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107 Cards in this Set
- Front
- Back
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B cells
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derived from common lymphoid progenitor
-make antibodies -a protein that can bind to an antigen and illicit an immune response |
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T cells
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derived from common lymphoid progenitor
-CD4+ = helper T cells or regulatory T cells -CD8+ = cytotoxic T lymphocyte |
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CD4+
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helper T cells
-tell other cells what to do by secreting certain things regulatory T cells -supress an immune response |
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CD8+
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cytotoxic T lymphocyte (killer T cells)
-go out and actually kill infected cells -cell surface proteins expressed on T cells -cluster of differentiation |
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lymphocyte
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B and T cells
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NK cells
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natural killer cells
-find infected cells and kill them -first ones, in innate immunity |
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eosionophil
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derived from common granulocyte precursor
- granules contain basic molecules -only when responding to parasites allergies |
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basophil
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derived from common granulocyte precursor
-basic granules -parasitic/allergic response activate certain b cell response |
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neutrophils
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derived from common granulocyte precursor
-phagoytosis - made all the time -can do one round of phagocytosis and then die -need lots of them -develop in bone marrow, enter blood stream |
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macrophages
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derived from monocytes
-macrophage once in circulation -capable of many rounds of phagocytosis -Antigen presenting cells -recognizes pathogen, triggers txn of cytokines - imflammatory response |
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dendritic cells
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derived from myeloid progenitor
-have dendrites -Ag presenting cells that activate T cells -can do phagocytosis but only so they can do Ag presenting to T cells |
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mast cells
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derived from myeloid progenitor
-have granules -parasitic/allergic response -contain histamine |
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what cells have APC function
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macrophages, B cells, and dendritic cells
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what cells have phagocytic function
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macrophages, neutrophils
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what cells have killing function
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natural killer cells and cytotoxic t lymphocytes
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what cells are involved in allergic and parasitic response
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eosinophil, basophil and mast cells
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What is the cell type that gives rise to all different cell types in the blood?
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pluripotent hematopoietic stem cell
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function of the hematopoietic stem cell
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has potiential to become any of the cells of the blood
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after the hematopoietic stem cell - what are the three possibilities?
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common _______ progenitor
-lymphoid -myeloid -erythroid megakaryocyte |
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what comes out of the common lymphoid progenitor line
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NK/T cell precursor - becomes T cells and NK cells
and B cells - become plasma cells |
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what comes out of the common myeloid progenitor line
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common granulocyte precorsor and "unknown precursor"
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what comes out of the common granulocyte precursor line
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neutrophil
basophil eosinophil |
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what comes out of the "unknown precursor line of the common myeloid progenitor line?
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monocytes - become dendritic cells and macrophages
and mast cells |
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what comes out of the common erythroid megakaryocyte progenitor line
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megakaryocytes and erythroblasts
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function of the megakaryocyte
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platelet formation and wound repair
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function of the erythrocyte
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oxygen transport
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what are the functions of b cells
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production of antibodies
plasma cell = fully differentiated B cell that secretes antibodies |
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what are the types of t cells
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cytotoxic t lymphocyte (CD8+)
helper T or T regs (CD4+) |
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what are the functions of NK cells
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kills cells infected with certain viruses
involved in innate immunity see if theres a problem and CTL comes in later |
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function of eosinophil
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killing of Ab-coated parasites through release of granule contents
