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Damon's Pile

MSII, Block 1, immuno and a little micro

flash card-side 1flash card-side 2
name the B- lactams -PCN V(oral), G(aqueous,acid labile), Methacillin(nafcillin/dicloxcillin) -Cephalosporins -Carbapenems
PCN coverage narrow spectrum -inhib cell wall synthesis (@ rxn #2, transpeptidation); is inactivated by B-lactamases & altered PCN binding Protiens 2a, bacterial L-forms, Loss of porins, Binding Protien overproduction, and influx/eflux pump effects.
Cephalosporin characteristics -Broad spectrum / inhib cell wall synthesis (@ transpeptidase); -1-4 generations with inc. potentcy against gr-, lesser against gr+. -20%psudomonas still resistant to generations 1-3. -doesnt cross blood brain barrier.
Carbapenems mechanism similar to PCN but are resistant to B-lactamases
Methacillin chemically modified pcn 'R' group. not used anymore. Nafcillin and dicloxicillin. for use on bacteria producing class A Beta-lactamase
amoxicillin Broad spectrum,
Ampicillin/ Amoxicillin "amino pens"; extended spectrum PCN's - otitis media - 4th gen pens= ticarcillin and piperacillin. used in combo with aminoglycosides with restricted use.
What are PBP's PCN Binding protien- PBP 1- binds pcn 2a- is altered pbp2 and doesnt bind any B-lactams. found as dominant form in resistant forms MRSA. pbp 3- binds Cephalosporins
what is MIC? minimum inhibitory concentration - the lowest conc of abx that causes significant reduction in growth after 18hr. in vitro incubation. -serum conc should be > 10x MIC to prevent resistance. -MIC-90 is the increased MIC to 90% of all px's isolates.
What is MBC? minimum bacterio-CIDAL concentration- - the lowest conc of abx that inhibits the growth of a clinical isolate even after incubation in abx-free medium (due to already being killed)
ABX breakpoints concentration level of abx that change bacterial reactions from S (susceptable), to I (intermediate) , to R(reduced)
ABX suicide molecules -have high affinity for B-lactamases= irreversibly bind and inactivate. used with other abx's
Augmentin Clauvulanate + Amoxicillin
Unasyn Sulbactam + Ampicillin
Zosyn Tazobactam + Piperacillin (4th gen antipsuedo pen)
Aminoglycosides - Streptomycin MA- Ihib protien synth/binds 30s tRNA PD-cidal for aerobes. OM active xport req. TU-rarely used alone.synergy with B-lactams adverse- 8th CN and nephrotoxicities Gentamicin- broad spectrum
Tetracylines Doxycycline, tigecycline MA-inhib protien synth/ binds 30s tRNA PD-activity/resistance regulated by active membrane import/export. -STATIC. inactivated by chelation (milk) TU-not for pregnancy (liver toxic) or peds (discolored teeth)
Macrolides Erythromicin, clarithromycin (extended coverage) MA- binds 50s tRNA (inhib protien synth) PD-STATIC. dose dep. cidal for certain gram +/- TU-substitute for PCN allergic px. used for Mycoplasma pnuemoniae ('walking pnuemonia')
Fluoroquinolones Cipro MA-interferes with DNA Topoisomerase II and IV PD-CIDAL (dose dep. for Gram+/-) oral or IV, not CSF TU-UTI and STD. Also, URI except for S. Pnumo. Moxifloxacin (4th gen. covers S. pnuemoniae)
Glycopeptides Vancomycin "like a van driving down GI" MA- inhib cell wall synth, binds to D-ala-D-ala terminus (rxn #1,glycosyl transfer/polymerization) PD- CIDAL. NARROW SPECTRUM (gr+). parenteral/ doesnt cross GI. TU- MRSA caused sepsis
Sulfonamides Sulfamethazole MA-competative inhib of PABA in folate synth(dihydrofolate is req in DNA synth) PD-STATIC. BROAD SPECTRUM. 5% adverse rxn= fever, rash, photosensitivity) TU-Synergy with Trimethoprim (TMP/SMX)"bactrim, Septra" for UTI
example of abx physical antagonism high dose ticarcillin inactivates gentamicin
'cidal-static' abx antagonism PCN + Tetracycline
central tolerance active process by which the B- cells (in bone) and T-cells (in thymus) are removed if too self reactive.
