Inflammation Study Guide Test 1 PDF

Inflammation Study Guide Test 1 Week 1 - The main Immune defense systems are: - Innate immunity - Adaptive immunity - Innate immunity is quick, non-specific, and can be found as physical, chemical, or cellular barrier. - Adaptive immunity is developed from RAG gene, prote...

Inflammation Study Guide Test 1 Week 1 - The main Immune defense systems are: - Innate immunity - Adaptive immunity - Innate immunity is quick, non-specific, and can be found as physical, chemical, or cellular barrier. - Adaptive immunity is developed from RAG gene, protection develops after infection, is slower in response time, antigen specific, and has memory for second responses. - Humoral immunity -- involves combatting pathogesn with antibodies - Cell-mediated immunity -- involves pathogen specific T cells to eradicate infections. - Myeloid lineage includes monocytes/macrpphages, dendritic cells, neutrophils, eosinophils, and basophils. - Monocytes/macrophages -- specialized in phagocytosis. Can differentiate into dendritic ells and present antigens to T lymphocytes. - Neutrophils -- involvd with vasodilation andinflammation. Cause direct hard to pathogrens through making digestive enzymes and free radicals. Help neutralize pathogens. - Eosionophils -- vasodilation, basophil degranulation. Anti viral and fight parasitic infections. - Basophils/mast cells -- release histamine for smooth muscle activation. Release heparin to increase blood flow. Involved with allergies. - Lymphoid lineage includes B and T cells. - B lymphtocytes develops in bone marrow, present antigen in secondary response, produces antibodies. - T lymphocytes involves cytotoxi T lympthocytes, T helper cells, T regulatory cells, NKT cells, and memory T cells. T cells develop in thymus. - Prumar lymphoid organs -- where immune cells develop - Secondary lymphoid organs -- where immune response is initiated. Secondary lymphoid organs include lymph nodes, spleen, mucosa-assocaited lymphoid tissues (MALT), and other diffuse and loosly organized areas. - A lymph node is a specialized organ where antigen-specific lymphocytes come in scan for foreight molecules funneled in there. - Dysfuncitons of immune system include allergies, autoimmune disease, and immunodeficiency. - Innate immunity uses microbial non-self and missing slef to recognize pathogens. - Microbial non-self molecules are pPAMPs which are produced by mcirobes but not by the host. - The host has receptors that recognize PAMPs. - The binding of PAMPS to pattern recognition receptor triggers immune response. PAMPs and PRR help link innate to adaptive immunity. - Macrophages link innate to adaptive immunity. - Innate lymphoid cells secrete cytokines that respond wuqickly to pathogenic tissue damage. Link inante and adaptive immntiy. - Missing self natural killer cells. Cytotoxic killing of virus infected or damaged cells. Usea AADC antibodu dependet cell cytotoxicity function to do this. - Inflammation cardinal signs are redness, heat, swelling, pain, loss of function. Week 2 - Adaptive immunity is acquired immunity with antigen specificity. - B and T cells have recetpros specific to a pathogen. - B cells have quartnerary struectures with 2 heavy and two light chains. - An antibody has 2 forms which are membrane bround or secreted. - Antibody either made by B lymphocytes or plasma cells. - BCR has two binding sites to allow cross-linking and proline rich hinge region allows an extension. - There are variable and constant region on antibody. - N terminal on antibody is angiten binding site and has Fab. **N** terminal has antige**n** - C terminal on antigen has Fc = crystallization and mediates biological activities of antibody. Think **C** terminal has F**c**. - Paratope is binding site found on antibodies. - Epitope is binding site found on antigens. - Hypervaraible regions closest contact with antigens. Specificty determined in this area. - Antigen- antibody interacts by non-covalent bonds. - Receptor-lgand interactions -- affinity is sterengh of an indivudal bond. avidity is the combine strength of binding of multipe interactions. - TCR aB recognizes and binds both antigen-deruved peptide and MHC to which peptide is bound. - The T cell receptor complexes