Term
| What is the effector in humoral immunity? |
|
Definition
|
|
Term
| Are T cells completely out of the picture in humoral immunity? |
|
Definition
| no - B cells require the cooperation of T cells to form a response (T dependent ag) |
|
|
Term
| What is the target of humoral immunity? |
|
Definition
|
|
Term
| What are the 6 steps a pathogen has to take in order to make you sick? |
|
Definition
| attachment, movement, proliferation of organisms, avoidance of phagocytes, damage to the host, toxic or invasive actions |
|
|
Term
| How do AB help in preventing pathogen attachment? |
|
Definition
| they cover up attachment points on the organism, i.e. like covering the fimbrae on gonorrhea so the bacteria will be flushed out with the urine, you can also make ab against lipotechoic acids and some capsules |
|
|
Term
| How do AB inhibit the motility of an organism? |
|
Definition
| they can clump ab on the flagella, inhibiting movement and they can also clump the bacteria together |
|
|
Term
| How do AB inhibit proliferation of organisms? |
|
Definition
| they can trigger complement, which damages the cells, esp in Gram neg bacteria, and they can block transport mechanisms, like for iron chelating compounds and food |
|
|
Term
| How do AB inhibit a pathogen from avoiding phagocytes? |
|
Definition
| it binds to M proteins which are spikes on the bacteria that normally prevent phagocytes from coming near*AB can neutralize immunorepellents also |
|
|
Term
| How do AB help with toxins made by a pathogen? |
|
Definition
|
|
Term
| How do ab help stop invasion of a pathogen? |
|
Definition
| they neutralize spreading factors and enyzmes needed to obtain nutrients, like hyaluronidase |
|
|
Term
| What are the 2 ways that ab can carry out effector functions? |
|
Definition
| direct activity - actually bind and cause their function by binding * adapter activity - activate complement and the complement actually does the job |
|
|
Term
| What are the effector functions of IgG? |
|
Definition
| *neutralization of microbes and toxins*opsinization of ag*activation of complement by the classical pathway*ADCC by NK cells*neonatal immunity*feedback inhibition of B cell activation |
|
|
Term
| What is the effector function of IgM? |
|
Definition
| activation of the classical pathway of complement |
|
|
Term
| What is the effector function of IgA? |
|
Definition
| mucosal immunity - neutralization of microbes and toxins |
|
|
Term
| What is the effector function of IgE? |
|
Definition
| ADCC mediated by eosinophils *mast cell degranulation (immediate hypersensitivity reactions) |
|
|
Term
| Why is it important for hose defenses to adapt? |
|
Definition
| to better respond to evolving pathogens |
|
|
Term
| How do antibodies prevent infection of a cell by a microbe? What about infection of adjacent cells? How do they block pathogenic effects of toxins? |
|
Definition
| *they bind to the microbe and prevent it from attaching * when an infected cell releases the microbe, the ab can bind it and prevent it from binding to an adjacent cell * it can bind to the toxin itself and prevent it from binding to the receptor on the cell |
|
|
Term
|
Definition
| the vaccine form of a toxin - it has the part that binds to the cell intact but the enzyme part is broken, so when you inject it you form ab to the binding part and when you see the real toxin it won't be able to bind |
|
|
Term
| What is the primary ab on mucosal surfaces? |
|
Definition
|
|
Term
|
Definition
| The plasma cell makes IgA, which is secreted as a dimer attached by a J chain - this binds to the polyIgR on the basal side, goes through the mucosal cells, and then gets cleaved on the luminal side, leaving sIgA |
|
|
Term
| Is sIgA actively or passively transported? What about other ab? |
|
Definition
| actively transported - others are just leaked out |
|
|
Term
| What types of microbes are phagocytized? |
|
Definition
|
|
Term
| How do ab's help get a small microbe phagocytized? |
|
Definition
| the Fab portions bind to the microbe, leaving the Fc portion sticking out - this binds to the FcgammaRI on the phagocyte - this binding also triggers the lysosomes to make ROIs, NO, and proteolytic enzymes |
|
|
Term
| What are the steps in phagocytosis, in general, starting with opsonization? |
|
Definition
| *microbe is opsonized with IgG *Fc portion binds to FcgammaR*phagocyte is activated*microbe is phagocytized and killed |
|
|
Term
| What is the relative strength of phagocyte/microbe binding with: nothing, complement, ab, and complement + ab? |
|
Definition
| nothing - +/-, ab - ++, complement - ++, C+A - ++++ |
|
|
Term
| What are the steps of phagocytosis, starting with the phagocyte eating the microbe (what happens inside the phagocyte)? |
|
Definition
| *microbe attaches to phagocyte pseudopodia *bacteria are ingested, forming a phagosome *phagosome fuses with lysosome (phagolysosome) * lysosomal enzymes digest captured material * digested products are released from the cell |
|
|
Term
| Does exposure to ROI require lysosomes? |
|
Definition
|
|
Term
| Does exposure to ROIs stop at fusion? |
|
Definition
|
|
Term
| When the lysosome fuses with the phagosome, what enzymes get released and in what order? |
|
Definition
| cationic proteins - punch holes in the cell membrane and acidic hydrolases acidify the vessicle, lowering the pH and activating the other enzymes * lactoferrin - strips the iron from transporter proteins, starving the microbe, SOD - generates H2O2, peroxidase - combines H2O2 with a halide like Cl to make hypochlorous acid |
|
|
Term
| Describe the peroxidase independent pathway of ROI killing. |
|
Definition
| phagocytosis of the microbe triggers a respiratory burst, releasing O2 and activating the hexose-mannose shunt that generates NADPH - the NADPH is a carrier for e- for SOD *O2 + e- + SOD = superoxide anion, hydroxyl radical, singlet oxgen and H2O2 - these all work on the bacteria and are toxic |
|
|
Term
| Decribe the peroxidase dependent pathway of microbe killing. |
|
Definition
| H2O2 from the peroxidase indep pathway + halide forms hypochlorious acid and water, which attacks amino groups in the bacteria - myeloperoxidases and catalase help this |
|
|
Term
| FcgammaRI - affinity for Ig, cell distribution, function? |
|
Definition
| high affinity - IgG1 and 3 esp, can bind monomeric Ig * on m'phages, neutrophils, and eosinophils * function - phagocytosis, activation of phagocytes |
|
|
Term
| FcgammaRIIA - affinity, distribution, function |
|
Definition
| low affinity - m'phages, eosinophils, neutrophils, platelets - phagocytosis, inefficient cell activation (has ITAMS) |
|
|
Term
| FcgammaRIIB - affinity, distribution, function |
|
Definition
| low affinity, B cells, feedback inhibition of B cells (has ITIMS) |
|
|
Term
| FcgammaRIIIA - affinity, distribution, function |
|
Definition
| low affinity - NK cells, m'phages, B on neutrophils - ADCC |
|
|
Term
| FcepsilonRI - affinity, distribution, function |
|
Definition
| high, binds monomeric IgE- mast cells, basophils, low levels on eosinophils - cell activation (degranulation) |
|
|
Term
| What is the main receptor for phagocytosis? |
|
Definition
|
|
Term
| What type of IgG does the FcgammaRII bind? |
|
Definition
|
|
Term
| What is the signalling chain for FcgammaRI and RIII? |
|
Definition
|
|
Term
| Are the functions of FcgammaRI and RIII only 1 thing? |
|
Definition
| no - I is better at phagocytosis, and III is better at ADCC, but it depends on what they bind - either can do either thing |
|
|
Term
| Describe the 2 types of Fcepsilon receptors in terms of affinity, where they're found, and unique properties. |
|
Definition
| Type I - very high affinity, found on mast cells, basophils, activation by crosslinking receptors causes degranulation, has the same gamma signalling chain as Fcgamma * type II - low affinity, found on m'phages and l'cytes, it's the only FcR not in the Ig superfamily - has a lectin homology domain and a proteolytic cleavage site |
|
|
Term
| How does ADCC work and what types of things does it work on? |
|
Definition
| big not self things - ab coats the surface of the cell, binding to the ag and the Fc portions bind to the FcR's on the NK cell (if IgG) or IgE and FcE on an eosinophil can happen |
|
|
Term
| What increases production of eosinophils? |
|
Definition
|
|
Term
| What do IgE and IgG ADCC do? |
|
Definition
| the eosinophil dissolves the outer wall and invades the schistosome |
|
|
Term
| What happens when m'phages or neutrophils try to attack really big things? |
|
Definition
| frustrated phagocytosis - functionally equivalent to ADCC, but the cells throw up on the target b/c they're mad |
|
|
Term
| What is the problem with frustrated phagocytosis as opposed to ADCC? |
|
Definition
| in eosinophils and NK cells have a pocket so the granules don't get out, but with neutrophils and m'phages there isn't, so things can leak out and damage neighboring cells |
|
|
Term
| How do T cells figure in fighting large extracellular parasites? |
|
Definition
| the response shifts to Th2, which shifts ab production to IgE, activating eosinophils and mast cells and IL-5 increases eosinophil production |
|
|
Term
| What are the 3 main functions of complement? |
|
Definition
| opsonization, aids in phagocytosis *direct lysis of the membranes via the MAC *activation of inflammation by releasing complexes |
|
|
Term
| Describe how complement opsonizes - what parts do it? |
|
Definition
| mainly C3b - they bind to the microbe, then bind to CR on the phagocyte, triggering phagocytosis |
|
|
Term
| Describe how complement causes lysis of a microbe. |
|
Definition
| Binding of C3b triggers binding of the later components, which form the MAC, which causes osmotic lysis of the microbe |