peripheral tolerace 'clonal anergy' occurs outside primary lymph organs
regulator T- cells CD25+ CD4+; can induce anergy/suppression of CDE4+ T-cell when bound to same epitope via FTLA-1:B7 receptor
b-cell clonal anergy usually by binding multi-valent Ag's. anergic b cells are later removed by apoptosis induced by CD4+ t cells via the Fas L:Fas
Auto Immune Dz type II mediated by Ab specific for cell surface components or EC matrix
Auto Immune Dz type III mediated by formation of immune complexes (mixed essentioal cryoglobulemia, SLE , sub-acute bacterial endocarditis)
Auto Immune Dz type IV mediated by effector T-cells (IDDM, RA, MS, and celiac dz)
IDDM susceptable MHC HLA-dq, position 57. Normally Asp in this position makes salt bridge with another Asp. Anything else here= no salt bridge= susceptability to IDDM. HLA-dr2 is protective
good test for Immune syst restoration post- BMT skin test. indicates that cell mediated immunity is working. bone marrow chimerism indicates the presence of both but not if they are working.
Hypersensity rxn, type IV cell mediated immunity to altered self-cell membrane -Tc mediated= cell assoc Ag-->cytotoxicity (contact derm from rings, watches) -Th1= sol' Ag-->Macro activation(contact derm, Tuberculin rxn) -Th2= Eos activation (asthma, allergic rhinitis)
Enzymoimmuno assay procedure 1. Ag is absorbed onto solid phase. 2. Ab-containing serum is allowed to react 3. enzyme labeled 2nd Ab is added. 4. substrate is added that developes color in presence of enzyme conjugated to 2nd Ab. color= level of serum AB
Primary immune response time 7-10 days
secondary immune response time 3 days; more, better, and faster
T-cell immune deficits present with ? increased viral and inter-cellular infections (granulomas)
B cell immune deficits present with ? lack germinal centers in 2ndary lymphoid tissue
complement system "a non-specific enhancer of specific immunity" due to the use of Ab in the classical pathway
Mortality of Allogeneic matched BMT 20-40%
mortality allogeneic matched unrelated donor 40-60%
HydroxyUrea tx of leukemia; slows proliferation of leukocytes
CML tx hydroxyurea, a-INF, and BMT. Blastic CML = poorest prognosis/ Chronic CML has best
pre-BMT Myoablative TX Busulfan and Cyclophosphamide.
pre-BMT prophylactic tx includes acylcovir and bactrim
post-BMT TX GVHD= cylcosporine adn methotrexate, tacrolimus and steroids(methylprednisone) to suppress lymphocytes during repopulation
GVHD stages mild GVHD on skin is good. GVHD with skin bullae or liver/GI is bad
Acute vs. Chronic GVHD before or after 100days
Erythropoietin inc RBC production in BM. used in myeodysplastic syndromes like anemia from chronic renal failure
IL-1 -from macrophages, endothelial cells, DC's, Langerhan's cells -induces IL-2 receptor expression; enhances B-cell activation;induces fever, Acute Phase reactants & IL-6; Inc. non-specific resistance -inhib by endogenous IL-1r antagonist
IL-2 Produced by Th1 cells *proliferation of T cells, B cells and NK cells. also enhance NK cell activity (LAK, lymphokine activated killer) *used in a number of malignancies (renal cell carcinoma, Malignant melanoma, and after BMT to eliminate original tumo
IL-3 - from T cells. - stimulates hematopoesis for all WBC types
IL-4 -from Th2 cells. -required stimulation for bcell development from small pre-b--> immature bcell. -B-cell synthesis of IgE -first cytokine released--> directly at bcell (paracrine) -induces MHCII expression (macrophages, etc)
IL-5 -from Th2 -acts on activated Bcells -down reg. IFN-g -stim growth/diff of eosinophils -enhances IgA synth.
IL-6 -from Monocytes, T cells, endothelial cells. -induces acute phase reactants, fever, and late B cell differentiation to plasma cells
IL-7 from bone marrow -stimulates pre-B and pre-T cells
IL-8 aka, CTCX-8. -from monocytes, endoth cells, lymphocytes, and fibroblasts. -is a CHEMOTACTIC for nuetrophils and T-cells
IL-10 from TH2 cells. -Inhib IFN-g synth by Th1's. suppresses other cytokine synth.
