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Toll Like Receptor PRR Uses signalling pathway TIR (Toll IL1 Receptor) for intracellular signalling |
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Gram negative LPS TLR 1:TLR 2 TLR 4 TLR 2:6
Flagellin: TLR 5
CPG Repeats: TLR 9
ssRNA: TLR 7 dsRNA: TLR 3 |
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LBP binds LPS and presents to CD14 on cell surface which conjugates with membrane of APC and TLR 4 Signal is ingested and broken down into CPG repeats and presented on TLR 9 for signal amplification
APC Travels to paracortex of regional lymph to present to lymphocytes with costimulatory molecules and cytokines |
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IL-1 - Enhances lymphocyte function IL-2 - Promotes CD8 Proliferation IL-4 - Induces IgE, Ihibits Th1 IL-6 - Promotes Th17, Inhibits Treg IL-8 - Chemoattractant for Neutrophils and Macrophages, promotes cell adhesion IL-12- Activates Th1, released by dendritic cells |
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Leakiness of vascular epithelium |
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Most immunogenic APC Bridge between innate and adaptive IS |
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TIR-MyD88 IRAK-TRAF6 .... NF-kB which is translocated to nucleus to upregulate cytokines, costim molecules, phagocytosis, and MHCs |
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CTL (Cytoxic T Lymphocytes) Recognize cells with intracellular virus or bacteria infection Binds MHC I at a1,a2 junction 2 Ig-like domains a B heterodimer Use cytotoxic granules - perforin and granzyme |
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Helper T cells Th1 - intracellular w/ B Cell Th2 - Extracellular w/ NK, Macrophage, CTL Th17 - Enhance neutrophil response - found in gut Th1, 2, 17 promote inflammation - effector T cells Treg - suppresses T cells
4 Ig like domains (D1-4) Binds to MHC II (D1-B2) |
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Antibodies (IgG strategies in different compartments) |
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Definition
Deal with extracellular pathogens Via complement (plasma) - lysis and phagocytosis Via opsonization (extracellular) - phagocytosis by macrophage Recognize whole antigen Via neutralization (toxin) - ingestion |
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IgG - extracellular, plasma IgM - plasma (pentamer) IgA - extracellular, (dimer) mucosa sites (gut) IgE - mast cells at mucosa |
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Predominant in early life Activates complement Pentamer |
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Opsonization, complement and Neutralization |
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Thymus-Dependent (TD) B Cell activation |
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Definition
B cells take up antigen present to Th cell in thymus Co stim by CD40 (on B cell) and CD40L interaction (T cell) and cytokine (if missing one....anergy) |
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Thymus-independent (Ti) B Cell activation |
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Definition
TIA Type 1 - TLR agonists TIA type 2 - Many ags activate antibodies on B cell |
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Antibodies change from one Ig to another CD40 ligand on T cell, cytokines to direct |
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Intracellular pathogens Makes IFN-y B cell activation CD40-CD40L Class switching (Especially to to IgE) |
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Inhibits IgE
Inhibits Th2, Th17
Upregulated by Th1 - B Cell conjugation |
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Activates IgA Promotes Th17, Treg |
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IL-4 - IgE (+) TGF-B - IgA (+) IFN-y - IgE (-) |
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For cell mediated killing - NK Macrophage CD8+CTL |
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NK cell or C8+ CTL or Macrophage Co stimulation by Th2 cells Recognize antigen epitopes on MHC |
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Definition
2 Heavy chains 2 light chains (k or lambda) Disulfide bonds on hinge region Variable region Constant Region 2 Fab portions - fragment for antigen binding |
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Recombination signal sequence DNA sequence on ends of V J and D sequences for recombination |
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Term
Order of factors in VDJ recombination (somatic recombination) |
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Definition
RAG-1, RAG-2 (Recombination Activating Genes) - brings RSS together Ku70, Ku80 - DNA Binding Protein (hairpin binding) Artemis - nuclease open hair pin DNA-PK - open hairpin TdT - Adds diversity Terminal deoxynucleotide transferase DNA ligase IV (XRCC4) - LIgates ends to finish region |
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Definition
Testing in bone marrow to ensure antibodies do not bind to strongly or too weakly to antigens. ensures against autoimmunity. Positive and negative selection |
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Inactivation of mature lymphocytes by secondary lymphoid organ |
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Common Lymphoid Progenitor - B and T cell precursor |
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Definition
Chemoattractants in extracellular space that promote inflammation C5a is the strongest |
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T cell receptor - TCR (binding and signalling) |
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Definition
Looks like Fab aB or yd coupled to CD3 RAG proteins ensure aB or yd only Binds to non-self MHC and Self-MHC with a non-self antigen |
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Definition
intracellular signalling portion of TCR-CD3 complex 5 invariant polypeptide chains yedzn in heterodimers ye de zz Signal transduction via ITAM immunoreceptor tyrosine activations motif |
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B Cell full extracellular antigen via antibody T Cell partial via MHC |
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Present on all nucleated cells peptide fragment made of a1:B2microglobulin and a2:a3 subunits Binding cleft is made of a1:a2 Exhibits endogenous/intracellular antigens to CD8+ T cell |
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Definition
MHC a1 and B1 make up the binding cleft with a2 and B2 subunits attached. Invariant chain attaches to binding cleft. MHC buds off via the golgi and the pH cause the invariant chain to break off leaving only CLIP in the binding cleft. A phagolysosome containing antigen phagocytosed from the environment fuses with the vesicle containing MHC II. HLA-DM dissociates CLIP and presents antigen to MHC II. MHC II vesicle is then fused with the membrane for recognition by CD4+ T cell |
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Definition
MHC a1 is bound to B2m with association to calnexin. Along with the non-covalently bound a2 and a3 chains calrectin, along with ERP 57 induces a change in the structure to keep the binding cleft open. Tapasin associates to the MHC along with TAP (tapasin associated antigen presenter. TAP takes an antigen which has been cleaved by the proteosome and presents it to MHC I by bringing it into the ER. MHC is then attached to the membrane for association by CD8+ T cells |
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Present on APCs a1b1 make up antigen binding cleft a2b2 bound non-covalently exhibits extracellular antigens phagocytosed by cell Binds CD4+ T Cell |
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Cortical - Positive Medullary - Negative Protects against too strong or too weak binding |
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DN T cells Bind whole antigens Resident in gut More common during gestation Determined at DN2 Stage |
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aB Thymocyte proliferation (Checkpoint, determination, stages, factors) |
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More common after birth c-kit and CD-44 through 1,2 CD-25 through 2,3 Go through DN2,3,4 Stages then DP stage then determination RAG are turned on in late DN2-DN3 stage B gets rearranged first need to express B and pre-T a receptor to become DP Tested for tolerance then determined to CD4+ vs CD8+ |
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Definition
Stem cell growth factor In T cell determination |
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adhesion molecule In T cell determination |
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IL-2 Receptor a chain In T cell determination |
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Transcription factor which expresses all peptides in genome for autoimmunity testing |
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Definition
1. Activation - MHC II-antigen-TCR binding 2. Survival - Co stimulation (upregulated by PRR PAMPS)- B7.1/B7.2-CD28 Binding 3. Differentiation - Cytokine - IL-6 IL-12 TGF-B |
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Exocytosed by CD8+ T cell Polymerize to form pore on cell Allows granzyme to enter and cause apoptosis |
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Passed through perforin pore to induce apoptosis by CD8+ CTL Chromatin and nucleus condensation then Phosphatidylserine residues flipped to outside to allow recognition by phagocyte |
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