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AB
Pre-B cellcytoplasmic mu heavy chain and pre-B receptor
Immature B cellMembrane IgM
Mature B cellMembrane IgM, IgD
Activated B cellLow rate Ig sec.; heavy chain isotype switching; affinity maturation
Antibody secreting cellHigh rate Ig secretion; reduced membrane Ig
IgAMucosal Immunity
IgDNaive B cell antigen receptor
IgEDefense against helminthic parasites
IgGOpponization of complement activation,
IgMNaive B cell antigen receptor
Binds macromolecules and small chemicalsImmunoglobulin (Ig)
Made up of three CDRs in V-alpha and three CDRs in V-betaT cell receptor (TCR)
Binds peptide-MHC complexesT cell receptor (TCR)
Peptide-binding cleft made of alpha-1 and alpha-2 (class I) or alpha-1 and beta-1 (class II)MHC molecules
Binds peptidesMHC molecules
two layers of beta-pleated sheet, held together with disulfide bondsIg domain
constant regions of the heavy chain that mediate effector functionscarboxy-terminal constant (C) regions of antibody heavy and light chains
variable regions that participate in antigen recognitionamino-terminal variable (V) regions of antibody heavy and light chains
allotopePolymorphisms within conserved Ig amino acid sequences
allotypeProtein product of a distinct allelic form of an Ig gene.
DETERMINANTepitope
HLAshuman leukocyte antigens; MHCs on human cells
epitopespecific portion of an antigen to which antibody binds
specific portion of an antigen to which antibody bindsdeterminant
F(ab')2retains bivalent;used in research
Fabretains monovalent; used in research
Fcproteolytic fragment of Ig containing only the s-s c-terminal regions of the two heavy chains
Fc receptorrcptr for c-terminal region of Ig
ADCCNK targets Ig coated cells for lysis; Fc(gamma)RIII
antiserumserum w/antibody to antigen
affinity maturationsomatic mutation of Ig genes
hinge regionflexible regions between Ch1 and 2 in some Ig molecules;
CDRsantigen-binding; 3 hypervariable regions
hypervariable segments3 loops connect adjacent B-sheets
Kabat-Wu plothistogram depitcting # of different aa res/Ig light chains
BiP, calnexinnacent Ig chaperones
antibody specific for one antigen, produced by a hybridoma; used in research and diagnosismonoclonal antibody
M-cellsspecialized epithelial cells; Peyer's; Ig transport
polyvalencemultiple identical copies of epitope/ one antigen;
Poly-Ig recpetorFc receptor expressed by mucosal epithelia;
Polyclonal activatorsagents capable of activating many clones of lymphocytes, regardless of their specificity
Poly-Ig recpetortranspt of IgA and IgM through epithelium into intestinal lumen
IgEimmediate hypersensitivity
IgGanti-body dep. cell mediated cytotoxicity
IgGfeedbk inhib. of B cells
IgGneonatal immunity
Polyclonal activatorsanti-IgM antibodies for B cells, anti-CD3 abs, bacterial superantigens, PHA for T-cells
CDRscomplementarity determining region)
affinity maturationleads to increased affinity of antibody for an antigen
affinity maturationconcurrent w/humoral response
affinity maturationgerminal centers of lymph nodes
IL-1source: macs, endothelial; tlr pathway to NF-kB/AP-1 synthesis of acute phase proteins
IL-2CD4+ activates transcription; uses Jak3-STAT5 path; Bcell growth factorand stimulus for antibody generation
IL-3CD4+ T cells Hematopoietic TH2 cytokine
IL-4Adaptive / Pathway Involving IRS-2/ Jak3/Jak4- STAT6
IL-5Adaptive/ Jak2-Stat 3 / helminth defense
IL-6source: macs, endo. & T cells; JAK1-STAT3 TO B cell prolif. ; acute phase protein synthesis
IL-7stromal cells of thymus, bone marrow promotes naive T and B cell survival
IL-8chemoattractant for PMNs; kry in margination
IL-9increases IL-6 from eosinophils; influences mast cells and lymphoid cells
IL-10source; regulatory T-cells; control of inflammation
IL-11stimulates megakaryocytopoiesis; increases IL-4; inhibits IFN-gamma; Jak-STAT; BM STROMA
IL-12IFN-y production by NK cells and T-cells
IL-13promotes fibrosis as part of tissue repair in chronic inflammation, stimulates mucus production in lung epithelia; induces IgE class switching
IL-14proliferative of active B cells; Th2 cytokine
IL-15source: macs & others in response to viral infect.; TYPE I CYTOKINE R JAK3/STAT5; Akt. dep. signaling path promotes cell survival/proliferation
IL-16chemoattractant of eophils & CD4+Tcells
IL-17Promotes tissue dmg. in hypersensitivity diseases; induces cells to produce hematopoietic cytokines; thought to be responsible for the destructive inflammation in many auto immune diseases
IL-18Enhances IFN-gamma production by T and NK cells
IL-19Innate; bind type II cytokine receptor; Regulate inflammatory reactions in tissues
IL-20Innate; bind type II cytokine receptor; Regulate inflammatory reactions in tissues
IL-21adaptive; secreted by activated CD4+ T-cells; JAK1/JAK2- STAT1/STAT3- synergistic cytokine; stim. CTLs, NKs
IL-22Innate; type II cytokine receptor; regulation of inflammatory reactions in tissues
IL-23unique subunits:19kD and 40kD-IL-12; inmmatory pathology of autoimmunue do; promotes diferentiation/maintenance of IL-17 T-cells
IL-25adaptive; secreted by Th2 cells; stimulates production of other Th2 cytokines ( IL-4, IL-5, IL-13)
IL-27SECRETED BY MACS, DCS IN RESPONSE TO MICROBE;inhibits Th1 cells; possible role in Th1 differentiation(?)
