BLG 307 Lecture Notes - Signal Transduction, Cytoskeleton, Exocytosis

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28 Jan 2013
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IMMUNOLOGY
CD8 CYTOLYTIC T LYMPHOCYTES (CTL)
-CTLS lyse target cells that display processed foreign antigens bound to MHC molecules.
-free virus and bacteria cant trigger CTLs
-pathogens replicating within host cells are protected from humoral immune response by intracellular
environment
-but peptide products appear on MHC I and are recognized by CD8 + CTLs
-CTLs can eliminate infected cells even in the presence of excess soluble antigen
Functions
virally infected cells (MAJOR) bacterial infected cells
tumor cells graft rejection
*Important that their activity is confined only to target cells*
Note: some CD4 and some NK cells also have cytolytic activity
PROTECTION AGAINST VIRAL INFECTION
-intravenous transfer of CD8 T cells specific for flue can protect against viral pneumonia!
-CTLs can recognize conserved NP abundantly synthesized on the cytoplasm (thus catches HA/NA
antigenic shift)
-Class I (B-2microglobluin) and CD8 knockoutsreduced CTL levels and don’t clear virus
-Perforin knockoutsnormal CD8+ numbers but don’t lyse virally infected cells
Perforin plays central role in lysis of target cells by CTL
-CTLs important in bone marrow transplant recipients and resoloving high vermia with HIV (delay
AIDS)
-Antigenic viral proteins can be cytosolic or nuclear-localized
-generate vaccines through CTLsbroader immunity
MECHANISM FOR VIRAL EXCAPE FROM HOST CTL
Mechanism Demonstrated for
1. Viral latency HIV, EBV, Herpes simplex virus
2. Replication in “privileged sites” Neurotrophic viruses
3. Infection of class I –ve cells Polio, rabies
4. Inhibition of class I expression Adenovirus, Cytomegalovirus
-E3-gp19K TM protein of Adenovirusthat associates in ER with MHCI and prevents export
-US11 of CMV dislocates newly made MHCI from the ER into the cytosol
5. Inhibition of TAP function Herpes simplex virus
-prevents transport of peptides into the ER
6. Mutation in CTL epitopes HIV, Epstein Barr virus, LCM virus (murine) ESCAPE
MUTANTS)
-mutations affecting processing, recognition by TCR, antagonism
PROTECTION AGAINST BACTERIAL INFECTION
-Several types of bacteria can reside and replicate WITHIN host cells
-production of hemolysin protein that creates pores in intracellular membranes
Salmonella: inside membrane vesicles
Listeria, Myobacteria: escape into the cytosol
-While this might elicit MHCII/CD4 response in some cells, certain cell types LACK these proteins
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