A&P 2 Innate and Adaptive Immunity Terms in this set (46) Immunity resistance to disease consist of two systems 1. Innate immunity: non-specific defense system. 2. Adaptive immunity a specific defense system. innate immunity The responses releas

A&P 2 Innate and Adaptive Immunity Terms in this set (46) Immunity resistance to disease consist of two systems 1. Innate immunity: non-specific defense system. 2. Adaptive immunity a specific defense system. innate immunity The responses release proteins that alert cells of the adaptive system to foreign molecules and antigens. The innate defense system has two lines of defenses. 1. External body membranes, like skin and mucosae 2. Antimicrobial proteins (interferons and complement proteins), phagocytes (neutrophils and macrophages), NK, that inhibit the spread of invaders. Also uses fever and inflammatory responses (macrophages, mast cells, WBCs and inflammatory chemicals) Innate immunity defenses 1. Surface barriers for warding of invading pathogens think of skin, mucous membranes, and their secretions. -The physical barrier keeps out most microorganisms -keratin is resistant to weak acids and bases, bacterial enzymes and toxins -mucosae provides similar mechanical barriers 2. Protective chemicals used to inhibit or destroy microorganisms. -The acidity of skin and secretions inhibits growth -enzymes or lysosomes of saliva, respiratory mucus, and lacrimal fluid kill many microorganisms - defensins like antimicrobial peptides that also inhibit growth -other chemicals think of lipids in sebum or dermicidin in sweat they are both toxic 3. Respiratory system modifications. -mucus coated hairs in the nose help to catch bacteria -Cilia of the upper respiratory tract sweeps, dust, and bacteria related mucus towards the mouth away from the lungs Innate immunity phagocytosis neutrophils: most abundant, but die fighting Macrophages: develop from a monocyte is the chief phagocytic cell - free macrophages wander through the tissue spaces (alveolar macrophages) - fixed macrophages permanent residence of some organs (brain microglia) Steps of phagocytosis 1. The phagocyte adheres to the pathogen. This is where opsonization occurs (the marking of the pathogen by coating it in complement proteins or antibodies) 2. The phagocyte forms pseudopods that eventually engulf the particles forming a phagosome. 3. Lysosomes fuse with the phagocytic vesicles forming a phagolysosome 4. Lysosomal enzymes digest the particles leaving a residual body. 5. Exocytosis of the vesicle removes indigestible and residual material. natural killer cells (NK cells) Attack cells that lack "self" cell-surface receptors like infected or cancerous cells (similar to T cells but lack antigen receptors) They then induce apoptosis and secrete potent chemicals that enhance inflammatory response Inflammatory responses Triggered whenever body tissue is injured and prevent the spreading of damaging agents it disposes of cell debris and pathogens and alerts the adaptive immune system. It also sets the stage for repair. Signs of acute information: 1. Redness (due to the blood flowing to the region) 2. Heat (due to all the metabolic active happening at the sight). 3. Swelling/Edema (due to increased blood flow to sight) 4. Pain. (Due to the swelling as it crushes the nearby nerves) 5. Impairment of function (due to the swelling and crushing of nerves) Triggering an inflammatory response It begins with chemicals like histamine released by mast cells being released into the ECF by injured tissues, setting off the chemical alarm macrophages and epithelial cells of the injured tissue also release cytokines that promote inflammation Inflammatory mediators, like histamine, kinins, prostaglandins, and complement proteins cause the local arterioles to dilate (hypermia) which leads to the redness and heat of the inflamed region, and makes the capillaries leaky which attracts leukocytes to the area, which also have an inflammatory role. The increased capillary permeability leads to: local swelling this swelling pushes on nerve endings, causing pain. Also leads to the delivering of clotting proteins in complement proteins, clotting factors which formed the fiber mesh the scaffolding for repair and isolates the injured area so invaders cannot spread. Phagocyte mobilization -Neutrophils flood area first and die fighting; macrophages (coming from monocytes) follow and replace the dying neutrophils -If inflammation is due to pathogens, complement is activated; adaptive immunity elements arrive 1. Leukocytosis: the release of neutrophils from bone marrow in response to a leukocytosis-inducing factor from injured cells. 2. Margination: neutrophil cling to walls of capillaries in inflamed area in response to CAMs (cell adhesion molecules, molecular Velcro) 3. Diapedesis- neutrophils flatten and squeeze out of capillaries. 