|
|
Term
| How does complement stimulate inflammatory reactions? |
|
Definition
| C3a, 4a, and 5a all cause recruitment and activation of leukocytes, they are chemotactants for neutrophils and they stimulate the release of inflammatory mediators and work on endothelial cells to increase vascular permeability |
|
|
Term
| Would you want an effector component to always be on? |
|
Definition
| no - you'd want an inactive form present that are converted to the active form by an activator that requires a signal that tells it that it's ok to activate (otherwise you might get damage to self and use up components, so you don't want activation unless you need it) |
|
|
Term
| Is the activation of complement a single or a multistep process? Why is this good? |
|
Definition
| multi-step - good b/c a single initial event leads to a large event |
|
|
Term
| Do you want the components in a complements system to have a long life? Why/why not? |
|
Definition
| want a short active life span so innocent bystanders won't be killed |
|
|
Term
| What 3 ways can complement be degraded? |
|
Definition
1)natural decay - certain parts are naturally unstable
2)they bind an inactivator
3)they get split by an inactivator |
|
|
Term
| Describe the classical initiation pathway of complement activation (just beginning). |
|
Definition
| triggered when IgM or IgG binds to AG - the Fc regions are accessible to complement proteins - C1 binds to Fc and becomes active |
|
|
Term
| What triggers the MBL pathway of complement activation? |
|
Definition
| MBL binding to mannose on microbes |
|
|
Term
| What triggers activation of the alternative pathway? |
|
Definition
| triggered by C3b binds to a microbe - it's usually present in low levels in the plasma from hydrolysis of C3 and normally breaks down rapidly |
|
|
Term
| If a protein is split, what part is designated a and what part is b? |
|
Definition
| the bigger part is b and the smaller part is a |
|
|
Term
| What do all of the complement pathways lead to? |
|
Definition
|
|
Term
| What 3 things do all complement pathways generate? |
|
Definition
| C3 convertase, C5 convertase and they all use C5b to activate the terminal components - C5b-C9 |
|
|
Term
| How does binding of an AB activate the classical complement pathway? |
|
Definition
| the binding causes a conformational change in the ab that reveals a binding site for C1 on the IgG or IgM classes |
|
|
Term
| Where is the C1 binding site on IgM? On IgG? |
|
Definition
| IgM - the CH3 domain, IgG - CH2 domain |
|
|
Term
| Is the classical pathway activated by ag-ab binding on soluble ag or ag bound to a microbe? |
|
Definition
|
|
Term
| Describe the structure of C1. |
|
Definition
| C1q is the central part and it has 6 heads - like olives on broken toothpicks that bind to the sites on the ab *2 C1r and C1s are between the "toothpicks" and the whole thing is held together with Ca |
|
|
Term
| How many C1 heads have to bind for activation in the classical pathway? |
|
Definition
|
|
Term
| How many IgMs are needed to activate C1? How many IgG? |
|
Definition
| 1 IgM, at least 2 IgG - 1 IgM is like having 1000 IgG b/c when an IgM binds it exposes multiple sites for C1q to bind |
|
|
Term
| What happens after C1q binds in the proper way and is activated? |
|
Definition
| 1 of the C1r's gets autoactivated, this one activates the other C1r and they each activate a C1s (C1r is a protease) - you now have activated C1s |
|
|
Term
| What are the substrates for C1s? |
|
Definition
|
|
Term
| Describe how C3 convertase is made in the classical pathway. |
|
Definition
| C1s hydrolyzes C4 into C4a and C4b - C4a diffuses away and C4b attaches to the target near C1, C2 proenzyme attaches to C4b and it gets hydrolyzed by C1s to C2a and C2b - C2b goes away and C2a sticks to C4b, creating C3 convertase |
|
|
Term
| How is C5 convertase made in the classical pathway? |
|
Definition
| C3 convertase hydrolyzes C3 into C3a and C3b - some C3b opsonizes things, but some sticks to C4b2a to make C5 convertase |
|
|
Term
| Describe the MBL pathway. |
|
Definition
| MBL is mannose binding lectin and structurally it's similar to C1q - it has associated with it MASP-1 and 2, 2 copies of each, which are like C1r and C1s - MBL binds to mannose resides on the surface of microbes and when after the MBL binds MASP-1 and 2 bind to it (these are serine proteases) - MASP-1 activates MASP-2, which cleaves C4 - get C4b and C2 to get C2a - these are C3 convertase - cleaves C3 to get C3b, which attaches to get C5 convertase |
|
|
Term
| What are the 2 bonds in C4 and C3 and what do they bind to? |
|
Definition
| 1 is an internal thioester bond that is exposed on activation - want it to bind to an amine or OH group on a surface protein or carbohydrate #2 is a binding site for C2 (on C4) - this bond holds C2 steady for cleavage by C1 or MASP-2 |
|
|
Term
| Is the internal thioester bond in C3 or C4 long lived? |
|
Definition
| no - if it doesn't bind to a target protein or carb it will be degraded by water |
|
|
Term
| If water attackes C4b or C3b what does it become? |
|
Definition
|
|
Term
| What are the parts in C3 convertase and what do they do? |
|
Definition
| C4b - positions C3 and C2a cleaves C3 into C3a and C3b |
|
|
Term
| What are the functions of C3b |
|
Definition
| some diffuse away and act as opsonins and some land close to C4b2a and stick to make C5 convertase |
|
|
Term
|
Definition
| no - it doesn't diffuse far b/c it has the same exposed thioester bond, so either it attaches to something or it's degraded by water |
|
|
Term
| How does C5 convertase work in classical/lectin pathway? |
|
Definition
| When C3b binds to C4b2a, it changes the affinity such that C5 now binds better than C3 - so C5 is now cleaved by C2a - C5b does not have an internal thioester bond so it's longer lived, and C5a diffuses away |
|
|
Term
| Describe the formation of MAC. |
|
Definition
| C5b has to bind to something or it gets inactivated, so it will bind to C6 and then C5b6 binds to C7 - this complex inserts into the membrane of the target cell (there's a change that exposes hydrophobic regions and this is how it binds to phospholipids) or they can bind in solution and attach to a different cell * after C5b67 insertion, C8 and C9 come in, poly C9 is generated and the whole thing is a MAC |
|
|
Term
| What is the function of the MAC? |
|
Definition
|
|
Term
|
Definition
| gram neg bacteria, mycoplasma, enveloped viruses, erythrocytes |
|
|
Term
| What cells can MAC not lyse? |
|
Definition
| gram + bacteria - b/c of the thick peptidoglycan wall and non-enveloped viruses b/c there's no membrane (you can coat them with C3b and opsonize them) |
|
|
Term
| Can the classical pathway cause cell lysis by itself? |
|
Definition
| no not normally, but it can do it with help |
|
|
Term
| What does activation of the alternative pathway start with? |
|
Definition
|
|
Term
| Where does the C3b that activates the classical pathway come from? |
|
Definition
| there are constant low levels of C3b in plasma - comes from classical or lectin pathway convertase, inflammation or blood clotting (plasmin can cut C3), and alternative pathway C3 convertase |
|
|
Term
| What is C3 tickover? How does it work? |
|
Definition
| the formation of C3b from water attacking C3 * C3 flexes sometimes, exposing its thioester bond to water - this generates C3H2O or C3b, which can bind to surface ag or the host's own cells |
|
|
Term
| If C3b generated by tickover binds to the host's cells, what happens? |
|
Definition
| nothing - mammalian cells have a lot of sialic acid, which deactivates it before it starts the alternative pathway |
|
|
Term
| How is C3 convertase generated in the alternative pathway? |
|
Definition
| some of the C3b generated by tickover binds to the surface of a target cell - factor B then binds and this binding exposes a site on factor B that is the substrate for factor D -factor D binds and then cleaves factor B into Bb and Ba - Ba diffuses away and Bb binds to C3b, so C3bBb is C3 convertase |
|
|
Term
| What happens after C3bBb is formed? What gets generated? |
|
Definition
| C3bBb is short lived normally, so properdin binds to it and extends its half life - if this happens it cleaves a lot of C3 and some of the C3b will stick to the C3bBb complex, forming C5 convertase - C3bBbC3b |
|
|
Term
| What controls C3b levels in the blood? |
|
Definition
| C3b and C3bBb are very susceptible to attack of their thioester bond by water - this lowers their activity and makes it more susceptible to cleavage by factor I |
|
|
Term
| What is the major mechanism for control of complement (alternative pathway) on host cells? |
|
Definition
| factor H - a regulatory component that binds to C3b and prevents or displaces factor B, so C3 convertase can't form - it also promotes factor I * other membrane proteins are CR1 and MCP (membrane cofactor protein) that act like factor H - they can bind C4b, etc to prevent C3 convertase from forming |
|
|
Term
| What does factor I do in the classical or lectin pathways? |
|
Definition
| factor I cleaves C4b into bound C4d and soluble C4c |
|
|
Term
| What does factor I do in the alternative pathway? |
|
Definition
| cleaves C3b inot bound iC3b and soluble C3f - then factor I cleaves iC3b into bound C3dg and soluble C3f |
|
|
Term
| What dissociates the C3 convertase before it can be made in the classical/lectin pathways? |
|
Definition
|
|
Term
| What dissociates C3 convertase after it's already been made? |
|
Definition
| C4bBP, CR1, Factor H, and DAF (decay accelerating factor) |
|
|
Term
| What is an activating surface? |
|
Definition
| a surface that promotes the binding of factor P over factor H, which promotes the C3 and C5 convertase |