with the co-receptor involved in antigen recognition - CD3 contains ITAMs that transmit signals to the cell - CD4 and CD8 function in increasing the avidity of peptide binding by TCR. - CD28 engages CD80 or CD86 on antigen presenting cell to fully activate a naïve T cell - The five immunoglobulins are IgG, IgA, IgM, IgE, and IgD. Mneumonic is gamed. - IgG -- is a monomer. Found in blood stream and tissue. Crosses placenta, except IgG. 4 different subclasses of IgG. Agglutinates, precipitates, opsonizes -- part of phagocytosis, mediates ADCC -- antibodies help bring microbes to surface of natural killer cell to then be lysed, actives complement, and neutralizes. - IgM -- membrane form is a pentamer. expressed on the cell surface of early B cells to serve as a B cell receptor. Agglutinates, activates complement, first immunoglobulin produced in an immune response, frist immunoglobulin produced in infants, provide early protection, produced in response to T-indpendent antigens, low affinity, and poor neutralization. - IgG and IgM most common antibodies. - IgD -- It is a monomer. Surface bound on mature B cells. Not secreted. Serves as a signal receptor and triggers further differentiation of B lymphocytes. - IgA -- Is a dimer. External secretions such as milk, saliva, mucus, sweat, and tears. Absorbed through intestinal lumen when ingested with milk. Agglutinates and neutralizes. - IgE is a monomer. H chains have extra domains by which it binds to IgE receptors on basophils and mast cells. Lowest in concentration compared to all other antibodies. It is the allergy antibody. Protection against parasitic infections. Induces degranulation. Binds to IgE Fc receptors on basophils/mast cells and eosinophils. - Variable and constant region on antibodies. - B cells are able to be diverse thrpugh a few strategies - selection of mnay mini-gene segments - recombination to join the randomly selected mini-genes - addition and deletion of nucleotides during joining of mini-gene segments - association of different light and heavy chains to form binding sites. - Somatic hyper-mutations (B cells only, not T cells) during clonal expansion - VDJ recombination through RAG1/2 recombinase - B cells develop in bone marrow. - Elimination fo self-reactive B cells. - In the spleen B cells undergo two stages. T1 is nerative selction where B cells with receotirs that react with self molecules encounter self antigens arnd are deleted. T2 is maturation with IgD where B cells grow to maturity. They end up with high levels of IgD and IgM on their surface. - BAFF is found on B cells and provides a survival signal. - B lymphocytes encounter antigens. B cells can switch to other isotypes during maturation. B cells expresiing IgM and IgD may express IgG, IgA, or IgE. - Memory B cell formed within germinal centers following primary infections. - Plasma cells secrete large nuber of antibody molecule but they lose the cell surface immunoglobulin. - Antibody has two forms either membrane bound or secreted Ig. - T cells arise from precursors in bone marrow and move to thyrmus. A receptor known as notch commits them to T lineage. - Two types of T cell receptors made - TCRaB and TCRyD. - Tab cells are CD-4 or CD-8 positive and predominate in lymph nodes and spleen. - Tyd are CD-4 or CD-8 negative and predominant in skin and mucosal surfaces. - T cells use same diverse mechanisms as BCR exept somatic hypermuytations to not occur. - T ab cells become double positive and then are selected for affinity to one MHC class and become single positive. - MHC molecyles are self-identiy molecules that have broad binding specificity. - MHC class I foun on almost every cell. CD8 cytotoxic T molcules bind to MHC class I. - MHC class II found on antigen presenting cells. CD4 T helper cells molecules bind to MHC II. - T cells that can't bidn MHC peptides are deleted. - The medullary thymic epithelial cells express and present proteins from all over the body. Autoimmune regulator induces them to express, process, and present many tissue specific proteins. - CD4 and CD8 T cells recognize foreign antigenic peptides presented to them on the MHC molecules. - T cell molecules can bind both self and non self peptides. - Somatic hypermutations do not occur