Mim - Lecture 9

Front 1

9.1

most bacteria and parasites replicate in:

Back 1

- endosomes and lysosomes that form the vesiclular system

Front 2

9.2

antigens that bind to MHC I:

Back 2

- viruses in the cytosal
- cytosolic pathogens are degraded in cytosal, bind to MHC I, presented to CD8T ->, killed

Front 3

9.3

antigens that bind to MHC II

Back 3

- intravesicular pathogens
- degraded in endocytic vesicles, low pH
- MHC II/peptide complex -> CD4T (helper)
- APC activated -> kill intravesicular bacteria or parasite

Front 4

9.4

facultative antigen presenting cells:

Back 4

- cells that can be induced to present antigens
- low levels of pagocytosis
- astrocytes (Macrophages of the brain) -> MHC II

Front 5

9.5

MHC I (endodenous) pathway of antigen presentation

Back 5

- leads to presentation of MHCI bound peptides to CD8+ T cells
- antigen is processed within cytosol (by proteasomes)
- processed peptides are transported across the ER membrane
- MHCI peptide complexes are formed in the ER and are transported through the conventional secretory pathway to the cell surface

Front 6

9.6

MHCI presentation pathway:

Back 6

- partly folded MHC I alpha chains bind to calnexin until beta2- microglobulin binds
- alpha:beta2m complex released from calnexin, binds a complex of chaperone proteins (calreticulin, Erp57) and binds to TAP via tapasin
- proteosome: cytosolic protein -> peptide fragment
- TAP delivers a peptide -> MHC I, complete folding, released from TAP, exported

Front 7

9.7

MHC II processing (endocytic/exogenous) pathway of antigen presention

Back 7

- leads to presentation of MHC II bound peptides to CD4+ T cells
- antigen is processed within endocytic vesicles
- upon its synthesis MHC II moves through endocytic pathway and binds antigenic peptides en route to the cell surface of an APC.

Front 8

9.8

MHC II presentation pathway

Back 8

- invariant chain (Ii) forms a complex with MHC II molecules, blocking the binding of peptides
- Ii is cleaved in an acidified endosome, leaving a short peptide fragment, CLIP, still bound to the MHC II
- CHP block the binding of antigen peptides to MHC II
- HLA DM bind to MHC II -> releasing CLIP, peptides bind
- MHC II travels to the surface

Front 9

9.9

supramolecular adhesion complex (SMAC)

Back 9

clustering of T and B receptors leads to the formation of an organized structure

Front 10

9.10

immunological synapse

Back 10

- formation of SMAC in T cells leads to formation of SMAC in APC.
- contact between T cell and APC is highly organized interface call immunological synpase

Front 11

9.11

LFA-1, ICAM-1:

Back 11

- T cell initially binds APC through low-affinity LFA-1, ICAM-1 interactions
- adhesion molecules
- if T is specific for the antigen presented by the APC -> conformational change in LFA -> increase affinity and prolong cell-cell contact

Front 12

9.12

activation of naive T cells requires 2 independent signals delivered by the same APC

Back 12

1st: recognition of MHC I or II
2nd: co-stimulatory molecule

Front 13

9.13

the principal co-stimulatory molecules expressed on APCs are B7:

Back 13

molecules which bind T cell protein CD28

Front 14

9.14

T cell activation through the TCR and CD28 leads to the:

Back 14

increased expression of CTLA4, an inhibitory receptor for B7 molecules

Front 15

9.15

At a minimum, activation of T cells requires:

Back 15

a specific signal via the TcR-MHC/peptide complex and a non-specific signal via CD28-B7 molecules