Block D - Microbial Growth Flashcards
What is signal transduction, in context to T cell activation (1 mark)
signal transduction refers to the cascade of intracellular biochemical events triggered when a T cell receptor (TCR) binds to an antigen presented on an APC.
What co-stimulatory signals are involved during T cell activation by a APC?
CD28 on T cell binds to CD80/CD86 on the APC
After the initial trigger of T activation, how are kinases activated by Lck? (2 marks)
-Lck is associated with CD4 or CD8 and becomes activated upon TCR
-Lck phosphorylates Immunoreceptor Tyrosine-Based Activation Motifs (ITAMs) within the CD3 and zeta subunits of the TCR complex
After the initial trigger of T activation, how are kinases activated by ZAP-70? (2 marks)
-ZAP-70 is recruited to phosphorylated ITAMs (see Lck question)
-Lck activates ZAP-70, initiating downstream signalling cascades
What 3 major pathways does T cell activation activate?
MAPK, PI3K-Akt and NF-κB
Why is signal transduction an important process?
it ensures that T cell activation is a highly regulated process.
Briefly describe the cytosolic/endogenous pathway?
presents intracellular antigens (viral proteins or proteins from intracellular bacteria) to CD8+ cytotoxic T cells
Which MHC class does the cytosolic/ endogenous pathway use?
MHC class I
Briefly describe the endocytic/exogenous pathway?
presents extracellular antigens (bacterial toxins, extracellular bacteria) to CD4+ helper T cells
Which MHC class does the endocytic/exogenous pathway use?
MHC II
Detail the steps in the endogenous/cytosolic pathway (5 marks)
-proteins are degraded into peptides by the proteasome
-immunoproteasomes, induced by interferons, optimise peptide generation for MHC I binding
-peptide transported into ER by TAP (transporter associated with antigen processing?)
-in the ER, peptides bind to MHC class I with the help of chaperones like tapasin and calnexin.
-MHC class I complexes are transported to the cell surface
Detail the steps in the exogenous/endocytic pathway (4 marks)
-antigens are internalized by APCs via phagocytosis
-these antigens are degraded into peptides in acidic endosomal and lysosomal compartments
-in the ER, the invariant chain directs MHC II to an endosomal compartment, where it is degraded, leaving a fragment called CLIP
-HLA-DM facilitates the exchange of CLIP for antigenic peptides, allowing peptide loading
Name 3 examples of APCs
dendritic cells, B cells, macrophages
What processing site does the endogenous/cytolytic pathway use? (2 marks)
cytoplasm and ER
What processing site does the exogenous/endolytic pathway use? (2 marks)
endosomes and lysosomes
Describe the structure for MHC class I? (4 marks)
-alpha chain is composed of 3 domains (α1, α2, and α3)
-α3 domain is a highly conserved Ig-like domain and interacts with CD8 co-receptors
-the beta 2 microglobulin stabilizes the MHC I molecule
-peptide-binding groove
Which segment stabilises the MHC class I molecule
β2-microglobulin
In which segment does small peptides bind to the MHC class I molecule
peptide-binding cleft
Describe the structure for MHC class II? (4 marks)
-two alpha chains α1 and α2
-two beta chains β1 and β2
-peptide binding groove formed by α1 and β1 domains
In MHC II, Peptide-binding cleft is ______, allowing accommodation of _____ peptides.
open-ended, longer
IN MHC I, is the end of binding groove open or closed?
closed
Describe the structure T cell Receptor. (3 marks)
-heterodimer stucture ( alpha and beta chain)
-each α and β chain has a variable and constant
-antigen-binding site is formed by the combination of the Vα and Vβ regions
How does the TCR stay anchored to the membrane? (2 marks)
-α and β chains of the TCR have regions that anchor the receptor in the T-cell membrane.
-the membrane-spanning regions of these chains are hydrophobic, allowing them to embed within the lipid bilayer of the cell membrane
What is the antigen binding site of the TCR formed by?
a combination of the Vα and Vβ regions
