Lecture 4 Flashcards
What is the structure of MHC
a hot dog bun –> 2 alpha helices and a beta pleated sheet
What does MHC stand for?
What is its relevance?
Major histocompatability complex.
MHC = Me. (ex. transplant rejection)
Describe the structure of MHC Class 1.
Where are they found?
What do they stimulate?
MHC 1: “shorter bun”; 9 - 12 AA long peptides
They are found on all cells.
Stimulate a CD8 Killer Cell..
Describe the structure of MHC Class 2.
Where are they found?
What do they stimulate?
- “foot long bun” –> 22 - 23 aa long peptides
- They are found ONLY on professional Ag presenting peptide cells (APCs) –> macrophages, dendritic cells and B cells
- they stimulate a CD4 helper cell
Describe the MHC Class 1 pathway.
originally described for a virally infected cell, but works for any antigen that gets into the cytoplasm
- Virus begins reproducing in cytoplasm
- Proteosome breaks virus into peptides (garbage disposal)
- TAP transporter moves peptides into the ER
- Peptides bind newly synthesized MHC class 1 in the ER
- Peptide-MHC complex is transported to cell surface via golgi app
- Stimulates a specific CD8 killer cell
What does TAP mean?
What does it do?
Transporter of Antigen Processing
- transports antigen peptides to the ER
Describe the MHC Class 2 pathway.
(Originally described for bacterial antigens, but it works for any EXTRACELLULAR antigen)
How long does this process take?
- bacteria binds to a recepter (TLR on macrophage or DC; antibody on a B cell)
- endocytosis of the bacteria (endosome + lysosome = endolysosome) –> digest bacteria with proteases, low pH and enzymes
- simultaneously, the cell is making new MHC II with the peptide binding groove blocked by an invariant chain (Ii)
- vesicle buds of ER with MHC II –> fuses with endolysosome
- degrades Ii and bacterial peptides bind MHC II
- MHC + Bacterial complex arrive at cell surface
- stimulates a specific CD4 help t cell response
- This process takes 24 hours
Why are superantigens (SAgs) so dangerous? Describe their activation pathway.
There is no processing pathway –> it non specifically links an MHC to a T cell
* It activates the T cell no matter what the T cell is specific for
A SuperAg can activate 2 - 20% of your T cells all at once, leading to the release of a lot of cytokines
Dangerous because you can end up with leaky blood vessels –> TOXIC! –> SHOCK!
What are some of the famous SuperAgs? Describe them.
- TSST-1: Toxic Shock Syndrome 1 Toxin; made by staph aureus, which is not dangerous itself, but in an anaerobic environment it creates TSST-1
- Staph Enterotoxin A (SEA) and Staph Enterotoxin B (SEB): food poisoning in potato salad; the enterotoxin is created in an anaerobic environment (produced with it hits the gut)
What is the source of pheromones?
MHC Polymorphisms
How are MHC polymorphisms created?
MHC Class 1: inherit 3 alleles from mom and 3 from dad (HLA-A,B, & C)
MHC Class 2: inherit 3 alleles from mom and 3 from dad (HLA-DQ, DR, and DP)
This results in 6 MHC Class I and 6 MHC Class II
* There is no allelic exclusion - all of these are expressed all of the time
What is an allograft?
What causes the rejection of an allograft?
What is the solution in medicine?
an organ transplant between two of the same species
allograft –> alloreactivity –> tissue rejection
The TLR doesn’t recognize the MHC on the macrophage as “self”
TLR binds –> not self –> kills the foreign tissues
Solution: immunosuppressives
What is a xenograft?
What is the immune response?
What is a possible solution?
an organ transplant from animal to human
The T cell can’t “see” the MHC because its too different
Natural Killer cells can see that tissue and can kill it
Solution: recombinant pigs: put your MHC into a pig –> the pig now has your MHC on all of its cells –> transplant –> accept
What is a proposed and generalized process for tissue regeneration?
stem cells: put them in a mold with cytokines to regrow an organ
What 2 signals are used for T cell activation?
1) MHC + Peptide : TLR
2) CD86 : CD28
How do TLRs help us to mount a specific immune response?
TLRs allow us to discriminate between types of Ags and trigger particular cytokine responses
How are T Cells activated?
By 2 signals:
1) MHC + peptide : TLR
2) CD86 : CD28
What are the T cells named after?
the Thymus
What is a TCR
The T cell receptor that binds with the MHC-peptide complex on the APC
TCR recombination
Genes rearrange like antibody genes - VDJ gene rearrangement - but there is not D (just V and J)
allelic exclusion: yes
receptor editing: not that we know of in humans
What are the chains on TCR?
alpha and beta: these are the T cells that we talk about
delta and gamma: evolutionary precursors; we see these associated with rheumatoid arthritis and they show up in mucosal tissues
What is central tolerance?
Where does it occur?
trying to get rid of the majority of T cells that are autoreactive
- -> this happens in the thymus
- This process is not perfect –>autoimmunity
How do we compensate for autoreactive cells on a daily basis?
cortisol burst in the am kills off cells
What is peripheral tolerance?
by the time that developing T cells reach the periphery of the thymus, they should be tolerant to self.
This requires 2 signals to activate a T cell: if a macrophage presents a self peptide, it will not present CD 86 and thus the T cell will remain anergic (in a coma)
