Adaptive Imm I

Question 1

MHC I

Answer 1

• Found on all nucleated cells
• Hold endogenous antigen from intracellular protein, including self
• Way to check is cells are healthy
• Present peptides generated in cytosolic compartment
• Present to CD8 T cells
• Some AA anchor the peptide in the groove
• Other AA are available to interact with TCR

Question 2

MHC II

Answer 2

• Found only on APCs (DC, MO, B cells)
• Hold petide from extracellular protein (Exogenous Ag)
• More restricted
• Helps direct responses against threats
• Peptides (Ags) are generated in endosomal-lysosomal compartments
• Recognized by CD4 T cells
• Peptide lays flat in groove

Question 3

MHC Polymorphic and Polygenic

Answer 3

• MHC I
  
  • Maternal and paternal chromosome each provide a unile HLA- A B C
  • 6 total combos
• MHC II
  
  • DQ DR DP 2 alleles, lambda or kappa
  • 12 combos
• Alleles are co-dominantly expressed

Question 4

Non-classical MHC

Answer 4

• Structurally same as classical MHC
• Present non-peptide Ag
• more numerous and diverse
• activate specialized T cells
• Peptide binding groove modified/absent
• special tissue distribution
• lack polymorphism
• Intermediate btw Adaptive and innate

Question 5

Endogenous Pathwy of Ag presenting

Answer 5

• Peptides generated by proteasomes
  
  • intracellular defective proteins tagged by ubiquitin for degradation
  • head to proteasome
  • immunoproteasome cleaves protein

Question 6

How are protein loaded onto MHC I

Answer 6

• MHC I is within ER
• Calnexin are bound to it
• Beta2 microglobulin is added to MHC 1
• Calreticulin replaces calnexin
• Calreticulin, Erp1, tapasin and TAP form peptide binding complex on MHC 1
• Once a defective protein has been cleaved by proteasome and binds to tightly the MHC 1 migrates to cell surface
• Presents to CD8 T cells

Question 7

How do viruses avoid MHC 1 detection

Answer 7

Down regulate MHC i

Absence of normal amt of MHC I is detected by NK cells

Question 8

Peptide loading into MHC II

Answer 8

• Within the ER lumen calnexin aids in MHC II formation
• an invariant chain binds MHC II and CLIP protects binding groove
• Released into an endosome
• Once a lysosomal endosome binds with the MHC II containing lysosomal the invariant chain is degraded
• Microbe proteins are loaded into the MHC II binding groove and DM is degraded
• MHC II present to CD4 T cells

Question 9

How are MHCs upregulated during infection

Answer 9

• MHC I are upregulated in infected cells
  
  • upreg by type 1 interferon
• IFN-gamma upreulates tapasin and TAP
  
  • also upregs cytosolic and ER aminopeptidases and immunoproteasomes
• MHC II are increased on B cells and macrophages

Question 10

Immature DC General info

Answer 10

Extremely efficient phagocytes

express low MHC I

No MHC II

Recognize inflammatory chemokines, CCR1, 2, 5

Question 11

Mature DC

Answer 11

Innate receptors and phagocytic activities are down regulated

High levels of MHC I and II

CCr1, 2, 4 replaced withCCR7 ( in nodes)

Question 12

Maturation of DC

Answer 12

• Spontaneous maturation
  
  • display fragments from cell devris
  • maitenance of tolerance and dont activate naive T cells
• Microbial components activate MO to produce IL-1 TNF
• Cytokines help increase the TLR signals DC have received and accelerates DC into activation
• Migrate to lymphoid and express high levels of MHCs and B7-1,2
• DC express the most B7s than MO and B cells

Question 13

Cross presentation of Exogenous Antigens

Answer 13

DC are primary cross presenting cells

Exogenous antigens are directed to endogenous presentation

Allows for their presentation on MHC I receptors to CD8 T cells