IL-11 from BM. stim hematopoesis and acute phase protien synth
IL-12 from macrophages/B-cells. -promotes Th1 diff and INF-1 synth -stim NK cells & CD4 cells --> Th1 variety.
IL-13 from Th2 cells.- inh. inflammatory cytokines (IL-1, 6, 8, 10 & MCP)
TNF-a -from Macrophages, Tcells, Bcells. -is cytotoxic for tumors;causes cachexia; mediates bacterial shock
INF-b -from fibroblasts, macrophages, and epith cells. -induced by viruses and bacterial products -inhibits viral replication
INF-g "gamma ray" -from Th1 and NK cells. -activates macrophages; strong immunomodulating agent; inhib IL-4 activation of mast cells and IgE synth
TNF-b -from Tcells -cytotoxic for tumors
TGF-b almost all normal cell types -inhibits proliferation of both T/B cells; reduces cytokine receptors; potent chemotactic agent for leukocytes; mediates inflammation and tissue repair. -secreted by some tumors--> escape immune attack
T independant Ag's bypass act. signal from tcells by binding to LBP (LPS binding protien) and to CD14. are polymeric in nature; induce IgM only w/o memory/an-amnestic, 2nd IgG response. Include (TI1)mitogens , or(TI2)endotoxin, LPS, bacterial capsules, flagellin, and EBV.
Th2 Cells -secrete IL-3, 5, 6, 10, and 13. -promote Bcell transformation/prolif -are potent chemoattractants for Bcell, basophil, eosinophil, and mast cells. promote humoral response by inducine bcells to inc Ab prod and Ig class switch. also promote IgE via IL-4
Th1 Cells Secrete IL-2, INF-g, and TNF-b -promote cell mediated immunity by activating Tc's, and killing intercell microbes by activating macrophages and other APC's
CD 40L B CELL SECOND SIGNAL!! expressed on t-cells after it has seen cognate Ag; ligand for CD40 on bcells. signals isotype switch. -hyperIgM syndrome= lack CD 40L
What happens in Pro-B cell stages early pro-b, heavy chain D-J rearrangement occurs on both chromosomes. Late pro-b, both start to V-DJ rearrange. first to make good copy shuts down the other. survival stimulus is by cell adhesions with bm stromal cells (c-kit:SCF) and IL-7.
B cell stem cell is recognized by? CD 34 on surface
what happens in the large Pre-Bcell stage heavy chain d-j and V-DJ rearrangement has happened. the Mu heavy chain and surrogate lt. chain (lambda5/Vpre-B) is expressed on surface. IGF-1 is the progression signal from late pro-B to Large pre-B.
what happens in small Pre-B cell stage has surface IgM chains:surragote light chain w/ Ig-a:b. the kappa lt chain rearrange first, then lambda chains. first good copy is expressed with IgM on surface. Positive selection is req. for progression. IL-4 signals go to immature Bcell.
Immature B cell lt chain V-J rearrange. membrane IgM expressed. also expressed= C3b, Fc, EBV receptors. -negative selection for bound Ag 'deleted' (die by apoptosis) and soluable,serum Ag 'inactivated' (by anergy) are removed.
Mature B cell has membrane bound IgM and D (equally expressed)
Activated B-cell Capping of S-Ig (pinocytosis)-->prolif of b-cells and migration into germinal centers or a few migrate into blood via lymphatics.
S-Ig surface Ig that binds Ag and then 'cap' by pinocytosis to present Ag to Tcell. Bcells are important APC's
Ig- a & b Bcell signal transduction molecules
CD 19, 20, 81 additional transduction molecules
CD 32 Fc receptor of IgG (Fc gamma RII)
MHC I presents processed Ag to Th cells. binds to TCR adn CD4 (on the a-3 subunit)
MHC II (blank)
CD 40 binds to CD 40L to induce Ig switch IT IS THE REQUIRED SECOND SIGNAL!
B7.1 and B7.2 interact with CD28 (stim) or CTLA-4 (inhib)on tcells. w/o B7 as second signal, if Tcell binds MHC I= anergy.
