Chapter 15 Notes
Chapter 15 Notes BIOL 3160
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This 10 page Class Notes was uploaded by MBattito on Tuesday March 29, 2016. The Class Notes belongs to BIOL 3160 at Clemson University taught by Dr. Tamara McNutt-Scott in Fall 2015. Since its upload, it has received 24 views. For similar materials see Human Physiology in Biological Sciences at Clemson University.
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Date Created: 03/29/16
Chapter 15 The lymphatic/Immune System • Comprised of: o Lymphoid tissues/organs/cells – scattered throughout body o Lymphatic vessels – meandering network of vessels • Functions: o Fluid balance § Returns fluid from interstitial space to circulation via lymphatic capillaries § Lymph: once it gets back into the capillaries – derived from trasidated plasma (filtered), the fluid part of blood and the part that tissues release into the interstitial space o Fat absorption: lacteals absorb the fats from the GI tract, then it is filtered through the blood § Absorb fats and other fat-‐soluble substances from digestive system via lacteals o Defense: § Organs/tissues serve as “filters” • Removing microbes and foreign substances § Cells • Provide immunological defense against disease-‐causing agents • Note design – lymph node, lymph will always flow through at lease one lymph node before returning through circulation – more inlets than outlets so fluid will build up and will stay there for a while to meander through the structure so the body can detect any problems before releasing it • Also note tonsils are a tissue, not an organ Lymphatic Vessels: • Lymphatic capillaries: blunt-‐ended tubes that form a vast network within intercellular spaces of most organs o Due to construction of porous junctions, wide array of molecules as well as wandering cells can enter à porous junctions great for taking in excess fluid • Endothelial cells overlapping form valves – as pressure rises in this area (lymph accumulates) and opens the valves, the lymph is drawn into the lymphatic capillaries à once the pressure outside drops, the valves close – no energy needed • Moves through peristaltic waves of the smooth muscle to transport lymph • One directional flow • Lymphatic ducts – “pacemaker” o When stretched, increased rate of contraction Immune System • Functional system rather than a structural one • “Organs” are represented by individual immune cells and a diverse array of molecules • Relies upon 2 intrinsic systems o Act both independently and cooperatively o Provide resistance to disease à immunity Defense Mechanisms • Innate (nonspecific) defenses: nonselective and act immediately; do not distinguish one threat from another – present at birth o First line of defense: skin and especially mucosa à defenses at body surface § External body membranes – physical barriers o Second line of defense: utilize antimicrobial proteins § Phagocytes and other specialized cells that act to inhibit further invasion § Includes inflammation § Signaled by chemicals released when first line of defense is penetrated § Sweat on the skin is acidic to bacteria • Adaptive (Specific) defense: represents body’s ability to mount an attack against specific foreign invaders o Third line of defense is body’s specific defenses o Function of lymphocyte activities Activation of Innate Immunity • Distinguishes between “self” – the body’s own cells – and invading/foreign organisms/molecules o Recognize PAMPs § Unique to invaders § LPS and peptidoglycan • Ie. Particular classes of carbohydrates or lipids in microbial cells wall • Innate immune cells display receptors for these RAMPs (toll-‐like receptors) – pathogen recognition receptors o Play role in triggering immune response § Recognize invading/foreign organisms § Once activated, release cytokines which promote inflammation, phagocytosis, fever, and attract WBCs to area of infection Phagocytes: • Cells that have the ability to ingest and destroy particulate substances • Perform janitorial and police services in peripheral tissues by removing cellular debris and responding to invasion • Observe 3 major groups o Neutrophils § Most abundant § Phagocytic upon encounter with foreign intruder § First to enter infected area – mobile and quick to phagocytize o Mononuclear phagocyte system § Monocytes in blood, macrophage when in tissues and dendritic cells o Organ-‐specific phagocytes of liver, spleen, lymph nodes, lungs and brain § Microglia in brain tissue § Kupffer cells in liver • Fixed vs. Free: o Macrophages are usually fixed – microglia o Free: more mobility § Go outside of the organ § Takes a trip in the blood stream to go to another organ Phagocytosis: • Migration of WBCs from circulation into tissues • Recruited to an area of infection by chemical attractants called chemokines (subclass of cytokines) à creates a “chemical trail” for phagocytes to follow o Process referred to as chemotaxis • Selectin: cell adhesion molecules that capture neutrophils • Neutrophils spread out and undergo diaphidesis à head towards the site of infection • Lysosomal enzymes: “free enzymes” – contribute to inflammation • Blood flow slows in infected area – PMNs roll along endothelium Fever • Defines as an abnormally high body temperature • A systematic response to infection, which involves resetting the body’s “thermostat” in the hypothalamus • Accomplished by the release of pyrogens from activated macrophages and leukocytes when exposed to foreign substances (referred to as endogenous pyrogens) o Exogenous pyrogens • Fever causes an increase in body metabolism – thus accelerating repair processes and impacts bacterial replication o Liver and spleen sequester zinc and iron to make them less available for bacterial (nutrients required for reproduction) Interferons • Small proteins that protect body against viral infections o Short-‐acting • Produced by viral infected cells • Are not virus-‐specific, so provide protection from a variety of viruses • Considered a cytokine: o Chemical messengers released by tissue cells to coordinate local activities Adaptive Immunity: • Involved the ability to recognize, response to and remember a particular substance • Requires a “meeting” or to be primed by an initial exposure to a specific antigen before it can protect the body • Three important aspects of adaptive immune response distinguish from innate immunity: o Specificity – ability to recognize and direct response against particular foreign substance that initiate an immune response o Systemic – not restricted to initial infection site o Memory – after initial response, it recognizes and mounts an even stronger attack than previous encounter • Observe two separate but overlapping arms of adaptive immunity that utilize a variety of attack mechanisms that vary with the intruder: o Humoral, or antibody-‐mediated immunity § B cells provide protection § Provided by antibodies in body fluids, produced by plasma cells § Our defense against antigens and pathogens in body fluids o Cellular, or cell-‐mediated immunity § T cells provide direct protection § Target virus and parasite-‐infected cells, cancer cells and tissue grafts § Our defense against abnormal cells and intruders into the cell o Both are important for they come into play under different circumstances – providing a wide array of protection Antigens: • Antigen – Any foreign molecules that can trigger a specific immune response against it • Represent structural differences present on the surface of antigen o Greater the complexity (more parts), the more immunogenic antigen will be • Immunocompetence – ability of a T cell or B cell to recognize a specific antigen and initiate immune response • Immunological tolerance – tolerating yourself; ignoring self antigens • Antigenic determinates • Immunogenicity – ability to stimulate production of specific lymphocytes • Reactivity – ability to react with products of these reactions • Haptens: small molecules that on their own are not immunogenic but reactive and bind with other proteins – making them “foreign” o Can combine with proteins to become antigens Functions of B Lymphocytes • Exposure of B cells to appropriate antigen initiated growth, forming memory cells and plasma cells o Memory cells: have seen antibody before § Involved with secondary immune response § Will recognize if we see that antigen again in the future o Plasma cells: activated B cells § Involved with primary immune response § Make and release antibodies into tissue fluids • Binding of antigen to antibody serves to ID the enemy as well as activate defense mechanisms to destroy invader • Immunocompetent b cells – B cell expressing receptors to a specific antigenic site will only recognize one antigen o Antigen comes in contact with B cell and activates B cell to proliferate through mitosis o B cell forms clones – differentiate into memory and plasma cells • Two proposed mechanisms for antibody diversity: o Antigen-‐independent diversification in bone marrow o Antigen-‐dependent diversification in secondary lymphoid organs • Five subclasses of antibodies: o IgM – pentamers § Have 5 of them § Can come in contact with large number of antigenic sites o IgG – monomer § Can come in contact with 2 antigenic sites o IgA – dimer § Found in secretions of human body (tears, milk, saliva) o IgD – monomer o Found on lymphocyte surface • IgE – monomer o Involved in allergic reaction • Antibody regions: o Constant region – found in Fc region § Determines subclass and function of antibody § Effector region of antibody – dictates what antibody can bind to o V (variable) – found in Fab region o Fc region – can bind to complement • Class switch recombination – plasma cells switch from making one kind of antibody to another à switch from IgM to IgGs • As B cells proliferate, see B cells somatic hypermutation – increased proliferation due to mutation in B cells from proliferation o Gives wide diversity of B cells Complement • Represent group of plasma proteins – inactive in circulation • Respond to antigen-‐antibody complex binding o Antigen-‐antibody complex activates complement system when • Opsonization – antibodies bind to outside of microbe (plasma membrane binding sites) o Ability to stimulate phagocytosis • Upon activation, via either the