Notes 4.1

I. A review of the role of T-cells in adaptive immunity
a. Adaptive vs. innate immunity
• adaptive: allows immune system to recognize microbial chemicals that aren’t shared by man kinds of microbs
*takes more time to respond than innate, more flexible
• innate: probably more important than adaptive, always on, NOT flexible
b. T-cell receptors
• Constant region: attaches to cell membrane, helps with signal transduction from outside to inside of cell
-same aa sequence in all Tcells
• Variable region: attaches to antigen
-different aa sequence in each Tcell
c. CD8+ T cells
• Kills cells
ii. host vs. graft disease
• Lots of different MHC1 among people
• Foreign MCH1 is recognized by CD8+ Tcell receptor as MHC1 presenting foreign antigen
-so, CD8+, cytotoxic Tcell kills “virally infected” cell
d. CD4+ T cells
• (type 2 MHC class)
• Present antigens, stimulates B cell to make more antigens
II. Dendritic Cells
a. Immature
• Hanging out in tissues between other cells (a few days or weeks)
• “interstitial dendritic cells” or “residential dendritic cells”
• Globular shape
• Constantly sampling environment (receptor mediated-phagocytosis or macropinocytosis)
• Spontaneously matures*
b. Mature
• Star-shaped morphology
• Expresses CCR7, CCR7migration to lymph nodes present self antigens to T cells
• *thought that presentation of antigens by mature, but not “activated” dendritic cells helps maintain tolerance to own antigens
c. Mature, activated
• Activatedexposed
• Detects microbial components via TLRs, or pro-inflammatory cytokines (IL1, TNF) via receptors for them which leads to a major increase in phagocytosis and macropinocytosis and increase MHC2, some increase in MHC1
• Express genes for costimulatory molecules (molecules that help activate T cells)
-here, B7 family=costimulatory proteins
-B7-costimulation of T-cells how T-cells “know” this dendritic cell
Is presenting foreign, not self antigens
III. Major Histocompatibility complex (MHC) molecules
a. Classical vs. non-classical MHCs
• Classical MHCs:
-jobs: present antigens to T-cell receptors (intracellular infection)
• Non-classical MHCs:
-don’t present antigens, cytoplasmic proteins that help load
antigens onto classical MHCs
b. Diversity of MHCs
• Lots of alpha- & beta-chain alleles: MHC components very polymorphic
• More than 500 alpha-chain alleles, so unlikely to be homozygous for alpha-chain alleles
1. Layout of MHC alleles in MHC gene complex
2. Evolution of MHC diversity
• Advantageous to have lots of variability in MHC antigen-binding sites because this allows a population of humans to bind more variable antigens, fight wider array of pathogens
c. Structure of MHC I
1. alpha chains
• 3 alpha-chains combine to make MHC I
• Alpha-3 attaches MHC I to cell membrane
• Beta-2 microglobulin stabilizes alpha-chainslittle/no variability in beta-2 microglobulins among people
2. peptide binding groove
• comprised of alpha-1 and alpha-2 chains
• where peptide (antigen to be presented to T-cell) is attached to MHC I
• MHC I peptide binding groove binds peptides only 8-10 AA in length
3. consensus binding
• a few amino acids in a few spots seem to be necessary for MHC I-peptide binding
d. Structure of MHC II
1. alpha and beta chains
• 2 alpha-chains, 2 beta-chains-both interacting with the cell membrane
• Also interact to form a peptide-binding groove
2. peptide binding groove
• doesn’t have consensus sites
• can accommodate much larger peptides (~20 AA in length)
a) Chaperone proteins:
*proteins that hold nascent proteins in correct shape so they’ll fold correctly
b) MHC I (presents intracellular path. Parts to CD8+ Tcells)
*mRNA translated by ribosomes attached to ER
*alpha-chains of MHC I unstable without peptide bound to peptide-binding
*so chaperone proteins bind to, protect new MHC I until peptide binds to it
peptide in cytoplasm of cell because that’s where pathogen was, then pathogen
proteins cleaved into peptides that fit MHC I
*enzymes that cut up pathogen proteins=proteasomein cytoplasm
—proteasome interacts with ER, allows transportation of peptides across
ER membrane, where can be loaded onto MHC I
*MHC I + peptide blebs off of ER in vacuole, transported to cell surface where
vacuole membrane integrates with cell membrane
*peptides from extracellular pathogens
*vacuole containing pathogen peptides fuses w/ vacuole from lumen of ER
Containing MHC II
*stabilized by binding CLIP in peptide binding groove
*CLIP-MHC II binding weak, easily displaced by peptide complementary to
peptide-binding groove
V. Antigen presentation by dendritic cell:
*TLR or cytokine receptor binding to ligandtrigger a burst of phagocytosis by dendritic cellleads to increase of MHC I and II expression
*after phagocytic burst, few rounds of increased MHC expression, MHC
Expression shut down
*Then, activated, mature dendritic cell migrates to secondary lymphoid tissue,
where it will interact with Tcell receptors to stimulate those T cells to become
Treg cells

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