4. Chemotaxis- inflammatory chemicals called chemotactic agents promote positive chemotaxis of neutrophils (neutrophils follow chemical trail) Innate immunity antimicrobial proteins- Interferons Family of immune modulating proteins have slightly different physiological effects virally infected cells, secrete IFN to warn neighboring cells I offends neighboring cells and produce proteins that block viral reproduction and degrade, viral RNA IFN alpha and beta also activate natural killer cells 1. A virus enters a cell. 2. Interfere on genes switch on. 3. Cell produces interferon molecules which are exocytosised out of cell and bind to next cell 4. Interferon binding stimulates that cell to turn on genes for antiviral proteins. 5. Antiviral proteins block viral reproduction. Innate immunity antimicrobial proteins the complement system There are about 20 blood proteins that circulate in an inactive form, including C1- C9 factors B,D, and P and regulatory proteins they are used for major mechanisms for destroying foreign substances, but our cells contain complement activation inhibitors to keep them in check Once activated, they only inflammatory chemicals to amplify all aspects of inflammatory response, kills bacteria and certain other cell types by cell lysis and enhances, both innate and adaptive defenses In a immunity compliment protein activation Three pathways to activation 1. Classical.-activated by antibodies, coding target cell. 2. Lectin pathway- activated by lectins binding to specific sugars on microorganisms surface. 3. Alternative pathway- activated spontaneously, a lack of inhibitors on microorganisms surface allows process to proceed. Each pathway involves activation of proteins in an orderly sequence, each pathway converges on C3, which cleaves into C3a and C3b. the common terminal pathway is initiated and leads too enhanced information. It promotes phagocytosis and causes cell lysis which begins when the C3b binds to target cell causes an insertion of complement protein called MAC(membrane attack complex) into the cell membrane forms, and stabilizes holes in the membrane which causes an influx of water leading to lysis C3b also causes opsonization (coats pathogens). While C3a and other cleavage products amplify inflammation mast/basofils release histamine, increased bv permeability, attracts phagocytes by chemotax Adaptive immunity defenses Is the specific (recognizes and targets specific antigens) defense system protects against infectious agents and abnormal body cells it amplifies inflammatory response and activates compliment. It must be primed by an initial exposure to a specific foreign substance in this priming takes time. It is systemic as it is not restricted to in its initial site and they also have memory so that previously encountered antigens are then attacked stronger than next time. Consist of two separate but overlapping branches 1. humoral (antibody mediated) immunity 2. Cellular (cell mediated) immunity There are three types of cells that compromise this system to our lymphocytes, including B and T cells and the next is an antigen presenting cells (APCs) that do not respond to specific antigens, but play an essential auxiliary role in immunity humoral immunity Antibodies produced by B lymphocytes circulate freely in fluids of the body these temporarily bind to target cells and inactivate them, marking them for destruction by phagocytes or compliments Humoral immunity has extracellular targets cell-mediated immunity T lymphocytes act against target cells by directly, killing infected cells and indirectly by releasing chemicals that enhance inflammatory response or activating other lymphocytes or macrophages Cellular immunity has cellular targets think of virus, infected cells, cancer cells, or cells A&P 2 Innate and Adaptive Immunity non-self antigens (foreign antigens) vs self antigens (MHC proteins) Non-self antigens are substances that can mobilize adaptive defenses and provoke an immune response they are the targets of all adaptive immune responses they are mostly large complex molecules, not normally found in the body think of foreign proteins, polysaccharides, lipids, and nucleic acids Self antigens are protein molecules on surfaces of cells that are not antigenic to self, but antigenic to others in transfusions or grafts like an MHC (major histocompatibility complex) glycol protein that are unique to each individual. They have grooves holding self or foreign antigens. T cells can only recognize antigens that are presented on MHC proteins. Immunogenicity Ability to stimulate proliferation of specific lymphocytes, only certain parts (called the antigenic determinants) of an entire antigen are immunogenic Reactivity Ability to react with activated, lymphocytes, and antibodies released by immunogenic reactions Antigenic determinants The parts of an antigen that are immunogenic, it is where antibodies and lymphocytes receptors bind to them Most naturally occurring antigens have numerous antigenic determinants that mobilize several different lymphocyte populations and form different kinds of antibodies against them Lymphocyte development, maturation, and activation steps 1. Origin-all originate in Redbone marrow 2. Maturation- either in the bone marrow(B) or the thymus(T), this is where they develop immunocompetence and self-tolerance 3. Seeding secondary lymphoid organs and circulation, the immunocompetent, but still naïve lymphocytes leave the thymus and bone