DCs, MHC & Antigen Presentation Flashcards
(42 cards)
What are dendritic cells?
Professional antigen presenters that bridge the innate and adaptive immune systems
What is the role of DCs?
Act as sentinels, sampling the environment in peripheral tissues, capturing antigens, and then migrating to lymph nodes to activate naive T cells
What do immature DCs do?
They are in tissue constantly sampling the environment via phagocytosis and PRR signaling
How do DCs become activated?
Upon recognition of a PAMP/DAMP via their PRRs (or indirectly through inflammatory mediators)
What happens once DCs are activated?
They capture antigens and migrate to the lymph nodes via the afferent lymphatic vessels
What do DCs do once they are in the lymph nodes?
- Present processed antigens on MHC I/II to T-cells
- Provide costimulatory signals
- Secrete cytokines
- Spread the antigen to other DCs, expanding the pool of cells capable of activating specific T-cells
What does MHC stand for?
Major histocompatibility complex
What is MHC?
Group of genes encoding molecules that present antigenic peptides to T cells.
They are extremely polymorphic, with no 2 individuals having the same
What are MHC molecules known as in humans?
HLA (human leukocyte antigen) complex
What are the different classes of MHCs?
MHC class I
MHC class II
MHC class III (poorly defined so ignore but acknowledge existence)
Where is MHC class I expressed?
On all nucleated cells
Where is MHC class II expressed?
On antigen-presenting cells (e.g. DCs)
What does class I present?
Endogenous antigens like tumours or viral antigens
What does class II present?
Exogenous antigens (from phagocytosed pathogens like bacteria)
What are class I MHCs recognised by?
CD8+ T cells
What are class II MHCs recognised by?
CD4+ T cells
What is the class I pathway?
- Cytosolic proteins (viral proteins/tumour) degraded by proteasome
- Peptides/epitope transported to ER by TAP (transporter)
- Peptides loaded onto newly synthesised MHC I molecules in ER
- MHC-epitope complexes transported via Golgi to cell surface
What is cross-priming?
When DCs internalise infected/tumour cells, capturing antigens to allow for presentation to naive CD8+ T cells
What is the class II pathway?
- Antigen uptake by phagocytosis or endocytosis (primarily by DCs)
- Degradation of antigen in acidic endosome
- MHC II is synthesised in ER with invariant chain blocking groove
- In endosome, invariant chain is degraded but leaves behind CLIP (which prevents premature binding to MHII)
- Epitope is exchanged with CLIP
- MHC II-epitope peptide is transported to the membrane
Why is cross-priming necessary?
It crucial to activate naive CD8+ T cells for anti-cancer/viral infection immune response
How does cross-priming work?
- Pathogen infects cells; antigens appear
- DCs internalise infected cells and use cross-presentation to load the peptides onto their own MHC I
- DCs migrate to lymph nodes and present MHC I-epitope complex to naive CD8+ T cells
- Activated CD8+ T cells proliferate and leave the lymph node to kill infected cells at infection site
Example of pathogen interrupting MHC presentation for immune evasion
M. tb blocks phagosome-lysosome fusion, preventing processing/degradation of antigen. This means no peptide to form complex with MHC II, so cannot be presented to CD4+ T cells- inhibits activation of adaptive immune system
What are the do T cells scan MHC-peptide complexes?
Naive T cells in the lymph nodes use their T cell receptor (TCR) to scan MHC-peptide complexes. If the TCR matches the peptide, the T cell will bind
What is required to fully activate the T cell?
Costimulation.
Antigen-presenting cells generate costimulatory molecules that bind to T cells to fully activate the T cell
