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082114 - MHC & T cell receptor, T cell dev & responses0
08/21/14, Worth
74
Immunology
Graduate
08/24/2014

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Cards

Term
MHC-Ag
Definition
Worth
Term
MHC aka HLA
Definition
Major Histocompatibility Complex AKA Human Leukocyte Antigen
Term
MHC I and II structures
Definition
MHC I: three alpha segments, + B2 microglobulin. MHC II: two alpha segments, two beta segments.
Term
MHC I and II locations
Definition
MHC I: on almost all cells. MHC II: on immune cells only
Term
MHC I and II number of types
Definition
MHC I: 6 types, MHC II: 8 types
Term
MHC I: types A, B, C function
Definition
Present antigen to cytotoxic CD8 T cells
Term
MHC I: types E, G function
Definition
Ligand for natural killer cells
Term
MHC I: type F function
Definition
Unknown
Term
MHC II: types DP, DQ, DR function
Definition
Present antigen to helper CD4 T cells
Term
MHC II: types DM, DO function
Definition
Regulate peptide binding
Term
Antigens presented by MHC I
Definition
Intracellular
Term
Antigens presented by MHC II
Definition
Extracellular
Term
MHC I Presentation
Definition
Intracellular Ag is processed by proteosome; goes to ER where it binds to MHC I. Bound MHC1 is exported to surface of cell
Term
Calnexin
Definition
In MHC I presentation, stabilizes Class 1 heavy chain until B2 microglobulin binds
Term
Peptide-Loading Complex
Definition
In MHC I Presentation, this forms after Calnexin is released. Contains Tapasin, TAP, ERp57, PDI;
Term
TAP
Definition
Delivers peptide, forms mature MHC I molecule
Term
MHC II Presentation
Definition
Extracellular Ag is internalized and a phagolysosome converts it to smaller peptides. A vesicle containing unbound MHC II fuses with the phagolysosome, allowing the peptide to bind MHC II, and the vesicle continues until it fuses with surface
Term
Invariant chain
Definition
Prevents peptide binding while MHC 2 is in the ER, before it goes into the vesicle
Term
CLIP fragment
Definition
Invariant chain is cleaved once MHC2 is in a vesicle, but CLIP fragment still blocks peptide access
Term
HLA-DM
Definition
Required to remove CLIP fragment and allow peptide binding in MHC2 recognition
Term
Binding grooves in MHC I and II, implications on what peptides may bind
Definition
MHC I: length of binding groove favors binding of a 9-mer. MHC II: shorter binding groove allows for more flexibility with binding peptide length
Term
Percolating hypothesis
Definition
T cells enter lymph nodes through high endothelial venules, and proceed to "shake hands" with all peptide+MHC combinations present
Term
Factors that guide T cells to make interactions with peptide+MHC
Definition
Selectin, chemoattractant, and an Ig family member
Term
Immunological synapse
Definition
Interaction that takes place between the proper MHC, peptide, and T-cell receptor
Term
Factors that assist the immunological synapse (5)
Definition
CD28 on T cell interacts with B7 on dendritic cell; CD4 or CD8 required to confirm specificity, integrins/ICAMs stablize
Term
Supramolecular Activation Complex
Definition
collection of factors contributing to immunological synapse
Term
Transcription factors activated by signaling cascade induced by immunological synapse
Definition
NFKB, NFAT, AP-1. NFKB and NFAT induce production of autocrine/paracrine IL-2, and all of the above contribute to cell proliferation and differentiation
Term
Cyclosporin A, Rapamycin
Definition
Drugs that target IL-2 for immune suppression in organ transplants. Cyclosporin A inhibits IL-2 transcription; Rapamycin inhibits IL-2R signaling
Term
Transplant rejection stages (3)
Definition
Hyperacute (anti-blood group Ag, local inflammation), Acute (CD8 T cells), Chronic (CD4 T cells, B cells)
Term
Direct/indirect allorecognition
Definition
T cells have varying affinity for MHC/peptide. Direct - days to weeks before response. Indirect - weeks-years
Term
Autograft, allograft, xenograft
Definition
Same person, same species, different species
Term
Syngenic
Definition
Genetically identical
Term
MHC-linked autoimmune diseases, examples (5)
Definition
Systemic lupus, Type 1 diabetes, myasthenia gravis, rheumatoid arthritis, celiac disease
Term
Viruses/bacteria that modulate MHC, examples (2)
Definition
Cytomegalovirus produces MHC1 homolog; mycobacterium inhibit MHC2 presentation
Term
T LYMPHOCYTE DEVELOPMENT
Definition
Worth
Term
Overview: Two types of T cell lineages based on TCR type
Definition
T cells expressing alpha:beta receptors, T cells expressing gamma:delta receptors
Term
Alpha:beta receptor-expressing cells go through positive and negative selection
Definition
+ selection = must be able to recognize self MHC; - selection = it can't be too strong. Allows for recognition of foreign antigen presented by self-MHC
Term
General path of T cells
Definition
Bone marrow --> thymus for development --> secondary lymph tissues
Term
T-cell receptor rearrangement: Progenitor expresses
Definition
CD34, stem cell marker
Term
T-cell receptor rearrangement: Factor that commits progenitor for T cell lineage
Definition
Notch 1
Term
T-cell receptor rearrangement: Changes that occur when progenitor commits
Definition
Loses CD34, begins expressing CD2, CD5, CD127 (<-- IL-7 receptor)
Term
T-cell receptor rearrangement: Possible fates of Beta, gamma, delta rearrangement
Definition
If B chain rearranges first: Double positive pre-TCR. If gamma/delta receptor is made before B chain: Gamma delta cell produced
Term
T-cell receptor rearrangement: B chain rearrangement, Pre-TCR details
Definition
B chain has V, D, J regions similar to Ig heavy chain. D-J first, followed by V-DJ. After rearrangement, pTalpha is a surrogate alpha chain that stops further B chain rearrangement.