TNFsource: MACS, T-CELLS; receptors on most cells, signals: cytokine to TRAF RECRUIT TO NF-kB TO AP-1; 1' mediator of acute inflam.; [high] leads to systemic effects
Type 1 IFNsEarly responses to viral infections; inhibit viral replication( dsRNA activated serine/threonine PK), transcrip/late; paracrine action; increases expression of MHC class I; NK cell activation
TGF-betaANTIGEN STIM. T-CELLS LPS ACTIVATED MACS, MONOS, OTHERS inhibits proliferation/effector functions of T-cells; mac activation; regulates differentiaion of T cells; stim. IgA prod.f IgA; tissue repair; SMADS, SER/THR KINASE DOMAIN
Chemokinesproduced by macs, endothelial, T cells, fibroblasts & platelets; promote leukocyte chemotaxis/activation/migration; GPCRs
MIFAdaptive; secreted by t-cells; immobilize mononuclear phagocytes; may cause cell retention at sites of inflammation; migration inhibition factor
APRILMONOCYTES, MACS;ACTIVATED T-CELLS;CYTOKINES TO TRAFF TO NF-kB & AP-1; TNFRI, II, TACI, BCMA
BAFFpmns, MONOCTS, MACS, DC, FDC, Ac'td T CELLS; CYTOKINE BINDING LEADS TO TRAF RECRUITMENT; TRAFS ACTIVATE NF-kB AND AP-1; B CELL SURVIVAL, TACI REQUIRED FOR CLASS SWITCHING
p-selectinleu receptor: sialyl-Lewis X PSGL-1; fnx rolling, neutrophils, monocytes, lymphocytes)
e-selectinleu receptor: sialyl-Lewis X fnx: rolling, adhesion to activated endothelium, ( neu, mono., Tcells)
ICAM-1CD11/CD18 (ntegrins) LFA-1, Mac-1; fnx adhesion, arrest, transmigration ( all leukocytes)
VCAM-1alpha-4beta1 (VLA4); (LPAM-1); adhesion (eophils, monocts, lymphcts)
GlyCam-1lymphocyte homing to high endothelial venules; L-selectin
CD31 PECAMleureceptor: CD31; fnx; leukocyte migration through endothelium
PAFredistributes p-selectin from normal intracellular stores in Weibel-Palade Bodies to the cell surface
LTT CELLS; TNFRI,II; CYTOKINE BINDING TO TRAF RECRUITMENT TO NF-kB AND AP-1; LINK BETWEEN T CELL ACTIVATION AND INFLAMMATION; REQUIRED FOR NORMAL DEV. OF LYMPHOID ORGANS (AKA TNF-beta)
IFN-yMac activation
IFN-gammaTYPE II CYTOKINE RCPT.JAK1/JAK2-STAT1; ACTIVATES MACS
TNFprimary response to gram-neg.; endothelial cell activation; stimulates chemokine secretion, microbicidal activity of macs/neutrophils
IFN-ALPHAMONONUCLEAR PHAGOCYTES; DCs; Tyk2/JAK1 & STAT1/STAT2; AND MAP KINASE AND PI3 KINASE PATHWAYS
IFN-BETAFIBROBLASTS; Tyk2/JAK1 & STAT1/STAT2; AND MAP KINASE AND PI3 KINASE PATHWAYS
IL-23STRUC. LIKE IL-6/IL-12; INFLAMMATORY PATHOLOGY OF AUTOIMMUNE DO
IL-27STRUC. LIKE IL-6/IL-12; stimulates NK cells: IFN-gamma synthesis
IL-13Th2 CD4+, CD8+, NK-T secrete in allergic resp.; has recpt. on B cells , macs, dc, eo/basophils; JAK1/TKY2-STAT6 IRS2 PHOSPHORYLATION
IL-15stimulates CD8+ T-cell PROLIF.; req. for NK differentiation and activation;
IL-12secreted by Dendritic cells, macs; Jak1/Tyk2-STAT4; key role in response to intracellular pathogens
IL-10PRODUCED BY MACS, regT's and nonlymphoid cells; shares a homologous gene w/ EBV
IL-1at [low] mediates local inflam.- 2 [high] stimulates systemic "calor"
CD11b/CD18; MAC 1mac integrin; can bind microbes for phagocytosis
ACTING REGULATING PROTEINSfilamin, gesolin, calmodulin, profilin
increased[Ca+2]; activated phosplAarachidonic acid metabolism
secreted by NK cells during innate and adaptive immune responsesthe major macrophage activating enzyme, IFN-y
FcyRI receptor on phagocytesIgG opsonized cells
Clq mac cell surface receptoropsonin mannose binding lectin
plasma protein opsoninsMBL, C-RP, fibrinigen, fibronectin
terminal sialic acid or N-acetylgalactosaminemammaliam glycoproteins and glycolipids