CD 5 Marker on B-1 cells, which arises earlier in devel. than 'normal' B-2 cells. B-1 cells only produce low affinity IgM against bacterial polysaccharide Ag's and hang out in the peritoneum/ plueral cavities.
APC's macrophages, monocytes, etc. that eat Ag and present Ag. produce IL-1. Bcells are also APC's but dont produce IL-1
TCR heterodimer of a-b (95%) or g-d (found mostly in GI epith) subunits. a-chain is on Chr 14; b-chain is on Chr 7. is associated with CD 3
CD 3 has 6 subunits, g, d, e, and two zeta chains that essentially transduce signals from TCR
CD2 earliest tcell marker. is an adhesion molecule for LFA-3 which allows binding to other cells
CD 4 Thelper TCR "CO-RECEPTOR" molecule that binds/associates with MHC II at the Beta 2 domain. remember the MHC II is a dimer (a&b)
CD 8 cytotoxic Tcell TCR "CO-RECEPTOR" molecule that binds/associates with MHC I molecules at the Alpha 3 domain. remeber the MHC I is a dimer with a1,2,3 domains and b2microglobulin
ontogeny of tcells CD3-4-8- cells from bm->thymus (gene rearrangement) cortex. Bchain d-j, v-dj. then achain v-j.(surrogate a chain= pTa). CD3+4+8+ interact w/ FDC's. only interacting CD4+ or CD8+ cells pass cort-medullary jxn. Mature CD4/8 cells exit via venule.
self restriction of Tcells only tcells that bind to self presenting MHC molecules in the cortex of thymus survive (positive selection)
negative selection of Tcells in medulla, tcells that have receptors with high affinity for self MHC's die by apoptosis= self tolerant.
CD 28 tcell ligand that binds to B7.1 or .2 (on APC's); is co-stimulatory molecule for tcells. also increases tcell proliferation. note: TCR:MHC + CD4/8 +CD28:B7.1. also, binding will inc expression of CTLA-4->B7 which is an inhib signal
CTLA-4 (CD 152) almost same as CD 28, but is inhibitory to Tcells to limit activation
LFA-1 t cell adhesion molecule that binds to ICAM (inter cellular adhesion molecule) on APCs and other cells.
MHC 1 presents self Ag to CD8 tcells for surveilance for viruses or transformed cells; has 3 subclasses HLA-A, B, and C; has two subunits, alpha and micro-globulin B
MHC II mainly expressed on APC's to present external Ag to CD4 tcells for survellance for Non-self Ag; has 3 subclasses HLA-DR, DP, and DQ
MHC III Ag's includes C2, C4, factor B, adn C3b receptor
Factor B -part of alternative pathway -in presence of Factor D, this will be cleaved into Bb, which assembles with C3b
Properdin part of alt. pathway -stabilizes C3bBb on sruface of zymosan or endotoxin and allows further cleaving of C3--> perpetuate cascade
Factor D -alternative pathway aids in cleaving of factor B to Bb which is an initial portion of alt. pathway
Factor I cleaves C3b and C4b
TAA tumor associated Ag. tumors express Ag that is normally found only in development. ie, AFP alpha-fetal-protien
C1-INH stops continued activation of C1. Lack of C1-inh= congenital hereditary angioedema
complement inactivators C3b inactivator (enzyme that destroys C3b activity), C6 inactivator, and anaphylatoxin inactivator (cleaves C-terminal Arg from C3a and C5a.
Hypersensitivity type I anaphylaxis w/in 15 min. from the degranulation of mast cells or basophils with bound IgE (Ab specific) to their FceRIII receptor. severe allergies
Hypersensitivity, type II Ab to surface Ag-->destruction of cell. ex, transfusion rxns, Rh incompatibility, goodpasture's syndrome (Ab to glomerular/bronchial basement membrane), myasthenia gravis (Ab to mm ACh receptors )
Hypersensitivity, Type III Immune complex reaction. where the Immune complexes with soluable Ag causes pathologic expression, edema, neutrophil infiltrate, and lesions in BV's and kidney glomeruli. ex, serum sickness(immunization w/ horse serum), farmers lung (Ab to Aspergillus),
Vasoactive mediators of Type I hypersensitivity Histamine; PAF (=coagulation); slow reacting substance of Anaphlyaxis (SRS-A)(leukotriens C4, D4, and E4); Prostaglandins and thromboxanes
Chemotactic mediators of Type I hypersensitivity eosinophil (ECF-A) and Nuetrophil factor.