|
|
Term
| Where are activating surfaces found? |
|
Definition
| Bacteria (LPS is a great surface, it prevents factor H from binding to C3b in gram neg), in gram pos, techoic acid prevents factor H binding * enveloped viruses * fungi * some parasites * ag-ab complexes |
|
|
Term
| What happens in an activation loop exactly? |
|
Definition
| C3b can still be inactivated, but it's a lot slower - properdin binding is favored on an activating surface, so C3bBb lasts longer, cleaves more C3, generates C3b and C3bBbC3b (C5 convertase) and you're making activated stuff faster than you're inactivating things |
|
|
Term
| Does C3bBbC3b require properdin? |
|
Definition
| no, but it stabilizes the complex |
|
|
Term
| How do nucleated cells get lysed, if they have repair mechanisms? |
|
Definition
| if the classical and alternative are activated or an activation loop starts, it will generate enough MAC to lyse the cell b/c it will attack faster than the cell can repair itself - you'll have 2 sets of C3 and C5 convertases |
|
|
Term
| What type of nucleated cells are usually lysed by complement? |
|
Definition
|
|
Term
| Is the lectin pathway involved with lysing nucleated cells? |
|
Definition
| MBP is usually in prokaryotes, which don't have a nucleus |
|
|
Term
| What is anaphylactic shock? |
|
Definition
| an extreme case of inflammation from anaphylotoxins |
|
|
Term
| Which complements are anaphylatoxins? |
|
Definition
| C5a (most effective), C3a, and C4a |
|
|
Term
| What do anaphylatoxins do? |
|
Definition
|
|
Term
| What does mast cell degranulation cause? |
|
Definition
| histamine release and the release of other inflammatory mediators - this causes: smooth muscle contraction, dilation and permeability of blood vessels, and subsequently an influx of fluid that carries AB and phagocytes into the site of ag entry |
|
|
Term
| Which complement frag is chemotactic for neutrophils and m'phages? |
|
Definition
|
|
Term
| What regulates anaphylatoxins? How does it work? |
|
Definition
| *regulated by carboxypeptidase N in plasma protein - this is a serum protease that inactivates C#a by removal of the C-terminal Arg making the C5a much less active and C3a and C4a completely inactive |
|
|
Term
| Which complement frags are most efficient at opsonization? |
|
Definition
| C3b and C4b, to a much smaller degree |
|
|
Term
| What does CR1 bind, what does it do, and where is it found? |
|
Definition
| binds C3b and C4b, blocks formation of C3 convertase and binds immune complexes to cells * on RBC, neutrophils, m'phages, eosinophils, FDC, B cells, and some T cells |
|
|
Term
| What does CR2 bind, what does it do, and where is it found? |
|
Definition
| binds C3d, C3dg, and iC3b - B cell coreceptor *B cells, some T cells, FDC |
|
|
Term
| What does CR3 and 4 bind, what do they do, and where are they found? |
|
Definition
| bind iC3b, facilitate extravasation of neutrophils, bind immune complexes helping them get phagocytized *monocytes, m'phages, neutrophils, NK, some T |
|
|
Term
| What does CR3a/4a bind, what does it do, and where is it found? |
|
Definition
| C3a, C4a - induces degranulation of mast cells and basophils * mast cells, basophils, granulocytes |
|
|
Term
| What does CR5a bind, what does it do, and where is it found? |
|
Definition
| C5a, induces degranulation of mast cells and basophils *mast cells, basophils, granulocytes, monocytes, m'phages, platelets, endothelial cells |
|
|
Term
| How does complement help to clear immune complexes? |
|
Definition
| complement breaks up big complexes into smaller complexes via stereohindrance and the little complexes bind to CR1 on RBC, these take the complex to the liver, where phagocytes with Fc and CR strip off the complexes and eat them - prevents buildup of complexes in the blood |
|
|
Term
| What does cobra venom factor do? |
|
Definition
| it mimics C3b and binds B making a complex that can't be turned off by H and I, so it generates a cycle that uses up all the C3, C5-9, depleting the components, so you're "decomplementing" the animal - you won't have anything when you really need it |
|
|
Term
| What is the role of complement in generating a secondary response? |
|
Definition
| it's necessary to make memory cells and good ag localization b/c CR is on B cells and FDC |
|
|
Term
| Describe the experiment that shows that complement is necessary for a secondary response. |
|
Definition
| give an ag, get a normal 1' response, give it again, get a normal 2' response - give CVF before you give 1st ag, you get a normal 1' response and another 1' response on 2nd exposure - give ag, then CVF with 2nd ag and you'll get a normal 2' response b/c you've already made memory cells |
|
|
Term
| How do you limit damage to host cells by complement? |
|
Definition
| *we don't have mannose on our cells, so we don't use the lectin path * sialic acid on host cells inhibit C3b binding * C4b is unstable and short lived, short lived intermediates |
|
|
Term
| What specifically does DAF do? |
|
Definition
|
|
Term
| What does MCP or CR1 do specifically? |
|
Definition
| act as cofactors for factor I cleavage of C3b |
|
|
Term
| What specifically does C1 INH do? |
|
Definition
| prevents C1r2s2 from becoming proteolytically active (binds it) |
|
|
Term
| How is the formation of a MAC inhibited? |
|
Definition
| S protein can bind to C5b and prevent C5b67 from inserting into the membrane, HRF (homologous restriction factor) and CD59 are membrane proteins that bind C8 and inhibit insertion of C9 |
|
|
Term
| Why won't complement work on your own cells (why should you use a different species complement in experiments)? |
|
Definition
| the HRF in your body inhibits complement in your cells |
|
|
Term
| What happens if you have systemic activation of complement? |
|
Definition
| you get all the pipes leaking and shock |
|
|
Term
| What happens if you damage cells in complement activation? |
|
Definition
| the cells release inflammatory substances |
|
|
Term
| What does immune complex activation lead to? |
|
Definition
|
|
Term
| If all normal controls are removed, what happens to B cells - how much could they proliferate? |
|
Definition
| 1 cell could generate 10^10 cells |
|
|
Term
| Why don't we get clonal expansion of B cells like 10^10? |
|
Definition
| b/c we have control mechanisms, and we only have 10^12 lymphocytes period, so they couldn't all be B cells |
|
|
Term
| How do you figure out the clonal expansion possibility of B cells? |
|
Definition
| immunize 1 mouse with ag, remove the spleen cells and transfer to an x-irad mouse, then take a sample and measure B cells, challenge it again,transfer another portion to another x-irrad mouse and rechallenge it, etc |
|
|
Term
| What are specific immune responses driven by? |
|
Definition
|
|
Term
| What happens to Th cells, B cells, and CTL if there is no ag interaction with a receptor? |
|
Definition
| T cells: no lymphokine prodyction, B cells - no ab production, CTL won't kill |
|
|
Term
| Is there clonal expansion without ag? |
|
Definition
|
|
Term
| What is the function of the immune response? |
|
Definition
|
|
Term
| What are the 3 mechanisms triggered by activation of mature Th cells that limit proliferation? |
|
Definition
|
|
Term
| Explain how CTLA-4 limits proliferation of T cells. |
|
Definition
| When a T cell is activated by ag it gets costimulation by CD28 on it interacting with B7 on the APC - CTLA-4 is a receptor on the T cell that gets put out at the same time and it competes for B7, except it inhibits rather than stimulates |
|
|
Term
| What specific signals does CTLA-4-B7 binding block? |
|
Definition
| it blocks signals from PI-3 kinase that activate the JNK pathway that leads to transcription factors NFAT and AP-1 |
|
|
Term
| What protein is made when a T cell is triggered? How is this combatted? What if there's no costimulation with the ag? |
|
Definition
| when a T cell is activated, apoptotic protein is made automatically - IL2-IL2R interaction triggers the making of antiapoptotic protein, so the cell doesn't undergo apoptosis - if there's activation with no costimulation, the antiapoptotic protein isn't made and the cell undergoes apoptosis |
|
|
Term
| What induces the production of Fas/FasL? How does Fas/FasL help with "population control"? |
|
Definition
| Repeated stimulation of the same T cells - they are likely to be responding to self-ag, so when Fas-FasL interact (either on the same cell or on different cells) it induces apoptosis - when there's too many T cells of a certain type this helps control the pop b/c they'll start bumping into each other and their Fas-FasL will interact - there's only so much room |
|
|
Term
| Why would repeated stimulation of the same T cells be a problem? |
|
Definition
| b/c the responses are ag specific and a normal ag should have been cleared, so either it's a chronic prob or a self prob |
|
|
Term
| What regulatory cytokines are produced by Th1 cells and what do they do? |
|
Definition
| TGF-beta 1 (transforming growth factor) - inhibits all l'cyte proliferation *IFN gamma - inhibits the Th2 pathway |
|
|
Term
| What regulatory cytokines are produced by Th2 cells and what do they do? |
|
Definition
| IL-10 - inhibits the Th1 pathway, inhibits MAC activation by decreasing costimulation |
|
|
Term
| What regulatory cytokines are produced by Th1 and Th0 cells and what do they do? |
|
Definition
| IL-2 - unknown mechanism, but high levels of IL-2 are inhibitory, low levels are stimulatory |
|
|
Term
| How do we know that IL-2 can be inhibitory at high levels? |
|
Definition
| knockout mice for either IL-2 or IL-2R have uncontrolled l'cyte proliferation |
|
|
Term
|
Definition