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function of basophil
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controlling immune responses to parasites
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function of neutrophil
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phagocytosis and killing of microorgansims
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what is the function of T regs
what is the function of helper t cells what are their numbers |
supress an immune response
tell other cells what to do by secreting certain things CD4 = helper T and T regs CD8 = CTLs |
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what is a monocyte
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circulating precursor cell to macrophage
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function of macrophage
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phagocytosis and killing of microorganisms
activation of t cells an initiation of immune response |
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stages of T cell development in the thymus
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DN1 - TCR genes in germline configuration
DN2 - Beta chain rearrangements (DJ recombination) DN3 - Beta chain rearrangements (V-DJ recombination starts expressing pre-t cell receptor DN4 - proliferation pre-t cell receptor stimulation Double positive stage - CD4 and CD8 expressed on surface ( with pre-t receptor. alpha chain rearrangements (just D and J). TCR expressed on cell surface with CD4 and CD8. positive and negative selection. Single positive stage - turning off of either CD4 or CD8 (lineage commitment) |
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discuss the mechanisms by which a BCR Ag binding specificity is generated. use bullet points
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1. VJ light chain rearrangement + VDJ heavy chain rearrangement - multiple copies of V, D, and J regions found on different loci
2. pairing of different H and L chains 3. Junctional Diversity - strands are cut, bent into hairpin, ends are cleaved, TdT adds NTs to extend ends of cleaved hairpins, strands are paired, gaps are filled. really changes the BCR and creates infinite possibilities 4. somatic hypermutation - improve Ab binding on gene level by AID.. after Ag encounter 5. isotype switching - IgM is default (at maturation). switch to IgG, IgA, or IgE ( after Ag encounter). switch sequences between C regions. when switch sequences join they cut out middle parts |
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sequences of events from t-cell in thymus to TH1 cell activating macrophages
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Thymus
naiive - has only gamma and beta chains - bind IL2 with moderate affinity activated - has gamma, beta, and alpha chains - bind IL2 with high affinity proliferation immature effector CD4 t cell interacts with macrophage -MCH-II binds CD4/TCR -CD40 binds CD40 Ligand -IFN-gamma receptor binds IFN-gamma activation of Tcell and kills macrophage |
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sequences of events from tcell in thymus and b cell in bone marrow to TH2 cell and b cell activation
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Thymus
naiive - has only gamma and beta chains - bind IL2 with moderate affinity activated - has gamma, beta, and alpha chains - bind IL2 with high affinity proliferation immature effector CD4 t cell B cell leaves bone marrow b cell encounters Ag from FDC presentation enters LN presents Ag on its MHC-II B cell binds TH2 cell LFA-1 binds ICAM-1 on B cell CD4/TCR binds MHCII CD40L binds CD40 on B cell helper T reorients cellular machinery secreting cytokines towards B cell b and t cells proliferate b cells differentiate in to plasma cells and start secreting Abs |
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what are the different antibody isotypes, what is their function, and what is their distribution in the body?
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IgM - complement, pentamer, found in heart or circulation
IgG - neutralization, complement, phagocytosis/opsonization - found everywhere, blood, in utero IgA - neutralization, dimer= mucosal area and in baby from mother, monomer = everywhere, IgE - allergic response, found in connective tissues |
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How do pathogens evade the immune system? list and discuss all of the examples
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genetic variation with in species (sterotypes)
mutation and recombination (antigenic drift and antigenic shift) rearrangement and changes in Ag (trypanosome- a parasite infecting only humans) viral latency (not active until triggered, herpes, chicken pox) subversion/sabotage of hose immune system (inhibit normal immune machinery, use human proteins) |
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list all of the inherited immunodeficiency diseases?
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antibody defects (XLA, selective IgA deficiency, or hyper-IgM syndrome)
compliment pathway defects (immune complex issues, DAF and CD59 defects, CI-inhibitor defects) Phagocytic cell defects (LAD, Chronic granulomatous disease, chediak-higashi syndrome) T-cell defects (gammaC defect, ADA, bare lymphocyte syndrome, digeorge syndrome) |
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XLA
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an Ab defect
Btk deficient (necessary for b cell development) therefore no Abs |
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selective IgA deficiency
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an Ab defect
have every ag isotype except igA therefore more mucosal infections |
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hyper IgM syndrome
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an Ab defect
make IgM but cant do isotype switching due to a mutation in CD40L on t cell. therefore cant activate B cells |
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immune complex issues
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compliment pathway defect
have trouble clearing the immune complexes by RBCs (Ag-Ab complex) |
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DAF and CD59 defects
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compliment pathway defect
compliment inhibitiors that make sure you dont kill own cells are defective. therefore you set compliment on own cells, esp RBCs |
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Ci-inhibitor defects