marrow. They "seed" the secondary lymphoid organs and circulate through blood and lymph which increases the chances of encountering an antigen 4. Antigen encounter and activation, when lymphocytes antigen receptors bind its antigen that lymphocyte CAN be activated, then I even besides first encounter with an ancient engine, leads to selection for further development, called clonal selection 5. Proliferation and differentiation, activated lymphocytes multiply and then differentiate into affect her cells and memory cells, which then circulate continuously in the blood and lymph and throughout the secondary lymphoid organs Maturation of B and T cells Their educated to become mature to be cells in the bone marrow and the T cells in the thymus Immunocompetence lymphocytes can recognize one specific non-or foreign antigen by binding to it cells display only one unique type of antigen receptor on their surface when they achieve maturity and can find only one antigen Self tolerance lymphocytes are unresponsive to self antigens. They should not bind to them. T cell education, adaptive defenses -> cellular immunity In the thymus, T cells mature and go through two selections 1. Positive selection, T cells, capable of recognizing the self MHC proteins T cells, that fail process or destroyed by apoptosis. 2. Negative selection prompts apoptosis of T cells that then bind to self antigens displayed by self MHC this insures self tolerance. Antigen-presenting cells (APCs) 1. Dendritic cells- phagocytize pathogens entering lymphatics to present antigens to T cells in the lymph nodes. They are the most effective antigen presenters, and the key link between innate and adaptive immunity. 2. Macrophages- widespread and lymphoid organs and connective tissue present antigens to T cells to activate themselves into voracious Fagot sides that secrete bactericidal chemicals 3. B cells- do not activate naïve T cells present antigens to help or T cells to assist own A&P 2 Innate and Adaptive Immunity Activation and differentiation of B cells The cells are activated when antigen bind to its surface receptors and cross-link them Clonal selection is receptor mediated endocytosis of cross-linked antigen receptor complexes They then proliferate and differentiate into affect her cells like plasma cells which secretes specific antibodies at rapid rates for four or five days, then die the antibodies circulate in blood or limp and buying to free antigens, marking them for destruction by the innate or adaptive mechanisms the plasma cells become memory cells provide immunological memory, and immediate response to future exposure to the same extent immunological memory starts with the primary immune response, will cells proliferate and different differentiate upon the first exposure to the foreign antigen and has a lag. Of 3 to 6 days with peak levels of plasma antibodies, reaching at 10 days the antibody levels then decline. The secondary immune response happens at exposure to the same antigen and gives a faster more prolonged more effective response. The sensitized memory cells respond within hours antibody levels, peak, two or three days at much higher levels in antibodies bind with greater affinity the remaining antibodies can stay high for weeks to months active humoral immunity When bee cells actually encounter antigens and produce specific antibodies against them, there are two types of active humoral immunity naturally acquired, which is the response to bacterial or viral infections and artificially acquired, which is the response to vaccines of a dead or attenuated pathogens like vaccines, including smallpox, whooping cough, polio, or measles passive humoral immunity His immunity gained due to ready-made antibodies introduced into the body. The bee cells are not challenged by antigens. There is no immunological memory and the protection ends when the antibodies degrade. Naturally acquired- antibodies delivered fetus via placenta or infant through breastmilk Artificially acquired- injections of serum such as gamma, globulin protection, immediate but ends when antibodies naturally degrade in the body think of treatment to poisonous snake bites using antivenom or rabies and tetanus using antitoxins Antibodies (immunoglobulins) Immunoglobulins (Igs) are gamma globulin proteins of blood. They secreted by plasma cells and are capable of binding specifically with antigen detected by B cells. There are five Ig classes. The basic antibody structure is T or Y shaped with an antibody monomer of four looping polypeptide chains linked by disulfide bond consist of two identical, heavy chains with a hinge region at the middle and two identical light chains, and then a variable region at one end of each arm to combine to form two identical antigen binding sites, then a constant region of the stem determines antibody class MADGE Immunoglobulin classes (MADGE) 1. IgM is the first immunoglobulin class secreted by plasma cells during the primary response. It readily fixes an activates compliment. It also has numerous antigen binding sites, making it a potent agglutinating agent. Looks like a snow flake has 5 stems and 10 binding sites 2. IgA or the dimer is referred to as secretory IgA just found in bi secretions, and it helps to stop pathogens from attaching to epithelial cell services like mucus membranes, and the epidermis (2 horizontal stems combined with 4 binding sites) 3. IgD found on B cell surface functions as B cell antigen receptor (like IgM) 4. IgG most abundant ant, body and plasma the main antibody of secondary and late primary responses readily fixes and activates compliment protects against bacteria viruses circulating in blood and lymph confers, passive immunity from mother to fetus. 