| T cells that don't show either a Th1 or Th2 profile |
|
|
Term
|
Definition
| regulatory T cells that develop in the thymus and they are self-reactive T cells that aren't killed upon reacting to self-ag |
|
|
Term
| How do T-regs suppress self-reacting l'cytes? |
|
Definition
| 1) they can make IL-10 and TGF beta, which shuts down m'phages and l'cytes,or 2) they can react directly with and suppress other l'cytes or APCs that are self-reacting |
|
|
Term
|
Definition
| you shouldn't b/c t cells shouldn't be activated w/o costimulation, which shouldn't happen with self-ag, but sometimes it does, so this prevents a lot of self-reactive T cells from proliferating |
|
|
Term
| Does giving specific IgM along with an AG increase or decrease the immune response? Why? |
|
Definition
| it increases the response b/c IgM complexes are taken up by APCs better and therefore presented better, or b/c IgM is really good at activating complement and CR2 increases AB production |
|
|
Term
| Does giving specific IgG along with an AG increase or decrease the immune response? Why? |
|
Definition
| Decreases - passive IgG may bind ag in competition with B cells, reducing the effective concentration or it might cross link ag receptors with FcgammaR on the same cell and this creates an inhibitory signal |
|
|
Term
| What happens to the quantity and quality of ab made if you give passive ab with an ag at immunization? Why? |
|
Definition
| you'll decrease the response in quantity, but what is made is of higher affinity *b/c when you give passive ab with ag it binds the ag, so it's like giving a smaller ag does, so fewer cells are activated to make ab, but those that do are the ones that have high affinity b/c there was competition for it |
|
|
Term
|
Definition
| they cover up the ag determinants, so they can't bind to membrane Ig |
|
|
Term
| How specifically does IgM enhance ag presentation? |
|
Definition
| it activates complement very efficiently, so the ag gets coated by complement, which attaches to an APC like a FDC by CR2 |
|
|
Term
|
Definition
| a unique 3D shape of a binding site - can be where ag binds or outside this region |
|
|
Term
| What is an anti-idiotype? |
|
Definition
| a shape that complements a binding site - can mimic an ag or not |
|
|
Term
| Describe the experiment where mice are given NP, then anti-146. What were the results? |
|
Definition
| mice were immunized with NP, which caused them to make the AB 146. If the mice were pretreated with a lot of anti-146, they did not make much 146 at all, but if they were pretreated with a small amount of 146 the response was very large |
|
|
Term
| WHy would pretreatment with a little anti-id cause a larger AB response, but treatment with a lot would reduce the response? |
|
Definition
| if you give a lot, it can cross-link all the receptors on the B cells and they will go basically anergic b/c it will cause all the receptors to be pulled in and it takes a long time to put all those out * if you give a little, it cross-links only a few receptors and it will stimulate a response |
|
|
Term
| What happens to an immune response in an adult if you give it a large dose of anti-id? WHat happens in a baby? |
|
Definition
| an adult will have temporary suppression of the AB response, a baby will have long-lasting suppression |
|
|
Term
| Can you get anti-anti idiotypes, etc? If so, what can they look like? |
|
Definition
| yes - you get anti-anti-idiotypes that look like AG, some like original AB, and some that are made to outside epitopes and look like neither |
|
|
Term
| Can you get an indefinite anti-idiotype cascade? |
|
Definition
| no - eventually the response is so small that you don't get a response |
|
|
Term
| What is an anti-id vaccine? |
|
Definition
| a vaccine that offers a way around the live vaccine problem - you take something like HIV, and generate a rabbit vaccine, purify the AB and separate it from any possible virus - you take that AB and immunize people with it - it will cause the person to generate a response that will protect them from the real HIV |
|
|
Term
| Why are anti-id vaccines not used? |
|
Definition
| you have to find that right AG that's in all the vaccines to get a protective response - it's much easier to kill the whole virus and inject people with it |
|
|
Term
| Who produces prostaglandin E and when? |
|
Definition
| macrophages, mast cells and platelets make PGE when stimulated |
|
|
Term
| What is the function of PGE? |
|
Definition
| it's a general shutter-offer - it suppresses the activities of m'phages and l'cytes |
|
|
Term
| Is PGE AG specific or nonspecific? |
|
Definition
|
|
Term
| Does PGE prevent a cell from being turned on? |
|
Definition
| no - it doesn't stop a cell from being activated, but it makes the cells require more signal to stay that way |
|
|
Term
| What major cytokines work on the neuroendocrine system? |
|
Definition
|
|
Term
| What do neuroendocrine cytokines cause? |
|
Definition
| fever - they reset the body's thermostat so that it's now outside the optimum range for the microbe |
|
|
Term
| What's the problem with fever? |
|
Definition
| you can cook and die - denature vital proteins |
|
|
Term
| What can stress hormones do? |
|
Definition
| suppress the immune response |
|
|
Term
|
Definition
| specific lack or decrease in immune response to an AG induced by prior exposure to the AG |
|
|
Term
| Describe an experiment that shows tolerance to skin grafts. |
|
Definition
| a newborn mouse (strain A) is injected with strain B mouse cells - 6 weeks later the mouse is given strain B and C skin grafts - at week 7 the B graft is accepted but the C strain is rejected |
|
|
Term
|
Definition
| both in AB or CMI responses |
|
|
Term
| Experimentally, which cells are easier to tolerize and why? |
|
Definition
| T cells - b/c they tend to be monitors of self |
|
|
Term
| What do you need to maintain tolerance? |
|
Definition
| continued presence of the ag |
|
|
Term
| What is the most important tolerance? What is second? |
|
Definition
| tolerance to self is the most important - maternal-fetal tolerance is next |
|
|
Term
|
Definition
| something that induces tolerance |
|
|
Term
|
Definition
| an inability to respond due to general suppression - this is immunosuppression |
|
|
Term
| What is the tolerance response and what is it not? |
|
Definition
| it's not no response - it's just a negative response |
|
|
Term
| Is tolerance caused by a genetic problem? |
|
Definition
| no - it's not the lack of a receptor, like a hole in the repertoire or a lack of MHC that can bind the peptide |
|
|
Term
| When does central tolerance develop? |
|
Definition
| it develops to ag that we're exposed to during development - mainly self ag |
|
|
Term
| What type of cells undergo peripheral tolerance? |
|
Definition
|
|
Term
| What does central tolerance cause? |
|
Definition
| the elimination of cells that self react |
|
|
Term
| What does peripheral tolerance cause? |
|
Definition
| elimination of anergy of cells that recognize self ag in peripheral tissue |
|
|
Term
|
Definition
| shutting down a cell so that it will not respond to an ag in later exposures |
|
|
Term
|
Definition
| stimulation of a cell in the absence of costimulation or too much CTLA-4/B7 interaction too early, so the cell isn't properly costimulated |
|
|
Term
| Experimentally, how do you show peripheral tolerance (using transgenics)with soluble ag? |
|
Definition
| you breed mice that make HEL protein and anti-HEL ab - non-transgenic mice make a lot of IgM, anti-HEL mice make B cells that make anti-HEL, and double transgenics make anti-HEL, but downregulate their IgM, so it's much harder for these cells to respond - they are anergic b/c even though they're making anti-HEL it won't respond to HEL b/c it sees HEL as native and goes anergic |
|
|
Term
| Describe the experiment with membrane bound ag and double transgenics. |
|
Definition
| breed transgenic mice to get a mouse that expresses MET-k^b and anti-kb, which means that Kb is only expressed in the liver, not everywhere else, so it's seen as foreign everywhere else - in the single transgenic (anti-Kb), you see B cells in the bone marrow and the lymph node that will attack Kb, but in the double transgenics, you see no Anti-Kb B cells in the lymph node - they've been eliminated |
|
|
Term
| What do soluble and membrane ag tend to cause in terms of tolerance? |
|
Definition
| soluble tends to make cells go anergic, membrane makes them eliminate |
|
|
Term
| How do you induce tolerance and what type of Th response do you get with each method? |
|
Definition
| high dose of ag - get high zone tolerance, mainly a Th2 response (IL-4), repeated low doses, like allergy shots, get a Th1 response - IFN gamma |
|
|
Term
| What types of ag physically are good for inducing tolerance? |
|
Definition
| proteins with no aggregates (soluble proteins) - these are harder to pick up, as opposed to slightly denatured ones which are easier for m'phages to pick up and process |
|
|
Term
| How are haptens used as toleragens? |
|
Definition
| either the hapten itself can be used or a hapten associated with a toleragenic carrier (like hapten on self protein) |
|
|
Term
| Should toleragens be degreable or mitogenic? |
|
Definition
| no - neither - these will stay around a long time and can't get processed, therefore they won't be presented |
|
|
Term
| Where should a toleragen be given? |
|
Definition
| IV rather than tissue - tissue injection usually causes inflammation and therefore danger signals or aerosol - snorting is less inflammatory |
|
|
Term
| Who is easier to tolerize in terms of immunologic state and age? why? |
|
Definition
