1. Bio 1b – Zoology Hannah Nevins Immunity: the body’s defense system An immune cell (macrophage) engulfs a yeast cell (pathogen)

2. Invaders : pathogens The immune system recognizes foreign bodies and responds with the production of immune cells and proteins Two strategies have evolved: the innate and the acquired immune systems

3. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Innate Immunity of Invertebrates The digestive system is protected by low pH and an enzyme that digests microbial cell walls called lysosome Hemocytes circulate within hemolymph and carry out phagocytosis, the ingestion and digestion of foreign substances including bacteria In insects, an exoskeleton made of chitin forms the first barrier to pathogens

4. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Innate Immunity of Vertebrates Innate defenses include: – barrier defenses, phagocytosis, antimicrobial peptides Additional defenses are unique to vertebrates: the inflammatory response and natural killer cells The immune system of mammals is the best understood of the vertebrates

5. Fig. 43-7 Adenoid Tonsil Lymph nodes Spleen Peyer’s patches (small intestine) Appendix Lymphatic vessels Lymph node Masses of defensive cells Blood capillary Lymphatic vessel Tissue cells Interstitial fluid Human Lymphatic system

6. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Barrier Defenses Mucus traps and allows for the removal of microbes Many body fluids including saliva, mucus, and tears are hostile to microbes The low pH of skin and the digestive system prevents growth of microbes Barrier defenses include the skin and mucous membranes of the respiratory, urinary, and reproductive tracts

7. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Cellular Innate Defenses White blood cells (leukocytes) engulf pathogens in the body Groups of pathogens are recognized by Toll- like receptors (TLR)

8. Fig. 43-3 Microbes PHAGOCYTIC CELL Vacuole Lysosome containing enzymes Phagocytosis: (=eating, =cells) engulfing pathogens Exocytosis – cellular debris is released

9. Phagocytosis A white blood cell engulfs a microbe, then fuses with a lysosome to destroy the microbe There are different types of phagocytic cells: Neutrophils engulf and destroy microbes Macrophages are part of the lymphatic system and are found throughout the body Eosinophils discharge destructive enzymes Dendritic cells stimulate development of acquired immunity

10. Cell Types: Red & White

11. Fig. 43-8-1 PathogenSplinter Macrophage Mast cell Chemical signals Capillary Phagocytic cell Red blood cells How your skin keeps out pathogens Ruptured mast cells (in tissue) release histamines  chemical signal to other phagocytic cells Capillaries dilate,  increase blood flow  increase phagocytic cells The clotting process also starts Platelets Clotting factors signal Fibrin produced

12. Fig. 43-8-2 PathogenSplinter Macrophage Mast cell Chemical signals Capillary Phagocytic cell Red blood cells Fluid

13. Fig. 43-8-3 PathogenSplinter Macrophage Mast cell Chemical signals Capillary Phagocytic cell Red blood cells Fluid Phagocytosis More phagocytic cells are released Pathogenic bacteria are engulfed and destroyed Pus, a fluid rich in white blood cells, dead microbes, and cell debris, accumulates at the site of inflammation

14. Fig. 43-7 Thymus Lymph nodes Spleen Lymphatic vessels Lymphocyte maturation White blood cells called lymphocytes recognize and respond to antigens, foreign molecules Lymphocytes that mature in the thymus above the heart are called T cells, and those that mature in bone marrow are called B cells

15. Acquired Immunity results from B- and T-cells T-cells Thymus Combats viruses (intracellular pathogens) B-cells Bone marrow & spleen Combats bacteria (extracellular pathogens)

16. Cell Types: Red & White

17. Pathogens have antigens, B-cells have antibodies Antigens: Each pathogen type has unique surface molecules Antibody binding: Causes antibodies to be secreted from B-cell Antibodies: Surface proteins of B- cell Match antigens

18. Fig. 43-9 Antigen- binding site Antigen- binding site Antigen- binding site Disulfide bridge Variable regions Constant regions Transmembrane region Plasma membrane Light chain Heavy chains T cell  chain  chain Disulfide bridge Cytoplasm of T cell (b) T cell receptor Cytoplasm of B cell (a) B cell receptor B cell V V C C V V CCCC VV Both B- and T-cells have Antigen binding sites

