immunology wk 2

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  1. Variable region on B and T cells
    • BCR - immunoglobulin variable heavy and light chains
    • TCR - variable alpha and beta chains
    • V(D)J genes (variability, diversity, joining)
    • variable region is the part that binds to antigens
  2. γδ T cell receptor binds to
    intact (unprocessed) antigen INDEPENDENTLY of MHC
  3. αβ T cell receptor binds to
    • processed peptides expressed on MHC molecules on antigen presenting cells
    • TCR is molecule expressed on cell surface
  4. B cell receptor binds to
    • unprocessed (intact) antigens
    • BCR is cell surface immunoglobulin plus signal transduction molecules
  5. ab T cell structure
    • Image Upload
    • variable region (aV, bV) binds to antigen, constant region (aC, bC) anchors to membrane and signals
  6. alpha beta T cell gene rearrangement
    • during development in thymus
    • a chain variable region has many V and J genes (like light chains in B cells)
    • B chain variable region has many V, D, J genes (like gamma T cells and heavy chains in B cells).  
    • any alpha can pair with any beta (more diversity)
    • recombinase (RAG) binds to DNA around chosen DNA, creates a loop.  DNA-PK (DNA-dependent protein kinase) cuts, discards. enzyme TdT (deoynucleotidyl transferase) adds random nucleotides to sticky ends of hairpin to reconnect (JUNCTIONAL DIVERSITY), extra variability
  7. gamma delta T cell rearrangement
    • fewer genes (less diversity), but
    • delta: D, J genes
    • gamma: V, D, J genes (like heavy chain B cells and beta T cells)
  8. B cell structure
    • Image Upload
    • 2 heavy chains, two light chains (light chains are shorter than heavy chains, only 1 constant region).  Heavy have 3.  
    • Heavy chains have V, D, J genes (like beta T cells and gamma T cells)
    • light chains have V, J (like alpha T cells), but in both KAPPA AND LAMBDA families
    • Constant is IgM initially (in most species)
    • Image Upload
    • includes signal transduction molecules (Igα and Igβ, two each)
  9. allelic exclusion
    • progenitor cells have 2 chromosomes so 2 alleles (mom and pop)
    • tries one, if successful, other allele is not tried or used.  If fails, tries the other.  
    • ONLY ONE WILL BE EXPRESSED (only ONE ANTIGENIC SPECIFICITY)
  10. B cell fate with self-molecules
    • Negative selection.  If BCR recognizes self (tested in bone marrow)
    • 1. apoptosis
    • 2. anergic (alive but a vegetable)
    • 3. edit variable light chain region (RECEPTOR EDITING) to fix.  Eventually run out of DNA, then apoptosis
  11. receptor editing
    • if B cell recognizes self when tested in bone marrow, can try to rearrange variable light chain region to fix.  
    • T CELLS DO NOT REARRANGE
  12. numbers of variable gene segments
    species-specific
  13. Chicken receptor rearrangement
    • all immature B cells have the same heavy and light chain genes
    • insert variable pseudogenes through gene conversion to be diverse
  14. pre-immune repertoire of B cell
    before meeting antigen (bone marrow, +/- Peyer's patches, bursa of fabricius, appendix
  15. coexpression of IgM and IgD
    • ONLY TIME two isotypes are expressed on same (immature B) cell.  Alternative splicing allows binding to delta vs mu chain to make both IgM and IgD.  VARIABLE REGION/ANTIGEN BINDING THE SAME
    • used to age cells (more IgM when leaving marrow, more IgD after circulating)
  16. selection in B and T cells
    • T cells undergo (in order) positive and negative selection
    • B cells undergo negative selection
  17. αβ  vs  γδ (T cell development)
    • produced in bone marrow CD4 and CD8 negative
    • move to thymus
    • try to develop β chain.  
    •         If successful, creates an α and becomes CD4+ and CD8+, then loses one.  
    •         If unsuccessful, becomes γδ
  18. Marker of T cells
    • CD3 molecule, bookend TCR as part of signal transduction molecule.
    • Image Upload
  19. T cell selection
    • positive selection (thymic cortex): αβTCR interacts with MHC expressed on thymic epithelial cells.