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compliment pathway defect
uncontrolled C2 cleavage and C2b overproduction. can get uncontrolled C2 cleavage too much causes inflamation and vaso-dialation, fluid leaks, fluid accumulation in lungs |
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LAD
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phagocytic cell defects
mutation in integrin (bind to glycams so the cell can get intot he SLT) so that now lymphocytes can circulate but can never get into the site of infection |
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chronic granulomatous disease
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phagocytic cell defects
oxygen radial production is inhibited problem making granulomatas causing apoptosis in infected cell |
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chediak higashi syndrome
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phagocytic cell defects
problem forming vesicles or fusing vesicles |
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gamma c defect
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t cell defect
defect in gamma chain of IL2 receptor IL2 cant bind with high affinity and therefore cells cant proliferate |
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ADA
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t cell defect
enzyme deficiency where metabolism pathway doesnt work properly so you get a build up of one of the by products which are toxic to T cells |
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bare lymphocyte syndrome
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t cell defect
do not have any mhc-II expressed on the surface therefore you cant present Ags |
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digeorge syndrome
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thymic epithelium that develops improperly therefore have improper tcell development
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modes of HIV transmission
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contaminated blood product
intercourse dirty needles maternal fetal transfer - birth or breast milk |
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course of HIV and development of aids
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infection
flu-like symptoms (sometimes) for 2-6 weeks then an asymptomatic phase then a symptomatic phase then AIDS CD4 T cell count is slowly going down |
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mechanism of CD4 t cell depletion in HIV infection
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direct viral lysis: virus infects cell, makes copies, start infecting other cells, causing direct lysis. cd4 cells more susceptible to apoptosis
HIV-specific CTLs kill CD4 cells CD4 count gets low enough to start showing symptoms and opportunistic infections occur AIDs = when cd4 cell count drops to 200 cells/microL and opportunistic infections |
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what are the receptors for HIV
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CD4 AND either
CCR5 (macrophages, DC, and Tcells) or CXCR4 (on activated T cell) |
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how does HIV enter cells
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gp120 and gp41 on viral surface bind CD4 and coreceptors
lipid bilayers merge and virus enters |
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discuss the function of the HIV enzymes:
integrase protease reverse transcriptase |
integrase = integrates viral DNA into host DNA
protease = breaks lipid bilayer membrane so the virus can enter reverse transcriptase = makes DNA from RNA, now have viral cDNA |
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how does activation of immune cells induce HIV viral production
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after the virus gets into T cells, the T cell gets activated, NFkB binds and starts txn of RNA of HIB genome. transcripts can be used to make protein and some are packaged
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discuss the function of rev and tat
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genes activated in HIV life/infection
two pieces combine, and need splicing to get final product transported to cytosol. tat will bind provirus and activate transcription rev binds RNA transcript and has it migrate to cytosol make proteins, synthesize birus, buds from cell, and then cell dies |
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how do some HIV therapeutic drugs work?
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target HIV enzymes to inhibit viral assembly and mechanisms
infected cells die soon so HIV must continually infect new cell AZT drug = NT analog, looks like a NT so reverse transcriptase thinks its a NT so it puts it in DNA BUT it infects human DNA protease inhibitors |
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why is it difficult to get vaccines produced for HIV
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high mutation rate
uncertainty over what type of immune system is necessary |
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Type I hypersensitivity
-how is it triggered -which cell types are involved -example of disease/symptoms it causes |
classic allergy
IgE reaction molecular type of Ags - proteins only induce t cell responses, low doses, low molecular weight, highly stable, highly soluble, contains peptides TH2 cells deliver signals that allow B cells to proliferate and differentiate into IgE producing Plasma cells Subcutaneous Ag (mast cell activation, increase vascular permeability leads to localized swelling) allergic rhinitis (inhaled Ag enters mucosa and activates mucosal mast cells. blood vessel permeability and epithelium activation) allergic asthma (mucosal mast cells capture Ag, inflammatory mediatiors contract smooth muscle, increase mucus secretion from airway epithelium and increase blood vessel permeability. mediated by cytokines and eosinophil products) food (ingested) allergens - ingestion of Ag activates mucosal mast cells, activated mast cells release histamine which acts on epithelium, blood vessels, and smooth muscle |
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systemic anaphylaxis
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drugs, serum, benoms, peanuts, shellfish
enters intravenously (either directly or after rapid absorption) causes edema, increased vascular permeability everywhere, tracheal occlusion so cant breathe, circulatory collapse, and death Ag in blood stream enters tissues and activates CT mast cells through out the body - mast cells degranulation and release of inflamatory cytokines |
