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Chapter 21: Immune System

Chapter 21: Immune System. Innate System. Nonspecific, rapid response Fast response First line of defense skin and mucous membranes second line of defense Phagocytes, NK Cells Inflammation Complement Fever . Adaptive System. Specific, slow response Third line of defense

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Chapter 21: Immune System

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  1. Chapter 21: Immune System

  2. Innate System Nonspecific, rapid response Fast response First line of defense skin and mucous membranes second line of defense Phagocytes, NK Cells Inflammation Complement Fever

  3. Adaptive System Specific, slow response Third line of defense Humoral Immunity (B Cells) Cellular Immunity (T Cells) Both systems work together

  4. Innate and Adaptive Defenses Figure 21.1

  5. Innate Barriers Epithelial Chemical barrier (pH of 3 to 5) Dermcidinin in sweat Lipids in sebum Vaginal secretions HCl in stomach secretions Lysozyme in saliva Mechanical Barrier Mucus Cillia

  6. Innate Barriers Physiological Temperature Low pH Chemical mediators Inflammation Non-specific cells Natural Killer Cells (NK cells) Macrophages Neutrophils

  7. Macrophage

  8. Natural Killer (NK) Cells Detect cancer and virus-infected cells Large granular lymphocytes Nonspecific Attack by releasing perforins and other cytolytic chemicals Enhance the inflammatory response

  9. Inflammation Response to tissue insult or injury Prevents the spread of damaging agents to nearby tissues Disposes of cell debris and pathogens Sets the stage for repair processes Five cardinal signs inflammation Mast cells play a key role http://www6.ufrgs.br/favet/imunovet/molecular_immunology/inflammation_cartoon.jpg

  10. 5 Cardinal Signs of Inflammation http://www6.ufrgs.br/favet/imunovet/molecular_immunology/inflammation_cartoon.jpg

  11. Inflammation Response Release of inflammatory mediators Kinins, prostaglandins (PGs), complement, and cytokines Bind to Toll-like receptors (TLRs) Cause local small blood vessels to dilate, resulting in hyperemia http://www6.ufrgs.br/favet/imunovet/molecular_immunology/inflammation_cartoon.jpg

  12. Toll-like Receptors (TLRs) Macrophages, epithelial cells in GI tract and respiratory system Detect specific classes of infecting microbes Cytokine release promotes inflammation and cellular responses

  13. Vascular Permeability Increased permeability of local capillaries Exudate—fluid containing proteins, clotting factors, and antibodies Exudate seeps into tissue spaces causing local edema (swelling), which contributes to the sensation of pain http://www6.ufrgs.br/favet/imunovet/molecular_immunology/inflammation_cartoon.jpg

  14. Edema The surge of protein-rich fluids into tissue spaces Dilute harmful substances Oxygen and nutrients needed for repair Clotting proteins prevent the spread of bacteria

  15. Phagocytic Mobilization Four main phases: Leukocytosis – neutrophils are released from the bone marrow in response to leukocytosis-inducing factors released by injured cells Margination – neutrophils cling to the walls of capillaries in the injured area Diapedesis – neutrophils squeeze through capillary walls and begin phagocytosis Chemotaxis – inflammatory chemicals attract neutrophils to the injury site Animation

  16. Figure 21.3

  17. Antimicrobial Proteins • Enhance the innate defenses by attacking microorganisms directly • The most important: • Interferon -chemotactic • Complement proteins -destructive

  18. Interferon (IFN) • Activated T cells and NK secret interferon • Interferon chemotactic, activating many other immune cells • Response may be phagocytic or directly interrupt viral replication • FDA-approved alpha IFN is used: • As an antiviral drug against hepatitis C virus • To treat genital warts caused by the herpes virus

  19. Interferon (IFN) Figure 21.5

  20. Complement • Circulating protein components which interact causing: • Lysis of cells, bacteria, viruses • Opsonization, promoting detection and phyagocytosis • Opsonization triggers inflammation and secretion of immunoregulatory molecules • Results in immune clearance

  21. Complement Pathways • Two pathways • Classical pathway is part of cell mediated immunity • Alternative pathway is part of innate immunity

  22. Complement: Classical Pathway • Cell mediated immunity • Antibodies bind to invading organisms • Binding of complement proteins to the antigen-antibody complexes (complement fixation) • Membrane Attack Complex (MAC) • Lysis of cells

  23. Complement: Alternative Pathway • Innate immunity • Antibody independent • Components of pathogens are recognized by complement proteins • Membrane Attack Complex (MAC) • Lysis of cells