Term
T-cell receptor rearrangement: How many chances to get B chain rearrangment right?
Definition
Four - two separate sets of D, J, and C segments on each allele. 80% success rate
Term
T-cell receptor rearrangement: Possible fates of Alpha, gamma, delta rearrangement
Definition
If A chain rearranges first: ++ A:B cell. If gamma/delta receptor made first: Gamma/delta cell produced
Term
T-cell receptor rearrangement: Alpha chain rearrangement
Definition
A chain has V, J regions similar to Ig light chain. This will not start unless B chain is already expressed. Successful rearrangement does NOT stop the second A chain allele from rearranging, this would lead to 2 different TCRs expressed on the same cell
Term
T-cell receptor rearrangement: Stages where Notch is expressed
Definition
All
Term
T-cell receptor rearrangement: Stages where RAG1/2 is expressed
Definition
During B,g,d and A,g,d rearrangements only
Term
T-cell receptor rearrangement: Stages where TdT is expressed
Definition
All
Term
Positive selection: overview
Definition
TCR must be able to recognize self-MHC
Term
Positive selection: where it occurs, which cells present MHC
Definition
Thymic cortex; cortical epithelial cells present MHC
Term
Positive selection: if MHC I is recognized? If MHC II?
Definition
MHC I --> retains CD8 and gets rid of CD4. MHC II --> retains CD4
Term
Positive selection: time course before a cell dies?
Definition
TCR has 3-4 days to recognize an MHC. If it fails, it has 3-4 days to do more alpha chain rearrangment to try recognizing an MHC. If this still fails, cell dies. A-chain rearrangement stops after + selection is complete
Term
Bare lymphocyte syndrome
Definition
Deficiency in MHC I --> CD8 T cells do not get produced. Deficiency in MHC II --> CD4 T cells do not get produced.
Term
Negative selection: overview
Definition
Cell must not recognize self-MHC:self-peptide complexes too strongly, or else it is too auto-reactive and is eliminated
Term
Negative selection: which cells present MHC:peptide?
Definition
Dendritic cells or macrophages in thymus
Term
Negative selection: Autoimmune Regulator (AIRE)
Definition
Transcribes lots of tissue-specific genes, so that TCRs have practice ignoring self-signals from many different tissue types before they can pass negative selection
Term
CD4 Regulatory T cells express factors (2)
Definition
CD25 = the IL-2 receptor alpha chain; FoxP3 = critical regulatory factor
Term
IPEX
Definition
Mutation of FoxP3, which is on X chromosome (Happens in boys)
Term
T CELL RESPONSES
Definition
Worth
Term
Types of effector T cells (3)
Definition
Th (helper), Tc (cytotoxic), Treg (regulatory)
Term
TH1 helper T cells
Definition
Cell-mediated; helps macrophage kill pathogens
Term
TH2 helper T cells
Definition
Humoral mediated; helps B cell make antibodies
Term
TH1 helper T cells are activated by which cytokine?
Definition
IL-12
Term
TH1 helper T cells produce which cytokines? (5)
Definition
TNF-a, INF-g, IL-2, CXCL2, IL-3
Term
TNF-a function
Definition
Changes vascular endothlium, allowing macrophages to adhere to blood vessel walls and leave
Term
INF-g function
Definition
Activates macrophage; can induce phagolysosome fusion that is inhibited by Mycobacterium tuberculosis; can induce killing of other pathogens within the phagosomes
Term
IL-2 function
Definition
Enhances T cell proliferation
Term
CXCL2 function
Definition
Macrophage chemoattractant
Term
IL-3 function
Definition
assist macrophage differentiation in bone marrow
Term
TH2 helper T cells are activated by which cytokines? (3)
Definition
IL-10, IFN-g, IL-4
Term
TH2 helper T cells produce which cytokines? (4)
Definition
IL-4, IL-5, IL-10, IL-13
Term
Naturak Killer Cells are activated by which cytokines (3)
Definition
IFN-a/b, IL-12, TNFa
Term
Positive feedback between natural killer cells and macrophages
Definition
NK cells release IFNg --> stimulates macrophages --> macrophages produce IL-12 --> activates NK cells
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