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hygiene hypothesis
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both genetic and environment cause
-high or low susceptibility -grow up in hygenic envt versus growing up in un-hygenic envt hygenic envt people are more susceptable to pathogens since youre not exposed to it as a child |
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type II hypersensitivities
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ab mediated cell destruction via IgG or IgM
ABO mismatched blood transfusion can cuase it reactions to certain Antibiotics can be type II |
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type III hypersensitivities
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immune complex mediated
serum sickness - bit by snake/spider and go to hospital, give you Ab against the enom, horse Ab that you make a Ab to horse Ab - second exposure to same venom, all this Av you already have against horse venom, not going to clear them away quickly |
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type IV hypersensitivities
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delayed type
mostly TH1 mediated reaction to dyes, cosmetics, metals, poison, etc. |
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types of autoimmune diseases
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organ specific AI diseases
systemic AI diseases |
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Hashimotos thyroiditis
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auto-Ab's against thyroid Ags
cause tissue destruction by macrophage and auto-Ab's hypothyroidism (not enough thyroid hormone) destruction and Ab's make it not work |
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autoimmune anemias
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pernicious anemia - auto ab to intrinsic factor > low B12 uptake> low RBC
autoimmune hemolytic anemia - auto ab to RBC Ag, Abs bind to RBC's |
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good pastures syndrome
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autoimmune ab to basement Ag (type IV callagen)
epithelial cells sit on basement membrane auto-ab activates compliment and damage tissues (esp kidney and lungs) compliment split products also cause inflammation |
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IDDM
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insulin dependent diabetes mellitus type I
altoreactive CTLs that destroy Beta cells that make insulin no insulin production |
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Graves disease
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too much thyroid hormone
auto Ab to TSH get an activated t cell that makes auto TSH |
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myasthenia gravis
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antibodies that bind to ach receptor
receptors get endocytosed and degraded therefore you dont get muscle contraction eventually paralysis |
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SLE
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systemic lupus erythematosus
auto Ab to a host of self Ag - make Abs to DNA or histones. immune complex deposit - type II damage higher amts of C5a - neutrophils aggregation and vasculitis |
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mutiple sclerosis
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autoimmune responses against the myelin sheath of nerve cells
motor weakness, impaired vision, impaired coordination, paralysis unknown trigger - cause local inflammation in CNS, BBB becomes permeable to leukocytes and blood proteins so that leukocytes get into the CNS t cells specific for CNS ag get activated destroy myelination |
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rheumatoid arthritis
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Chronic inflammation of joints (other problems as well)
Auto-Ab (often IgM) is specific to IgG. IgG-IgM immune complexes form - Type III hypersensitivity |
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what are the major and minor histocompatibility antigens?
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antigens that trigger transplantation rejection
Major histocompatibility antigen = MHC or human leukocyte antigen (HLA) Polygenic: 3 genes (HLA-A, B, C) for class I, 3 genes (HLA-DP, DQ, DR) for class II (Per haploid genome) Polymorphic: many allelic variations in a population at each gene Minor histocompatibility antigen - not one molecule but is any Ag that is different between two people. functionally the same but presentation of Ag is different |
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why do patients t cells recognize donors allogeneic mhc
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only t cells can recognize your own mhc so how can they recognize a donor mhc?
no negative selection against the donors mhc start with total t cell repertoire selected for MHCx.. ones that bind too strongly are negatively selected. some of the t cells will cross react with MHCw from someone else. if you get a donor with MHCz you will have t cells cross reacting with MHCz. |
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what are the methods of tissue typing? how do they work?
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microcytotoxicity test
-take cells from recipient and from two potiential donors and then on a plate with lots of little wells. each column has an Ab for a different HLA allotype.. HLA-a for example. trying to match MHC II first. mixed lymphocyte reaction - irradiate cells so they can no longer proliferate themselves, then mix donor and recipient lymphocytes measure t cell proliferation and t cell cytotoxicity |
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what are direct vs. indirect allorecognition?
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direct - t cells are activated by donor DCs and then migrate to donor tissue to kill donor graft
indirect - donor tissue presents MHC.. donor mhc is picked up by recipient DCs, digested, and presented to t cells |
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what are the three different types of rejection?
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hyper-acute rejection
acute rejection chronic rejection |
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what are the drugs currently used for transplantation rejection?