| partially impaired people are easier b/c their immune system is less active and it's easier to overload the system, which drives tolerance * neonates are easier b/c they just have less immune system **in either, they have smaller numbers of mature immune cells and therefore the dose is effectively much higher |
|
|
Term
| How do you tolerize B cells to T-independent AG? |
|
Definition
| AG blockade of AB forming cells - binding of all the receptors causes them to be sucked in and it takes a long time to put them back out (mimicked by anti-id) * clonal exhaustion - T ind ag can drive all cells to be ab forming cells - short lived, have no memory cells |
|
|
Term
| Can you get clonal exhaustion with T dependent ag? |
|
Definition
| no - you have hypermutation and generation of memory cells |
|
|
Term
| How do Th responses suppress each other? |
|
Definition
| Th1 and 2 express cytokines that block the other pathway and push their pathway * anti-id for T cells is an ab to TCR that blocks activity and anti-id for B cells suppresses ab with that id |
|
|
Term
|
Definition
| self, allergies, graft survival, and pregnancy |
|
|
Term
| What are you doing when you give allergy shots? |
|
Definition
| inducing partial tolerance to ag by deleting IgE producers and shifting the balance from Th2 to Th1, since Th1 makes IgG, which doesn't give allergies |
|
|
Term
| What is a hypersensitivity? |
|
Definition
| an inappropriate immune response - either an overreaction or under-control of normal responses |
|
|
Term
| What is an immediate hypersensitivity? |
|
Definition
| one that takes place within minutes to hours of an exposure - mediated by ab, usually IgE |
|
|
Term
| What is a delayed type hypersensitivity? |
|
Definition
| one that takes days to show up - mediated by l'cytes (type IV) |
|
|
Term
| Are most h'sensitive reactions purely 1 type? |
|
Definition
| no - most are a mix - often they're a lesion with 1 type dominant |
|
|
Term
| Is inflammation a component of a hypersensitivity reaction? Why? |
|
Definition
| yes - b/c you're having tissue damage and you always get inflammation with that |
|
|
Term
| What are type I-IV caused by, generally? |
|
Definition
| I: IgE, II- AB attacking ag on your cells, III - immune (AG-AB) complex, IV-T cell mediated |
|
|
Term
| What are type I reactions caused by? |
|
Definition
|
|
Term
|
Definition
| describes someone who tends to produce IgE in response to common, normally harmless ag and has clinical symptoms |
|
|
Term
|
Definition
| it means you have a tendency toward clinical reactions to a normally harmless ag |
|
|
Term
| What are the "classic allergies"? |
|
Definition
| hay fever, food allergies, hives, eczema |
|
|
Term
| What happens in type I reactions when the person is 1st exposed to ag? |
|
Definition
| the AG cross-links receptors on B cell and activates a Th2 response (make IL-4 and 13) that induces class switching to make IgE - the IgE coats the mast cells, binding to the Fcepsilon receptors and sensitizing them |
|
|
Term
| What happens upon subsequent exposures to the same ag in a type I response? |
|
Definition
| the ag binds the IgE on the mast cells and causes the release of inflammatory mediators and you get the allergy symptoms |
|
|
Term
| If both parents have allergies, what is the likelihood that their child will? |
|
Definition
|
|
Term
| If 1 parent has allergies, what's the likelihood that the child will? |
|
Definition
|
|
Term
| If neither parent has allergies, what's the likelihood that the child will? |
|
Definition
|
|
Term
| If both parents have allergies, is there ever a 100% chance that the child will have them? |
|
Definition
| no - there are multiple loci involved - it's not a single gene that determines if you have allergies |
|
|
Term
| Is there an association between certain MHCs and a particular AG? |
|
Definition
| there are associations, but it's not causal - they are associated b/c certain MHC bind better to certain TCR and are therefore more efficient at getting a response |
|
|
Term
| What is the structure of a high affinity IgE receptor? |
|
Definition
| an alpha chain and a beta chain and 2 gamma chains with ITAMs - the alpha chain looks like an Ig receptor |
|
|
Term
| Where are high affinity IgE receptors found? |
|
Definition
|
|
Term
| What type of IgE receptor is high affinity? Low affinity? |
|
Definition
| high -type I, low - type II |
|
|
Term
| Where are low affinity IgE receptors found? |
|
Definition
| macrophages, B cells, eosinophils |
|
|
Term
| What is unusual about the structure of low affinity IgE receptors? |
|
Definition
| the carboxy terminal is outside the cell and the amino terminal is inside |
|
|
Term
| What is different about the IgE on mast cells in normal people as opposed to people with allergies? |
|
Definition
| in normal people, the IgE is of many different specificities, not just a few like in people with allergies - lots of AG cause the formation of IgE, just not enough to cause any problems |
|
|
Term
| Wbat happens after an AG crosslinks the IgE on the mast cell? |
|
Definition
| the ITAMS get phosphorylated by protein tyrosine kinases on the beta and gamma chains - this causes methylation of the phospholipid membranes and subsequent calciu channel formation - there is an increase in Ca from 2 sources - extracellular uptake and intracellular release from the ER, which leads to other signalling cascades |
|
|
Term
| What is used in the lab to make calcium channels? |
|
Definition
|
|
Term
| What are the things released when the mast cell is activated? |
|
Definition
| preformed granules, lipid mediators, and cytokines |
|
|
Term
| What causes the release of mediators from mast cells (intracellularly, not cross-linking)? |
|
Definition
| influx of calcium, phospholipase A2 activation (causes arachidonic acid production), transient activation of adenylate cyclase, causing cAMP levels to rise then fall, activating other kinases |
|
|
Term
| Are primary mediators preformed or are they made upon activation? |
|
Definition
| preformed and stored in granules |
|
|
Term
| Are secondary mediators preformed or made upon activation? |
|
Definition
| newly synthesized - these are arachidonic acid metabolites (lipid mediators) and cytokines |
|
|
Term
| What is in the preformed granules released from mast cells? |
|
Definition
| histamine, heparin, proteolytic enzymes, and chemotactic factors |
|
|
Term
| What does histamine cause? |
|
Definition
| inflammation: vasodilation, increased capillary permeability, smooth muscle contraction particularly around bronchioles, which causes wheezing and small airways |
|
|
Term
| What is heparin? What does it do? |
|
Definition
| it's an anticoagulant and an antiinflammatory - suppresses and limits inflammation |
|
|
Term
| What do proteolytic enzymes released from mast cells do? |
|
Definition
| activate complement and kinins and cause more inflammation |
|
|
Term
| What do the chemotactic factors released from mast cells attract? |
|
Definition
| neutrophils and eosinophils |
|
|
Term
| What pathways are activated by arachidonic acid? |
|
Definition
| cyclooxygenase and lipoxygenase |
|
|
Term
| What are the results of the cyclooxyenase pathway? What do these things cause? |
|
Definition
| prostaglandins and thromboxanes - cause vasodilation, increased vascular permeability, smooth muscle contraction, and platelet aggregation *PGE - generalized suppressor |
|
|
Term
| What are the results of lipoxygenase pathway activation? What does it cause? |
|
Definition
| leukotrienes - LTC4 and LTD4 - cause prolonged contraction of smooth muscle (aka slow reacting substance of anaphylaxis) and are chemotactic |
|
|
Term
| What cytokines are released in type I reactions and what do they do? |
|
Definition
| IL-4 and 5 - promote Th2, push class switch toward IgG *IL-8 - chemokine * TNF is both newly made and premade - chemotactic and activates cells |
|
|
Term
| What is platelet aggregating factor - where does it come from and what does it do? |
|
Definition
| comes from phospholipase A2, but it's a different pathway than arachidonic acid - aggregates platelets and causes them to release mediators, increasing inflammation |
|
|
Term
| What are the symptoms of allergic rhinitis sinusitis? |
|
Definition
| increased mucus and inflammation of the upper airways and sinuses |
|
|
Term
| What are the symptoms of food allergies? |
|
Definition
|
|
Term
| What are the symptoms of bronchial asthma? |
|
Definition
| bronchial hyper-responsiveness, inflammation and tissue injury caused by late phase reaction |
|
|
Term
| What are the symptoms of anaphylaxis? |
|
Definition
| shock, airway obstruction due to laryngeal edema |
|
|
Term
| What causes hayfever (the reaction) and what is the antigen? |
|
Definition
| ag is pollen in the eyes and airways, it's due to the mediator release of mast cells and basophils lining the respiratory tract |
|
|
Term
| What are the symptoms and antigens in hives? |
|
Definition
| swollen red patches and leaky vessels - inflammation * oral ag absorbed into the blood *each hive is the result of an ag leaving the blood stream and binding to a mast cell around a small venule in the dermis |
|
|
Term
| What types of things are associated with causing type I reactions? |
|
Definition
| food - nuts, eggs, seafood, etc, *drugs - penicillin, sulfonamides, saliylates, local anesthetics * proteins - foreign serum, vaccines* insect products - bee venom, wasp venom, dust mites, *mold * animal dander* plant pollen |
|
|
Term
| What is household dust made of? |
|
Definition
| common allergens, dead skin cells, and microscopic bugs |
|
|
Term
| What happens in bronchial asthma? |
|
Definition