necause after MHC selection, mutations lead to loss of MHC recognition and T cells would not be able to receive signals from antigen presenting cells. - Recognigtion of self-antigens by immautere T cells in thymus may lead to death of cells or development of regulatory T cells that enter peripheral tissue. - Removes autoreactive cells before T cells released into peripheral bloodstteram so body does not attack itself. - Some thymotcutes that see self-antigens in thymus differentiate to CD4+ T reg cells. They leave thymus and inhibit response against self-tissues in periphery. - T cells for lipid antigens -Tyd cells arise from unsuccessful rearrangement of B chain. - TCRyd lymothcytes important in early development to protect young. Protect our barrier from outsie. Join innate immune cells in first line of attack. Does not recognize antigen + MHc. Recognizes protein and nonpreoteina angitgen directly on the surface. - Natural killer cells are a heterogenous group of T cell with TCR assembled with an invariant a chain and a limited number ofB chains. They bind foreign and self lipids and glycol;lipids. They react to lipid antigens presented by CD1, a non-polymorphic MHC class- like angten presenting molecule. - MHC complex called a complex because of genetic locus encoding MHC molecules. Also known as human leukocyte antigen (HLA) in humans. - Hisocompaitvity -- in histological tissue transplant, animals that differ in aray of alleles were rejected. Not rejected if it is self with same MHC molecules -- auto transplant. - Class I and II MHC molecules act on cell surface Bessel for holding or displaung fragments of antigens. Allows TaB cells to engage with his molecule via their Tc cell receptors. - Allelic forms of MHC are inherited in liked groups called haplotypes. - There is genetic polymorphism of MHC in human population -- each molecule is different between people. Can be used for signature/fingerprint molecules or paternity testing. - Polymorphism exhibited in region that binds to peptides. - MHC molecule presents antigens. - Class I MHC molecules - a peptide with 3 domains (a1, a2, and a3) and transmembrane C-terminal + B2-microglobulin. Has broad speicificity. CD8 molecules on T cells bind to the a3 domain. - MHC class I molecules present endogenous (from inside the body) antigens to CD8+ cytotoxic T cells. Week 3 - Once MHC class I molecules present endogenous antigens to CD8+ cells, the CD8+ cells lyse the virus infected cells and eliminate the virus. - MHC class I processing in proteasomes. - MHC class II molecules have a peptide with 2 domains (a1 and a2) and a transmembrane C cerminal and B peptide with 2 odomains (B1 and B2) with a transmembrane C terminal. CD4 binds to B2 domains. - MHC II found on antigen presenting cells and present angitens to CD-4 helper T cells. - Thee are professional antigen preneng cells which always express MHC class II molecule. These are macrophage cells such as Langerhands cells and dendritic cells. - There are occasional antigen presenting cells that express MHC class II molecules when induced. These include cytokines from T cells, keratinocytes, endothelial cells, and epithelial cells. - MHC class II moelcules present exogenous (from outside the body) antigens to CD4+ T helpers. Antigen presenting cells and T cells interact leading to their mutual activation and cytokine production. - MHC class II processing in endosome. - Each individual MHC molecules bind a different panel of antigenic peptides. Therefore we respond to infections/antigens differently. - Diversity at MHC locus imparts an evolutionary survival advangae for a species against mortality from infections diseases. The advanatege is that survival of race, not individuals. The disadvange is certain alleles are associated with diseases. - Presentation of non-peptide antigens CD-1 shares structural similatit t MHC class I but functionally overlaps with class II. Presnetsl lipid-containing antigens. Binding grooves accommodate hydrophobic structes. Presnets lipid containing antigens to NKT cells and Tyd cells. - 3 signas required to activate naïve T cells - 1\. TCR signaling - 2\. Costimulatory interaction - 3.cytokine signaling - TCR signaling through TCRaB peptide/MHC, Cd4or CD8 