terminal mannose or fucosemicrobial cell wall glycoproteins/glycolipids
C-C; attract mono/lymphoctyes, baso/eoisinophilsMCP-1 EOTAXIN;MIP-1alpha;RANTES
PENTRAXINc-reactive protein; opsonination, complement activation
MBLmannose binding lectin (complement)
IFN-yNK, CD8+, Th1 CD4+ ; STIM. DIFF. CD4+ TO Th1; INIB. Th2; STIM MCH I & II AND COSTIMULATORS
copper containing serum proteinceruloplasmin
iron free fraction of serumtransferrin
catalasedetoxifies H2O2
glutathione peroxidaseH2O2 detoxifier
serotoninpreformed vasoactive mediator released from platelets at aggregation; present in chromaffiin cells
lymphotoxiincytokine req. for HEV development
CLA-1 cutaneous lymphocyte antigen-1E-selectin ligand; xp'sd by skin homing effector T cells
IL-1pyrogen - mediator of acute phase response;activates IL-6 IL-2R IL-8 adhesion molecules
IL-2T cell proliferation (mainly CD4 in autocrine manner) activates IFN-gamma IL-6 NK cell growth
IL-3expansion of bone marrow progenitor cells
IL-4inhibits other inflammatory cytokines IgE isotype switching MHC II in B cells TH0-->TH2
IL-5increases eosinophils B cell growth and differentiation IgE production (with IL-4)
IL-6mediatory of acute phase response activates B cell growth and differentiation increased by TNF & IL-1
IL-7increases IL-2 IL-2R
IL-8chemoattractant and activator of neutrophils
IL-9increases IL-6 from eosinophils
IL-10inhibits other inflammatory cytokines suppresses TH1 response inhibits IL-17 actions
IL-11increases IL-4 inhibits IFN-γ
IL-12increases IFN-γ major initator of TH1 response decreases TNF increases B cells and MHC II expression
IL-13inhibits inflammatory cytokines increases B cell growth
IL-14proliferation of ACTIVE B cells
IL-15T cell proliferation activation of NKs B cells and essential for prolonged inflammation; maintains MEMORY cells
IL-16chemotaxis of CD4+ T cells and eosinophils
IL-17maintains inflammation increases IL-6
IL-18increases IFN-gamma T cell proliferation activates NK cells
IL-23similar to IL-12 but has actions on memory T cells and IL-12
TNF-αpyrogen;leading to inflammation causes release of IL-1 IL-6 and IL-8 from MΦ
TNF-βnot inflammatory;maintains architecture of secondary lymphoid organs
IFN-γactivates mononuclear phag. increases MHC I II increased CAMs activates NK cells and neutrophils increases IL-12R on TH1s
IFN-αall cells: initiates antiviral state increases MHC I expression
IFN-βNK cells: activation
GM-CSFincreases production of granulocytes and monocytes in marrow
G-CSFincreases production of granulocytes especially neutrophils
M-CSFacts locally to turn precursor cells into monocytes
TGF-αactivates epithelial and mesenchymal growth
TGF-βhas both activation and inhibitory effects --> inhibits T cell growth CTL activation and macrophage activation
TH1 cells(IL-2 TNF IFN-γ) -activated by DC --> (DTH & CMI)activates mΦ increases Ag presentation and Fc receptor expression
TH2 cells(IL-3 IL-4 IL-5 IL-10 IL13) - activated by DC --> mediates humoral responses and allergies via IgE
plasminproteolytic enzyme present in inflammatory exudate
kinninogensvasoactive peptides generated from plasma proteins by kallikreins
bradykininvasoactive nonpeptide
effects of bradykininincreased vascular permeability
Hageman's FactorFACTOR XII of intrinsic clotting pathways
cleaves glycoprotein precursor,"high molecular weight kinniogen," to produce bradykininkallikrein
alternative pathwaycleavage of C3 in response to endotoxin, microbial LPS...cobra venom,etc...