5. IgE the stem binds to mast or basophils and when the antigen binds at the receptor A&P 2 Innate and Adaptive Immunity Antibody targets and functions Antibodies, inactivate and tag antigens they do not destroy them. They form antigen- antibody (immune) complexes. They use defense mechanisms like: 1. neutralization: antibodies block specific sites on viruses or bacterial exotoxins, preventing these foreign antigens from binding to receptors on cell tissues, the antigen antibodies complexes, then undergo phagocytosis 2. agglutination antibodies, buying the same determinant on more than one cell-bound antigen 3. precipitation sable molecules are cross linked. The complex is precipitate in our subjective phagocytosis like agglutination but for smaller cells 4. compliment fixation several antibodies find close together on cellular, antigens and trigger complement fixations unto self surfaces cell lysis possible through NAC and then amplifies inflammatory responses promotes phagocytosis via opsonization cellular immunity response T cells provide defense against intracellular antigens some T cells directly kill cells while others release chemicals that regulate the immune response. There are two major populations of T cells based on which glycol protein surface receptors are displayed either CD4 or CD8 which can become helper T cells, Regulatory T cells or a cytotoxic Tcell Helper T cells Are an activated CD4 cell surface receptors they work to activate B cells, T cells, and macrophages and direct the adaptive immune response Recognize MHC II proteins (exogenous) They activate both humoral and cellular arms once primed by APC presentation of antigen. They help activate T and B cells, induce TNB cell proliferation and their sines recruit other immune cells. Helper T cell activation of B cell Interact directly with B cells displaying antigen fragments bound to MHC II receptors which stimulates the bile to divide more rapidly and begin antibiotic formation, the cells may be activated without helper, T cells by binding to T cell independent antigens most antigens require helper T cell cost stimulation to activate the cells which are T cell dependent antigens 1. Help her sell vines with his self non-self complexes of a Beso that has encountered its antigen and its displayed it on its MHC II 2. Helper T cells release Interlaken as co-stimulatory signals to complete the cell activation. Helper T cell activation of CD8 cells CD8 cells require Th cell activation into destructive cytoctoxic T cells They cause dendritic cells to express co-stimulatory molecules required for CD8 cell activation 1 Th cells binds dendritic cell 2 Th cell stimulates dendritic cell to express coast stimulatory molecules 3. Dendritic cell can now activate CD8 cell with the help of interlukins 2 secreted by Th cell Helper, T cells amplification of innate defenses The amplify responses of the immune system by activating macrophages leads to more potent killers. They also mobilize lymphocytes and macrophages, and attract other types of WBCs. Regulatory T cells Are a activated CD4 cell they moderate immune response and can become memory T cells They dampen the immune response by direct contact or by inhibitory cytokines. They are important in preventing auto immune reactions as they suppress self reactive lymphocytes in the periphery. Cytotoxic T cells Are an activated CD8 cell, they destroy cells harboring foreign antigens, and can become memory T cells recognize MHC I proteins (endogenous) These circulate in the blood and lymph and lymphoid organs and search for body cells displaying antigens they recognize Their targets are virus, infected cells, cells with intracellular, bacteria, or parasites, cancer cells, and foreign cells They administer their lethal hit by two methods 1. The cell releases perforins and granzymes by exocytosis which create pores through which the grand enzymes can enter the target cells and stimulate a apoptosis. 