| chronic allergen exposure over time leads to thickening of the basement membrane and an influx of cells - the ciliated epithelial cells slough and leave bare patches, making it harder to get rid of mucus, airways constrict |
|
|
Term
| Why do you wheeze with asthma? What can you do and not do? |
|
Definition
| caused by constricted airways + decreased ability to get rid of mucus - you can breathe in but not out |
|
|
Term
| What is the big problem with asthma? |
|
Definition
| the airways lose plasticity over time |
|
|
Term
| What causes eczema and what happens? |
|
Definition
| oral ag - it's a chronic skin irritation due to a type I response - the chronic version of hives |
|
|
Term
| What causes anaphylaxis? What are examples? |
|
Definition
| ag getting into the system and generating a systemic rather than a local response *bee venom getting into a blood vessel, food ag getting rapidly absorbed from the gut into the blood |
|
|
Term
| What is the animal model for anaphylaxis? |
|
Definition
|
|
Term
| What are the 2 ways to test for allergies and what are they looking for? |
|
Definition
| skin testing - looking for a local mucosal IgE response *blood tests - looking for Ag-specific IgE, but there's very little IgE in the blood b/c it's all stuck to the mast cells |
|
|
Term
| What are the 2 methods of skin testing and what do positive results look like? |
|
Definition
| intradermal injection - put a small dose just under the skin - looks like a weal and flare in about an hour * patch test - ag is applied to abraded skin and it looks like eczema in 48 hours |
|
|
Term
| What are the 2 methods of blood testing - describe them and what they can tell you? |
|
Definition
RIST - paper disk coated with anti-IgE, add patient blood and radiolabeled anti-IgE and count the bound radiolabel - if the patient has IgE it will be bound to the paper and the radiolabel - only tells you that you're allergic to something
*RAST - allergen is coupled to a solid phase, add patient blood, so IgE spec for that AG binds, nonspecific is washed away, add radiolabeled anti-IgE and count - this will tell you specific allergies, but is really expensive |
|
|
Term
| How do emotions affect allergic reactions and why? |
|
Definition
| mast cells have receptors for neurotransmiters of the autonomic nervous system * these neurotransmitters can increase or decrease mediator release and therefore can affect the severity of type I responses |
|
|
Term
| What are allergy shots and how do they work? |
|
Definition
| increasing doses of ag *mech not totally known, but it can shift response TH1 - makes IgG not IgE and this binds up the ag for phagocytosis - it's an anti-id |
|
|
Term
| What causes type II hypersensitivities? |
|
Definition
| ab mediated desctruction of cells |
|
|
Term
| What are 3 ways ab can cause cell damage? |
|
Definition
| 1) ab can induce inflammation by activating complement (IgM) or by binding to leukocytes or neutrophils (IgG 1 or 3) and activating them, causing them to release ROIs and damaging neighboring cells 2)ab can opsonize a cell, making them easier targets for phagocytosis 3) ab can block receptors, i.e like a block that causes a neurotransmitter to not be able to bind or by binding to a hormone receptor and activating the cell without hormone |
|
|
Term
| What types of Ig work well with effector cells and complement? |
|
Definition
|
|
Term
| What type of Ig works well only really with complement? |
|
Definition
|
|
Term
| What is the target ag, mechanism of disease and clinical manifestations of autoimmune hemolytic anemia? |
|
Definition
| RBC membrane proteins (Rh blood group ag), opsonization and phagocytosis of RBCs, hemolysis and anemia |
|
|
Term
| What is the target ag, mechanism of disease and clinical manifestations of autoimmune thrombocytopenic purpura? |
|
Definition
| platelet membrane proteins, opsonization and phago of platelets, bleeding |
|
|
Term
| What is the target ag, mechanism of disease and clinical manifestations of pemphigus vulgaris? |
|
Definition
| proteins in intercellular junctions of epidermal cells* ab-mediated activation of proteases, disruption of intercellular adhesions *skin vesicles |
|
|
Term
| What is the target ag, mechanism of disease and clinical manifestations of goodpasture's syndrome? |
|
Definition
| noncollagenous protein in the basement membrane of kidney glomeruli and lung alveoli *complement and Fc receptor mediated inflammation *nephritis, lung hemorrhages |
|
|
Term
| What is the target ag, mechanism of disease and clinical manifestations of acute rheumatic fever? |
|
Definition
| streptococcal cell wall ag, ab cross=reacts with myocardial ag *inflammation, m'phage activation * myocarditis, arthritis |
|
|
Term
| What is the target ag, mechanism of disease and clinical manifestations of myasthenia gravis? |
|
Definition
| Ach receptor *ab inhibits Ach binding, down-modulates receptors *muscle weakness, paralysis |
|
|
Term
| What is the target ag, mechanism of disease and clinical manifestations of graves' disease? |
|
Definition
| TSH receptor *ab-mediated stimuation of TSH receptors *hyperthyroidism |
|
|
Term
| What is the target ag, mechanism of disease and clinical manifestations of pernicious anemia? |
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Definition
| intrinsic factor of gastric parietal cells *neutralization of intrinic factor, decreased absorption of B12 *abnormal erythropoeisis, anemia |
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Term
| What are the 2 types of transfusion reactions - what ab are made and what causes them? |
|
Definition
| ABO - usually make IgM, you're making ab to the blood groups you don't have or it's from exposure to cross reacting natural ag (bacterial surfaces of normal flora) * other blood groups, MN, Rhesus, etc - make IgG - get this reaction from previous transfusions |
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Term
| What is the base structure of the ABO blood group? How do the other types differ? |
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Definition
| type O - genes code for enzymes that add carbs to the base structure to make A, B, or both - they differ from each other by 1 sugar moiety |
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|
Term
| How are blood group genes expressed? |
|
Definition
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Term
| If you're A, B, AB, or O, what antigens are on your RBC and what are the serum ab present? |
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Definition
| A - A ag, anti-B ab *B - B ag, anti-A ab *AB - A&B ag, no ab * O - no ag, anti-A and B ab |
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Term
| What is the universal donor blood type and is this really possible? |
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Definition
| O- it works for the cells, since your body won't see any ag on the cells, but since the O blood has anti-A and anti-B ab, these will attack the cells with those ag if the recipient is A or B |
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Term
| What is the universal recipient blood type and is this really possible? |
|
Definition
| AB - again, the plasma from the donor will react with the recipient blood but there's no problem with the cells b/c there are no ab in the recipient plasma |
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|
Term
| What happens in cross matching? |
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Definition
| you separate cells and plasma from donor and recipient and mix donor cells + recip plasma and vice versa to see if there's a reaction |
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|
Term
| Why is cross matching blood important? |
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Definition
| the recipient may have had other blood transfusions or other exposures so they may react in more ways than basic ABO |
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|
Term
| How do you type blood for ABO and Rh? |
|
Definition
| direct agglutination - mix the blood with anti-sera and wait for a reaction |
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Term
| How do you type blood for types other than ABO or Rh? |
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Definition
| a Coombs test - you mix a blood sample with anti-antibody (specify species) and if AB are present on the RBCs the anti-ab will cause the cells to clump - you can also use this to test for autoimmune ab |
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|
Term
| What happens in haemolytic disease of newborn? |
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Definition
| the mom is Rh- and gives birth to an Rh+ baby - the 1st pregnancy is no problem, but after delivery, the fetal and maternal blood mix and mom makes IgG ab to the fetal Rh - second pregnancy with an Rh+ baby, the IgG to the Rh will cross the placenta and attack the fetal RBC, causing anemia |
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|
Term
| What increases the chances of HDN? |
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Definition
| ABO compatibility between mom and baby - if the baby has a different blood type than mom, that blood will be bound up and cleared before mom will make an ab response |
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|
Term
|
Definition
| Rhogam - anti-D serum within 3 days postpartum, but the sooner the better |
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|
Term
|
Definition
| It binds and clears fetal Rh+ blood from mom's system so she won't make AB to it |
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|
Term
| How can drugs cause RBC lysis? |
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Definition
