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Immunology Test 2
MCH & Antigen Processing; Antigen Processing; T-Cells; T-Cell Immunity; T-Reg; Cytokines; B-Cells
20
Science
Undergraduate 4
10/23/2014

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Term
MHC I Complex: Peptide
Definition
  • Not all peptides will bind to all MHC
  • They bind to MHC through Anchor Residues and the amino and carboy terminus

  • No specificity other that what is able to bind in MHC cleft
Term
MHC Restriction
Definition
  • The T Cell Receptor recognizes BOTH the peptide and MHC molecule
    • Very specific interaction-even a single residue change can be distinguished
    • Contact Residue
    • Anchor Residue
    • Polymorphic Residue
    • Pocket of MHC
Term
MHC Diversity: Combatting Pathogens
Definition
  • Pathogens are constantly evolving and changing their peptide makekup
    • Evasion of MHC presentation also occurs (EX. Malaria parasites infect red blood cells - no MHC
  • The vast diversity of MHC is belived to protect the population as whole from being completely wiped out by single pathogen - Natural immunity to pathogens (HIV, Malaria, Ebola)
Term
Haplotype
Definition
  • The set of HLA genes from one parent
  • HLA typing is done using panels of monoclonal antibodies specific for the different allelic products or by PCR using specific primers
Term
MHC Diversity: Tissue Transplantation
Definition
  • Due to MHC diversity, a complete match between donor and recipient is unlikely
  • MHC 'mis-match' is the primary reason for tissue regection - Graft vs. Host disease
  • T cells see MHC as foreign, non-self material
  • HLA typing (extensive) used to screen for closest donor match
Term
Antigen Processing: Two Pathways
Definition
  • Cytosolic (intracellular Antigens)
    • degraded in cytosol 
    • MHC I
    • Effector CD8 T cells
    • Cell death
  • Endocytic (extracellular Antigens)
    • Endocytic vesicles (low pH)
    • MHC II
    • Efector CD4 T cells
    • Activation of B cells to secrete Ig to eliminate extracellular bacteria/toxins
Term

Peptide loading of MHC I

 

Definition
  • Newly synthesized MHC I heavy chain molecules associate with TAP and B2M (beta2microglobulin)
  • Certain peptides bind and stabilize the complex of heavy chain and B2M
  • Peptides/class I HLA heavy chain/B2M ternary complexes move through ER, Golgi, and then cell surface
Term
Processing of intracellular Antigens in the cytosol, binding to MHC I molecules in the endoplasmic reticulum, and transport to the cell surface
Definition
  • Partly folded MHC I alpha chains bind to calnexin until B2M binds
  • MHC class I complex is released from calnexin, binds a complex of chaperone proteins (calreticulin, ERp57) and binds to TAP via tapasin
  • Cytosolic proteins and defective ribosomal products (DRiPs) are degraded to peptide fragments by the proteosome. TAP delivers peptides to ER
  • A peptide binds the MHC I molecule and completes folding. The MHC I is released from the TAP complex and exported to cell membrane
Term
Chaperones Function:
Definition
  • Assist in folding of MHC I
  • Association w/ B2M
  • Binding Peptide
Term
Proteosome: Large Protein Complex
Definition
  • Degrades misfolded, defective, and aged proteins in cytoplasm
  • Exists in two forms: CONSTITUTIVE proteosome (all cells) and IMMUNOPROTEOSOME (in all cells stimulated with interferons)
  • Immunoproteosome conatians: all induced by interferons to alter enzymatic specificity of proteosome
    • LMP2
    • LMP7
    • MECL-1 
  • Further cleavage of peptides occurs in the ER by aminopeptidase (ERAAP), tailoring them to binding MHC I molecules
Term
Transporters
Definition
  • Associate with antigen processing (TAP1/2)
  • Bring Peptides to ER
  • Bind MHC I
Term
Immunoevasins
Definition
  • Produced by viruses interfere with antigen processing
Term

Processing of extracellular Antigens by acidic pH-activated proteases occurs in endosomes

 

Definition
  1. Ag taken up from extracellular space to intracellular vesicles
  2. Endosomal proteases inactivate in neutral pH
  3. Acidification (vesicles) activates proteases to degraded antigen (peptides)
  4. Vesicles w/ peptides fuse w/ vesicles containing MHC II
Term
Newly formed MHC II are stabilized by the invariant chain which is cleaved and the associated peptide (CLIP) is removed byHLA-DM
Definition
  1. Ii: blocks binding of peptides & misfolded proteins (MHC II)
  2. Ii cleave in acidified endosome (CLIP) - still bound
  3. CLIP blocks binding of peptides to MHC II
  4. HLA-DM releases CLIP and allows binding MHC II - cell surface
Term
The invariant chain (Ii) serves as a chaperone for newly synthesized MHC II molecules guarding the peptide binding groove
Definition
  1. Ii binds in MHC II groove
  2. Ii is cleaved - initially to leave a fragement bound to MHC II and to membrane
  3. Further cleavage leaves short peptide fragment, CLIP, bound to the MHC II molecule
Term
Sometimes extracellular antigens are processed in the cell and presented by MHC I moleculess; intracellular antigens may be presented by MHC II molecules
Definition
  • MHC I:
    • Phagolysosome
    • Antigens
    • ER
    • Phagosome
  • MHC II:
    • CD4 binding 
    • Auto-phagosome
    • Self antigens
Term
Dendritic cell Types:
Definition
  • Conventional (T Cell activatiors)
    • CCR7, CCL18
    • ICAM-2
    • LFA-1
    • CD58, CD11c
    • B7.1, B7.2
  • Plasmacytoid (Anti-Viral mediators that may help conventional DCs to sustain IL-12 production
    • CXCR3
    • IFN-Beta
    • TLR-7, TLR-9
    • INF-alpha
    • BDCA-2
Term
T cells require 3 signals to become activated
Definition
  1. TCR ligation by peptide-MHC molecule (signal 1)
  2. Ligation of CD28 on the T cell by B7 (co-stim) on the APC (signal 2)
  3. Cytokines bound to corresponding receptors on the T cell surface (signal 3)
  • If T cells receive signal 1 w/out signal 2 such was was found to occur w/ paraformaldehyde-fixed macrophages pulsed with peptide Ag, the T cells is rendered anergic or non-responsive to Ag
Term
DC binding
Definition
  • The co-stimulatory molecule B7 on the DC binds CD28 on the naive T cell
  • W/out signal 2 cell is rendered anergic-non responsive to antigens
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