2. The cell binding specific membrane receptors on the target cell and stimulates apoptosis. MHC proteins (major histocompatibility complex) T cells respond only to processed fragments of antigens displayed on services of cells. Antigen presentation is vital for activation of the naïve T cells. There are two types of MHC proteins to T cell activation 1. Class I MHC proteins are displayed by all cells except RBCs. These proteins bind with fragments of protein, synthesized in the cell (endogenous antigen) it is crucial for CD8 cell activation, and informs cytotoxic T cells of microorganisms hiding in cells 2. Class II MHC proteins are displayed by APCs these bind with fragments of exogenous antigens that have been engulfed and broken down in a phagolysosome they signal CD4 cells that help is required and recognized by helper, T cells T cell activation Requires antigen binding and co-stimulation both occur on the surface of the same APC both required for clonal selection Tessa that are activated in large in proliferate and response to cytokines they differentiate and perform functions according to their T cell class 1. antigen presentation: dendritic cells and exogenous antigen processes it displays it fragments on class II MHC protein 2. Double recognition: C4 T cell recognizes antigen MHC complex, both TCR and CD4 proteins buying to antigen MHC complex and then co-stimulatory molecules buying together. 3. Clone formation: activated CD4, T cells, proliferate and become memory and effector cells. Cytokines Chemical messengers of the immune system, the mediate cell development, differentiation and response in immune system. They include interferons and interleukins Organ transplants 1. Autografts from one body site to another in the same person. 2. Isografts between identical twins. 3. Allografts between individuals who are not identical twins 4. xenografts form another animal species The success depends on the similarity of tissues with the first two being the ideal donor tissues, and are almost always successful the ABO blood antigens MHC antigens should be matched as closely as possible Prevention of rejection after surgery includes treatment with immunosuppressive therapy Corticoteroid drugs to suppress anti-proliferative drugs and immunosuppressant drugs but overtime as the patient immune system is depressed. It cannot protect itself from foreign antigens, so bacterial and viral infections can lead to death. You have to balance drugs for graft survival but no toxicity and use antibiotics to control infections. Immunodeficiencies congenital and acquired Impairs the function or production of immune cells or molecules, such as complement or antibodies -SCID severe combined immunodeficiency syndrome caused by genetic mutations is a marked deficit in BNT cells is treated with bone marrow transplants -Hodgkin lymphoma, an acquired immunodeficiency is the cancer of B cells leads to immunodeficiency by depressing lymph node cells AIDS and HIV Cripples immune system by interfering with activity of helper, T cells caused by a retrovirus called the human immunodeficiency virus and is transmitted via bodily fluids HIV destroys helper, T cells thus depressing the cellular immunity it multiplies in lymph nodes throughout the asymptomatic period and and symptoms include immune system collapse. The virus also invades the brain leading to dementia the HIV coded glycoprotein complex, attaches the CD4 receptors and then enters the cell and uses reverse transcriptions to produce DNA from its viral RNA the DNA copy a provirus directs hostels to make viral RNA and proteins, enabling the virus to reproduce treatment includes antiviral drugs, anti-retrieval therapy and HIV reverse transcript test Autoimmune diseases Immune system loses its ability to distinguish self from foreign the production of auto antibodies and sensitize side, toxic cells, destroy body tissues. Examples would be multiple sclerosis Graves' disease DB and rheumatoid arthritis. Treatment options include suppressing the entire immune system via anti-inflammatory drugs, like corticosteroids, blockingcytokine and blocking co stimulatory molecules Weekly self reactive lymphocytes may be activated by foreign antigens that may resemble self antigens. The antibodies against the foreign antigen may cross react with self antigen and new self antigens may appear generated by gene mutations changes and self antigens by infection or the release of a novel self antigen by trauma to barrier . Hypersensitivities Immune responses to perceived threat caused tissue damage. The types are distinguished by their time course and whether antibodies or T cells are involved. Antibodies are the immediate type one and subacute type two and three hypersensitivities T cells are delayed for hypersensitivity Type one hypersensitivity immediate Acute type one hypersensitivities are allergies that begin in second after contact with an allergen initial contact is a symptomatic but sensitizes the person the reaction can be local or systemic. The B cells stimulated produced IGE antibodies, which bind the cells and basil that flood histamine release and introduced inflammatory response later encounter with the same allergy yields an allergic reaction that could be local or systemic Local: mass cells of skin and respiratory and gastrointestinal mucosa release histamine, causing blood vessels to dilate and be leaky. She causes a runny nose, hives and watery eyes the allergy asthma. Systemic: anaphylactic shock systemic response to allergen that directly enters blood and circulates rapidly based off, fills in mass cells, enlisted throughout the body and systemic release of histamine which causes construction of bronchioles. The tongue may swell sudden Vaso dilation and fluid loss from bloodstream that may cause circulatory collapse.