Section 9: Lymphatic system and immunity A. Definitions 1. Microbes = microscopic organisms such as bacteria Some microbes are useful to humans: contribute to production of yogurt, cheese, bread, beer, wine and many pickled foods as well as some drugs Also act as decomposers break down inorganic nutrients Some bad human infectious diseases are typically caused by bacteria and viruses these are then called = pathogens 2. Pathogens = disease causing agents = nonself body i.e. bacteria, pollen, virus, prion Bacteria: single celled prokaryotes ie., strep throat, botulism, food poisoning, gangrene, gonorrhoea, syphilis all are bacterial diseases Viruses: bridge the gap between living and nonliving. Outside host they are basically a chemical lying in wait, when opportunity arises they replicate inside cells and appear to be alive. They are acellular not composed of cells. They are obligate parasites and do not live independently. (Viruses cause disease colds, flu, measles, chickenpox, polio, rabies, AIDS, genital warts and genital herpes, other deadly viruses such as Ebola, avian flu). Prions: proteinaceous particles cause a group of degenerative diseases of the nervous system also called wasting diseases. 3. Immune system lymphatic organs, tissues, cells and cell products (antibodies, regulating agents) that protect us from disease agents 4. Antibodies proteins produced by B lymphocytes due to presence of antigen (foreign body) in body 5. Antigen protein or polysaccharide on foreign body - WBC receptor binds to antigen and stimulates production of antibodies by B lymphocyte/ or antibodies bind to antigen and other WBC can recognize and attack it. 6. Immunity ability to react to antigens (foreign proteins (usually) on nonself) B. Lines of Defence: How we fight the invaders Body has 2 lines of defence against pathogens: 1. Non-specific defence - Barriers to entry: i.e., skin and mucous membranes, First responders: i.e., phagocytotic WBC 2. Specific defences = adaptive immunity: overcome infection by killing disease causing agent C. The Lymphatic system: 1. Functions Lymphatic system: consists of lymphatic vessels and the lymphatic organs. Closely associated with cardiovascular system. Has 4 main functions that contribute to the body s homeostasis 1. Lymphatic capillaries absorb excess tissue fluid and return it to bloodstream 2. Lymphatic capillaries in small intestine, absorbs fats 3. Responsible for the production, maintenance, and distribution of lymphocytes 4. Helps defend body against pathogens
2. Lymphatic vessels: Form a 1 way system: capillaries vessels ducts that take lymph to cardiovascular veins in shoulders (rt and lft subclavian veins) Valves and skeleton muscle contraction moves lymph in lymph vessels Fluid in lymphatic vessels = lymph 3. Lymphatic organs organs location Cells or products produced 1 o Red bone marrow In adults- end of long bones, skull, sternum, Stem cells B & T lymphocytes made here /B mature here pelvic bones 1 o Thymus Behind sternum Has Thymic hormones = thymosin T lymphocytes mature here 2 o Spleen Upper lft behind stomach - Contain Macrophages act as vaccum cleaners and engulf pathogens as it passes thru spleen 2 o Lymph nodes Along lymphatic vessels - Don t produce anything but they Filter lymph 2 o Tonsils Ring around pharynx 2 o Peyers patch Intestinal wall 2 o Lymph tissue in appendix Cecum of Large intestine D. Nonspecific defences =Innate defences our built in defences Nonspecific effective against many types of infectious agents 1. Physical and chemical barriers = Barriers to entry - 1 o line of defence Skin and mucous membranes mechanical barriers Oil glands secrete chemical to kill bacteria on skin Upper respiratory tract cilia and mucous Stomach acid kills bacteria Local area bacteria prevents pathogens from entering 2. Inflammatory response Inflammatory response is 2 nd line of defence - Due to tissue damage Mostly uses neutrophils and macrophages to engulf pathogens 4 symptoms: redness, heat, swelling, pain. These 4 signs due to changes in capillaries in area.
Process: a. Damaged tissue cells release histamines-histamines cause capillaries to dilate which blood flow which brings extra WBC to area skin red and warm temp can inhibit growth of some pathogens permeability allows proteins + fluids escape from capillaries into tissues swelling and pain b. Blood clotting begins as well c. the arriving neutrophils (Phagocytotic WBC) also squeeze out thru capillary wall and enter tissue fluid and attack pathogens (if lots of neutrophils die off they form yellowy substance called puss) d. usually neutrophils can control and keep infection from spreading - if neutrophils are overwhelmed they realease cytokines that call reinforcements e. cytokines attract other WBC s to area including monocytes which turn into macrophages (and are longer living then neutrophils) that engulf pathogens macrophages can enlist the further help of lymphocytes. 3. Phagocytes and Natural Killer Cells Neutrophils - Pagocytes ( Cell eating ) that go to areas that are inflamed and engulf the pathogens within the neutrophil the engulfed pathogen will join with a lysosome which destroys the pathogen. Monocytes (macrophages) - If needed, these are called for reinforcements - come to the infected area and engulf pathogens work the same way as neutrophils but are longer lasting and larger than neutrophils. Natural Killer Cells (NK) a type of granular lymphocyte (B and T appear agranular) NK cells target cells that don t have the molecule markers on the cell surface that mark it as self this can happen to cells that are infected by virus or are cancerous NK cells release perforin which perforates the infected cell, then injects it with granzymes which causes cell to undergo apoptosis. are faster acting than T cells. 4. Protective proteins Complement system = blood plasma proteins activated when pathogens enter the body Called complement because they complement a number of immune responses i.e. Trigger histamine release from mast cells (a type of cell that contains basophil granules) help trigger inflammatory response binds to surface of pathogen and attracts phagocytes to pathogens (along with antibodies) Form membrane attack complexes that makes holes in cell and cuases fluid to enter and burst cell interferons are proteins produced by virus infected cells bind to non-infected cells to warn them of possible attack