MHC, adhesion molecules. - Co-stimulatory molecules binding btween CD-80/86 (APC) and CD28(T cells) necessary for activation of T cells. - Co-inhibtors on T cells -- lack of binding between CD-80/86 and CD28 leads to no response, engagement of CD-80/86 and CL-4 leads to no response, and engagement of PD-1 and PDL1/2 leadz to anergy of T cells in periphery. - Cytokines activated different transcription factors that guide the T cells to differentiate T cells into various subsets. - T helper 1 - T helper 2 - T helper 17 - T follicular helpers - T regulatory - Cytokines produced by the APC induce each subset. Which cytokine will the APC produce depend on the infections. - Transcription factors for cytokines - T-bet = Th1 - Gata3=Th2 - RORYt = Th17 - Polarization of response for cytokines -- each T cell subset produces cytokines tha mplify itself byt inhibit the others. So response becomes increasinyl polarized. TH1 Activtates macrophages, stimulates production of IgG to enhance phagocytosis. Produces IFNy, TNFb ------ --------------------------------------------------------------------------------------------------------------- ------------------------------------------------------------------------------------------- Th2 Effective against worms, mediates antibody class switching to IgE, IgE activates mast cell degraunlation Produces IL-4, IL 5, Il10, and IL 13 Th17 Increase barrier function, such as in the gastrointestinal tract. Critical for ungal and bactieral infections Produces IL-17 and IL-22. Produces pro-inflammatory cytokines such as TNF, Il-1, and IL-6 - IL-4 and IL-13 induce alternative activated macrophages (M2). M2 inhibits inflammation of classically activated marcophages whcb T helpe 1 activated. Promotes tissue repair. - T reg cells -- inhibit profileration and activation of CD4+ and CD8+ cells. Treg consitutively express the co-inhibitory molecules CD8+ cells. - Cytotoxic T lymphocytes -- Th1 cells engage with CTL to provide IL-2 proliferation and differentiation to mature CTL. IL-2 helps with differentaitoon of T cells. - Memory T/B cells -- In the absence of antigen but presences of IL-7 and IL-15 the effector cells become memory cells. Mainetnace of memory cells is dependent on cytokines but does not reuire antigen recognition. - Superantigens -- stimulate T lymphocytes in uncontrolled manner and can cause shock. - Cytokines are proteins that mediate effector functions of immune system. - Cytokines act through - Autocrine action -- released, but bound to receptors on scell that produced them. - Paracrine action -- released to affect nearby cells - Endocrne action -- released into blood stream to affect distant cells. - Cytokines can have pleiotropic activity, redundant activity, synergy effect, antagonistic effect, and casade effect. - Cytokines can both induce and suppress inflmattion Cytokines that induce inflammation Cytokines that suppress inflammatiojn ------------------------------------ --------------------------------------- -- IL-1B, TNFa, and IL-6 TGFB - Chemokines affect lymphocyte movement and induce adhesion moelecules. - Four families of adhesion molecules - Selectins -- bind to carbohydrates and adhere weakly. They mediate the rolling and thumbling. If you select to try you are rolling and thumbling movement and what works gets picked up on the way. - Integrins -- mediate interactions between cells and the extracellular matrix -- arrest and adhesion. Mneumonic is integrins integrate cells and extracellular matrix. - Immunoglobulin-like adhesion molecules -- intercellular adhesion molecule 1 (ICAM-1) on endothelium plays an important role in trans-endothelial migration (extravasion) of leulocutes. Intercellular adhesion molecule helps between cell migration. - Cadherins -- involved on embryonic development, tumor metastasis - Cytokines regulate hematopoiesis -- blood cell production. - IL-2 helps with T cell differentiation. - IFN-antiproliferative and antiviral - IFN-y -- immunostimulatory and antivral - IL-2 immunostimulatory - Erythropoietin -- stimulates erythropoiesis - G-CSF -- stimulates granulocyte and monocyte/macropaheg production. - Monoclonal (Mab)antibodies speicif for cytokines or cytokine receptors in clinical use. - Receptor decoy -- is a drug that