classical or alternative pathway, final product is a MAC that causes cell lysis o MAC – membrane attacking complex à punches hole in plasma membrane to cause lysis o Classical pathway – binding of antibodies of IgG and IgM to antigens on invading cells § Antibody binds to antigenà activates C1 to bind à when C1 binds to antigen-‐antibody complex, it is activated to cleave C4 à C4 becomes C4a and C4bà C4b is inserted into plasma membrane (complement fixation) à forms MAC o Alternative pathway – triggered by specific polysaccharides on membrane – quicker • Complements get inserted into cell membrane and form MAC à creates a pore to water can come in and kill cell • Other fragments created which serve to initiate chemotaxis, phagocytosis and histamine release • C4a – chemotaxic agent • C3a and C5a – stimulate mast cells and basophils o Mast cells produce histamine o Basophils release histamine • C3b – facilitate phagocytosis Functions of T Lymphocytes • T cells are a diverse lot and more complex than B cells in both classification and function o Observe 2 major populations of effector T cells, based on CD proteins, CD4 and CD5 (cell surface receptors; are not T-‐cell antigen receptors) § CD4 cells are helper T cells § CD8 cells are cytoxic T cells (killer T cells) § CD25 cells are regulatory T cells (also contain CD4 – make sure killer T cells don’t get too excited) • T cells most efficient against microorganisms that live inside the cells of the body o Utilize cell-‐mediated destruction § Perforins – form pores in victim cells plasma membrane § Granzymes – enter victim cell and via capasases activation destroy DNA • Immunocompetence occurs in thymus for T cells o Occurs in bone barrow for B cells • Defend against viral and fungal infections – responsible for transplant graft rejections and provides immunological surveillance against cancer • Requires physical contact with “victimized cell” T-‐Lymphocyte Activation • T cell receptor does not recognize free antigen, so antigen must be presented to a T cell via an APC or antigen-‐presenting cell • APC release chemokines to attract T cells • Antigen presented on MHC protein (class II) by dendritic cells but are other cells can serve as APCs – such as macrophages or B cell Histocompatability Antigens • Act as genetic marker to recognize self • MHC proteins (aka HLA – human leukocyte-‐associated antigens) coded by a group a genes called the major histocompatibility complex; represent cellular “identity tags” – genetic markers of biological self o Class I MHC – produced by all cells of body o Class II MHC – produced only by antigen presenting cells à activate helper T cells • Restriction elements ability to restrict T cell activation/re-‐binding o Only occurs if antigen complexed to MHC protein • Exogenous – pull antigens from outside cell • Endogenous – pull antigen from inside cell T-‐Cell Activation • Antigen must be presented to T cell for it to be activated • Antigen presented on class II cell à activates helper T cell à helper T cell binds to antigen • Co-‐stimulation through CD proteins – non antigenic matching proteins between APC and helper T cell that check that it’s the right cell • Release of cytokine signaling o Cytokine produced by APC à tells T cell to proliferate • Helper T cell releases other cytokines that serve to activate the cytotoxic T cells o Cytotoxic T cells bind to infected cell à divides and takes care of infected cell Inflammation • A localized event involving aspects of innate and adaptive immunity • Neutrophils first to scene – release chemical signals to recruit other immune cells • As immune cells “gear up” for combat and then clean up, a variety of chemicals are released that lead to the characteristic signs of inflammation o Redness and warmth (histamine-‐stimulated vasodilation) o Swelling (edema) o Pain • Protective response designed to contain and eliminate harmful intruders • DAMPs – danger associated molecular patterns o If tissues get damaged that can’t be repaired, it releases DAMPS o Support an immune response to take care of damage Active and Passive Humoral (B cell) Immunity • Active: involves B cells being exposed to antigen o Immunological memory develops o Long term protection o Naturally acquired through infection – contact with a pathogen o Artificially acquired through vaccine – dead or attenuated pathogens • Passive: administration of antibodies o Does not convey memory o No B cell challenged o Short-‐lived protection o Naturally acquired from antibodies assed from mother to fetus via placenta – or to infant from her milk o Artificially acquired through injection of immune serum – gamma globulin Immunological Memory • Represented by memory cells and responsible for what occurs during next exposure to a particular antigen o Secondary immune response o Rapid, prolonged and more efficient • Begins with a primary response • Takes 5-‐7 days to get antibodies going naturally • Need antibody given early – unnaturally so they can be protected quicker o Get the benefits of contracting the disease without actually getting the disease
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