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Immune System Innate Immune response = fast response to wide range of microbes; born with. Acquired/Adaptive response = slower response to specific microbes; develops over time due to exposure. - Only found in vertebrates Antigen = protein or glycoprotein on cell surface of “invader” that stimulates a response by the immune system via leukocytes (WBC) o Epitope = specific area on antigens surface receptors where (our) defense mechanisms will attach. Antigen may be: - may be a pathogen = microbe - or, may cause allergic reaction Leukocytes (WBCs) destroy “invader” by phagocytosis or chemically. Attach to microbe via cell surface receptors - Generalized by groups of different antigens [innate] 1 Vesicle (of WBC) fuses with lysosome = chemicals/enzymes for destruction of antigen. 5 types of leukocytes (WBCs) 1. Neutrophils - targets bacteria & fungi (by phagocytosis) - usually self-destructive = short lived (live only a few days) 2. Eosinophils - chemical release for targeting large parasites (not phagocytosis) 3. Basophils - Release histamine for inflammatory response 2 4. Monocytes - Produces interferon (protein) for: 1. Tells infected cells and neighboring uninfected cells produce this chemical to limit spread of virus. o complement system (not phagocytosis) 2. Other interferons help stimulate production of…. ******MACROPHAGES (“BIG EATERS”) = tissue resident (lymph nodes, spleen, tonsils, adenoids, appendix); body’s primary phagocytes Acquired response achieved by… 5. *****LYMPHOCYTE (T-CELLS & B-CELLS) Originate from stem cells in the bone marrow… - T-cells (mature in Thymus gland); clonal 1. Helper T-cells: produces proteins called cytokines to activate: a. B-cell to make antibodies (stay in Bone marrow to mature); clonal - Helps macrophage find the antigen. b. Cytotoxic T-cells - (killer T-cells) – eliminates body’s infected cells (microbes/cancer) by enzymes and/or chemicals that will cause leakage of target cells by creating pores in the cell membrane; clonal c. Suppressor T-cells - shuts down immune responses after they have successfully eliminated invading organisms; also prevents autoimmunity 3 Autoimmunity = when the body’s immune system attacks itself o Produces antibodies against healthy body cells if suppressor cells cannot shut down response to antigen after infection is cleared. 2. Memory T-cells (both Helper and Cytotoxic) - can reproduce a faster and stronger immune response than the first time the immune system responded to the invader; clonal - Secondary response More about B-cells… - B-Cells (mature in Bone marrow) = creates antibodies 1. Plasma cells – clonal B-cells; secretes antibodies 1st exposure - short lived effectors 2nd exposure - more produced = longer lived effect Due to…. 2. Memory B-cells – same function as memory T-cells - faster response to infection after 1st exposure: clonal Let’s get attacked… Two kinds of defense: (1. Innate & 2. Acquired Immunity) 1. Innate response Non-specific = effective at birth - Responds to wide range of microbes Examples of physical barriers: skin, mucous membranes, internal chemical defenses 4 - Skin Sweat and oil gland decrease pH = not inhabitable by microbes Secretions = lysozymes (enzymes) - Kill microbes; degrade microbial components - Mucous membranes Tears, saliva = also contain lysozymes Stomach = HCl and mucous If microbe breaks innate physical barriers, chemical barriers kick in… Inflammatory response - In Mast Cells of connective tissue & basophils release histamine = dilation & greater permeability of nearby capillaries - Increases blood flow to injured cells - Capillaries engorge - Leak into tissues = swelling & heat - Deliver antimicrobial proteins (interferon) and clotting factors made by monocytes. • Limits the spread of infection - Increase WBC’s (phagocytes) killing compounds. • Neutrophils for bacteria and parasites 5 • Monocytes, specifically macrophages, for viruses If the innate immune response doesn’t work entirely,… - Some background first: 2. Acquired (adaptive) response First time body is attacked by new antigen = primary immune response - Slow = 10 to 20 days after exposure Specific = after initial exposure to antigen/abnormal body cells = secondary response - Distinguishes one microbe from another Two forms of Acquired response: achieved by lymphocytes B-cells 6 - Humoral defense (in the fluid of the body; blood, lymph, interstitial fluid) = production of antibodies by (B-cells) Antibodies = proteins secreted by B-cells that bind to a specific antigen for elimination. T-cells - Cell mediated defense = cell to cell contact; cytotoxic T-cells destroy already infected body cells OK, let’s continue with the attack…A pathogen bypasses the body's innate physical/chemical barriers… inflammatory response did not do the job… (innate to acquired) Monocytes (innate) macrophages: initiate attack - nonspecifically engulf invaders [innate] - incorporate antigens into own membrane - “presents” to helper T-cells = activation results in fever • compliment system = interferon does its job preventing spreading of infection Lymphocytes (connection of innate to acquired) helper T cells: initiation of cell–mediated response 7 - produces cytokines - cytokines stimulate production of: 1. B-cells: initiate humoral response - produce antibodies specific to antigen to neutralize antigen so macrophage can “eat antigen” 2. cytotoxic T-cells (killer T-cells) destroy already infected cells: cell mediated At the end of infection: suppressor T cells: - multiply slowly - shuts down antibody response after few weeks; limits production of: a. b. c. helper T-cells that activate B-cells to make antibodies Cytotoxic T-Cells to stop destruction of body’s cells. *Memory: some T cells and B cells are cloned and remain circulating - provides accelerated response to reinfection = secondary immune response (2 to 7 days) 8 Let’s look at antibodies a little closer… Antibodies are (glycol-)proteins belong to a group of molecules = immunoglobulins Secreted by B-cells - Considered soluble when released from B-cells into the blood and tissue fluids surveying for microbes Antibodies have the same general “Y” shape. 2 regions to antibody 9 1. Getting the antibody delivered to the correct location in the body and disposal of antigen = tail end of the “Y” - This is region establishes 5 classes of antibodies - These classes perform different roles and help direct the appropriate immune response for each antigen they encounter 2. Specific antigen-binding site = how antibodies recognize specific antigens (the top of the “Y”) - variable region = antigen specific - 100,000’s of different varieties in this region is due to splicing together different exons of the same gene. - random mutations in this area of the antibody gene, which create further diversity 10 Antibodies: Leads to destruction by 1. Neutralization – coats pathogen with toxins = blocks binding sites 2. Agglutination – clumps pathogen where they can be phagocytized by macrophages 3. Lysis – activation of (different) complement system; results in the lysis of microbes Vaccines – inactive bacterial toxin, killed microbes, parts of microbes, viable but weak microbes - Injection stimulates immune response - Make memory cells - Quick secondary response if exposed to pathogen See page 915 and Fig 43.1 – blood groups and transfusions Antigens on the surface of blood cells - A blood = A antigen - B blood = B antigen - AB blood = A & B antigens - O blood = no antigens 11 The body does not produce antibodies against these antigens = self-tolerant “Self and Non-self” - Antibodies to foreign blood groups are innately present for certain blood groups; even though the body hasn’t been exposed to the foreign blood group - A blood = antibodies for B blood antigen - B blood = antibodies for A blood antigen - AB blood = NO antibodies for either A or B blood Universal acceptor - O blood = antibodies for both A and B blood Universal donor 12 Universal acceptor Universal donor 13