Immunology Chapter 6
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Immunology Chapter 6
Ag Presentation cells
Define and compare exogenous Ags and endogenous Ags.
1. Exogenous Ags - Ags that originated outside of the body
2. Endogenous - Ags that were generated inside the body due to abnormal metabolism or infection
How are exogenous and endogenous Ags processed and presented?
1. Degraded in the cytosol of any cell
2. Peptide fragments bind to MHC I molecules
3. Presented to CD8 T cells
4. Results in cell death
Ags in a Mf (Intravesicular Ag)
1. Degraded in endocytic vessicle in Mfs
2. Peptide fragments bind to MHC II molecules
3. Presented to CD4 T cells
4. Results in Mf activation to kill intravesicular bacteria/parasites
1. Degraded in endocytic vessicles in B cells
2. Peptide fragments presented to MHC II molecules
3. Presented to CD4 T cells
4. Results in activation of B cells to secrete Abs to eliminate extracellular bacteria/toxins
What is the location and function of TAP (Transporters associated with Ag processing)?
1. Location - spans the ER membrane
2. Function - Actively transports (ATP) peptides that bind MHC I molecules from the cytosol to the ER
What is the basic function of the proteasome and how is it regulated?
1. Degrades proteins into peptides
2. Peptides that are presented by MHC I molecules are generated by the proteasome
3. Proteosome exists in all cells as inactive constituitive proteasome
4. Stimulated by interferons, the constituitive proteasome becomes the active immunoproteasome
Describe in detail the pathway for peptide loading onto MHC I molecules
1. Partly folded MHC I alpha chians bind to calnexin until beta
2. This complex is released from calnexin and binds to chaperons, which bind to TAP via tapasin
3. Peptide fragments created by the proteosome in the cytosol are transported into the ER by TAP
4. A peptide fragment binds to MHC I which completes its folding and is transported to the cell membrane
How do viruses evade Ag processing and presentation pathways of the host cell
1. See Fig. 6.7
2. Viral evasins block Ag presentation by preventing peptide movement through TAP
3. Some adenoviruses can compete with tapasin and inhibit peptide loading onto nascent MHC I
4. Herpes virus ligase can target MHC I for degradation by the proteasome
Describe in detail the pathway for peptide loading onto MHC II molecules.
1. Invariant chain binds in the grove of MHC II
2. Invariant chain is cleaved in an acidified endosome, leaving a short peptide fragment (CLIP) still bound in the MHC II groove
3. Ag is taken up from extracellular space into endosome
4. Acidification of endosome activates proteases to degrade Ag into peptide fragments
5. HLA-DM binds to MHC II, releasing CLIP and allowing Ag peptide fragments to bind
6. MHC II:Ag complex moves to cell surface
Why is cross-presentation necessary to the antiviral immune response?
1. The process by which extracellular proteins taken up by DCs can give rise to peptides presented by MHC I molecules
2. Allows Ag from extracellular sources to be presented on MHC class I molecules and activate CD8 T cells
What are the possible molecular pathway of cross-presentation?
1. Translocation of ingested proteins from phagolysosome into the cytosol -> degradation by proteasome -> enter ER through TAP -> loaded onto MHC I molecule
2. Transport of Ag directly from phagolysosome into a vesicular campartment -> peptides bind to MHC I molecules
Containing several separate loci encoding MHC molecules of identical functions
1. MHC genes with more than one allele at a gene locus
2. Allelic variation
1. MHC product of both alleles at a locus are expressed equally in the cell
2. Both gene products can present Ags to T cells
MHC genes with only one allele
Define MHC haplotype
The particular combination of MHC alleles found on a single chromosome
What is are the mechanisms that drive gene evolution in the MHC?
1. Ancestral MHC gene undergoes gene duplication and divergence resulting in multiple genes
2. Multiple genes undergo gene conversion between misaligned chromosomes during meiosis
3. DNA sequences from one chromosome is substituted on the other
What is MHC restriction?
1. The fact that an Ag can only be recognized by a given T cell if it is bound to a particular self MHC molecule
2. A consequence of events that occur during T cell development
What is alloreactivity?
The recognition by T cells of MHC molecules other than self
How do you test for alloreactivity
1. Mixed lymphocyte rxn
2. lymphocytes from donor and recipient are cultured together
3. If the 2 people are histoincompatible, the recipient's T cells recognize the allogeneic MHC molecules on the cells of the donor as 'foreign' and proliferate
What are superAgs and how do they function?
1. Bind simultaneously MHC II molecules and V-beta domains of TCRs
2. Cause massive production of cytokines by CD4 T cells
3. Results in toxic shock syndrome
Why is it important to have extensive MHC polymorphism in a population?
MHC polymorphism extends the range of Ag to which the immune system can respond
What is the function of MIC-A and MIC-B?
1. Expressed in the GI tract
2. Stressed-induced activation of NK and CD8 cells
What is the function of HLA-E?
NK cell inhibition
What is the function of HLA-G?
Modulates maternal/fetal interaction
What is the basic function of CD1?
1. Small family of MHC class I-like proteins
2. Not encoded in the MHC
3. Can present glycolipid Ags to CD4 T cells