • “Inflammation” = pain, swelling, fever, redness, itching, and pus

14. Causes of Inflammation • Injuries • Exposure to microbes/pathogens • Exposure to foreign objects or chemicals (insect bites, stings, medications, etc) • Exposure to allergens (pollen, pet dander, foods, etc) • Rare: sunlight, temperature, self!

15. The Inflammatory Response3 Steps: 1.Tissue damage = release of chemical signals~ • Mast cells release chemicals known as Histamine & Prostaglandins that trigger inflammation 2.Dilation increases permeability of capillaries~ • Increased blood flow; leukocytes leak out to infected area • Delivery of clotting factors & antimicrobial proteins 3. Phagocytosis of pathogens~ • WBC’s engulf microbes or damaged tissue • Fever: leukocyte-released chemicals increase body temperature

16. Acquired Immunity:Lymphocytes are the Key Defenders

17. Specific Immunity • Antigen: • a foreign molecule that elicits a response from a lymphocyte • Lymphocyctes: • WBC’s that originate from stem cells in bone marrow • B Cells (mature in bone marrow) • T Cells (mature in thymus) • Antibodies: • antigen-binding immunoglobulin, produced by B cells • Antigen receptors: • membrane receptors on B and T cells

18. Ch. 43 Research: • Humoral vs. Cell-mediated Responses • B cells vs. T cells • Memory cells • Clonal selection • Autoimmune disease

19. T cells: Mature in Thymus Target antigen fragments bound to MHC molecules on Infected Cells Part of Cell Mediated Response B cells: Mature in Bone Marrow Target in-tact Antigens Part of Humoral Response T cells vs. B cells

20. Humoral vs. Cell-Mediated Humoral immunity • B cell activation • Production of antibodies • Defend against intact antigens free in the lymph and blood plasma • (bacteria, toxins, and viruses)

21. Humoral response: B cells • Stimulated by an antigen-presenting macrophage(WBC w/ a germ on it) • Activates Helper T cells • T cells secrete cytokine chemicals that activate B cells • B cells differentiate into memory B cells and antibody-producing plasma cells

22. Cytokines • Cytokine: • Proteins secreted by phagocytic cells (macrophages, etc.) and T-helper cells • Activate Lymphocytes (B & T cells)

23. Humoral Response: • B cells activate. • Plasma cells secrete antibodies. • Antibodies attach to antigens. • Antigens agglutinate (stick together) & get disposed. • Macrophages phagocytose or lyse the cell.

24. Cell-Mediated Cell-mediated immunity • T cells are activated. • T cells bind to and/or lyse infected cells. • Defend against cells infected with bacteria, viruses, fungi, protozoa, parasites, even cancer!

25. Cell-mediated Response • 1) Cell surface molecules expose antigens (foreign proteins). • 2) Cytotoxic T cell releases perforin, a protein that forms pores in the target cell membrane. • causes cell lysis and exposes pathogens to circulating antibodies for disposal

26. Cell Mediated Response Humoral Response Antigens on Infected Cells In Tact Antigens B Cell Activation T Cell Activation Secrete antibodies that defend against pathogens & toxins in extracellular fluid Defend against infected cells, cancer and transplanted tissues

27. Clonal Selection • Clonal selection: • antigen-driven cloning of lymphocytes • Effector cells: • short-lived cells that combat the antigen initially • Memory cells: • long-lived cells that bear receptors for the antigen and activate upon subsequent exposure.

28. Active vs. Passive Immunity • Active: natural exposure to antigens causes one’s own lymphocytes to activate and produce antibodies • May also be acquired by Immunizations • Passive: direct transfer of antibodies through placenta or mother’s milk

29. HIV • Human Immunodeficiency Virus • Causes AIDS (Acquired Immune Deficiency Virus) • HIV (a retrovirus) attacks helper T cells by binding with their cell receptor (CD4) • This impacts both the Humoral and Cell Mediated responses 

30. Clonal Selection Hypothesis • Each lymphocyte bears one specific type of receptor. • Receptor/antigen binding is required for cell activation. • Activated lymphocytes divide and give rise to cells with identical receptors to the parent. • This is how your immune system “remembers” a pathogen later!

31. Clonal Selection Hypothesis • First, those lymphocytes bearing receptors compatible to “self” tissues are destroyed (3) • Second, those bearing receptors that match foreign antigens are activated then cloned (5/6)

32. Self/Nonself Recognition • Self-tolerance: • Capacity to distinguish self from non-self molecules • Autoimmune diseases: • Failure of self-tolerance mechanisms • Multiple sclerosis, lupus, rheumatoid arthritis, insulin-dependent diabetes mellitus, Crohn’s disease

33. Abnormal immune function • Allergies: • hypersensitive responses to environmental antigens (allergens) • causes dilation and blood vessel permeability • Histamines are released from Mast cells • Autoimmune disease: • multiple sclerosis • Lupus • rheumatoid arthritis • insulin-dependent diabetes mellitus • Immunodeficiency disease: • SCIDS (bubble-boy) • A.I.D.S. (HIV)

34. Cancer & the Immune System • Tumor cells are targeted by both Cytotoxic T cells and Natural Killer (NK) cells • How might some tumors escape detection??

35. Treg research: Article Review • What are “Regulatory T Cells” (Tregs)? • What is their role in immunity? • How might they be linked with cancer? • Article: “Regulatory T cells and tumour immunity – observations in mice and men” by Gallimore and Godkin, 2007

36. Major Histocompatibility Complex • Aka: “MHC” • Cell surface proteins that display fragments of antigens or processed proteins on the cell surface • Epitope: • region of antigen surface recognized by antibodies

37. Induction of Immune Responses • Primary immune response: • lymphocyte proliferation and differentiation the 1st time the body is exposed to an antigen • Plasma cells: • antibody-producing B-cells • Secondary immune response: • immune response if the individual is exposed to the same antigen at a later time~ Immunological memory

38. Types of Immunoglobins • IgM: • 1st to circulate; indicates infection; too large to cross placenta • IgG: • most abundant; crosses walls of blood vessels and placenta; protects against bacteria, viruses, & toxins; activates complement • IgA: • produced by cells in mucous membranes; prevent attachment of viruses/bacteria to epithelial surfaces; also found in saliva, tears, and perspiration • IgE: • very large; small quantity; releases histamines-allergic reaction

39. Antibody-Mediated Antigen Disposal • Neutralization (opsonization): • antibody binds to and blocks antigen activity • Agglutination: • antigen clumping • Precipitation: • cross-linking of soluble antigens • Complement fixation: • lyses viruses and pathogenic cells & activates cell surface proteins to break down the cell

40. Immunity in Health & Disease • Active immunity: • natural: conferred immunity by recovering from disease • artificial: immunization and vaccination; produces a primary response • Passive immunity: • transfer of immunity from one individual to another • natural: mother to fetus; breast milk • artificial: rabies antibodies • ABO & Rh blood groups (antigen presence)