E. Specific defences = Acquired Defences =adaptive immunity When nonspecific defences fail Effective against one particular infectious agent or cancer Immune system distinguishes self from nonself Specific defences primarily rely on the actions of lymphocytes differentiate into B and T cells o These lymphocytes recognize antigens due to antigen receptors o The antigen receptors are receptor proteins in plasma membrane on lymphocytestheir shape allows them to combine with particular antigen on pathogen or cancer cell They provide immunity through: 1) Antibody mediated immunity = B lymphocytes produced in bone marrow and become either: 1. plasma cellsproduce antibodiesneutralize antigens 2. Memory B cells for future 2) Cell mediated immunity =T lymphocytes made in bone marrow, mature in thymus - Do not produce antibodiesattach to nonself cells with plasma membrane receptor T cells become either: 1. Helper T cells release chemicals and regulate immunity 2. Cytotoxic T cells - kill virus infected cells and cancer cells 3. Memory T cells 1. B cells = Antibody Mediated Immunity a) Where its made, matures and hangs out B cell produced in red bone marrow, matures in bone marrow B cells reside in lymph nodes and spleen, in blood and lymph b) How it recognizes antigen B cell has B Cell Receptor (BCR) each type of B cell has different shape BCR these BCR match various types of antigens (B cells have been found to make >2 million different antibodies) antigen will bind to its matching BCR this is the signal for this particular type of B Cell to clone itself (as long as cytokines from T cells are present) called clonal selection theory B cell divides many times (mitotically) these become plasma cells or memory B cells Plasma cells mass produce and secretes antibodies against that specific antigen the antibody it produces also matches the BCR c) Clonal selection theory (Clonal expansion of B cell) B cell that has a matching BCR to the antigen, recognizes antigen then this cell undergoes clonal expansionproduces more of this particular B cell Causes B cells to divide = clonal expansion B cell Produced and mature in bone marrow antigen Specific antigen receptor (BCR=B cell receptor) activation Cytokines from helping T cells (must be present for B cells to clone) Into plasma cells and memory cells Plasma cells secrete antibodies and after threat of infection passes most undergo apoptosis (programmed cell death)
d) Antibodies = immunoglobulins i. Structure of antibody: Y shaped protein 1) Constant regions: where sequence of aa setsame within same class of antibodies 2) Variable regions: aa varies between antibodies specific to each antigen reaction can cause a clump of antigens and antibodies = immune complex this complex marks it for destruction ii. Classes of antibodies 5 classes of circulatory antibody proteins (or immunoglobulins) Class is determined by structure of antibodies constant region 1) IgG (major type in blood) binds to pathogens, activates complement, helps phagocytosis 2) IgM activate complement system, clumps cell 3) IgA bind to pathogens before they reach blood on epithelial layer, in respiratory and digestive tract. 4) IgD found on immature B cells indicates ready to respond to antigen 5) IgE helps body react to allergic responses and certain parasites
2. T cells and Cell Mediated Immunity a) Where its made, matures and hangs out Work against virus infection and cancer cells T cell produced in bone marrow matures in thymus T cells congregate in lymph nodes and spleen b) How it recognizes antigen has T receptor (TCR) > unlike B cell, T cell needs help to recognize antigen so antigen must be displayed to them by antigen presenting cell the antigen presenting cell is usually a macrophage brings a bit of the antigen to the T cell to show it the T cell that matches the one that the antigen presenting cell brought, is activated and clonal expansion will occur. c) Clonal selection theory (Clonal expansion of T cell) Clonal expansion produces: i. Helper T cells (which do not fight directly) regulate immunity by secreting cytokinesthese enhance immune response ii. iii. B cells cannot be activated w/o this help Help activate cytotoxic T cells Cytotoxic T cells contain storage vacuoles with perforins and storage vacuoles with enzymes (granzymes) after cytotoxic T cell binds to virus or tumor cell perforins punch holes in plasma membranes creating a pore and the cytotoxic T cell delivers granzymes into pore cause cell to undergo apoptosis -once this is done, the cytotxic T cell moves on to the next target cell memory T cells can kick start an immune response next time - respond to an antigen that it was previously exposed to
F. Acquired Immunity 1)Active produced by individual (can be from vaccine) 2) Passive given prepared antibodies 1) Active: a) Individual produces own antibodies or induced by given vaccines b) rely on presence of memory B cells and memory T cells c) Long lasting (although may need a booster after many years for some vaccines) d) Vaccines: contain antigen, immune system responds 1 0 response small, minimal 2 0 response after booster - larger, big rise in antibodies produced - Helps prevent disease symptoms in future by producing memory B and T cells 2) Passive: Individual given injection of prepared antibodies (immunoglobulins) to combat diseases Temporary Antibodies not produced by the persons own plasma cells An example of passive immunity - a newborn can be passively immune to some diseases due to presence of IgG antibodies from Mum s blood disappear in baby in a few months can be prolonged thru breast feeding that has IgG and IgA antibodies in it Research into the use of cytokines and monoclonal antibodies: Cytokines : are signalling molecules produced by T lymphocytes, macrophages, and other cells because they regulate WBC formation and function, scientists are looking at these as possible forms of therapy for cancer and aids Monoclonal antibodies: every plasma cell derived from the same B cell, secretes antibodies against a specific antigen these are called monoclonal antibodies (because all of them are the same type and are produced by plasma cells from same B cell) these can be produced in vitro (outside the body) * their presence can be used to diagnose certain conditions such as infections and pregnancy.