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corticosteroids - bind to steroid receptors and changes gene expression. turns on genes that have immune effects. reduce cytokine transcription, reduce enzyme production, and causes anti-inflammation
mitotic inhibitors - stops cells from proliferating, stop DNA replication, stop proliferation of all cells FK506, cyclosporin, rapamycin - targets more specific factors like nfat... preventing t-lymphocyte activation. |
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what are some specific therapies (ab-mediated) in development for transplantation
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anti-cd4 therapy and other mAb Therapy
mAb's are injected into people and they act as either blockers or depleters. deplete of APC in organ using anti-APC Ag Ab CTLA4-Ig - if the t cells recognize graft Ags they become activated.. however, if you give CTLA4, T cells that recognize graft Ags lack co-stimulation and become anergic... bCTLA4 binds B7 anti-cd40 ligand - |
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hyper-acute rejection
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recipient has to have pre-existing Ab to the donor molecules (mhc) already.. this person has seen the donors HLA before, form abs, so next encounter the Abs bind vasculature of donor, causing inflammation and cut off blood circulation to new organ and organ will be rejected
if you do not match the blood groups, then the person has ab's against this blood type |
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acute rejection
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kidney will have APCs from the donor. once kidney is connected to recipient, apcs migrage out and they start activating recipient t cells.. effector t cells migrate to the graft and launch an immune response. graft gets destroyed by effector t cells
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acute rejection
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kidney will have APCs from the donor. once kidney is connected to recipient, apcs migrage out and they start activating recipient t cells.. effector t cells migrate to the graft and launch an immune response. graft gets destroyed by effector t cells
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chronic rejection
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happens when you have minor histocompatibility differences
alloantibodies recruit inflammatory cells to the bood vessel walls of the transplanted organ increasing damage enables immune effectors to enter the tissue of the blood vessel wall and to inflict increasing damage |
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how is bone marrow transplantation done, and what is graft vs. host disease?
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1. find bone marrow compatible match
2. pt undergoes irradiation and chemotherapy to get rid of their own immune cells 3. bone marrow infusion 4. stem cells will start hematopoiesis and are selected for the thymic epithelial cells 5. healthy patient GVHD when bone marrow is transplanted the t cells in the transplant attack the recipients tissues |
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why is it necessary to humanize abs for therapies
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to avoid serum sickness
do so by making transgenic mice with human Ab genes or by doing molecular sub-cloning of chimeric Ab |
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passive immunization
advantages and disadvantages |
when you dont give a pathogen you give actual Abs usually when disease is mediated by toxins and when you need it to work really fast. either horse Abs or Human pooled abs
+ works fast and does clear away toxin - not a lasting immune memory and if you need a second immunization you will have an immune response to the ab |
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active immunization
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give a pathogen for people to "practice on"
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what are three different types of active immunization vaccines
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whole organism, purified molecule vaccines or DNA based vaccines
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types of whole organism vaccines
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live attenuated or killed
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live attenuated vaccines
examples, +- |
alive but modified like polio vaccine
BCG is the vaccine for TB, + is its really affective -might turn virulent, contamination, storage is difficult |
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killed whole organism vaccine
examples, +- |
killed with formaldehyde or heat
+ is that it wont turn virulent - not alive so it floats around in system, not as effective, fails to kill all of it, process of killing might get rid of some Ags |
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types of pruified molecule vaccines
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polysacchaide vaccine, toxoid vaccine, recombinant Ag vaccine
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polysaccharide vaccine
examples, +- |
carbohydrates of Ag is what the Ab binds to but need t cell help, need a protein presented by MHC therefore you give a protein linked to a polysaccharide called a toxoid
tetanus uses this linked recognition |
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toxoid vaccine
examples +_ |
have to be modified, just give toxins
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recombinant Ag vaccine
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first one was HepB
gene for Ag is cloned into yeast they make the protein, and you harvest it and give it as a vaccine |
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what are the DNA based vaccines
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recombinant vector vaccine or DNA vaccine
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recombinant vector vaccine
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clone a gene in a plasmid, put it into a virus, thats the recombinant vector vaccine
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DNA vaccine
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clone a gene in a plasmid inject into muscle
+ is that DNA is very stable and can last a long time |