C3 convertasesplits C3 to C3a and C3b
C3bfunctional fragment of C3; covalently attaches to complement target; then to other c-fragments to form C5-convertase
C5-convertasecleaves C5 to C5b and C5a; binds late components C6-9 together to form MAC
C5a activateslipoxygenase pathway of arachidonic acid met. in PMNs and Monocytes
C5apowerful chemotactant for neutrophils, monocytes, eoisinophils, basophils
C3b, iC3bopsonins, fix to bacterial cell wall, enhance affinity for phagocytosis
PARs (protease activated receptors)GPCRs on platelets, endothelialsm. muscle; bind various trypsin like serine proteases
engagement of PAR-1 by factor IIa triggers...mobilization of P-selectin; prod. chemokines, PAF, NO, prostaglandins;
major coagulation protease, cleaves circulating soluble fibrinogen to...thrombin; ...form insoluble fibrin clot
thrombin (factor IIa)protease; main link between coagulation and inflammation
kallikreinpotent activator of Hageman Factor; autocatalytic amplification of initial stimulus
kallikreindirectly converts C5 to chemotractant C5a
effects of complement activationincrease opsonation, chemotaxis, vascular permeability, proteolytic enzymes
lectin pathwayplasma mannose bindinig lectin binds carbs on microbes--> C1
VASOCONSTRICTIONthromboxane A2; leukotriense C4, D4, E4
VASODILATIONPGI2, PGE1, PGE2, PGD2
CHEMOTAXIS; LEUKOCYTE ADHESIONLeukotriene B4; HETE, lipotoxins
Prostaglandins, NO, HistamineVASODILATION
Increased Vascular PermeabilityVasoactive Amines, Bradykinin; C3a, C5a; PAF, leukotrienes C4,D4,E4
chemotaxis, leukocyte recruitment/activationC5a; leukotrienes B4; chemokines; IL-1; TNF;prostaglandins
Painprostaglandinis; bradykinin
tissue damagelysosomal enzymes from MACS & PMNs; ROS, NO
chemokinesincreased avidity of integrins
leukocyte diapedesis; vascular permeabiltypredominantly in venules; capillaries of lungs
1st 6-24 hours of inflammatory infiltrateneutrophils predominate
hours 24-48 of inflammatory infiltratemonocytes predominate
pre-formed, chemical mediators of inflammation in secretory granulesHISTAMINE; SEROTONIN; LYSOSOMAL ENZYMES
sources of pre-formed mediators in secretory granulesMCs; basophils; platelets; PMNs, Macs
cellular; newly synthesized chemical mediators of inflamm.prostaglandins; leukotrienes; PAF; ROS; NO; Cytokines
source of synthesized cellularallleukocytes, platelets, EC, Macs, No, Cytokines, Macs, lymphocyres
chemical mediators of inflam. from liver/plasma; Factor XII activationKinin System (bradykinin)
chemical mediators of inflam. from liver/plasma/complement activation; anaphalotoxinC3a; C5a
chemical mediators of inflam. from liver/plasma/complement activation; membrane attack complexC3b; C5b-C9
IL-1pyrogen - mediator of acute phase response;activates IL-6 IL-2R IL-8 adhesion molecules
IL-2T cell proliferation (mainly CD4 in autocrine manner) activates IFN-gamma IL-6 NK cell growth
IL-3expansion of bone marrow progenitor cells
IL-4inhibits other inflammatory cytokines IgE isotype switching MHC II in B cells TH0-->TH2
IL-5increases eosinophils B cell growth and differentiation IgE production (with IL-4)
IL-6mediatory of acute phase response activates B cell growth and differentiation increased by TNF & IL-1
IL-7increases IL-2 IL-2R
IL-8chemoattractant and activator of neutrophils
IL-9increases IL-6 from eosinophils
IL-10inhibits other inflammatory cytokines suppresses TH1 response inhibits IL-17 actions
IL-11increases IL-4 inhibits IFN-γ
IL-12increases IFN-γ major initator of TH1 response decreases TNF increases B cells and MHC II expression
