The Body’s Defenses Chapter 43

Lines of Defense Innate Immunity: Rapid Response Acquired Immunity: Slower Response

Skin and secretions create a hostile environment for microbes 1st Line Nonspecific Defense Mechanisms: Innate Immunity Barrier Defenses Skin & mucous membrane linings of: digestive, respiratory, urinary, and reproductive systems Mucus – thick fluid to trap microbes and particles Skin and secretions create a hostile environment for microbes

Natural killer (NK) cells 2nd Line Nonspecific Defense Mechanisms: Innate Immunity Phagocytic WBC’s and Natural Killer Cells Neutrophils 60-70% WBCs; engulf and destroy microbes at infected tissue Macrophages engulf and enzymatically destroy microbes (big eaters) Eosinophils 1.5% WBCs; discharge enzymes to destroy multicellular parasitic invaders (blood flukes) Natural killer (NK) cells destroy virus-infected body cells & abnormal cells (tumor cells)

2nd Line Nonspecific Defense Mechanisms: Innate Immunity Inflammatory Response 1. Tissue injury; release of chemical signals histamine released from mast cells and signals from macrophages increases blood flow & blood vessel permeability to injured area 2. Swelling occurs Increased blood flow causes excess fluid to exit capillaries causing swelling, heat, and redness 3. Phagocytosis of pathogens Phagocytic WBC’s enter the injured site from the blood stream and inactivate any microbes An accumulation of WBC’s forms pus – fluid rich in WBC’s, dead microbes, and cell debris Toxins released by pathogens and pyrogens released by macrophages can cause fever

Antibodies: antigen-binding protein, produced by B cells 3rd Line Specific Defense Mechanisms: Acquired Immunity What’s Involved? Lymphocytes: from pluripotent stem cells in marrow; recognize and inactivate foreign cells and molecules B Cells (bone marrow) T Cells (thymus) Antigen: a foreign molecule that elicits a response by lymphocytes (virus, bacteria, fungus, protozoa, parasitic worms) Antibodies: antigen-binding protein, produced by B cells Antigen receptors: plasma membrane receptors on B and T cells B cells make antibodies that bind directly to the pathogen’s antigens T cells bind to antigens that are displayed by antigen-presenting cells on their MHC’s (infected body cells) causing them to lyse

Self-tolerance: capacity to distinguish self from non-self 3rd Line Specific Defense Mechanisms: Acquired Immunity Self vs. Non-Self Recognition Major Histocompatibility Complex (MHC): body cell surface proteins that can present foreign antigen fragments; coded for by a family of genes Class I MHC molecules: found on all nucleated cells; display foreign peptide antigens synthesized from viral/bacterial mRNA; signals to cytotoxic T cells; death of cell Class II MHC molecules: found on dendritic cells, macrophages, & B cells; display antigen epitopes from pathogen’s that have been engulfed; signals cytotoxic T cells and helper T cells Self-tolerance: capacity to distinguish self from non-self Autoimmune diseases: failure of self-tolerance; multiple sclerosis, lupus, rheumatoid arthritis, insulin-dependent diabetes mellitus Class I MHC molecules present peptide fragments of antigens that are produced in virus hijacked cells. Viruses insert their DNA or RNA into a host cell and the host cell begins manufacturing the antigens/glycoproteins for the membrane. These antigens are broken down by proteasomes and the fragments (small amino acid fragments – aka peptides) are attached to a Class I MHC molecule and sent to the cell membrane for display

Class I MHC Class II MHC

Activated B and T cells divide many times producing: 3rd Line Specific Defense Mechanisms: Acquired Immunity B and T Cell Activation: Clonal Selection Activated B and T cells divide many times producing: Effector cells: short-lived cells that combat the antigen and any pathogens producing that antigen (B cells = plasma cells; T cells = cytotoxic and helper) Memory cells: long-lived cells that bear receptors for the antigen These cells are specific for the particular antigen

Acquired Immune Responses Primary immune response: lymphocyte activation the 1st time the body is exposed to an antigen; includes clonal selection Secondary immune response: immune response if the individual is exposed to the same antigen at some later time - immunological memory (memory cells)

Types of Acquired Immune Responses Humoral Immune Response Activation and clonal selection of: Effector B cells (plasma cells), which produce antibodies that circulate in the blood & lymph Memory B cells Cell-mediated Immune Response Effector T cells (cytotoxic & helper), which identify and destroy infected cells Memory cytotoxic & helper T cells

Helper T Cells Function in enhancing humoral & cell-mediated responses Stimulated by antigen-presenting cells (Class II MHC) Dendritic cells, macrophages, & B cells CD4 surface protein enhances activation Secreted cytokines stimulate helper T cell to clone additional activated helper T cells with the same antigen receptor New helper T cells then release other cytokines to activate B cells and cytotoxic T cells

Cytotoxic T Cells Destroy cells infected by intracellular pathogens and cancer cells Stimulated by nucleated body cells presenting foreign antigen fragments (Class I MHC) CD8 surface protein enhances activation Cytotoxic T cell releases perforin, a protein that forms pores in the infected cell’s membrane; cell lyses and pathogen is exposed to circulating antibodies marking it for disposal Cytotoxic T cell can move on and destroy more infected cells

Active and Passive Immunity Active immunity: develops naturally in response to an infection or artificially by immunization (vaccines) Passive immunity: transfer of immunity from one individual to another natural: mother to fetus via breast milk artificial: rabies antibodies via 1 painful shot followed by 4 vaccine shots to develop active immunity Rabies post-exposure vaccinations consists of a dose of human rabies immune globulin and four doses of rabies vaccine given on the day of the exposure, and then again on days 3, 7, and 14. The vaccine is given in a muscle, usually in the upper arm. This set of vaccinations is highly effective at preventing rabies if given as soon as possible following an exposure. Administration of rabies immunoglobulin (RIG) should be infiltrated into the depth of the wound and around the wound as much as anatomically feasible. Any remainder should be injected at an intramuscular site distant from that of vaccine inoculation e.g. into the anterior thigh. Amount given depends on your weight.

Abnormal Immune Function Allergies (anaphylactic shock): hypersensitive responses to environmental antigens (allergens); causes dilation and blood vessel permeability (by histamines) which lowers blood pressure; epinephrine Autoimmune disease: multiple sclerosis, lupus, rheumatoid arthritis, insulin-dependent diabetes mellitus Immunodeficiency disease: SCIDS (bubble-boy); A.I.D.S. HIV attacks helper T cells rendering them nonfunctional and then HIV multiplies within the deactivated T cells When the immune system can no longer fight normal infections then the person is diagnosed with A.I.D.S.