Tx for Anaphylaxis * secure airway * 0.01mg/kg (max .3-.5ml) 1000:1 Epi q15min *apply tourniquet at sting site. *recumbent position, legs elevated, frequent vital signs.
congenital Agammaglobulemia 'of Bruton", sex-linked (m); pyogenic infections and digestive tract d/o's by 5-6mo. absent tonsils, germinal centers, and bcells w/ serum Ig <10%. Normal cell mediated Immunity. tx- IgG
Common Variable HypoGammaglobulimia have bcells but dont secrete Ig. px are susceptable to pyogenic infections and autoimmune dz's
congenital thymic Aplasia (DiGeorge Syndrome) CATCH 22. deletion of Chr 22q11= Cardiac defects, abnormal facies, Absent thyroid, hypothyroid and parathyroidism; susceptable to opportunistic pathogens, candida, pnuemocystis, and viral infections. have normal germinal centers, plasma cells and S-Ig
chronic mucocutaneous Candidiasis from tcell clonal absence for candida. have normal Tcell totals and fxns. also often have hypothyroidism.
Wiscott-Aldrich Syndrom x-linked(m); triad of thrombocytopenia, eczema, and recurrent infections. have lower cell-mediated immuntiy and S-IgM, but normal IgG &A. px respond poorly to polysaccharide Ags
SCID Lack Adenosine Deaminase= toxic b/u of dATP -->inhib ribonucliotide reductase and prevents DNA synth. Poor Prognosis
Chronic Granulomatous Dz dec Neutrophil, and macrophage, activity due to a defect in NADPH oxidase system. Dx- by failure to reduce NBT dye.
Sjogren's Syndrome Ab against salivary duct Ab; have dryness of mouth, eyes, nose, skin and bronchi. unknown etiology
polyarteritis nodosa Ab:Ag complexes (often of Hep B) that are deposited on vessel wall leading to inflammatory response.
Bence Jones Protiens Ig-light chains seen in urine of person with MML that produces excessive S-IgG, A, E, etc
MS decreased Suppressor Tcell fxn leads to mononuclear infiltration and Ab against Mylin of CNS. -experimental in mice models is the use of 'anti-myelin basic protien' that reacts with the Macrophage presentation of MBP to tcells-->activation. given orally.
Chronic Thyroiditis auto-Ab and cell mediated immunity to thyroglobulin or thyroid microsomes
Graves's Dz Hyperthyroidism from Ab to THS receptor on thyroid as well as tcell/bcell infiltriation of thyroid
pernicious Anemia auto Ab against gastric parietal cells and intrinsic factor=> unable to absorb Vit B12
Ulcerative Colitis Chronic inflam. lesions confined to rectum and colon w/ infiltrates of monocytes, lyphocytes, and plasma cells. Px'sAbs are cross-reactive with E. coli and Tc's are reactive to colon epith cells.
Crohn's Dz inflammatory granulomatous dz usually in the submucosal are of the terminal ilium.
Chronic active hepatitis infiltration of liver by tcells, bcells, and monocytes due to faulty immunoregulation
mode of steroid fxn pass thru cell mem and bind to heat shock protien:steroid receptor, releaseing steroid:steroid receptor to travel to nucleus to change activity there. decrease inflammation, NO,
NK cells part of the innate immune system. need both stim. and inhib. signal. lack of MHC I will also induce attack
graft rejection via direct recognition mechanism grafted, foreign DC goes to lymph node to present Ag in normal sort of way, but tcells are of host there for react.
graft rejection via indirect recognition mechanism where the tcell is activated in the process of normal peptide presentation due to minor differences in histocompatability.
primary and secondary graft rejection times first graft from donor A will be rejected in about 12 days; the second graft will be rejected in about 5-7d with increased inflammation, hemmorrhage, and necrosis
tests for matching donor to reciepient MLR= (mixed lymphcyte reaction) mix tcells from one with irradiated APCs from anouther. add H3 thymidine. a proliferation rxn will incorporate the radio nuclide and give a large geiger response.