IL-13inhibits inflammatory cytokines increases B cell growth
IL-14proliferation of ACTIVE B cells
IL-15T cell proliferation activation of NKs B cells and essential for prolonged inflammation; maintains MEMORY cells
IL-16chemotaxis of CD4+ T cells and eosinophils
IL-17maintains inflammation increases IL-6
IL-18increases IFN-gamma T cell proliferation activates NK cells
IL-23similar to IL-12 but has actions on memory T cells and IL-12
TNF-αpyrogen;leading to inflammation causes release of IL-1 IL-6 and IL-8 from MΦ
TNF-βnot inflammatory;maintains architecture of secondary lymphoid organs
IFN-γactivates mononuclear phag. increases MHC I II increased CAMs activates NK cells and neutrophils increases IL-12R on TH1s
IFN-αall cells: initiates antiviral state increases MHC I expression
IFN-βNK cells: activation
GM-CSFincreases production of granulocytes and monocytes in marrow
G-CSFincreases production of granulocytes especially neutrophils
M-CSFacts locally to turn precursor cells into monocytes
TGF-αactivates epithelial and mesenchymal growth
TGF-βhas both activation and inhibitory effects --> inhibits T cell growth CTL activation and macrophage activation
TH1 cells(IL-2 TNF IFN-γ) -activated by DC --> (DTH & CMI)activates mΦ increases Ag presentation and Fc receptor expression
TH2 cells(IL-3 IL-4 IL-5 IL-10 IL13) - activated by DC --> mediates humoral responses and allergies via IgE
Lysyl-oxidasecrosslinkstropocollagen molecules
Lysyl-hydroxylaseEhlos Danhers
Procollagen peptidasePro-to-tropocollagen;enzymatic removal of nonhelical domain
Collagen-fibrilself-aggregation in staggered array
FACITmediates cross linking of fibrils
Type-I-collagenCONNECTIVE TISSUE;XII SKIN/PLACENTA
Type-II-collagenCARTILAGE;ASSOCIATEDW/TYPE IX
Type-III-collagenRETICULAR TISSUE
Type-IV-collagenBASAL LAMINA
ELASTIC-FIBERSSTAIN BLACK
Pro-elastincontains isodesmosine&isodesmosine
MAGPMICROFIBRIL ASSOCIATED GLYCOPROTEIN
Fibrillin-1force bearing structural support
Fibrillin-2regulates assembly of elastic fiber
Marfan's-Syndromefibrillin 1 deficiency
Reticular-fibersstain black w/silver stain
Sudan-redstain frozen section of lipid
Para-aortic LP Splanchnic MesodermHematopoietic stem cells (@ week 5) that seed: Thymus (just before birth), Peyer’s Patches (after birth), Lingual tonsil (after birth), Palatine tonsils (after birth),Pharyngeal tonsils (after birth),Appendix (after birth), Spleen (Wk 10), Bone Marrow (Wk 12), Liver (Wk 6)
LP Splanchnic MesodermGALT, stroma of appendix, sroma of peyer's patches, liver; stroma and parenchyma of spleen; lymph nodes
LP Somatic MesodermGALT, Lymph nodes; dermis: body trunk
Cranial EctomesenchymeDermis: head ·  Dentin, pulp cavity of teeth · Thymus ·  Lingual tonsil ·  Palatine tonsil (inner) ·  Stroma of pharyngeal tonsils
Neural CrestTeeth pulp cavity; teeth innervation; pigment of skin, hair and retina ( melanocytes)
Surface Ectodermhair, eyebrows, eyelashes, fingernails, toenails, teeth enamel, epidermis, pharyngeal and lingual tonsils of oral cavity
Dermatomal Somatic MesodermDermis: back over vertebral columns; GALT
Appendicular EctomesenchymeDermis: appendages; GALT
Scleretomal Somitic MesodermLymph nodes
Extra-Embryonic LP Splanchnic MesodermHofbauer cells (@ week 3)
Dermatomal Somitic MesodermLymph nodes
EndodermParenchyma of appendix and liver; lining of 3rd, 4th pharyngeal pouches-thymus; lining of 2nd pharyngeal pouch-palantine tonsil
morbilliformeruptionsw/erythematous macules and papules; named for resemblance to measles; caused by exposure to medications or viral infections.