    • Recognize MHC I = CD8
    • Recognize MHC II = CD4
    • negative selection (thymic medulla): elimination/apoptosis if bind too strongly with self-peptide complex presented by macrophages and dendritic cells
    • more selection after encountering antigen in secondary tissues
  20. central tolerance
    • gene AIRE is expressed in thymus, allows production and expression of all the proteins in the body
    • allows APCs to perform negative selection of T cells on more self-proteins
  21. Inflammation (def)
    • VASCULAR, cellular, chemical response to injury meant to destroy, dilute or wall off
    • initiation, amplification, repair
    • Classification: distribution (organ involvement), extent (severity), duration, exudate, etiology
  22. distribution of inflammation
    • focal: single discrete
    • multifocal: several lesions separated by normal
    • coalescing: lesions grow into each other
    • locally extensive: a LOT but not all of an organ
    • generalized: multiple lesions distributed throughout whole organ/lobe, often add another word.  Lots of tiny dots are miliary pattern
    • diffuse: entire organ affected
    • interstitial: in interstitial/CT of organ
    • Can also be unilateral/bilateral in paired organs
    • symmetrical or asymmetrical
    • cortex vs medulla
    • specific lobe
    • unique anatomic structure based on organ
  23. extent of involvement or severity of inflammation
    mild, moderate, severe
  24. duration of inflammation
    • peracute: Exceptionally rapid and severe
    • acute: edema, neutrophils, around 48h (could be up to 5 days)
    • subacute: 3-4d to 1w, acute inflammation with some signs of early repair, lymphocytes, macrophages
    • chronic: FIBROSIS, signs of persistence/repair, fibroblasts and new vessels
  25. acute inflammation signs (path)
    • exudative
    • edema, neutrophils (suppurative)
    • rubor, tumor, calor, dolor, loss of function
  26. chronic inflammation signs (path)
    • non-exudative, proliferative
    • recurrent (don't seem to re-start at acute)
    • proliferation of vessels and CT
    • emigration of leukocytes: lymphocytic, plasmacytic, granulomatous
  27. exudate character (path) of inflammation
    • transudates (lear, low protein from starling, sodium or blocked lymph) vs exudates (proteins, leukocytes due to vascular permeability.  
    • serous (inflammatory transudate like anaphylaxis)
    • fibrinous (fibrinogen leaking, coag contacting collagen and making fibrin, becomes fibrosis in 7 days)
    • purulent (suppurative - can be abscess vs cellulitis)
    • hemorrhagic
    • mucoid (catarrhal).  
    • Cause can be infectious vs non-infectious
  28. etiology of inflammation
    sometimes not known, describe location (enteritis, pleuropneumonia, blepharitis)
  29. problems with low MHC diversity
    • accept tumors as self ("transmissible allograft").  Non-genetic infectious tumors like canine transmissible venereal tumor and tasmanian devil facial tumor
    • This is the danger of the bottleneck--no variety in MHC so all susceptible to same diseases
  30. antigen
    molecule that can be recognized by a T or B lymphocyte receptor
  31. epitope
    part of antigen bound by lymphocyte receptor
  32. immunogen (and what makes it up)
    • antigen that induces immune response
    • must be organic, large (more epitopes), complex (whole microbes are more immunogenic than peptides)
  33. antigen presenting cells and why they're important
    • T cells only recognize PROCESSED antigens from APCs
    • dendritic cells (SUPREME - can activate naieve T cells
    • macrophages
    • B lymphocytes (only recognize one antigen)
    • Pathogen gets into cell, "processed" or broken down to size, put onto MHC (dimer) for presentation, recognized by appropriate T cell (antigen and MHC both recognized)
  34. Major histocompatibility complex I
    • for INTRACELLULAR/endogenous to trigger CD8 T cells
    • can be on ANY nucleated cell
    • proteosome chops up intracellular antigen, sent to ER by TAP.  Chaperones are helping MHC I fold, bind.  MHC has single transmembrane protein and a beta2 microglobulin.  Once assembled, golgi exocytic vesicle to cell surface.  CD8 recognizes BOTH MHCI and antigen ON APC to activate.  
    • Activated T cell = proliferation (clonal expansion) and cytotoxic molecule increase (perforin and granzyme)
  35. Major histocompatibility complex II
    • EXTRACELLULAR antigens trigger CD4 helper T cells
    • ONLY EXPRESSED ON APC
    • Endocytosis (phag, pino, clathrin-mediated).  Processed, peptides loaded into special phagolysosome.  
    • MHCII created in ER, alpha and beta segments with transmembrane proteins, "clip" in groove until released, fuses with phagolysosome and exchanges for antigenic peptide.  Traffics to surface.  
    • CD4 T cell binds, recognizes both MHC II and antigen (and APC), activates, proliferates, produces cytokines (not cytotoxic) to communicate with other cells
  36. Cross-presentation
    • Viruses often don't infect APC, but only MHCI (INTRACELLULAR) can activate CD8.  
    • So Exogenous antigens are taken up by APC, shuttled to cytoplasm and given to MHCI
  37. MHC genes
    • encoded in clusters.  Multiple genes that encode for same protein (POLYGENIC), three major loci (so three alleles from each parent, 6 total).  POLYMORPHIC too, multiple alleles that can be inherited at each locus (LOTS of variations in population).
    • ALL SIX are expressed (CO-DOMINANCE)
  38. MHC haplotype
    • a series of HLA "genes" (loci-alleles) on the chomosomes, one passed from mother and the other from father.  
    • each animal has two complete sets of MHC genes, inherited together as a haplotype
  39. MHC rules
    • can bind many peptides but only one at a time
    • no discrimination between self and pathogen - gives a snapshot of every peptide
    • ANCHOR RESIDUES are specific spots on a peptide that the MHC binds (a specific amino acid in a particular place) - determines which peptides bind to which MHCs.  
    • Also T-cell rules.  LOTS of checks and balances.
  40. T-cell MHC response rules
    TCR only engages with appropriate MHC (T4 to MHCII, T8 to MHCI) and presenting correct antigen.

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Author:
XQWCat
ID:
324125
Filename:
immunology wk 2
Updated:
2016-10-08 17:46:39
Tags:
IV
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IV wk 2
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