What are the 3 professional antigen presenting cells
- Dendridic cells (cDC)
- Macrophages
- B cells
What are the 2 ways antigens are sampled
endocytosis
- Phagocytosis
- Pinocytosis
- receptor mediated endocytosis
Direct fusion
What are the 2 types of antigens (locations they are found)
endosomal antigens are called exogenous
cytosolic antigens are called endogenous
How many of each type of MHC does each APC express
3-6 MHC1 pros
3-8 MHC2 pros
Where are do MHC1 + 2 cells expressed on predominatly and how many polypeptide chains does each have
MHC1- expressed on all nucleated cells ( 1 chain)
MHC2- expressed predominatly on APCs ( 2 chains)
overall pathway of endogenous antigens and exogenous antigens (what are they loaded on and present to)
endo- on MHC1 to CD8 t cells (killa)
Exo- on MHC2 to CD4 tcells (helpa)
Where does the start of MHC1 loading happen and what pro holds its structure (and when is it removed)
Endoplasmic Reticulum
protein called calnexin helps it maintain its structure and then is subsequently removed when interactin with TAP (transporter associated w peptide processing)
how are foriegn antigens tagged and trimmed down in cytosol
foreign antigens are identified and tagged by ubiquitination and fragmented up by proteasome
TAP then transports peptides from cytosol to ER where its further broken down by ERAAP
When the MHC1 complex is loaded what occurs
The chaparon protein complex is released and MHCs migrate to the surface of the plasma membrane via the golgi apparatus
Where does the MHC2 complex made and what stabalizes it
assemble in the ER and are stabziled by a pro called the invarient chain (li)
Once stabalized can make its way to cell surface via (golgi)
What happens to the MHC2 complex on the way to the cell surface
- fuses with endosome which degrades invarient chain and leaves CLIP in binding groove
What removes CLIP from the MHC2 complex binding groove on the way to the surface of the cell
HLA-DM removes CLIP and allows exogenous antigens in the endosome to bind to peptide groove
How many aa long is antigens that attach to MHC2
12-18 aa long
What are the 2 activation signals that APCs need before they are mature
- proinflammatory cytokines (TnFa + IL6)
2. PAMPs (LPS, DSRNA)
What two things are expressed more in mature APCs
- increased exprssion of loaded MHC1/2 (better odds for antigen presenting)
- Express chemokine receptor CCR7 and co stim molecules
What are the 3 major co sim molecules found on the APC and T cell
APC——–tcell
- CD80-CD28
- CD86-CD28
- CD40-CD40L
What is the the function of CCR7 and what is it attracted to
Produced by mature APCs and are attracted to CL19 and CCL21 in peripheral lympod organs (to the t cells)
What are the 3 main signals needed
- Antigen presentation
- Co stim (On APC + T)
- Cytokines environment
How does signal 1: antigen presentation work + what else binds for it to work
Mature APC with MHC loaded with epitope binds with t cell receptor
-T cells coreceptor needs to bind to the MHC as well
(MHC1->CD8, MHC2->Cd4)
What confirms that the antigen has minded to the t cell receptor and what relays the signal inside of the cell
CD3
ITAMs relay signals downstream activating transcription factors that favour t cell activation
What is different of super antigens compared to regular antigens
bind to TCR outside of normal groove
-no need for co stem but can cause >20% of t cells released (cytokine storm)
Why is co stim: signal 2 needed
Necessary step for t cell proliferation, differentiation and survival
-can lead to t cell anergy, t cell deletion or immune tolerance
What happens in signal 3: cytokine environment
cytokines present during t cell activation help determine differentiation and effector function of the activated t cell
What MHC activates CD8 and CD4 t cells
MHC1 activate CD8
MHC2 activate CD4
