Block C Lecture 2: Antigen Presentation Flashcards
How are antigens generated?
By phagocytes chewing things up, which generates short peptides from pathogen-associated proteins- these are antigens
(Lecture 2, Slide 4)
How do phagocytes take up antigens?
Through the process of phagocytosis
(Lecture 2, Slide 4)
How do phagocytes - such as macrophages get antigens to their MHC Class II receptors?
The antigen is taken from the extracellular space, and stored in intracellular vesicles - called endosomes, which are inactive until the macrophage becomes activated, which occurs when their pH is decreased. This activates proteases which degrade the antigen into peptide fragments. Vesicles containing peptide fragments then fuse with vesicles containing MHCII receptors. One of these fragments will fit the receptor.
(Lecture 2, Slide 5)
What is an epitope?
The specific region on an antigen, which an antibody or T cell receptor binds to
(Lecture 2, Slide 8)
Where are T cell receptor epitopes located in the antigen?
They can be any portion of the protein molecule, and can even be buried in the molecule
(Lecture 2, Slide 8)
Where are antibody epitopes located in the antigen and why?
They must be on the surface as antibodies recognise things in their 3D conformations
(Lecture 2, Slide 8)
How do MHC receptors on T cells gain access to buried epitopes?
The antigen is first broken down into peptide fragments, and then epitope peptides binds to an MHC molecule
(Lecture 2, Slide 8)
How do peptides bind to MHC molecules?
They interact with molecules on the MHC binding cleft and form covalent bonds
(Lecture 2, Slide 9)
What antigens do MHC class I and II receptors deal with?
MHC class I is for intracellular antigens (on CD8+ / cytotoxic T cells)
MHC class II is for extracellular antigens (on CD4+ / helper T cells)
(Lecture 2, Slide 10)
What is the first step of the pathway to recognise intracellular antigens such as those coming from a virus?
The virus binds to the surface of the cell and infiltrates it, translocating to the nucleus where it starts its replication
(Lecture 2, Slide 11)
What happens in the intracellular pathway of antigen recognition, after the virus starts it’s replication in the nucleus?
During it’s replication, the virus will produce and release proteins into the cytoplasm, such as spike proteins
(Lecture 2, Slide 11)
What happens in the intracellular pathway of antigen recognition, after the virus releases proteins such as spike proteins into the cytoplasm?
These proteins are degraded into small peptides (8-9 amino acids long) by a proteosome which are then loaded into peptide transporters (TAP-1 and TAP-2)
(Lecture 2, Slide 11)
What are molecular chaperones?
A diverse group of proteins that play a crucial role in assisting the proper folding, assembly, and stabilization of other proteins
(Lecture 2, Slide 11)
What happens in the intracellular pathway of antigen recognition, after the small peptides generated by a proteosome are loaded into peptide transporters?
MHC class I produced in the rough endoplasmic reticulum (RER) associated with molecular chaperones including ß2M and binds the peptide
(Lecture 2, Slide 11)
What happens in the intracellular pathway of antigen recognition, after the MHC class I molecule forms a complex with its peptide?
The complex is transported via the Golgi apparatus to the cell surface for presentation to a cytotoxic (CD8+) T cell
(Lecture 2, Slide 11)
What is the first step of the pathway to recognise extracellular antigens such as an allergen or protein from a pathogen?
The antigen is taken up and degraded by phagocytosis in endosomes
(Lecture 2, Slide 12)
What happens in the extracellular pathway of antigen recognition, after the antigen is taken up and degraded by phagocytosis?
MHC class II receptor is assembled in the endoplasmic reticulum (ER), packed in endosomes and trafficked via the Golgi apparatus
(Lecture 2, Slide 12)
What happens in the extracellular pathway of antigen recognition, after the MHC class II receptor is packed in endosomes and trafficked via the Golgi apparatus?
Upon encountering endosomes containing peptides, the endosome containing the MHC class II receptor and the endosome containing the protein fuse and the antigen can be loaded onto the MHC class II receptor
(Lecture 2, Slide 12)
What happens in the extracellular pathway of antigen recognition, after the MHC class II receptor forms a complex with its peptide?
It is transported to the surface where it can be presented to helper (CD4+ T cells)
(Lecture 2, Slide 12)
Are the majority of T cells helper or cytotoxic T cells?
Helper T cells
(Lecture 2, Slide 13)
What are the 2 roles of helper (CD4+) T cells?
To direct, help or orchestrate the cell mediated immune response and to regulate the B cells response to the antigen
(Lecture 2, Slide 13)
What are the 4 ways in which dendritic cells can process antigens?
Receptor mediated phagocytosis
Micropinocytosis
Cross presentation
Transfer
(Lecture 2, Slide 14)
What type of pathogen’s antigens does the dendritic cells receptor mediated phagocytosis method of antigen processing present and what occurs in this method?
It presents extracellular bacteria and can involve a TLR or the antigen being bound by antibodies or complement
(Lecture 2, Slide 14)
What type of pathogen’s antigens does the dendritic cells micropinocytosis method of antigen processing present and what occurs in this method?
It presents extracellular bacteria, soluble antigens and virus particles and is the direct uptake of soluble antigens or virus particles in the milieu
(Lecture 2, Slide 14)
What type of pathogen’s antigens does the dendritic cells cross presentation method of antigen processing present and what occurs in this method?
It presents viruses and is when the receptor mediated phagocytosis has occurred but the antigen has been released into the cytosol
(Lecture 2, Slide 14)
What type of pathogen’s antigens does the dendritic cells transfer method of antigen processing present and what occurs in this method?
It presents viruses and is when an incoming dendritic cell transfers to a resident dendritic cell
(Lecture 2, Slide 14)
What type of cells express MHC class II receptors?
“Professional” antigen presenting cells
(Lecture 2, Slide 15)
Why is co-stimulation required in addition to MHC receptors in order to stimulate helper (CD4+) T cells and cytotoxic (CD8+) T cells?
As MHC is often not enough to stimulate them
(Lecture 2, Slide 15)
What are 4 types of professional APCs?
B cells, macrophages, dendritic cells and epithelial cells
(Lecture 2, Slide 15)
What cells can viruses infect?
Any cell in the body
(Lecture 2, Slide 16)
What does the body need to be able to do before it can respond to a virus?
Recognise which cells have been infected with a virus and then be able to respond
(Lecture 2, Slide 16)
What cells are able to express MHC class I receptors?
Essentially every cell in the body with the exception of red blood cells
(Lecture 2, Slide 16)
Why can red blood cells not express MHC class I receptors?
As they don’t have a nucleus
(Lecture 2, Slide 16)
Do the progeny (descendants) within a species have a increased or decreased diversity of MHC receptors?
Increased
(Lecture 2, Slide 17)
What does the high diversity of MHC haplotypes within the population enable?
An increased in the range of peptides presented to the immune system within a species, reducing the chance of a pathogen evading the immune system
(Lecture 2, Slide 17)
What would happen if everybody had the same MHC haplotype (genes)?
The species as a whole would be susceptible
(Lecture 2, Slide 17)
What does MHC polymorphism affect?
How antigens can be recognised by T cells
(Lecture 2, Slide 18)
What 3 things must match for the fit to be correct and recognition of antigen to occur?
MHC binding the antigen
MHC and TCR fitting each other
Peptide antigen and TCR fitting each other
(Lecture 2, Slide 18)