mimics natural TNF-a receptor for rheumatoid arthritis. Instead of being functional receptor on cells, it is a fake receptor that floats around the blood stream. It traps TNF-a, the receptor decoy reduces inflammation and helps relieve rheumatoid arthritis. - Complement system functions - Kill microorganisms, including bacteria, viruses, yeasts, and certain cells, directly. - Induce inflammation - Increase phagocytosis by opsonization - Clear insoluble immune complexes. - Activation of complement system is a three stepped process - Recognition - Enzyme activation - Expression of biological activity - Three activation pathway - Classical pathway -- intiated by antigen-antibody complex - Alternate pathway -- activated by cell wall of bacteria and yeats - Lectin pathway -- initated by lectins that bind mannosde - Classical pathway is antibody mediated and is part of adaptive immunity - Consists of 9 proteins - Formation of antigen-antibody complex (aggregates) - C1 complex starts and binding needs two moelcules of IgG or one molecule of IgM. - C1 cleaves c4 and c2 to form C4bC2a which is C3 converatase. - C3 convertase cleaves C3. C3 is the central step in all complement pathways. Is largest amblipifcation step. - C3b and c3a are anaphalytoxins that come off of the complement activation. - C4bC2aC3b forms a complex called C5 convertase. - C5b then intiates the formation of membrane attack complex. - Eventually get to C9. - Kill microorganisms including certain cells, bacteria, viruses, and yeast, directly. - PAMPs can activate complement pathway. - Lectin pathway - Mannose minding lectin binds to carbohydrates on the surface of bacteria nad yeasts. - MBL-associated serine proteases cleaves C4 nd C2. - C3 convertase forms complex on membrane - The rest is similar to the classical pathway. - Altnerate pathway - C3 hydrolyzed by H2O molecules to C3b on activation b pathogens - C3b binds factor B - Factor D cleaves factor B to form C3 convertase. - Properdine binds to form a more stable complex - Amplification loop occurs. - C3bBbP cleaves C5 to form C5b which intiates mebrane attack complex. After that same as in classical pathway and lectin pathway. - Alternate pathway - Factor B: activator of C3 convertase - Factor D: cleaves factor B - Propertine protein: helps in attaching C3b molecule towards cell membrane on pathogrn. - C3 is the largest amplification step in all complement pathways, classical, lectin, and alternate. - The anaphalytoxins broken off in the complement pathways induce inflammation. These molecules are C3a, C4a, c5a. - C-reactive protein used as a marker to test for inflammation. - Anigen antibody complexes get very large. Activate complement cascade. Complex binds to complement receptors. Engance phagocytosis to clear these compelxes. - Deficeny in complement causes diseases. Ex. lupus where there is an inability to clear immune complexes. - Defieciency in alternative pathway -- increased susceptibility to recurrent infection with pyogenic bacteria. - Regulation of complement pathway - Cleavage inhibited by C1 inhibitor for classical pathway - Decay accelerating factor (DAF) -- a protein that binds C4 dissociates C4bC2a -- blocks formation of C3 convertase inhibits classical pathway. - C1 inhibitor can cause antioedema where uncontrolled activation of C cause lips to swell - Alternate pathway -- factor H causes dissociation of C3 convertase. - Alternate pathway -- factor I and membrane cofactor protein cleave C3b forming an inactive C3b. - C59 blocls C9 fbinding and prevent formation of MAC. - Serum carboxypeptidae inactitve anaphalytoxins C3a, C5a, and C4a - NK cells and ILC1s in epithelium act on frontlinke, quickly produing IFNy in response to antigens. - T helper 17 protect against fungal infections. - IgA found in salivary gland and slaiva. - Th2 cells produce IL-5 helps B cells switch to IgA isotypes. - In the intestinal tract, the immune system must hae folerance to normal intestinal flora, yet repond to pathogenic microorganis,s. - TGf-B helps suppress inflammation. - Treg cells also help baalce active immunity versus immunological tolerance in face of diverse antigenic exposures. Week 4 - Hypersensitivity is an over reaction to foreign agents: harmful or benign - 