scarlitiniformeruptions w/confluent blanching erythema; name was derived from their similarity to the eruption of scarlet fever
exantheman acute generalized eruption of the skin
Herpesvirusevaricella-zoster virus
ParvovirusesB19 virus
Paramyxovirusesmeasles virus
Poxvirusessmallpox
Togavirusesrubella virus
acutehaving severe symptoms and a short course
chronicpersisting for a long time
serouspertainng to/resembling/containg serum
purulentsuppurative;pus
suppurativepus
fibrino-purulentcharacterized by the presence of fibrin and pus
catarrhalinflammation of a mucous membrane
cellulitisan infection of the deep subcutaneous tissue of the skin
phlegmondiffuse inflammation of the soft or connective tissuedue to infection
abscesslocalized collection of pus in a cavity formed by disintegration of tissues
ulcerlocal excavation of surface tissue due tosloughing or inflammatory necrosis
cytokinenon-antibody signaling proteins sent betweeen cell pops. on contact w/antigen
chemokinecytokine that can induce chemotaxis
granulomatouscontaining granulomas
leukocytosistransient increasee in # of blood leukocytes
leukemoid reactionresembling leukemia (neoplastic leukocytes)
leukopenialess than 5000 leukocytes ml blood
neutrophiliaincrease 3 of blood neutrophils
neutropeniadiminished 3 blood neutrophils
eosinophiliaabnormal increase blood [eosinophils]
basophiliabnormal increase in blood [basophils]
lymphangitisinflammation of lymph vessel
lymphadenitisinflammation of lymph node(s)
bacteremiapresence of bacteria in the blood
sepsispresence of microbes or their toxins in blood
stem cellgeneralized mother cell; pluripotent
progenitor cellmultipotent; more differentiated than stem cell
Zeta-potentialnet- charge on RBC due to sialic acid residues
Increased-sed-rateacute inflammatory response (fibrinogen)
Net-positive-charge”fibrinogen
Increased-sed-rateincreased immunoglobulin synthesis
→AP-1MAP KINASES
→MAP-KINASES”Ras-GTP
PLCγ1-activation→incr. Ca+2
→incr.Ca+2→calcineurin
→calcineurin→NFAT
PLCγ1-activation→DAG
→DAG→PKC
→PKCNF-κB
Cyclosporine-blocksNF-AT activation
Steroids-inhibitNF-κB and AP-1(Fos/Jun)
NF-ATtranscription factor req. for IL-2 gene
NF-κBtranscription factor req. for IL-2 gene
AP-1(Fos/Jun)transcription factor req. for IL-2 gene
c-mycgene req. for T cell activation
CD40Lgene req. for T cell activation
IL-2Rgene req. for T cell activation
TAP/LMPLOCATED ON CHROMOSOME 6
Clonal-selectiongerminal follicle
Germinal-follicleaffinity maturation
Memory“peripheral
CD44LEUKOCYTE HOMING
CD25IL-2 RECEPTOR
CD3PART OF TCR COMPLEX
CD4MHC-II CORECEPTOR
CD8MHC-I CORECEPTOR
Chromosome-14Heavy chain genes
Ig-κChromosome 2
Ig-λChromosome 22
DC1myeliod IL-12+++
DC2lymphoid Il-12+/-
early-IL-4DC1;IL-12;Th1
persistent-IL-4DC2;Th1;Th2
SIALOMUCINSGlyCAM-1 CD34
CCL19produced by HEV
MadCAMPEYER’S L-selectin ligand
pre-brecomb Hc VDJ; µ mRNA
Immature-BIgM; recmb Hc: κ γ (VJ)
Immature-Bnegative selection
Mature-balternative splicing
TH1macrophage activation
TH2eosinophils/mast cells
CTLScytotoxicity/macrophage activation
NKcytotoxicity/macrophage activation
ADCMCNK cells
NKcellantibody depdt cell med. cytotoxicity
FcRSallow overlap btwn humoral and innate
inductionexpansion
TH1IL-18
TH2dev
RANTESMIP-α/β bind CCR5
TH1IFN-γ; tbet
TH1stat 4→IFN-γ ↑ th1
IFN-γactivates macrophages
activate-neutrophilslymphotoxin & tnf
T-cell-amplification↑ B7 xprsn costims on MCH (B7)
Pro-BCD43;CD19;CD10
stemcellCD43
Pre-BB220;CD43
DC1myeliod IL-12+++
DC2lymphoid Il-12+/-
early-IL-4DC1;IL-12;Th1
persistent-IL-4DC2;Tha;Th2
pre-bµ ; pre-b rcptr
pre-brecomb Hc VDJ; µ mRNA
Immature-BIgM; recmb Hc: κ γ (VJ)
Immature-Bnegative selection
Mature-balternative splicing
TH1macrophage activation
TH2eosinophils/mast cells
CTLScytotoxicity/macrophage activation
NKcytotoxicity/macrophage activation
ADCMCNK cells
NKcellantibody depdt cell med. cytotoxicity
FcRSallow overlap btwn humoral and innate
CD40CD54
TH1IL-18
TH2dev
TH1IFN-γ; tbet
TH1stat 4→IFN-γ ↑ th1
IFN-γactivates macrophages
activate-neutrophilslymphotoxin & tnf
T-cell-amplification↑ B7 xprsn costims on MCH (B7)
CRC3antigen-binding, diversity
junctional diversity+/- nucltds @ V+D or D+J
Rag 1/Rag 2cleaves exons, forms hairpin
N nucleotidesnon-template encoded
P nucleotidesARTEMIS/complementary/VDJ
fetal liver derived stem cellsB-1 B-cells
BONE MARROW DERIVED HSCFOLLICULAR B-CELLS
CLPCOMMON LYMPHIOD PROGENITOR
NEGATIVE SELECTIONSTRONG SELF ANTIGEN BINDING
POSITIVE SELECTIONWEAK SELF ANTIGEN BINDING
TdTmediates nucleotide addition at junctions
PCRdetect tumor cells in blod or tissue
ARTEMISCLEAVES GERMLINE ENDS, ASYMETRICALLY
TdTNON-TEMPLATE ADDITION OF NCLTDS
EBF-E2A-Pax5 encodeRag1 and 2
EBF-EZA-Pax 5B-cell committment
Notch-1, GATA 3T-cell committment
Pro-B to Pre-BIgM rearrangement
IgA deficiencyGiardia, TACI mutation
ICAMLFA-1
1-3 HOURSC-fos
4-24HRSCD40 LIGAND
3 HRS-4 DAYSIL-2 RECEPTOR
6 HRS-2 DAYSIL-2
6 HRS-4 DAYSDNA SYNTHESIS
4DAYS- 1-2WKSVLA-4,-5,-6
DC1 USESIL-12
DC2 USESIFN-ALPHA, -BETA
PRE-DC1GM-CSF + IL-4 + CD40L
DC1 MAKESIFN-GAMMA
DC2 MAKESIFN-GAMMA, IL-10
CD28B-7
CD45IMMUNE SYNAPSE
c-KITPRE-PRO T-CELL
UNIVERSAL SURVIVAL SURFACE SIGNALc-KIT
UNIVERSAL T-CELL JUICEINTERLEUKIN-2
MEDUALLARY CORTICAL JUNCTIONNEGATIVE SELECTION
SMP/SMP1EXIT GERMINAL CENTER
DE-ADENINE DEAMINASETH1 TH2 MIGRATION?
INCREASE IN IL-7CHANGE IN M/E RATIO
plasminproteolytic enzyme present in inflammatory exudate
kinninogensvasoactive peptides generated from plasma proteins by kallikreins
bradykininvasoactive nonpeptide
effects of bradykininincreased vascular permeability
Hageman's FactorFACTOR XII of intrinsic clotting pathways
cleaves glycoprotein precursor,"high molecular weight kinniogen," to produce bradykininkallikrein
alternative pathwaycleavage of C3 in response to endotoxin, microbial LPS...cobra venom,etc...
