L6 - Adaptive Immune System 3 Flashcards
ANTIGEN PRESENTING CELLS
i) why do T cells need antigen presentation?
ii) what is the broadest range of APC? what type of T cells does it activate?
iii) what role do macrophages play? (2)
iv) which cells internalise antigen bound to its receptor then present it to T cells?
i) they cant recognise native antigen - it needs to be processed and presented by an APC
ii) broadest range of APCs are dendritic cells
- potent activators of T helper cells
iii) macrophages engulf pathogen and process it to make immunogenic peptides
iv) B cells can internalise antigen bound to receptor and present it to T cells
ACTIVATION OF T CELLS
i) what determines which peptides will be presented on MHC?
ii) where are MHC class I found? where are MHC class II found?
iii) what do T cells need to be able to distinguish between?
iv) pathogens inside which types of cell may be hard to find?
i) the APC will determine which cells are presented
ii) class I found on all nucleated cells class II only found on APCs
iii) T cells need to distinguish between external antigens taken up by APCs eg bacteria and internal antigens (eg viral infected cell)
iv) pathogens inside anucleated cells eg malaria hiding in RBCs
ANTIGEN PROCESSING
i) what is it?
ii) what does it require? (2)
iii) which T cells recognise a) MHC I, b) MHC II
i) an enzymatic process of degrating proteins through proteases into antigenic peptides
ii) requires ATP and movement of endocytic vesicles
iii) CD8 cytotoxic T cells recog MHC I
CD4 T helper cells recog MHC II
ENDOGENOUS VS EXOGENOUS ANTIGENS
i) which type of antigen is presented on MHC I? where is the antigen first processed? where does it head for further processing and to be loaded onto MHC I?
ii) which type of antigen is presented on MHC II? where does the antigen first go? what structure is produced that allows protein degradation?
iii) where is protein loaded onto MHC II?
iv) which T cell recognises MHC I? what type of antigen?
v) which T cell recognises MHC II? what type of antigen?
i) intracellular antigen presented on MHC I
- antigen is first processed in the proteosome
- head to ER for more processing and loading onto MHC I
ii) extracellular antigen is presented on MHC II
- antigen taken into cell by endocytosis then into endosome
- fusion of endosome with lysosome > phagolyososome where protein degredation happens
iii) protein is loaded onto MHC II in endocytic vesicles then transported to cell surface
iv) MHC I recog by CD8 T cell > intracell antigen
v) MHC II recog by CD4 T cell > extracell antigen
ENDOGENOUS ANTIGENS
i) where do these come from? give two examples
ii) what two types of antigen can it include?
iii) where do these peptides bind MHC I? which type of T cell do they activate?
iv) how are the levels of protein in the cell detected? which protein can target cells for degredation
i) from proteins produced inside the cell
- viral proteins or proteins synthesised by cancer cells
ii) can include self protein antigens or foreign protein antigens
iii) peptides bind MHC I in the endoplasmic reticulum
- activate CD8 T cells > kill infected cell
iv) levels of protein are detected by rate of synthesis and rate of degredation
- ubiquitin can target proteins for proteolysis in the proteosome
ENDOGENOUS ANTIGENS - PROTEOSOME
i) which type of proteosome processes peptides to be loaded onto MHC I?
ii) which type of proteosome may be found in immune cells?
iii) where is the thymo proteosome exclusively expressed?
iv) what does the proteosome do?
i) standard proteosome (26s proteosome)
ii) immuno proteosome
iii) thymo proteosome is exclusively expressed by thymic epithelial cells
iv) proteosome unfolds proteins then cleaves them into pepties and amino acids
ENDOGENOUS ANTIGENS - TAP PROTEINS
i) what do TAP proteins do?
ii) where are they found?
iii) which two TAP proteins form a heterodimer? what does this facilitate?
iv) what length of peptide does the TAP pump preferentially transport?
i) transport endogenous antigens from the cytoplasm into the lumen of the ER
ii) found in the membrane of the ER
iii) TAP 1 and TAP 2 form a heterodimer which facilitates selective transport of peptides cyto > ER
iv) TAP pump transports peptides with a length of 8-15 amino acids (length made by proteosome)
MHC I LOADING
i) where are MHC I found?
ii) which two components does it contain? where are these assembled?
iii) what is the role of calnexin?
iv) what class of protein stabilises the components of the MHCI before peptide is loaded on? what is this called?
v) which protein delivers the peptide? where is it delivered from? what part of the MHC does the peptie bind?