| the drug binds to RBC proteins, causing a hapten-carrier complex of sorts that triggers complement and subsequent lysis or the drug can form immune complexes that bind to the RBC and activate complement |
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|
Term
| What does ab mediated autoimmunity mean? |
|
Definition
| that there are ab reactions to ag on your own cells |
|
|
Term
| What are a lot of autoimmune problems caused by? |
|
Definition
| mistakes in eliminating self-reactive cells either in central or peripheral tolerance |
|
|
Term
| What are the 2 main reasons someone would develop autoimune haemolytic anemia? |
|
Definition
| they start making ab to ag on their own RBC or they get infected with a microbe that has an ag that looks like a self ag on RBCs - you get a cross reacting ab to a microbial ag |
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|
Term
| How do cross reacting ab contribute to an autoimmune problem? |
|
Definition
| they allow the responding cell to get 2nd signals that they normally wouldn't get |
|
|
Term
| What are cold reacting ab and what do they cause? |
|
Definition
| these ab only react with epitopes at low temps (30 C or less) - these can cause immune complexes and tissue damaage in vulnerable spots like the tips of the fingers and the nose |
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|
Term
| What happens in low temps to cold reactive autoab? |
|
Definition
| the cold temp causes a conformational change in the ag |
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|
Term
| What is an example of a cold reacting autoab? |
|
Definition
| mycoplasm pneumoniae - this gives off polyclonal activators that thurn on plasma cells in a nonspecific way, so you may turn on cells that are self reactive that normally wouldn't have been turned on |
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|
Term
| In Goodpasture's syndrome and Pemphigus, is the epitope distributed evenly on the cell surfaces or unevenly? |
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Definition
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|
Term
| What happens in hashimoto's thyroiditis? |
|
Definition
| you make ab directed against thyroglobulin and cellular ag in the thyroid - you get an enlargement of the thyroid due to inflammation and infiltration of inflammatory cells which leads to loss of thyroid function |
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|
Term
| What happens in Graves' disease specifically? |
|
Definition
| you get ab to the receptor for TSH and it mimics the hormone - this binds to the receptor and increases thyroid function - normally you get feedback inhibition by the hormone so when enough is produced, the thyroid shuts off, but in this case that doesn't happen, the thyroid is on too much and you get hyperthyroid |
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|
Term
| How do you get neonatal graves' disease? |
|
Definition
| AB from the mom with the condition crosses over (IgG) and you get increased thryoid function in the fetus - the condition goes away as the maternal ab is lost |
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|
Term
| What happens specifically in pernicious anemia? |
|
Definition
| vitamin B12 requires a transport protein called intrinsic factor to be taken up from the gut into the blood - ab binds to IF so it can't bind to B12 and you get a B12 shortage |
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|
Term
| What are type III hypersensitivities caused by? |
|
Definition
| large amounts of ag-ab complexes that aren't cleared from the system |
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|
Term
| What normally clears ag-ab complexes from the system? |
|
Definition
| mononuclear phagocyte system and complement |
|
|
Term
| What organ normally clears ag-ab complexes? |
|
Definition
|
|
Term
| What is the pattern of circulation in the liver? |
|
Definition
| in through the portal vein, out through the hepatic vein |
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|
Term
| How exactly are immune complexes cleared in the blood and the liver? |
|
Definition
| C3b is part of the immune complex and gets attached to RBC by CR1 - CR1 sets up C3b to be cleaved by factor I into iC3b which the RBC has much less affinity for - the immune complex is stripped off in the liver by mononuclear phagocytes (have CR1, 3, and 4) and taken to the Kuppfer cells in the liver |
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|
Term
| What are the requirements to have a type III hypersensitivity? |
|
Definition
| have to have a LOT of ag-ab complexes, initiation of inflammation, and a deposition of the complexes in the tissue |
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|
Term
| What do the symptoms of a type III reaction depend on? |
|
Definition
| where the ag-ab complexes are deposited |
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|
Term
| If you have a persistant infection, what is the ag and where will you get deposition of ag-ab complexes? |
|
Definition
| microbial ag, deposition in the infected organs and the kidney |
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|
Term
| If you have an autoimmune problem, what is the ag and where will you get deposition of ag-ab complexes? |
|
Definition
| self ag, deposited in the kidney, joints, arteries, skin |
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|
Term
| If you have an inhaled ag, what is the ag and where will you get deposition of ag-ab complexes? |
|
Definition
| mold, plant, or animal ag, lungs |
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|
Term
| Why do you get immune complex deposition in tissue? |
|
Definition
| b/c of increased vascular permeability - 2 reasons: complement (C3a, C5a) degranulate basophils and mast cells which have vasoactive amines causing increased vascular permeability and vasodilation or the immune complexes themselves act on mast cells and basophils to cause the same thing |
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|
Term
| What are the ways to combat immune complex deposition in tissue? |
|
Definition
| block vasoactive amines - then you're decreasing vasodilation and vascular permeability - you could block complement, but then you're blocking any immune complex clearance |
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|
Term
| What happens when there's low complement in the blood? |
|
Definition
| you don't get clearance of the complexes, things start to bump into the blood cell walls and stick and clump more |
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|
Term
| Where are the most common places to get ag-ab complex problems? |
|
Definition
| kidneys b/c the vessels are really looped and slightly leaky anyway, choroid plexus, ciliary body, bifurcated arteries (has a lot of turbulance) |
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|
Term
| What happens to large, medium, and small immune complexes in the blood vessels? |
|
Definition
| large stay in there b/c they can't get out - medium get stuck halfway through and are lodged in the basement membrane vessel side - small, get lodged below the basement membrane - very small go all the way through |
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|
Term
| What do endotoxins produced by renal damage cause? |
|
Definition
| the endotoxins cause DNA to be released from cells - this binds to collagen and due to polyclonal activation, anti-DNA ab and anti-antibodies are also made, generating complexes that form bumpy deposits in the kidney glomerulus |
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|
Term
| What causes serum sickness? |
|
Definition
| large amounts of ag being given |
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|
Term
| How do you get serum sickness? |
|
Definition
| you're given a specific ab that you need, but it's in whole serum, so while you're getting that 1 ab that you need you're also getting a ton of foreign ag that your body makes ab to, forming immune complexes |
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|
Term
| What was serum sickness 1st discovered in? |
|
Definition
| horses that were given anti-diptheria ab in whole serum - the horses were exposed to huge amounts of foreign ag in the serum and made ab to it |
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|
Term
| What 2 things do immune complexes cause? |
|
Definition
| activation of complement (get C3a and C5a which cause degranulation and release of vasoactive amines) and degranulation of mast basophils (FcRIII and C3a and 5aR) and platelets (FcRII) |
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|
Term
| How exactly do immune complexes damage blood vessels? |
|
Definition
| the complex causes increased vascular permeability, so the endothelial cells are loosened up - you get complex deposition in between and into the cell wall - you're getting inflammation and microclot formation b/c the cell guts are being exposed to the collagen underneath - the platelets that aggregate release more factors, causing more inflammation - the polys try to clear the complexes by phagocytosis, but the Fc ends are stuck to something that's stuck in the wall of the blood vessel, so they release enzymes bc they think it's a big threat, except that the threat is really your blood vessel walls |
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|
Term
| What 2 big clinical manifestations are there with immune complexes? |
|
Definition
| glomerularnephritis - inflammation to the glomerulus, and arteritis - inflammation to arteries |
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|
Term
| Do veins normally get damaged by immune complexes and why? |
|
Definition