Cr51 release assay another way of matching donor-host. Chromium is taken up and => will release it if there is a cytotoxic reaction due to mismatch
Why arent fetuses rejected? they are natural allografts in the mother, and are tolerated b/c trophoblasts lack MHC or lack secretion of Th2 inducing cytokines
which grafts are better accepted? solid organ grafts b/c they have fewer leukocytes => less GVHD
Chronic graft rejection mech? rejection by interaction btwn 'anti-HLA class I' allo-Ab's with blood vessels of transplanted organ via INDIRCT RECOGNITION (minor histocompat diffs being recognized)
what is the most common cause of death after transplant? MI
name two monoclonal Ab used in transplantation -OKT3= mouse/human chimera against CD3.for single time use only!! -Basilizimab (simulect) or daclizumab = humanized version of CD3 anti-Ab. these are humanized, nontoxic, and for induction only.
which transplants are easier to maintain? hearts and lungs
post transplant drugs for life? prednisone, cellcept, and tacrolimus
tx for acute rejection? high dose steroids, OKT3, or thymoglobulin
DDx in decreased renal function, post transplant rejection, necrosis, toxicity, vascular problems, obstruction, or infection
what causes the increase in Eosinophils during asthma CFU-eo; also IL5 (from bm stromal cells, not cause CFU-eo but is necc for proliferation)
what is needed for eosinophil maturation Tcells, IL5 and cysteinyl leukotrienes
what suppresses eosinophils? IL 4
CD 25 associated with IL2 receptors on tcells
CD10 marker for leukemic cells
CD 19 Marker for mature Bcells
what causes psuedomembranous colitis? C. dificile
bacterial do/do not have mitochondria? DO NOT. we do.
what is the size of bacterial ribosomes? 70s (50s+30s).
gram stain proceedure 1. transfer sample and heat fix 2. flood with crystal violet- 1 min, rinse 3. flood with grams iodine - 1 min 4. rinse with ETOH 5. flood with safarin- one min, rinse, blot. done
characteristics of Gr +bacteria gram stain attatched to huge peptidoglycan cell wall with TEICHOIC ACID. used for attachment. glycan units of NAG (n-acetyl-glucosamine) and NAM (n-acetyl- muramic acid peptide) cross-linked via D-ala to L-lys via 5 glycines. Can make spores! (gr- cant)
characteristics of Gr - bacteria have OUTER MEMBRANES (small) with periplasmic space. O Ag polysaccharides (LPS=exotoxin) on outer leaflet of membrane. Lipid A (inner-most portion) is a component of LPS and is essential for growth. use an ISOPEPTIDE bond to bind D-ala to L-DAP
process of Bacterial cell wall construction -glycosy transfer and BP(bactoprenol) flips back inside -transpeptidase(cross-linking) with gly 5 -carboxypeptidae adds D-ala's
What is a M-protien is used by bacteria for cell wall adhesion to target cells
difference btwn Mycoplasms and Mycobacteria Mycoplasms= dont have cell walls, dont stain well, and are very small. Mycobacteria (TB and Leprosy) = have waxy thick cell walls, adn are stained with "acid-fast" stain
protien secretion from bacteria type III= syringe exports protein directly into host cell that modifies host cell. type I= chunnel pathway of fully folded protiens (imp for virulence)
hemochromatosis most common hereditary dz in US
fxn of catalase convert H2O2-->water and O2
fxn of superoxide dismutase convert Superoxide-->to H2O2
purpose of DNA gyrase wind DNA to allow progression- negatively supercoiling by breaking both chains. this the targe of Fluoroquinolones
What is purpose of DNA A? a cellular mocule whose concentration signals cell replication. it opens DNA to allow helicase to bind and start replication.
sensor kinase a mem bound molecule that binds to single molecule to form dimer. the dimer is a active kinase that gives cell signals of external environment, osmolarity, heat, catabolites, etc. phosphoralation of 'response regulator" that works intercellularly
bacterial transformation naked DNA from environment. often virulence factors, typically from same species, bound to specific mem bound protiens and imported. 'electro-poration' increases uptake of DNA
bacterial transduction DNA transfer via viruses- in the packaging of virus protiens, a bacterial DNA segment can be accidentally packaged. Have both specialized and general transduction
specialized transduction assoc. with toxic genes. where the 'temperate' virus DNA becomes permanently associated with bacteria toxin gene that is next to the inserted phage DNA so that it is carried out (and into the next bacteria) with the virus DNA.
generalized transduction similar to specialized but the DNA can come from anywhere in Bacteria genome, and is a mistake of packaging, not a specific aquisition.
