Host Defense Mechanisms Sofronio Agustin Professor Sofronio Agustin Professor LECTURES IN MICROBIOLOGY LECTURES IN MICROBIOLOGY 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 Resistanceability of the host to ward off disease Nonspecific resistancehost defenses against any pathogen Specific resistancehost 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 Ciliary escalatorLacrimal glands

7 Chemical Factors  Fungistatic fatty acids in sebum  Low pH (3-5) of skin  Low pH ( ) 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): TH1Activate cells related to cell-mediated immunity. TH2Activate 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

51 Cell-Mediated Cytotoxicity

52 Nonspecific Cells Activated macrophages: Macrophages stimulated by ingesting antigen or by cytokines Natural killer cells: Lymphocytes that destroy virus-infected cells and tumor cells

53 Antibody-Dependent Cell-Mediated Cytotoxicity

54 Duality of the Immune System