Immunology 4 Flashcards by Andre Lee

T or F: antigens must be presented to a T-cell in order for them to recognize the antigen

True

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what are HLA proteins?

human leukocyte antigen protein
present to the T-cell with antigens bound to it

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what are the 2 types of HLA proteins

HLA class I
HLA class II

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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

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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

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HLA type I molecule subtypes are all indicated by the designation…

A, B, or C

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HLA type II molecule subtypes are all indicated by the designation…

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HLA-1 proteins bind intracelular antigens via the ?

endogenous pathway

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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

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what are immunoproteosomes?

specialized proteasomes that are very good at presenting HLA-1 bound peptides to T-cells

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what is the protein that translocate the peptide fragment into the RER for loading onto the HLA-1?

TAP

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what are the receptors that increase transcription of HLA-1 protein in the presence of intracellular invaders?

NOD-like receptors

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what does NOD-like receptors activate that in turn increase transcription of HLA-1 proteins

NFkB

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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)

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T or F: cytokines can also increase the expression of HLA-1 molecules

true

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what cytokines can increase the expression of HLA-1 molecules

both type 1 and type 2 interferons
tumour necrosis factor alpha (TNFa)

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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

1. Enhances the strength of signal between the T-cell and the antigen presenting cell 2. 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