4 categories - Type 1 -- immediate hypersensitivity, mediated by IgE, atopy-allergic reaction due to inhaling of allergy, anaphylaxis -- systemic reaction - Type II -- mediated by soluble antibodies to molecules on cells and tissues - Type III -- mediated by immune complexes rfom chronic exposre to antigens - Type IV = delayed hypersneisitivty, mediated by cells, immunocytss. - Type I hypersensitivity -- mediated by IgE, mast cells, eosinophils, immediate hypersensitivity, reaction time in minutes. Examples include respiratory tract allergies, skin reactions, GI tract allergies, and anaphylaxis. - Events in type 1 - Sensitization phase -- activation of Th2 cells, production of Il-4, activation of B lymphocytes, production of IgE, generation of memory repsonses - Activation phase -- IgE binds to high affinity IgE specific Fc receptors. Receptors cross linked by allergens. IgE activates basophils and mast cells - Immediate effector phase -- activation of mast cells/nbasophils. Immediate reaction. Degranulation of mast cells. Mast cells release histamine. - Late effector phase -- in 6-24 hours with production of cytokines. Mast cells produce eosinophil chemotactic factor that recrutits eosinophils. Reaction persists for days. - Wheal and flare test for allergies. - Anaphylatic shock is a systemic and violent reaction body has to allergies. - Eosinophils have anti- parasitic activity - Interventions for allergies if environmental avoid exposure. If pharmological can give epinephrine for anaphylaxis. Can also give anti-IgE antibody or anithistamines, or cromolyn to help with response. If immunological can modify allergens, hyposensitiation of t helper cells or IgG. - Type II hypersnsitiivty mediated by soluble IgG and IgM antibodies. - Blood transfusion reaction -IgM - Hemolytic disease of newborn -IgG - For type II, antibody directed against surface molecules on target cells - Interaction with complement. Activation and production of inflammation and tissue destructive mediators. - Type II hypersensitivity is typified by a transfusion reaction in which mismatched red blood cells are rapidly destroyed by specific preformed antibodies (anti-ABO or -Rh) and complement. - Environment carbohydrates induce production of IgM in a T independent manner. - Symptoms include fever, nausea, and vomiting. - Rh factor for mother's Rh being compatible with baby. If incompatible, IgG crosses placenta to destroy red blood cells of rh+ fetus. - Treatment for Rh factor -- give rh immune globulin after delivery to prevent sensitivation. Remove fetal red cells before mother can produce an immune response. - Type III hypersensisitivy mediate by antibody complexes -- antigen and IgG. Week 5 +-----------------------------------+-----------------------------------+ | Name of vaccine | Type of vaccine | +===================================+===================================+ | RotaTeq rotavirus | Attenuated live virus | +-----------------------------------+-----------------------------------+ | Salk's polio vaccine | Inactivated poliovirus | +-----------------------------------+-----------------------------------+ | Sabin's polio vaccine | Attenuated poliovirus | +-----------------------------------+-----------------------------------+ | Hep B vaccine Recombivax HB | Non-infectious protein subunit | +-----------------------------------+-----------------------------------+ | Pneumococal conjuagetd vaccines | Polysacchardige vaccine | +-----------------------------------+-----------------------------------+ | Meningoccoal vaccine | Polysachharide vaccine | +-----------------------------------+-----------------------------------+ | DTaP vaccine | 3 vaccines combined and is | | | inactive (acellular) | +-----------------------------------+-----------------------------------+ | MMR vaccine | Combined vaccine attenuated virus | +-----------------------------------+-----------------------------------+ | Covid 19 vaccines | Non-replicating RNA or mRA for | | | Moderna, Pfizer, BioNTech | | | | | | Non-replicating -- DNA in viral | | | vector | | | | | | Protein subunit | | | | | | Inactivated whole virus | +-----------------------------------+-----------------------------------+ - Vaccines very important. We still need them.