Conjugation use pilus to transmit plasmids( often with Resistance to Abx= "R-plasmids") as well as the gene for making the pilus (F+ factor)
antigenic variation of bacteria allows random switching of Ag'ic outer components to allow immune syst escape (salmonella flagella). gene has inverted repeats that when read 1 way, codes for gene and a suppressor for later genes. read other way = codes for gene=> will make the other.
complement deficientcies - lack C3= recurrent bacterial infections. -C5,6,7,8= recurrent neisseria infections
cell mediated immunity screening -CBC, w/ diff and platelet count -flow cytometry (tcell compartment and surface ID marker) -delayed hypersensitivity skin test -invitro prolifertion tests -enzyme assays -cytokine production assays
immunodeficientcy screening -CBC, WBC count and morphology. platelet size. Lympocyte count. -IgM, IgG, IgA, & IgE - delayed hypersensitivity test - HIV test -vaccine responses
b cell activation signaling signal 1= crosslink Ag:Ag receptors. Blk, Fyn, Lyn phos ITAMS on Iga, b. Syk binds to phos tails of Igb-->Syk phos other Syk's. CD45 tyrosine phosphotase augments activ. of receptor-assoc kinases.CD19-synergizes signal with CD3. CD40 is second signal
tcell activation signaling TCR:Peptide:MHC binds/clusters->phos. of ITAMs (e & zeta subunits) by Lck on co-receptor(CD4/8)->allows zap70 to bind. Lck activates Zap70->->->activates nucleus transcription factors NFkB, NFAT, and AP-1. CD45 also activates Lck and Fyn.
hapten epitope recongnized by bcell that is experimentally antigenic, but not immunogenic
cytokines that stimulate bcell proliferation IL 2, 4, 5
cytokines that drive bcell differentiation IL 2, 4, 5, INF-g, TGF-b
BCL-xl bcell receptor expressed during infection/affinity maturation that prevent apoptosis. life of unstim bcell is 3-5days; stimulated bcell life= 1month. -note:this protien is constituitivley expressed on folicular lymphoma.
how is bcells told to switch to IgA? increase amt of IL5
how are bcells directed to isotype switch? high levels of IL4-->drive production of IgG1 and IgE. inh IgG2 and 3 and IgM classes
Antibody Dependant Cellular Cytotoxicity ADCC target cell dies by apop due to Fc receptor recognition by NK cells rather than Th crossliking of Fc regions
ontogony of bcells (overview) 1 early pro-bcell (heavy d-j rearrange both chr), late pro-b (heavy V-dj); pro-b (express IL7R); large pre-B (divides. has surrogate lt:heavy Mu); small pre-B (stops divide. v-j lambda then kappa lt chain) once lt chain viable, move to periphery.
TdT terminal deoxynucleotide transferase- adds nucleotides at recombined ends that are random (=variable)until there is matching sequences on other side to allow for pairing. the mismatched nucl's are excised and repair DNAase finishes.
Rag1/Rag2 protiens expressed that bind germline Ig DNA and allow for recombination/rearrangement using 12-23 rule. are temporally expressed= only at certain times to control rearrangment processes and allow for salvaging of un-viable transcrips of Ig.
Tap1/Tap2 protiens(of exogenous pathway)in ER membrane that act as gates to proteosome digested Ag into the ER, and bind MHC I associated protiens to facilitate/regulate loading MHC. other ER protiens are calnexin, Erp57, calreticulin, and tapasin.
package of MHC I peptides partially folded MHC I binds to calnexin. B2 microglobulin binds and tapasin binds the complex to TAP1/2. Erp57/calreticulin bind, releasing calnexin. peptide via Tap1/2 is ANCHORED AT ENDS OF CLEFT and Erp57,calreticulin released. loaded MHC-->cell mem.