C3 convertasesplits C3 to C3a and C3b
C3bfunctional fragment of C3; covalently attaches to complement target; then to other c-fragments to form C5-convertase
C5-convertasecleaves C5 to C5b and C5a; binds late components C6-9 together to form MAC
C5a activateslipoxygenase pathway of arachidonic acid met. in PMNs and Monocytes
C5apowerful chemotactant for neutrophils, monocytes, eoisinophils, basophils
C3b, iC3bopsonins, fix to bacterial cell wall, enhance affinity for phagocytosis
PARs (protease activated receptors)GPCRs on platelets, endothelialsm. muscle; bind various trypsin like serine proteases
engagement of PAR-1 by factor IIa triggers...mobilization of P-selectin; prod. chemokines, PAF, NO, prostaglandins;
major coagulation protease, cleaves circulating soluble fibrinogen to...thrombin; ...form insoluble fibrin clot
thrombin (factor IIa)protease; main link between coagulation and inflammation
kallikreinpotent activator of Hageman Factor; autocatalytic amplification of initial stimulus
kallikreindirectly converts C5 to chemotractant C5a
effects of complement activationincrease opsonation, chemotaxis, vascular permeability, proteolytic enzymes
lectin pathwayplasma mannose bindinig lectin binds carbs on microbes--> C1
VASOCONSTRICTIONthromboxane A2; leukotriense C4, D4, E4
VASODILATIONPGI2, PGE1, PGE2, PGD2
CHEMOTAXIS; LEUKOCYTE ADHESIONLeukotriene B4; HETE, lipotoxins
Prostaglandins, NO, HistamineVASODILATION
Increased Vascular PermeabilityVasoactive Amines, Bradykinin; C3a, C5a; PAF, leukotrienes C4,D4,E4
chemotaxis, leukocyte recruitment/activationC5a; leukotrienes B4; chemokines; IL-1; TNF;prostaglandins
Painprostaglandinis; bradykinin
tissue damagelysosomal enzymes from MACS & PMNs; ROS, NO
chemokinesincreased avidity of integrins
leukocyte diapedesis; vascular permeabiltypredominantly in venules; capillaries of lungs
1st 6-24 hours of inflammatory infiltrateneutrophils predominate
hours 24-48 of inflammatory infiltratemonocytes predominate
pre-formed, chemical mediators of inflammation in secretory granulesHISTAMINE; SEROTONIN; LYSOSOMAL ENZYMES
sources of pre-formed mediators in secretory granulesMCs; basophils; platelets; PMNs, Macs
cellular; newly synthesized chemical mediators of inflamm.prostaglandins; leukotrienes; PAF; ROS; NO; Cytokines
source of synthesized cellularallleukocytes, platelets, EC, Macs, No, Cytokines, Macs, lymphocyres
chemical mediators of inflam. from liver/plasma; Factor XII activationKinin System (bradykinin)
chemical mediators of inflam. from liver/plasma/complement activation; anaphalotoxinC3a; C5a
chemical mediators of inflam. from liver/plasma/complement activation; membrane attack complexC3b; C5b-C9
CD4+ HELPER T-LYMPHOCYTESB-CELL DIFFERENTIATION, MACROPHAGE ACTIVATION
CD8+ CYTOTOXIC T-LYMPHOCYTESKILLING OF CELLS INFECTED WITH MICROBES, TUMOR CELLS
CD4+ HELPER T-LYMPHOCYTESCLASS II MHC COMPLEXES
CD8+ CYTOTOXIC T-LYMPHOCYTESCLASS I MHC COMPLEXES
REGULATORY T CELLSALPHA-BETA HETERODIMERS, supression of T-cell activity
gamma/& T-LymphocytesHELPER AND CYTOTOXIC FUNCTIONS IN INNATE IMMUNITY
B-LYMPHOCYTESHUMORAL IMMUNITY (Fc RECEPTORS, CLASS II MHC, CD19; CD21)
NATURAL KILLER CELLSKILLING OF INFECTED/DMGED CELLS; CD16; Fc receptor for IgG
Natural Killer T-cellssuppress or activate, innate or adaptive
Natural Killer T-cellsCD16; CD3; Fcrecpetor for IgG
B-cellsRespond to cell-free and plasma membrane-bound antigens
T-cellsRespond to cell-bound antigens
Natural-killer-cellsCell population lacking T cell receptor (TCR) and CD4 and CD8 coreceptors
MacrophagesMonocyte-derived cells
Dendritic-cellsMonocyte-derived cells (e.g.
Follicular-dendritic-cellsFound in lymphatic nodules
Effector-cellsMacrophages
plasminproteolytic enzyme present in inflammatory exudate
kinninogensvasoactive peptides generated from plasma proteins by kallikreins
bradykininvasoactive nonpeptide
effects of bradykininincreased vascular permeability
Hageman's FactorFACTOR XII of intrinsic clotting pathways
cleaves glycoprotein precursor,"high molecular weight kinniogen," to produce bradykininkallikrein
alternative pathwaycleavage of C3 in response to endotoxin, microbial LPS...cobra venom,etc...
C3 convertasesplits C3 to C3a and C3b
C3bfunctional fragment of C3; covalently attaches to complement target; then to other c-fragments to form C5-convertase
C5-convertasecleaves C5 to C5b and C5a; binds late components C6-9 together to form MAC
C5a activateslipoxygenase pathway of arachidonic acid met. in PMNs and Monocytes
C5apowerful chemotactant for neutrophils, monocytes, eoisinophils, basophils
C3b, iC3bopsonins, fix to bacterial cell wall, enhance affinity for phagocytosis
PARs (protease activated receptors)GPCRs on platelets, endothelialsm. muscle; bind various trypsin like serine proteases
engagement of PAR-1 by factor IIa triggers...mobilization of P-selectin; prod. chemokines, PAF, NO, prostaglandins;
major coagulation protease, cleaves circulating soluble fibrinogen to...thrombin; ...form insoluble fibrin clot
