T cell endogenous infection

cell mediated immunity (CMI) and cytotoxic T lymphocyte (CTL) and endogenous processing

dendritic cells and macrophages

a pathogen that lives w/in a host cell's cytoplasm and depends on host cell machinery (per esempio viruses)

degradation by proteosome, MHC-1, tapisin, TAP, ubiquitin, IFN-gamma

cytokine assoc w/ inflammation; up-regulates activities of proteosomes in endogenous processing

ubiquitin

Transporters Associated w/ antigen Processing; recognizes digested antigen from proteosome and acts as doorway into ER lumen for digested antigen

assoc temporarily with MHC-1 via tapisin

molecular "glue" for MHC-1 prot to attach to TAP prot in ER lumen

expressed on all nuc cells (i.e. NOT RBCs)

HLA-A, HLA-B, HLA-C

• alpha heavy chain w/ 3 domains
• B2 microglobulin
• TM tail on alpha-3 only

• alpha-1 and alpha-2: form antigen binding pocket, no TM region; stabilized by B2 microglobulin
• alpha-3: does not participate in antigen binding pocket, has TM tail to anchor to mem

non-cov assoc w/ heavy chain; not genetically in MHC complex; absolutely necessary for MHC-1 to be expressed on surface

NO!!!

• Polygenic: 3 isoforms for HLA
• Polymorphic: hundreds of alleles for each isoform
• Diploid
• Codominant expression: all products of alleles being expressed on cell surface
• Low freq of XO (reduces diversity)

alpha-1 and alpha-2 domains fold to create a groove in which 2 alpha helical walls are surrounded by a beta floor---hot dog bun analogy

certain specifically placed amino acids in antigen peptide that bind to alpha helical groove of MHC-1 binding pocket

allows many peptides w/ same anchor residues (does not need to be all of the AAs) to bind to the same MHC binding site

TCR must simultaneously bind to exposed AA in peptide and to polymorphic AA in MHC-1 (primarily in alpha helical walls)

T cell recog of peptides is restricted to the certain MHC in the ind (i.e. isoforms and alleles expressed)

• determined by:
• 1. antigen peptide created w/ high freq during processing by proteosome
• 2. antigen peptide has correct anchor residues for MHC-1 present in ind
• 3. antigen peptide was chopped up into the right length (8-10AA)
• 4. specific TCRs are available in the ind

each ind has diff alleles present for MHC-1 domains which gives a diff specificity in the binding pocket of alpha-1 and alpha-2 along with diff TCR repetoirs (VDJ rearrangment and N P disjunction)

allows evolutionary adv in species...not everyone can be killed by same pathogen!

binding of peptide/MHC-1 complex by TCR..results in passing of signals to CD3 complex

peptide/MHC-1 complex is not stable enough

CD8: "glue"

"glue" for MHC-1/antigen/TCR complex

binds to non-polymorphic region of alpha-3 in MHC-1...aka CD8 is highly conserved; has TM tails in T cell

co-stimulatory molecules

needed as second signal for CD8+T cells to become fully activated

• CD28 (on T cell); has TM tails into mem
• CD80/CD86 (on APC)

only needed in T cell ACTIVATION..once T cell has been activated once, co-stimulation is not necessary

cytokine that is necessary to maintain growth and activation of T cells

• effector cell of CD8+ T cells; acts as a serial killer; results in apoptosis of cell which can then trigger a cascade of other enzymatic activities:
• 1. cyt C of mit
• 2. caspases
• 3. caspase-activated DNase (CAD): causes DNA fragmentation

granzymes and FAS ligand

proteolytic enz in cytoplasmic granules; randomly distributed until CTL bound to target cell; granules become polarized next to target cell

move into target cell and trigger apoptosis after perforins act

prot stored in granules; released from CTL and forms pores in target cell lipid bilayer mem

on surface of CTL; when brought close to target cell, Fas ligand engages Fas on surface of target cell which triggers caspase cascade leading to apoptosis

Tumor Necrosis Factor; directly kills some target cells

technically lymphocytes but does not resemble B or T cells; aka lg granular lymphocytes

part of innate system of host defenses bc considered partially active; able to perform effector functions w/o conventional activation against antigen

one of first line of defenses, hard to charac rec

NOT by MHC molecules; preferentially attach host cells w/ decreased MHC-1 expression

• receptors:
• activating: can recog ALL cells
• inhibiting: turns NK off when finds MHC-1 non-polymorphic regions

some viruses try to beat the host defenses by killing host MHC-1 molecules; w/o MHC-1 molecules present, NK are left on (inhib recep cannot bind to anything!), NK attack viruses

• 1. cytolysis
• 2. cytokine prod (IFN-gamma) to activate macrophages
• 3. not MHC-1 restricted