Package of MHC II peptides Recycled MHCII is primed with invariant chain in ER-->vessicles, invariant chain cleaved to clip frag. HLA-DM releases clip and holds open MHC. fused lysozome w/ peptides-->peptide anchored ALONG LENGTH of cleft, HLA-DM released. MHC-->cell membrane
cytokine IGF-1 from bm stromal cell that signals late pro-Bcell to Large pre-Bcell
What cytokines are needed to make Th1 cells IL 12 and INF-g. note: Th1 cells secrete INF-g that inhibits Th2 proliferation note: Th1 cells activates Macrophages to kill (oxidative burst) internal bacteria and induces bcells to produce opsonizing Ab
What cytokines are needed to make Th2 cells Th2 secrete TGF-b and IL10 -->inhib activation of Th1 cells. note: Th2 cells activates Bcells to make nuetralizing Ab; also have various effects on macrophages
principle cytokines for acute phase response IL1, 6 and INF-g-->fever, activation of compliment (CRP are like C1, mannose 6p-->alt.pathway), PMN mobilization, energy mobilization, migration DC to lymph nodes.
what is required to send B-cells thru Sphase the second (AND MAJOR) signal for bcell activation CD40 (on bcells) binding CD40Ligand on Th2 cells. Cytokines IL-2, 4, and 5 also drive proliferation.
CDR where the Ag binds. has 3 regions per subunit. has some constant regions and some hypervariable regions that play a part in affinity maturation as well as Ag recognition diversity
AID (activation-induced Cytidine Deaminase allows for isotype switch and hypermutation rates. w/o AID= no switch and monoclonal Ag produced
super antigen bind outside MHC:TCR binding clefts, on the constant regions themselves, and activate large groups of tcells. toxins and some viruses do this.
t cell adhesion molecules tcells bind/roll along using weak interactions with thier LFA-1. if TCR binds, LFA- 1 conformation changes allowing stronger binding
IL-2Receptor Tcell receptor with 3 subunits. g,b subunits (weak affinity for IL2) normally present. a subunit induced w/ expression of IL-2(autocrine)
principle cytokines produced by Tc's INF-g, TNF-a, TNF-b
principle cytokines produced by Th1's INF-g, GM-CSF, TNF-a, CD40L, Fas ligand
principle cytokines produced by Th2's IL4, 5, 15, CD 40L
Complement Receptors (CR) found on most cells; allows binding of complement for phagocytosis (macrophages or part of CD3d on bcells), or for clearing bacteria (on RBC's) in liver kupfer cells.
C1 inh binds to C1qrs and breaks the sub units up. HANE (hereditary angioneurotic edema) have reduced levels of C1inh=> get edema in skin, gut and airways due to stress
C4 binding Protien Binds C4, dissociates C4C2, and allows Factor I to cleave C4= inactive
MCP found on human cell surface that binds C3 convertase: dissociates C2 from C4 and makes C4 target for factor I
DAF found on human cell surface, binds to C3convertase, and dissociates C2a from C4b
CD59 found on human cells surfaces, binds C5, 6, 7, 8 complex and prevents recruitment of C9=> no pore formation
PAMPs pathogen assoc. molecular patterns bind with MBLs to activate the mannose binding - complement pathway
SIGN-R1 lectin in spleen that captures microbial polysaccharides
plasma protease inhibitors alpha 2 macroglobulin and serpin that change conformation when encountering protease to 'trap' by covalent binding
cytokines released from Macrophages IL1b (fever), TNFa (Fever), IL6 (lymphocyte activation/ Ab production), CXCL8 (chemotaxis of WBCs), IL12 (activates NK's, Tcells->Th1)
septic shock caused by activatio of macrophages in liver releasing cytokines systemically causing DIC, multiple organ failure, hypovolemia, and neutropenia.
process of Lymphocytes leaving Blood vessel 1. rolling adhesion 2. tightbinding 3. diapedesis 4. migration
acute phase protiens CRP, fibrinogen, and mannose binding lectin
NK activation/inhibition must have both inh. signal (via MHC I) and activation signal (receptor +ligand (HLA-A, B, or E)
What is protien MIC Molecules expressed on intercellularly infected "stressed" cells that bind Tcellsd:g, or NK cells
CD 45RO form of CD45 that is expressed in memory bcells.
Created by: Damon