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Host Defense Mechanisms

LECTURES IN MICROBIOLOGY. Host Defense Mechanisms. Sofronio Agustin Professor. LESSON 12. Topics. Nonspecific Resistance: (1) Intact skin, mucous membranes, normal microbiota. (2) Phagocytic leukocytes, inflammation, fever Specific Resistance: (1) Antibodies

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Host Defense Mechanisms

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  1. LECTURES IN MICROBIOLOGY Host Defense Mechanisms Sofronio Agustin Professor LESSON 12

  2. Topics Nonspecific Resistance: (1) Intact skin, mucous membranes, normal microbiota. (2) Phagocytic leukocytes, inflammation, fever Specific Resistance: (1) Antibodies (2) Specialized T- and B-cells

  3. Terms • Susceptibilityvulnerability of the host to disease • Resistance ability of the host to ward off disease • Nonspecific resistance host defenses against any pathogen • Specific resistance host defenses against a specific pathogen

  4. Mechanical Factors • Skin • Epidermis consists of tightly packed cells with protective layer of keratin

  5. Mechanical Factors • Mucous membranes • Ciliary escalator– transport microbes trapped in mucus away from the lungs • Lacrimal apparatus – washes eye • Saliva– washes microbes off • Urine– flows out • Vaginal Secretions – flows out

  6. Mechanical Factors Lacrimal glands Ciliary escalator

  7. Chemical Factors • Fungistatic fatty acids in sebum • Low pH (3-5) of skin • Low pH (1.2-3.0) of gastric juice • Lysozyme in sweat, tears, saliva and tissue fluids

  8. Normal Microbiota • Microbial antagonism – normal microbiota compete with pathogens for food and space. • Also known as Competitive exclusion

  9. Formed Elements in Blood

  10. Leukocytes

  11. Leukocytes Neutrophils Phagocytic Basophils Produce histamine Eosinophils Toxic to parasites Monocytes Phagocytic as mature macrophages Lymphocytes Involved in specific immunity Mast cells Wandering macrophages that roam tissues Fixed macrophages in lungs, liver, bronchi

  12. Macrophage

  13. Phagocytosis

  14. Inflammation Redness Pain Heat Swelling (edema) Acute-phase proteins activated - complement, cytokine, kinins Vasodilation - histamine, kinins, prostaglandins, leukotrienes Margination and emigration of WBCs Tissue repair

  15. Inflammation

  16. Inflammation

  17. Fever • Hypothalamus normally set at 37°C • Gram-negative endotoxin cause phagocytes to release interleukin 1 • Hypothalamus releases prostaglandins that reset the hypothalamus to a high temperature • Body increases rate of metabolism and shivering to raise temperature • When IL-1 is eliminated, body temperature falls. (Crisis)

  18. The Complement System Serum proteins are activated in a cascading fashion

  19. Effects of Complement Activation Opsonization or immune adherence: enhanced phagocytosis Membrane attack complex: cytolysis Attract phagocytes

  20. Interferons Alpha IFN & Beta IFN - cause cells to produce antiviral proteins that inhibit viral replication Gamma IFN - causes neutrophils and macrophages to phagocytize bacteria

  21. Interferons

  22. The Immune Response Immunity ability of the host to counteract effects of invading microbes and other foreign substances. Innate immunity genetically predetermined resistance of the host to certain diseases. Acquired immunity specific resistance to diseases developed after birth or during the life of the individual.

  23. Acquired Immunity

  24. Antigen Antigen (Ag)a substance that causes the body to produce antibodies and sensitized T cells. “Foreign” substance with molecular weight > 10,000.

  25. Hapten Hapten - low molecular weight substance that reacts with antibody but cannot stimulate antibody formation without a carrier molecule.

  26. Epitopes

  27. Humoral Immunity Antibody (Ab) a protein, specifically an immunoglobulin (Ig) produced in response to antigenic stimulation Humoral response involves antibodies produced by B cells Sensitized T Cells specialized lymphocytes that interact with and respond to cellular and intracellular antigens.

  28. Cell-mediated Immunity Sensitized T Cells specialized lymphocytes that interact with and respond to cellular and intracellular antigens Cellular response involves activated specialized T cells

  29. Lymphocytes Lymphocyte subsets involved in immune response

  30. Antibodies Antibodies are serum proteins that migrate as gamma globulin in electrophoresis; hence, sometimes called immunoglobulins (Ig).

  31. Antibody Structure

  32. Antibody Structure

  33. Immunoglobulin Classes

  34. IgG Antibodies • Monomer • 80% of serum antibodies • Fix complement • In blood, lymph, intestine • Cross placenta • Enhance phagocytosis • Neutralize toxins & viruses • Protects fetus & newborn • Half-life = 23 days

  35. IgM Antibodies • Pentamer • 5-10% of serum antibodies • Fix complement • In blood, lymph, on B cells • First Ab produced in response to infection • Agglutinates microbes • Half-life = 5 days

  36. IgA Antibodies • Dimer • 10-15% of serum antibodies • In secretions • Mucosal protection • Half-life = 6 days

  37. IgD Antibodies • Monomer • 0.2% of serum antibodies • In blood, lymph, on B cells • On B cells, initiate immune response • Half-life = 3 days

  38. IgE Antibodies • Monomer • 0.002% of serum antibodies • On mast cells and basophils • Allergic reactions • Lysis of parasitic worms • Half-life = 2 days

  39. Clonal Selection Bone marrow gives rise to B cells. Mature B cells migrate to lymphoid organs. A mature B cells recognizes epitopes.

  40. Clonal Selection

  41. Self-Tolerance • Self-tolerance - body does not make Ab against self • Clonal deletion - the process of destroying B and T cells that react to self antigens

  42. Ag-Ab Binding

  43. Antibody Titer

  44. Cell-Mediated Immunity • Specialized lymphocytes, mostly T cells that respond to intracellular antigens. • After differentiating in the thymus, T cells migrate to lymphoid tissue. • T cells differentiate into effector T cells when stimulated by an antigen. • Some effector T cells become memory cells.

  45. Antigen-Presenting Cells • Pathogens entering the gastrointestinal and respiratory tracts pass through: • M (Microfold) cells in Peyer's patches which contains Dendritic cells which are antigen- presenting cells and T cells.

  46. Dendritic Cells An antigen-presenting cell

  47. Cell-Mediated Immunity

  48. T Cells • Helper T Cells (CD4, TH): • TH1 Activate cells related to cell-mediated immunity. • TH2 Activate B cells to produce eosinophils, IgM, and IgE • Cytotoxic T Cells (CD8, TC): • Destroy target cells with perforin

  49. T Cells • Delayed Hypersensitivity T Cells (TD): • Associated with allergic reaction, transplant rejection, and tuberculin skin test. • Suppressor T cells (TS): • Turn off immune response when antigen is • no longer present.

  50. Helper T Cells

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