The body’s defenders

1. The body’s defenders

2. Core concepts • Infectious diseases are caused by pathogens • Nonspecific defenses against infection • Plants and animals have mechanisms that are not targeted to specific pathogens that help them combat infection • Skin and mucous membranes provide first-line barriers to infection • Phagocytic cells, inflammation, and antimicrobial proteins function as the second line of defense • Specific immunity arises from lymphocyte-antigen interactions • Lymphocytes provide the specificity and diversity of the immune system • Antigens interact with specific lymphocytes, inducing immune responses and immunological memory • Lymphocyte development gives rise to an immune system that distinguishes self from nonself • Immune responses take two forms: humoral and cell-mediated • Helper T-lymphocytes function in both humoral and cell-mediated immunity • Cytotoxic T-cells counter intracellular pathogens • B-cells make antibodies against extracellular pathogens • Memory B- and T-cells are responsible for faster and stronger secondary immune responses • Immunity in health and disease • Immunity can be achieved naturally or artificially • The immune system limits blood transfusion and tissue transplantation • Abnormal immune function can lead to disease • AIDS is an immunodeficiency disease caused by a virus

3. Keywords • memory cell • monocytes • natural killer cells • neutrophils • nonspecific defense • opportunistic disease • passive immunity pathogen • perforin • phagocytosis • plasma cell • primary immune response • prostaglandins • pyrogens • Rh factor • secondary immune response • suppressor T cell • T cell • T cell receptor • target cell • tumor antigen • vaccine • chemokines • class I MHC • class II MHC • clonal selection • complement fixation • complement system • cytokine • cytotoxic T cell • effector cell • eosinophils • helper T cell • histamine • HIV • humoral immunity • immunity • immunodeficiency disease • immunoglobulin • inflammatory response • interferon • interleukin • lysozyme • macrophages • major histocompatibility complex • mast cells • membrane attack complex • ABO blood groups • active immunity • agglutination • AIDS • allergy • anaphylactic shock • antibody • antigen • antigen receptor • antigen-presenting cell • apoptosis • autoimmune disease • B cell • basophils • CD4 • CD8 • cell-mediated immunity

4. Pathogens and disease Fungi Viruses Protozoa Bacteria Large parasites

5. INNATE (NONSPECIFIC) IMMUNITY Rapid responses to a broad range of microbes ACQUIRED (SPECIFIC) IMMUNITY Slower responses to specific microbes External defenses Internal defenses Skin Phagocytic cells Humoral response (antibodies) Mucous membranes Antimicrobial proteins Secretions Inflammatory response Cell-mediated response (cytotoxic lymphocytes) Invading microbes (pathogens) Natural killer cells Two major types of defenses

6. Innate (nonspecific) immunity First line: External defenses Mucus, cilia Tears Mouth bacteria, saliva Skin, oil, sweat, acidity Intestinal flora Gastric juice Acid conditions

7. Microbes MACROPHAGE Vacuole Lysosome containing enzymes Innate immunity Second line: Internal defenses Phagocytic cell 1 • Phagocytes • Attach to and ingest invading microorganisms • Initiate the inflammatory response • Macrophages – migrants or in lymph organs, lungs, kidneys, connective tissues • Antimicrobial proteins • Complement system – lysis of invading cells, triggers inflammation • Interferons – activate macrophages, prevent cell-to-cell spread of viruses • Defensins – secreted by macrophages to damage pathogens 2 3 4 5 6

8. 70% chemotaxis 5% 1.5% histamine

9. Innate immunity Second line: Internal defenses (con’t.) • Inflammatory response • Chemicals involved • Histamines • Prostaglandins • Chemokines • Pyrogens http://www.sumanasinc.com/webcontent/anisamples/dynamicillustrations/inflammatory.html

10. Innate immunity Second line: Internal defenses (con’t.) • Natural killer (NK) cells • Attack virus-infected body cells and cancer cells • Apoptosis (cell death) in cells attacked • Coelomocytes and hemocytes – phagocytes in invertebrates

11. Specific (acquired) immunityThird line of defense Lymphocytes • In blood and lymph • Types • B – cells – mature in marrow • T – cells – mature in thymus • Helper • Cytotoxic/Killer • Regulatory/Suppressor • Memory • Activated by cytokines from phagocytes • Display specificity to epitopes on antigens (antibody generator) • Have specific membrane-bound antigen-receptors

13. Two types of specific immune responses • B and T cells generate clones of • short-lived activated effector cells • long-lived memory cells

14. MHC molecules and T cell function • Class I MHC molecules • Most nucleated cells of the body • Infected/cancerous cells display parts of foreign antigens on surfaces • Recognized by cytotoxic T cells • Class II MHC molecules • Dendritic cells, macrophages, B cells (APCs) display phagocytized antigen fragments on surfaces • Recognized by helper T cells • T cells that have receptors for self-molecules are destroyed  self-tolerance

15. image/svg+xml \\ Clonal selectionantigen-driven cloning of lymphocytes

16. Antibody action

17. Immunity– memory cells initiate a faster, more efficient response upon reinfection

18. Active immunity • Own system develops antibodies • Develops naturally in response to infection • Develops following immunization (artificial immunity) • Long-lasting protection but may take a long time Passive immunity • Antibodies are passed from mother to fetus via the placenta • Antibodies are passed from mother to infant via breast milk (colostrum) • Antibodies may be injected into a nonimmune person (artificial immunity) • Immediate, short-term protection

19. Blood groups and transfusions • Problems with transfusions and transplants • Antigens on RBC’s will determine a person’s blood type: A, B, AB, O blood • Another RBC antigen: Rh factor  Rh+ or Rh-

20. Immune disorders/diseases • Allergies – hypersensitive responses to antigens called allergens • Autoimmune diseases – immune system loses tolerance for self and turns against certain molecules of the body (SLE, diabetes type I, rheumatoid arthritis) • Immunodeficient diseases • Inborn or primary (severe combined ID) • Acquired or secondary • AIDS – HIV attacks CD4 molecules on helper T cells, macrophages, dendritic cells

21. IgE Allergen Histamine 1 3 2 Granule Mast cell 2 Degranulation of the cell, triggered by cross-linking of adjacent IgE molecules, releases histamine and other chemicals, leading to allergy symptoms. 3 1 IgE antibodies bind to receptors or mast cells. On subsequent exposure to the same allergen, IgE molecules attached to a mast cell recog- nize and bind the allergen.