CD8+ T cells immune Responses to Cytosolic Antigens Flashcards
Dendritic Cell encounters
exogenous antigen in circulation, it is endocytosis, processing and presentation en route to secondary lymphoid tissue
Dendritic cells present
peptide MHC class II to CD4+Thp that secrete IL-2
Clonal expansion happens after
Thp following IL-2 to IL2R
cross presentation of endocytosed antigen leads to
peptide-MHC class I on antigen presenting cell hence presentation to pCTL
Cross priming of
pCTL
pCTL interactions
CD2 and LFA1 interact with dendritic cell LFA-3 and ICAM 1,2
IL-2:IL2R interaction leads to
proliferation of the activated pCTL
Proliferation =
clonal expansion
Maturation from pCTL to CTL requies
7-10 days, IL-2 IFN-gamma
Mature CTL functions in
immunosurveillance
IL2R=
CD25
Processing and Presentation to CD4+ T cells starts with
endocytosis of antigen into endosome, lysosome fuses with endosome and enzymes degrade the antigen
Endosome lysosome vesicle fuses with
vesicle transporting class II MHC/invariant chain in vesicle and the lysosome degrades invariant chain
Peptides bind to groove in
MHC class II
Binding of peptide to MHC class I in
a vacuole and transport to the cell surface and then it is expressed on cell surface
Presentation to pCTL=
Cross Priming
Target cells of Mature CTLs have
antigenic peptide-MHC class I molecules on their cell surface
antigen for mature CTL mustpresent in
target cell cytosol
antigen destroyed by proteosome fragments presented to
TAP-1 and TAP-2 bind to MHC class I in endoplasmic reticulum, golgi vesicle transport complext to the cell membrane
MHC class I peptide expressed on target cell surface is
recognized by circulating mature CTLs that are doing immunosurveillance(they have differentiated becasue of the same antigen)
Interaction of the CTL with target cell leads to
destruction of target cell with perforin and granzymes
after destroying a target cell a CTL will
continue with immunosurveillance
Most activate CTLs will undergo
apoptosis but some will survive as memory cells.
Virus is outside the cell when
released form cells or duing infectivity stage
Host defenses when outside the cell
phagocytes, dendritic cells, B cells
Dendritic cells when virus are outside the cell become
APCS for CD4+ Thp cells and cross presentation to CD8+ pCTL
when virus is inside the cell, the cell
produces and secretes IFN Alpha
IFN alpha binds to
cognate receptors on neighboring cells which leads to production of 25oligoadenylate synthetase
2,5-OAS leads to
activation of RNaseL which degrades the viral and cellular RNA
Host defenses when virus is inside the cell
NK cells and Cytotoxic T cells
Plasma cells secrete
IgG antibodies that play a role in phagocytosis and NK cell mediated ADCC
increased MHC expression on Target
reduces the likelihood that the infected cell will be destroyed by NK cells and strengthens the likelihood of desturction by CTLs
decreased MHC expression on target
strengthens likelihood of destruction by NK cells and reduces for destruction by CTLs
Human Immunodeficiency Virus infection receptor on target cells
GP120 on HIV binds to CD4 on target cells
Target cells for HIV
CD4+ T cells, dendritic cells, macrophages
Coreceptors on target cell for HIV
CXCR4 required for M-tropic strains of HIB and CCR5 required by T-tropic strains of HIV
