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AHS C&T5 11/2/12 Role of the Immune System (IS)! A network of cells and tissues that:! 1. Defends the body against invading pathogens! 2. Destroys abnormal/mutant cells within the body (e.g. control of cancer)! 3. Removes ‘worn-out’ cells! Immune System can also have harmful effects:! 1. Allergies / autoimmune diseases! 2. Tissue rejection.! Infection-causing organisms (Pathogens) PARASITE Tapeworm VIRUS BACTERIA Staphylococcus aureus (causes sepsis) Polio FUNGUS Epidermophyton floccosum (Athlete’s foot) Introduction to the immune system • Tissues » Primary and secondary lymphoid organs • Cells » Lymphocytes » Granulocytes (Neutrophils, Eosinophils, Basophils) » Monocytes/Macrophages » Dendritic cells » Natural killer cells • Soluble mediators » Cytokines & chemokines » Complement proteins 1 AHS C&T5 11/2/12 Lymphoid Tissues CENTRAL (PRIMARY) LYMPHOID TISSUES ! – Bone marrow - site of B cell development (and pre-T cell)! – Thymus – site of T cell development! PERIPHERAL (SECONDARY) LYMPHOID TISSUES! – Spleen! – Lymph nodes! – Gut-associated lymphoid tissue (GALT) [Peyer’s Patches]! – Adenoids! – Appendix! – Tonsils! White blood cells (WBCs)/Leucocytes Mobile units of body’s immune defense system 2 AHS C&T5 11/2/12 Neutrophils! • Destroy bacteria by phagocytosis! – First defenders on scene of bacterial invasion! – Scavenge to clean up debris! • Most abundant leukocyte (60-70%)! Eosinophils! • Increase in circulating eosinophils (eosinophilia) is associated with! – Allergic conditions such as asthma and hay fever! – Internal parasite infestations, such as worms! • Attach to worm and secrete substances to kill it! • Make up 1-4% of Leukocytes! Monocytes! • Emerge from bone marrow while still immature and circulate for day or two before settling down in various tissues in body! • Mature and enlarge in resident tissue and become known as macrophages (“large eaters”)! – Life span can range from several months to years! • Become professional phagocytes and can act as antigen presenting cells! • Note: Dendritic cells are similar to monocytes but are more efficient antigen presenting cells! 3 AHS C&T5 11/2/12 Organisation of the immune system Nonspecific vs. Specific Immunity! Nonspecific (Innate)! Specific (Adaptive)! (Lymphocytes)! (Phagocytosis, Inflammation)! Initial & immediate response against invasion by any pathogens ! Comes into play after nonspecific responses have begun.! Main mechanisms! 1. Physical barriers (skin, mucous membranes)! 2. Inflammation & Phagocytosis (by neutrophils & macrophages)! 3. Interferon, NK cells! 4. Complement! Responds to specific pathogens on 2nd or later exposure! Nonspecific— 2. Inflammatory Response! Results Destroys or inactivate invaders Removes debris Prepares for healing & repair. Signs Redness Heat Swelling Pain 4 AHS C&T5 11/2/12 Nonspecific— 2. Phagocytosis SEM macrophage engulfing bacteria Stages of Phagocytosis 1. Attachment 2. Internalisation (0.1 s) 3. Degradation 4. Exocytosis S&G 23.3! Nonspecific— 3. Interferon, NK Cells Interferon! Natural Killer cells α,β,γ Cytokine released by virus-infected cells Protects other cells from any virus Attack virus-infected cells… …Cause lysis via release of perforins NK cells are also a major source of interferonγ Induces expression of enzymes that prevent viral replication Anti-cancer effects Slows cell division Enhances action of NK cells and cytotoxic T cells 5 AHS C&T5 11/2/12 Nonspecific— 4. Complement System! Consists of a number of small proteins that normally circulate as inactive precursors in the blood. ! They account for about 5% of the globulin fraction of blood plasma! Over 25 proteins and protein fragments make up the complement system.! Activation of the complement cascade results in the formation of a cell-killing membrane attack complex. ! Induces lysis of invading microorganisms! Also complements the ability of other immune mechanisms to clear pathogens [hence name!].! Specific Immunity! 1. Specificity! • Lymphocytes (B and T cells) bind and respond to foreign molecules known as antigens via antigen receptors! 2. Diversity! • The body possesses millions of lymphocytes that can recognise and respond to millions of antigens (one each)! 3. Memory! • 1st exposure to an antigen generates lymphocytes & longlived memory cells – next exposure to the same antigen, memory cells react faster & with stronger response! 4. Self-Tolerance! • Lymphocytes can distinguish ‘self’ (our normal antigens) from ‘non-self’ (antigens from foreign material).! 6 AHS C&T5 11/2/12 Lymphocytes! 2 types of lymphocytes! B lymphocytes (B-cells)! Produce antibodies which circulate in blood! Defend mainly against bacteria toxins and viruses present in body fluids! Responsible for antibody-mediated or humoral immunity! T lymphocytes (T-cells)! Do not produce antibodies! Directly destroy specific target cells by releasing chemicals that punch holes in the victim cell (cell-mediated immunity)! Target cells include body cells invaded by viruses and cancer cells! Specific Immunity: 1. Specificity Antigen receptors are present on B and T cells Antibody-antigen interactions are specific Specific Immunity: 4. Self-tolerance! B or T cells that may detect and attack ‘self’ are usually destroyed in the bone marrow. This process of self-tolerance fails in autoimmune diseases. 7 AHS C&T5 11/2/12 Specific Immunity: 2. Diversity & 3. Memory! A single B or T cell has approx 100,000 specific antigen receptors – each cell can detect just a few of the millions of possible antigens CLONAL SELECTION 1. Plasma cells! • Produce antibodies in blood! • Short-lived! 2. Memory cells (clone)! • With same receptor! • Long-lived.! Antigen fits B cell’s receptors…! Proliferation and differentiation into: Humoral immunity: How do antibodies function? www.gcarlson.com! Remember, antibodies are produced by B lymphocytes 5 classes: IgM IgD IgG IgE IgA 8 AHS C&T5 11/2/12 Cell mediated immunity T Cells: Helper vs. Cytotoxic HELPER T CELLS (~70% of T cells)! • • • www.gcarlson.com! Activated by MHC (Class II) on antigen-presenting cell (e.g. macrophage)! Secrete cytokines that enhance the activity of cytotoxic T cells; enhance phagocytosis! Stimulate development of B cells into plasma cells (indirect action)! CYTOTOXIC T CELLS! • • Activated by MHC (Class I) on virus-infected cell! Kill infected cells by lysis (direct action)! Antigen presentation and Helper T-cell activation: A central process in specific immunity In an infected cell, Class I MHC molecules present antigen at cell surface so cytotoxic T cells can kill the infected cell In a phagocytic immune cell, Class II MHC molecules present antigen at cell surface so Helper T cells can bind it and secrete cytokines that will amplify the immune response 9 AHS C&T5 11/2/12 Immune Disorders – Autoimmune Diseases! If immune system does not recognise its ‘self’ (e.g. MHC), it reacts against normal cells and tissues! Immune Disorders - AIDS! • • • • • AIDS is caused by Human Immunodeficiency Virus (HIV)! HIV binds to the surface of helper T cells and its nucleic acids (RNA and DNA) enter the T cell! Inside the cell, HIV uses the cell to make copies of itself! HIV slowly destroys helper T cells in the body! (Helper T cells = 70% of all T cells)! When T cell function is impaired, immune responses weaken and other diseases develop (Opportunistic infections)! 10