| no - there's a lot higher pressure in arteries, so high pressure shoves things into the walls |
|
|
Term
| What happens eventually in type III reactions? |
|
Definition
| the ag gets cleared and you get free ab and the symptoms get better |
|
|
Term
| What causes an arthus reaction? |
|
Definition
| booster immunizations - if you already have ab to the ag in the booster, injecting it causes some tissue damage, leading to increased vascular permeability and b/c the vessels are leaky, some of the ab gets out and mixes with the ag in the tissue, setting up an immune complex reaction - some ag also deposits near venules and gets into the blood stream, reacting with the ab in the blood |
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|
Term
| What specifically happens in the tissues in an arthus reaction after the ab get out of the blood vessels and into the tissue? |
|
Definition
| the ab activate complement, including C3a and C5a *essential* - these degranulate mast cells, which release vasoactive amines and activate m'phages which release IL-6 and TNF to act on endothelial cells - platelets aggregate and release more vasoactive materials - more ab get to the site and polys try to clean up the damage, but release enzymes when they can't and you get tissue damage - like serum sickness, only this is outside the vessels as opposed to inside |
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|
Term
| What is the time frame for an arthus reaction? |
|
Definition
|
|
Term
| What is the antibody specificity, mechanism of disease, and clinical manifestations of lupus? |
|
Definition
| DNA * Fc and complement receptor mediated inflammation *nephritis, vasculitis, arthritis |
|
|
Term
| What is the antibody specificity, mechanism of disease, and clinical manifestations of polyarteritis nodosa? |
|
Definition
| hepatitis B surface ag *Fc and complement receptor mediated inflammation *vasculitis |
|
|
Term
| What is the antibody specificity, mechanism of disease, and clinical manifestations of polyarteritis nodosa? |
|
Definition
| hepatitis B surface ag *Fc and complement receptor mediated inflammation *vasculitis |
|
|
Term
| What is the antibody specificity, mechanism of disease, and clinical manifestations of post-streptococcal glomerulonephritis? |
|
Definition
| streptococcal cell wall ag*Fc and complement receptor mediated inflammation *nephritis |
|
|
Term
| How does group A strep cause problems in the heart and kidney? |
|
Definition
| the ag on group A strep look a lot like the ag on the basement membrane of the heart and kidneys, so ab that react to strep can cross react with the heart and kidneys causing rheumatic fever (type II reaction), and concomitant with that, you get ag-ab complexes in the kidneys causing nephritis |
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|
Term
| What is the animal model for lupus? |
|
Definition
| NZW/NZB mouse - cross mouse |
|
|
Term
| Who is lupus more common in and at what age? |
|
Definition
| females - 1st shows up in teens, 20's |
|
|
Term
| What is the treatment for lupus? |
|
Definition
|
|
Term
| What is the 1st clinical symptom of lupus? |
|
Definition
| symptoms similar to mononucleosis |
|
|
Term
| How do you diagnose lupus? |
|
Definition
| do a kidney biopsy and look for anti-red cell ab (causes hemolytic anemia)in there and anti-nuclear ab in the blood and anti-DNA ab |
|
|
Term
| Why do a kidney biopsy to test for lupus? |
|
Definition
| b/c ag-ab complexes are attracted to kidneys - lots of collagen that attracts DNA |
|
|
Term
| What does lupus lead to the formation of? |
|
Definition
| circulating immune complexes |
|
|
Term
| Where do circulating immune complexes in lupus go? |
|
Definition
| kidneys - glomerulus, leads to renal failure and proteinurea *choroid plexus, interferes with CSF, causes headaches *arteries - get probs with cold ab and circulation |
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|
Term
| What is extrinis allergic alveolitis? What happens, what causes it? |
|
Definition
Inflammation of the alveoli*
Occurs from repeated exposure to external (environmental) antigens leads to production of Ab -IgG*
Ag leaks out into the alvoelar space, Ag combines with Ab
Activate complement
Induce inflammation
*Leads to tissue damage (alveolar lining) – bad b/c the blood vessels are just on the other side – damage the endothelial cells in blood vessels and you can bleed into the lungs *
Type IV hypersensitivity reaction may cause initial inflammation *
Farmer’s Lung – become allergic to a mold that’s in the silage – hay |
|
|
Term
| What type of reactions are Type IV? |
|
Definition
|
|
Term
| What is necessary to get a type IV reaction? |
|
Definition
|
|
Term
| How do you transfer reactivity in a type IV reaction? |
|
Definition
| transfer with T cells but not serum |
|
|
Term
| What are the 2 mechanisms for cell damage in type IV reactions? |
|
Definition
| direct CMI or indirect - Th cells and CTL are activated, release inflammatory mediators that cause damage |
|
|
Term
| What are the 3 types of type IV reactions? |
|
Definition
| contact, tuberculin, granuloma |
|
|
Term
| What is the reaction time, clinical appearance, histology, and antigen for contact reactions? |
|
Definition
| 24-48 hours, eczema, lymphocytes and later m'phages, edema, epidermal ag |
|
|
Term
| What is the reaction time, clinical appearance, histology, and antigen for tuberculin reactions? |
|
Definition
| 48-72hours, local induration, l'cytes, monocytes, m'phages*intradermal ag |
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|
Term
| What is the reaction time, clinical appearance, histology, and antigen for granuloma reactions? |
|
Definition
| 21-28 days*hardening of the area* m'phages, giant cells, epitheloid cells*persistent ag/ab complexes or non-Ig stimuli like talc |
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|
Term
| What happens on a 1st exposure when you get poison ivy? What actually causes the response? |
|
Definition
| the oil itself is not immunogenic - it complexes with a self protein and that is - the complex is picked up by langerhans cells and presented in the lymph node - get induction of T cells and start making cytokines - you get memory T cells |
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|
Term
| What happens if you have a subsequent exposure to poison ivy? How do you get rid of it? |
|
Definition
| the oil-protein complex interacts with memory T cells and you get an infiltrate of m'phages and l'cytes - you get a reaction in the epidermis that is edema, cells, and vesicles * the skin has to slough off to get rid of the vesicles |
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|
Term
| How does a TB test administered and how do you get a positive result? |
|
Definition
| you inject the purified supernatent from M. tuberculosis into the dermal-epidermal border - if you have been exposed to the bacteria, this ag will interact with memory T cells by ag presentation by langerhans cells - the T cells make TNF and this induces expression of adhesion molecules on endothelial cells so you get inflammation and infiltration |
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|
Term
| What happens if you inject too deeply in a TB test? |
|
Definition
|
|
Term
| What does a positive TB result look like? |
|
Definition
| swelling and edema but no vessicles - you get monocytes and l'cytes in the dermis around the blood vessel |
|
|
Term
|
Definition
| ag that are persistent - like microbes that live in phagocytes after they've been eaten |
|
|
Term
| What is the time frame for developing a granuloma? |
|
Definition
|
|
Term
| What is the initial reaction in a granuloma? |
|
Definition
| lymphocytes make cytokines that activate m'phages |
|
|
Term
| What do you have to have to get a granuloma? |
|
Definition
| IFN gamma and activated T cells |
|
|
Term
| What is an example of a disease that can be bad or not so bad depending on the immune response and granuloma formation? |
|
Definition
| leprosy - tuberculoid induces a strong Th1 response - lots of granulomas and little viable organism *lepromatous - few granulomas, lots of organism, Th2 response |
|
|
Term
| What are the bacterial diseases with a hypersensitivity component? |
|
Definition
| tuberculosis, leprosy, listeriosis |
|
|
Term
| What are parasitic conditions that have hypersensitivity components? |
|
Definition
| leishmaniasis and schistosomiasis |
|
|
Term
| What are other problems with hypersensitivity components? |
|
Definition
| sarcoidosis,fungal problems |
|
|
Term
| What is the target for T cells in experimental allergic encephalomyelitis? |
|
Definition
| myelin basic protein, proteolipid protein |
|
|
Term
| Describe what causes MS and the symptoms. What type HS is this? |
|
Definition
| type IV - T cells react with the myelin sheath (may be virally induced) and cause inflammatory lesions around the nerve, impinging on nerve function |
|
|
Term
| What causes type I diabetes? |
|
Definition
| a virus gets into the pancreas and the activated T cells call in m'phages that release inflammatory mediators, causing damage and destruction of beta cells - it's a DTH in the pancreas |
|
|
Term
| What are the 3 main reasons we have autoimmune diseases? |
|
Definition
| *failure to eliminate self-reactive T cells and B cells *cross-reacting ag (group A strep)*misregulation of cytokines or costimulatory factors |
|
|
Term
| How do you experimentally induce diabetes? |
|
Definition
| put the IFN gene under control of the insulin promoter so that beta cells secrete IFN gamma. This causes an upregulation of MHC on the beta cell and causes them to present self ag |
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