Immunology 4 Flashcards
T or F: antigens must be presented to a T-cell in order for them to recognize the antigen
True
what are HLA proteins?
human leukocyte antigen protein
present to the T-cell with antigens bound to it
what are the 2 types of HLA proteins
HLA class I
HLA class II
what do HLA class I proteins interact with?
cytotoxic T-cells and binds intracellular antigens - interact with a CD8 co-receptor on the cytotoxic T-cell
what do HLA class II proteins interact with?
T-helper cells and binds extracellular antigens - interacts with CD4 co-receptor on the T-helper cell
HLA type I molecule subtypes are all indicated by the designation…
A, B, or C
HLA type II molecule subtypes are all indicated by the designation…
D
HLA-1 proteins bind intracelular antigens via the ?
endogenous pathway
explain the endogenous pathway
antigenic peptide come from the cytosol, the peptide is derived from proteasomal degradation of foreign proteins, the peptide is then transported into the RER to be loaded onto the HLA-1 protein, then the loaded HLA-1 is then expressed on the cell surface
what are immunoproteosomes?
specialized proteasomes that are very good at presenting HLA-1 bound peptides to T-cells
what is the protein that translocate the peptide fragment into the RER for loading onto the HLA-1?
TAP
what are the receptors that increase transcription of HLA-1 protein in the presence of intracellular invaders?
NOD-like receptors
what does NOD-like receptors activate that in turn increase transcription of HLA-1 proteins
NFkB
what is the protein that inhibit NFkB and is phosphorylated and degraded when you need to increase the transcription of HLA-1 protein?
IkB (inhibitory protein)
T or F: cytokines can also increase the expression of HLA-1 molecules
true
what cytokines can increase the expression of HLA-1 molecules
- both type 1 and type 2 interferons
- tumour necrosis factor alpha (TNFa)
Once a peptide-bound HLA-1 is expressed on the surface of a cell, what happens next?
- It can bind a CD8+ T-cells Cytotoxic T cell and activate it
- Once activated, a cytotoxic T-cells can kill infected cells by inducing apoptosis
HLA-2 types are expressed exclusively on ?
antigen presenting cells (APCs)
what are the two types of antigen presenting cells categorized into?
“professional” and “non-professional”
what are the “professional” APCs?
- dendritic cells
- macrophages
- B-cells
what are the “non-professional” APCs?
- fibroblasts
- glial cells
- pancreatic beta cells
- thymic epithelial cells
- intraepithelial lymphocytes
- vascular endothelial cells
Dendritic cells constitutively (aka always) express ? and are very good at co-stimulating helper T cells
high levels of HLA-2
Macrophages need to be ? before they express HLA-2, but they are also good at co-stimulating helper T-cells
activated
B-cells constitutively express HLA-2 at ? and are good at co-stimulating helper T-cells
low levels
Nonprofessional APCs will only express HLA-2 under
particular conditions
HLA-2 proteins bind extracellular antigens via the ?
exogenous pathway
HLA-2 expression is up-regulated by ? such as ?
particular cytokines
- interferon-gamma (IFN-y) (except for B-cells)
- IL-4
what needs to be upregulated in concurrence with HLA-2 expression
phagocytosis
What is the source of the peptides that are loaded onto the HLA-2
Phagocytosis
Phagocytosis by B-cells can be ?
antibody-mediated
Antigen binds to specific antibody on the surface of the B-cell (aka B-cell receptor) Antigen and the antibody are phagocytosed together, this process is called
receptor-mediated endocytosis
How do we ensure an cytosolic antigen isn’t loaded onto an HLA-2 (rather than an HLA-1) in the RER?
In the RER, the HLA-2 protein associates with the invariant chain, This prevents a cytosolic antigen from being loaded onto the HLA-2 while in the RER
As the HLA-2 containing vesicle merges with the phagosome/endosome containing the antigen, the ? is chopped up. The “chopped version” is called ? , and it will remain bound to the HLA-2 peptide binding region until displaced
invariant chain
CLIP
Once a peptide-bound HLA-2 is expressed on the surface of a cell, what happens next?
It can bind a CD4+ T-cells, ie, a helper T-cell, and activate it
Helper T-cells need a co-receptor to bind to the HLA-2 molecule, this co-receptor is known as ?
CD4
Helper T-cells also need a co-stimulatory activation, a key co-stimulatory interaction is ?
CD28 (on T-cell) with CD80/86 on the APC
only what have the capacity to express CD80/86 (CD28 ligand)
professional APCs
How does CD28 signaling add to the effects of TCR signaling
- Enhances the strength of signal between the T-cell and the antigen presenting cell
- Initiates a cell-signaling cascade to promote T cell survival and proliferation
○ CD28 will recruit PI3 Kinase
The interactions between the T-cell and the antigen presenting cell can be divided into 2 categories:
CSMAC and PSMAC
what is CSMAC
central supremolecular activation complex
- TCR and HLA-2 (with co-activator CD4)
- Co-stimulator interaction (CD28 and CD80 /86)
what is PSMAC
peripheral supramolecular activation complex
- Includes other receptor-ligand interactions that help to strength the connection between the T-cell and APC to sustain the signal