19. Fig. 43-10 Antigen-binding sites Antigen- binding sites Epitopes (antigenic determinants) Antigen Antibody B Antibody C Antibody A CC C V V V V C

20. Lymphocyte Development The acquired immune system has three important properties: Receptor diversity A lack of reactivity against host cells Immunological memory

21. A Pathogen is tagged for Attack; a B-cell is “selected for cloning Antibodies cause: Neutralization Agglutination Precipitation rupture Selection causes rapid clonal replication Selection Replication

22. Fig. 43-14 B cells that differ in antigen specificity Antibody molecules Antigen receptor Antigen molecules Clone of memory cellsClone of plasma cells

23. The B-cells form Two cell Types: Memory Cells Long-lived Await future encounters with specific antigen Plasma Cells Secrete many antibodies to mark and block more bacteria Selection Replication

24. Secondary Immune Response Get a disease, you get natural immunization e.g. chicken pox Immunization: injecting chemical or heat inactivated antigens a.k.a vaccination Antibodies to A Antibodies to B Secondary immune response Primary immune response Antibody concentration Exposure to antigen A Exposure to antigens A and B Time (days) 10 4 10 3 10 2 10 1 10 0 0714212835424956

25. Fig. 43-15 Antibodies to A Antibodies to B Secondary immune response to antigen A produces antibodies to A; primary immune response to antigen B produces antibodies to B. Primary immune response to antigen A produces antibodies to A. Antibody concentration (arbitrary units) Exposure to antigen A Exposure to antigens A and B Time (days) 10 4 10 3 10 2 10 1 10 0 0714212835424956

26. Pathogens can evolve to avoid detection Some pathogens change surface proteins Memory cells can not recognize Pathogens have shorter generation time relative to host, :. they can evolve faster What does this mean for the efficacy of any given human-made antibiotic? Some pathogens like AIDS hide inside your body’s cells Intracellular invaders are dealt with by T-cells

27. Like B-cells, T-cells have… Diverse antigen receptors Two types: Cytotoxic T-cell, Helper T-cell Fig. 43-12 Infected cell Antigen fragment Class I MHC molecule T cell receptor (a) Antigen associates with MHC molecule T cell recognizes combination Cytotoxic T cell(b)Helper T cell T cell receptor Class II MHC molecule Antigen fragment Antigen- presenting cell Microbe 1 1 1 2 2 2

28. Fig. 43-18-1 Cytotoxic T cell Perforin Granzymes TCR CD8 Class I MHC molecule Target cell Peptide antigen Once bound to CD8 receptor, T-cell becomes an “active killer” Cytotoxic T-cells

29. Fig. 43-18-2 Cytotoxic T cell Perforin Granzymes TCR CD8 Class I MHC molecule Target cell Peptide antigen Pore Perforins – create pores in surface of target cell Granzymes – enter cell initiate apoptosis (cell death) Cytotoxic T-cells

30. Fig. 43-18-3 Cytotoxic T cell Perforin Granzymes TCR CD8 Class I MHC molecule Target cell Peptide antigen Pore Released cytotoxic T cell Dying target cell Perforins – create pores in surface of target cell Granzymes – initiate apoptosis (cell death) Cytotoxic T-cells

31. Fig. 43-17 Antigen- presenting cell Peptide antigen Cell-mediated immunity (attack on infected cells) Class II MHC molecule CD4 TCR (T cell receptor) Helper T cell Humoral immunity (secretion of antibodies by plasma cells) Cytotoxic T cell Cytokines B cell Bacterium + ++ +

32. Cytotoxic T-cells attack diseased of cancerous cells labeled with MHCs Normal cells make MHC (Major Histocompatibility Complex) molecules Abnormal cells –like those with viruses – make MHCs which bind to viral proteins Those antigens are presented on the surface of the infected cell Then detected by cytotoxic T-cells … and the infected cell is destroyed

33. Major Histocompatibility Complex Genes have ~100 Alternative Alleles Each MHC type presents a different type of antigen for T-cells to recognize as alien Gene polymorphism increases chances of matching antigens Thus increased MHC diversity = increased disease resistance One study looked at male selection using old t-shirts and MHC analysis: females favor males with MHCs which differ from their own --- why is this adaptive?