The Immune System

1. The Immune System • The Innate System • The Adaptive System

2. The Innate Immune System “Nonspecific” system • Surface Barriers • Cell and Chemical Responses

3. Innate Immunity: Surface Barriers

4. Innate Immunity: Cell and Chemical Defenses • They do not target specific pathogens • They target abnormal or foreign cells • Six categories: • Phagocytes • Natural killer (NK) cells • Inflammation response • The complement system • Interferons • Fever

5. Phagocytes • Macrophages, neutrophils, eosinophils Adherence and endocytosis Phagocyticendosome Lysosome fuses with endosome, releases hydrolytic acids/enzymes Microbe is killed and digested Exocytosis

6. Natural Killer Cells • Lymphocytes that destroy tumor cells and cells infected with viruses • Not phagocytes, instead release chemicals onto cell membranes • Cytolytic, perforin complexes • The target cell lyses & nucleus disintegrates • NK cells also release substances to stimulate inflammation

12. Inflammation Response • Redness • Increased • Temperature • Swelling • Pain

16. The Complement System • > 20 plasma proteins • Activation triggers cascade of chemical reactions • Molecular Complexes form: • Membrane Attack Complex creates holes in bacterial cell membranes • C3b marks them for phagocytes • C3a and C5a stimulate mast cells to release histamines

17. Interferons- Interfere with viral replication- Block protein synthesis at ribosomes- Activate macrophages- Mobilize NK cells

18. Fever • When macrophages attack foreign matter, they release chemicals called pyrogens into the blood • Endogenous: interleukins, tumor necrosis factors, macrophage inflammatory protein, interferons • Exogenous: Lipopolysaccharides of gram-negative bacteria trigger endogenous factors • The hypothalamus is stimulated to increase body temperature – fever • Liver and spleen sequester iron and zinc • High temp. unfavorable for microbes

19. The Adaptive Immune System “Specific” defense mechanisms • Three characteristics: • recognizes & targets specific foreign substances • protects the entire body, not a specific injury or infection site • has a "memory" to store information from past exposures

20. Cell Recognition Proteins, polysaccharides, glycoproteins signal the identity of the cell (host or foreign) • Major histocompatibility complexes (MHC) • Molecular markers on host cells • Antigens • Substances that mobilize the immune response • Molecular markers on foreign cells, abnormal/infected or cancerous host cells Auto-immune diseases arise when our immune system cannot differentiate “host” from “foreign” cells

21. Key to Adaptive Immune System • Lymphocytes • Originate from stem cells in bone marrow • 30% of circulating WBCs • B cells • mature in Bone marrow • T cells • mature in Thymus Gland • Both types are made in the bone marrow • Immune response may be antibody-mediated (humoral) or cell-mediated

22. Antibody-mediated Immunity • Antibodies: Y-shaped proteins (4 polypeptides) • Made by mature B-lymphocytes • Binds to antigens to form antigen-antibody complex

23. Antibody-mediated Immunity • Immunoglobulin classes • IgD: antigen receptor of B cell • IgM: antigen receptor of B cell (monomer); released by plasma cells during primary response (pentamer) • IgG: most abundant and diverse; targets bacteria, viruses, toxins; main antibody for both primary and secondary response • IgA: found in exocrine secretions; prevents pathogens from attaching to epithelial surface • IgE: bound to mast cells and basophils; mediates inflammation and allergic reaction

24. Antibody-mediated Immunity

25. Antigen Antibody-mediated Immunity Pathogen MHC Macrophage MHC+Antigen • WBC detects a pathogen or abnormal cell • Attacks pathogen • Alerts Helper T cells and B cells • T cells attracted by chemical signals • B cells alerted by using the pathogen’s own antigens Signaling molecules B cell Helper T cell

26. Antibody-mediated Immunity • Antigens bind to specific antibodies on B cell surface • Activation causes B cells to divide rapidly • Plasma cells • produce antibodies • 100 million antibodies/hour • Memory B cells • Remain on “stand by” until activated by helper T cells • Surveillance

27. Cell-mediated Immunity • MHC + antigen complex waves a warning flag • Class II MHC’s found on B cells, some T cells, and antigen-presenting cells • Class I MHC’s found on most cells, except RBCs

28. Antigen Pathogen Cell-mediated Immunity MHC Macrophage MHC + Antigen Signaling molecules • Helper T cells (CD4): • recognize class II MHC • stimulate other immune cells • Cytotoxic T cells (CD8): • recognize class I MHC • kill infected, cancer, or foreign cells • Memory T cells: • reactivate on re-exposure • Suppressor T cells: • suppresses other immune cells Helper T cell Signaling molecules Memory T cell Cytotoxic T cell Activated Cytotoxic T cell Perforin molecules form pores in pathogen cell membrane

29. Cell-mediated Immunity • Helper T-cells facilitate both cell-mediated and antibody-mediated immune responses • Cytotoxic T cells function similar to NK cells, however they only see specific MHC I + antigen complexes

30. Memory B and T Cells are Like…

31. Immune Memory • Primary immune response • first exposure to pathogen • recognition, production of B & T cells • 3 to 6 day lag time • antibodies peak in 10 to 12 days • B & T memory cells created • basis for "immunity" from the disease • Secondary immune response • Memory B & T cells immediately identify the pathogen • faster, longer lasting, more effective than the first • at subsequent infection, new legions of B & T cells form in a few days • often no symptoms are noticed