thrombin (factor IIa)protease; main link between coagulation and inflammation
kallikreinpotent activator of Hageman Factor; autocatalytic amplification of initial stimulus
kallikreindirectly converts C5 to chemotractant C5a
effects of complement activationincrease opsonation, chemotaxis, vascular permeability, proteolytic enzymes
lectin pathwayplasma mannose bindinig lectin binds carbs on microbes--> C1
VASOCONSTRICTIONthromboxane A2; leukotriense C4, D4, E4
VASODILATIONPGI2, PGE1, PGE2, PGD2
CHEMOTAXIS; LEUKOCYTE ADHESIONLeukotriene B4; HETE, lipotoxins
Prostaglandins, NO, HistamineVASODILATION
Increased Vascular PermeabilityVasoactive Amines, Bradykinin; C3a, C5a; PAF, leukotrienes C4,D4,E4
chemotaxis, leukocyte recruitment/activationC5a; leukotrienes B4; chemokines; IL-1; TNF;prostaglandins
tissue damagelysosomal enzymes from MACS & PMNs; ROS, NO
chemokinesincreased avidity of integrins
leukocyte diapedesis; vascular permeabiltypredominantly in venules; capillaries of lungs
1st 6-24 hours of inflammatory infiltrateneutrophils predominate
hours 24-48 of inflammatory infiltratemonocytes predominate
pre-formed, chemical mediators of inflammation in secretory granulesHISTAMINE; SEROTONIN; LYSOSOMAL ENZYMES
sources of pre-formed mediators in secretory granulesMCs; basophils; platelets; PMNs, Macs
cellular; newly synthesized chemical mediators of inflamm.prostaglandins; leukotrienes; PAF; ROS; NO; Cytokines
source of synthesized cellularallleukocytes, platelets, EC, Macs, No, Cytokines, Macs, lymphocyres
chemical mediators of inflam. from liver/plasma; Factor XII activationKinin System (bradykinin)
chemical mediators of inflam. from liver/plasma/complement activation; anaphalotoxinC3a; C5a
chemical mediators of inflam. from liver/plasma/complement activation; membrane attack complexC3b; C5b-C9
VasodilationProstaglandins
VasodilationNitric oxide
VasodilationHistamine
Chemotaxis-leukocyte-recruitment-and-activationC5a
Chemotaxis-leukocyte-recruitment-and-activationLeukotriene B4
Chemotaxis-leukocyte-recruitment-and-activationChemokines
Chemotaxis-leukocyte-recruitment-and-activationIL-1
Chemotaxis-leukocyte-recruitment-and-activationBacterial products
FeverIL-1& TNF
FeverProstaglandins
PainProstaglandins
PainBradykinin
Tissue damageNeutrophil and macrophage lysosomal enzymes
Tissue damageNitric oxide
Tissue damageOxygen metabolites
histaminemast cells, platelets
serotoninmast cells, platelets
bradykininplasma substrate, pain
C3aPlasma protien via liver, opsonic fragment
C5amacrophages, leukocyte adhesion, activation
prostaglandinsmast cells from membrane phospholipids, vasodilation, pain, fever
leukotriene B4leukocytes; leukocyte adhesion, activation
Leukotriene C4, D4, E4leukocytes, mast cells; bronchoconstriction, vasoconstriction
oxygen metabolitesleukocytes, endothelial damage, tissue damage
PAFleukocytes, mast cells; bronchoconstriction, leukocyte priming
IL-1macrophages, other; acute-phase reactions, endothelial activation
TNFmacrophages, other; acute-phase reactions, endothelial activation
Chemokinesleukocytes, other; leukocyte activation
Nitric OxideMacrophages, endothelium; vasodilation, cytotoxicity
C-reactive Protein (CRP)ACUTE PHASE PROTEINS up regulated by IL-6
FibrinogenACUTE PHASE PROTEINS up regulated by IL-6
serum almyloid A protein (SAA)ACUTE PHASE PROTEINS up regulated by IL-1 or TNF
bacterial triacylated lipopeptidesTLR1
Bacterial peptidoglycan and lipoproteinTLR2
bacterial porinsTLR2
lipotechoic acid, bacterial di- and tri-acylated lipopeptidesTLR2
viral hemagglutininTLR2
Gram-negative LipopolysachharidesTLR4
Fungal mannansTLR4
parasitic phospholipidsTLR4
viral envelope proteinsTLR4
host shock proteinsTLR4
bacterial flagellinTLR5
lipotechoic acid, diacylated lipopeptidesTLR6
TLR 1Plasma membrane
TLR2Plasma membrane
TLR4Plasma membrane
TLR5Plasma membrane
TLR6Plasma membrane
viral double strand RNATLR3
viral single strand RNATLR7/TLR8
viral and bacterial unmethylated CpG DNATLR9
TNFINFLAMMATORY CYTOKINES
IL-1INFLAMMATORY CYTOKINES
IL-12INFLAMMATORY CYTOKINES
IL-8CHEMOKINES
MCP-1CHEMOKINES
RANTESCHEMOKINES
E-SELECTINENDOTHELIAL ADHESION MOLECULES
CD80COSTIMULATORY MOLECULES
CD86COSTIMULATORY MOLECULES
IFN alpha/betaANTI-VIRAL CYTOKINES
TLR3Endosomal Membrane
TLR7Endosomal Membrane
TLR8Endosomal Membrane
TLR9Endosomal Membrane
cathespin Ghydrolyzes bac. envelope proteins
cathespin Dcleaves cartlige proteoglycans
collagen break-down productschemotactic for PMN, monocyts, fibroblsts
defensins30-50% of 1' granule proteins
protease inhibitorsprotect tissue vs. lysosomal proteases
formyl-met peptide chemoattractantpresent in azurophillic granules
Chediak Higashiabnormal lg. lysoml granules
catalase counter actsmyeloperoxidase
fMLP"follow me to le prokaryote"
cyt-b558 cytosolic subunitsp40 p67 p47
cyt-b558 integral membrn. subunitsgp91 p22 phox
protease inhibitorsalpha2- macroglobulin
protease inhibitorsalpha1-antiprotease



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