vi) once the peptide is bound to MHC, what happens? (2)
i) MHC I found on all nucleated cells
ii) contains heavy chain and B2 microglobulin
- these are assembled in the ER
iii) calnexin stabilises the heavy chain before B2m binds
iv) chaperone proteins stabilise MHC (heavy and B2m) before peptide binds > peptide binding complex (calreticulin, tapasin, TAP, ERp57)
v) TAP protein delivers the peptide (proteosome in cyto > ER) and binds to the heavy chain
vi) after peptide binds > molecule dissoc from protein loading complex and is exported from ER > cell surface
CD8+ T CELLS (CTLs)
i) what are effector CD8 T cells primarily needed for?
ii) what is their target when activated against cancer cells?
iii) where do antigens that stimulate CTLs come from? which MHC are they presented on?
iv) which virus can interfere with MHC I expression? how does it do this? what does it result in?
v) how do some parasites evade recognition by CD8 T cells?
i) needed to eradicate infected cells
ii) neoantigens/tumour specific antigens
iii) antigens that stim CTL come from inside the cell and are presented on MHC I
iv) Herpes simplex virus can interdere with MHC I express
- ICP47 protein from HSV can selectively bind TAP and inhibit transfer of peptides into ER
- results in peptides not presented on MHC I
v) some parasites infect anucleated cells eg RBC therefore wont be presented to the immune system as the cell doesnt express MHC
EXOGENOUS ANTIGEN PATHWAY - PEPTIDE GENERATION
i) how are pathogens taken into the cell? (2) give an example of two receptors that it may bind
ii) what structure are pathogens in once taken into the cell? why are proteases inactive here?
iii) what allows activation of proteases? when does this happen?
iv) which MHC molecule is peptide loaded onto? how does this happen?
i) pathogens taken into the cell by endocytosis or phagocytosis
- may bind APC receptor or Fc receptor on B cells
ii) pathogens in endosome > proteases inactive as there is a neutral pH
iii) proteases are activated at an acidic pH which happens when endosome fuses with lysosome > endolysosome
iv) peptide loaded onto MHC II when vesicles containing peptides fuse with vesicles containing MHC II molecs
TRAFFICKING OF MHC II MOLECULES
i) where does it begin? which two chains associate here?
ii) where is it then trafficked to? what happens here?
iii) where does the MHC then head to?
iv) what blocks MHC II from binding self peptides?
i) begins in the ER where alpha and beta chains associate
ii) trafficked to the trans golgi network where its sorted into vesicles
iii) MHC then heads to compartments where peptide loading occurs (endolysosome)
iv) invariant chain binds to MHC II and blocks it from binding self peptides
CONTROL OF MHC II BINDING
i) what blocks peptide binding to MHC II in the ER?
ii) what happens to this block when the MHC II is in vesicles? what allows this to happen?
iii) what molecule then remains in the MHC II in vesicles?
iv) once a peptide is present - which protein allows the peptide to bind? how does it do this? what class of protein is it?
i) invariant chain blocks MHC II binding in ER
ii) once in vesicles the invariant chain is cleaved
- acidic pH activates cathepsin which digests the invar chain
iii) CLIP molecule remains and still blocks MHC II from binding
iv) when peptide is present - HLA DM catalyses release of CLIP which allows it to bind
- HLA DM is a chaperone protein
MHC II PEPTIDE LOADING
i) what is this essential for?
ii) where does MHC II loading take place? what conditions are required for protein > peptide?
iii) what two events take place before the peptide can bind MHC II?
i) essential for CD4 cells to recognise exogenous peptide
ii) MHC loading takes place in endosomes
- acidic pH required for protein degradation
iii) invariant chain needs to be degraded and CLIP is removed
CD4+ T CELLS
i) what are they activated by?
ii) which cells do they recognise antigen from?
iii) what antigen recognition activate? (2)
i) activated by exogenous antigens
ii) recognise antigen from APCs
iii) antigen recognition > activation of macrophage and production of secreted antibody by plasma cells (B cells)
IMMUNE EVASION FROM MHC II
i) which virus interferes with MHC II upregulation in APCs?
ii) what is the HSV viral envelope protein? what effect does this have on MHC II (2)
iii) name another virus that interferes with MHC II processing
iv) what do leishmania and mycobacteria TB prevent?
i) adenovirus interferes with MHC II upregulation in APCs
ii) HSC viral envelope protein is glycoprotein B
- reduces MHC II processing and inhibits the production of invariant chain peptide
iii) HIV interferes with MHC II processing
iv) leishmania and TB prevent phagosome and lysosome fusion