  24. Complement Pathways • Each pathway is a cascade • complement proteins are activated in a sequence • Each step catalyzes the next • Pathways converge and follow the same final cascade • Membrane Attack Complex (MAC) forms channels in target cells plasma membrane • Result is lysis of cell

  25. Complement Pathways Figure 21.6

  26. C-reactive Protein (CRP) • Produced by the liver in response to inflammatory molecules • Activates complement • CRP is a clinical marker used to assess: • The presence of an acute infection • inflammatory condition and its response to treatment

  27. Fever • Increase in body temperature in response to infection • Pyrogen -cytokines secreted by leukocytes and macrophages • Activate temperature control sites in hypothalamus • Most pathogens thrive at temperatures lower than 37°C • High fever is dangerous, proteins denature

  28. Innate Immunity Summery • Surface Barriers • Epithelia: chemical, acidity, sebum, mucus, cillia • Cellular Barriers • Mast cells, Neutrophils, NK cells, macrophages • Physiological Barriers • Antimicrobial Proteins: TLR, CRP, Complement • Inflammation • Fever

  29. Adaptive (Specific) Defenses • Recognizes specific foreign substances • Immobilizes, neutralizes, or destroys foreign substances • Amplifies inflammatory response • Activates complement • Antigen-specific, systemic, and has memory • Two divisions • Humoral, or antibody-mediated immunity (B cell) • Cellular, or cell-mediated immunity (T cell)

  30. Vocabulary

  31. Antigens • Any substance that binds specifically to an antibody or a T-cell receptor • Immunogenicity – ability of a substance to induce an immune response under a given set of circumstances • Antigenicity (Reactivity) – ability to combine specifically with the final products of immunogenicity • Examples: foreign protein, nucleic acid, some lipids, and large polysaccharides

  32. Haptens (Incomplete Antigens) • Small molecules, • Not immunogenic but are antigenic • Attached to protein carriers • Adaptive immune system may recognize them as foreign and mount a harmful attack (allergy) • Examples: poison ivy, dander, some detergents, and cosmetics

  33. Epitopes (Antigenic Determinants) • Specific part of antigen that is immunogenic • Epitopes are bound by antibodies and activated lymphocytes • Some antigens have numerous epitopes • Mobilize several lymphocyte populations • Varied antibodies formed

  34. Epitopes Epitope Figure 21.7

  35. MHC Proteins • Major Histocompatability Complex Proteins • Antigen presenting glycoproteins • Two classes of MHC proteins are: • Class I MHC proteins – present peptide antigens from intracellular replicating pathogens • Viruses and some bacteria • Class II MHC proteins – present peptide antigens from extracellular pathogens • Bacteria

  36. Cells

  37. Adaptive Immune System Cells • Lymphocytes • B lymphocytes – oversee humoral (antibody) immunity • T lymphocytes – non-antibody-producing cells that constitute the cell-mediated arm of immunity • Antigen-presenting cells (APCs): • Do not respond to specific antigens • Present or display antigens

  38. Lymphocytes • Immature lymphocytes released from bone marrow are essentially identical • Type of lymphocyte determined by the tissue cells mature in • B cells mature in the bone marrow • T cells mature in the thymus

  39. T Cells • T cells mature in the thymus under negative and positive selection pressures • Negative selection – eliminates T cells that are strongly anti-self • Positive selection – selects T cells with a weak response to self-antigens • Self tolerant and immunocompetent

  40. T Cell Selection in the Thymus Figure 21.9

  41. Antigen-Presenting Cells (APCs) • Engulf foreign particles • Present antigen to T cells • Major APCs are dendritic cells (DCs), macrophages, and activated B cells • Dendritic cells are initiators of adaptive immunity

  42. Humoral Response

  43. Humoral Immune Response • Clonal selection of B cells • Immunological Memory • Active and Passive Immunity • Antibodies

  44. B Cells • B cells become immunocompetent and self-tolerant in bone marrow • Exposed to initial antigen creating memory cell • Subsequent antigen challenge results in plasma cell • Specificity due to rearrangements of receptors

  45. Immunological Memory • Primary immune response • Cellular differentiation and proliferation • First exposure to a specific antigen • Lag period: 3 to 6 days after antigen challenge • Peak levels of plasma antibody are achieved in 10 days • Antibody levels then decline

  46. Immunological Memory • Secondary immune response • Re-exposure to the same antigen • Sensitized memory cells respond within hours • Antibody levels peak in 2 to 3 days at much higher levels than in the primary response • Antibodies bind with greater affinity • Levels in the blood can remain high for weeks to months

  47. Humoral Responses Figure 21.11

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