antigen presentation 2

Question 1

the extracellular pathway of antigen presentation by class 2 MHC molecules

Answer 1

class 3 mhc molecules alert t cells to extracellular infections
engulfed peptides bind to mhc class 2 and are transported to the surface
helper t cells recognise the complex of peptide antigen and mhc class 2 and activates a macrophage
class 2 mhc is expressed only on b cells, dendritic ccells and macrophages
captures peptides from exogenous antigens
displays them to t cells which express cd4 coreceptor
phagocytosis, macropinocytosis and receptor mediated endocytosis drives antigen capture
boosted by inflammatory signals (PAMPs)

Question 2

process of phagocytosis (7 steps)

Answer 2

1. chemotaxis and adherence of microbe to phagocyte
2. injestion of microbe by phagocyte
3. formation of phagosome
4. fusion of phagosome with lysosome to form phagolysosome
5. digestion of injested microbe by enzymes
6. formation of residual body containing indigestible material
7. discharge of waste materials

Question 3

how do empty MHC 2 reach the endosomal compartment

Answer 3

in ER needs to prevent newely synthesised unfolded self proteins from binding of immature MHC
invariant chain stabilises mhc class 2 by non covalent binding to immature mhc class 2 molecule forming a non monomeric complex - this prevents premature loading

Question 4

how are exogenous peptides generated and loaded onto mhc 2/ invariant chain complexes in the endo-lyssoomal compartment?

Answer 4

1. endo-lysosomal proteases perform 2 key roles
   -generate peptides from antigen
   - initiate cleavage of invariant chain
   limited antigen proteolysis is required for mhc class 2 peptide loading
   cystine proteases, asparatate proteases and serine proteases
2. HLA-DM catalyses ejection of CLIP and aids optimal peptide selection
   - replaces CLIP with an antigen using catalytic mechanism
   - discovered using mutant cell lines that failed to present antigens
3. successful peptide capture triggers export to cell surface
   - MIIC compartment sorts peptide-MHC complexes for surface expression of lysosomal degradation

Question 5

what changes occur in dendritic cells following TLR signalling

Answer 5

transient increased antigen capture
increased mhc biosynthesis
- increased translocation of mhc to cell surface
increased expression of costimulatory molecules
increased expression of cytokines that influence t cell polarisation
increased expression of CCR7
- chemokine receptor that guide migration of dendritic cells toward CCL21 - a chemokine expressed in lymphoid tissues
increased cross presentation

Question 6

cross presentation of extracellular antigens by class 1 mhc molecules

Answer 6

exogenous antigens are presented on mhc class 1 molecules crucial for the generation of effector cd8T+ cell responses
in vitro this is mainly carried out by certain subsets of dendritic cells

Question 7

how do dendritic cells take up and present antigens in different ways

Answer 7

by receptor mediated endocytosis
macro-phagocytosis
viral infection
cross presentation is necessary for immunity against tumours and virsuss that do not readily infect antigen presenting cells or impair dendritic cell normal function
-plays a role in immune defence against many viruses and intracellular bacteria
required for induction of cytotoxic immunity by vaccination with protein antigens

Question 8

how do class 1 and 2 mhc molecules capture peptides from different cellular components

Answer 8

cross presentation permits presentation of exogenous antigens normally presented by mhc 2 on surface of infected dendritic cells to also be presented by mhc1 without infecting the dendritic cell

Question 9

b cell activation by specific antigens

Answer 9

b cells and antibodies they make can recognise virtually any chemical structure
t cells can only recognise short peptides presented by mhc molecules
opsonised antigens are trapped by:
- subscapular and medullary sinus macrophages
- FDcs
- dendritic cells

Question 10

what are FDCs

Answer 10

follicular dendritic cells - in lymphoid follicules they store and display intact antigens to b cells
they serve as a vast depository on intact antigens that have not been subject to degradation and are available for interaction with antigen receptors for circulatory b cells
extensive surface area of dendrites allow large quantities of antigens and intact viral particles to accumulate
they lack phagocytic activity and preserve antigens intact on cell surfaces over long periods.