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
The TCR complex is associated with the ____ signaling complex, which transduces signals to activate the T-cell upon ______
CD3, antigen binding
Describe what SH2 binds to in TCR signalling? (3 marks)
-SH2 domains are found in ZAP-70, which is a key player in T cell activation.
-upon TCR engagement, the CD3ζ chains become phosphorylated on tyrosine residues. -ZAP-70 contains SH2 domains that recognize and bind to these phosphotyrosines, helping to recruit ZAP-70 to the receptor complex and initiate downstream signaling.
Describe what SH3 binds to in TCR signalling? (3 marks)
-SH3 domains in signaling proteins like Grb2 or SHP-1 (a tyrosine phosphatase) also participate in TCR signaling by binding to proline-rich sequences in target proteins.
-These interactions help in organizing the signaling complexes and regulating the activation of downstream pathways.
SH2 domain binds specifically to _________ residues in proteins
phosphotyrosine
SH3 domain binds to _________ sequences in proteins
proline-rich
Describe the alternative to TCR structure (not α or β chains) and in what cells are these found in? (2 marks)
γ (gamma) chain and δ (delta) chain. These are found in γδ T-cells, which are less common and have different functions compared to the more common αβ T-cells.
What is the function of the ζ (zeta) chain? (2 marks)
Its a critical signaling molecule and contains ITAMs, which are phosphorylated upon TCR engagement to initiate downstream signaling.
What’s the function of the CD3 complex? (1 mark)
its composed of several proteins that help transmit the signal inside the T cell when the TCR binds to its antigen.
What is the CD3 complex composed of? (3 marks)
CD3γ (gamma), CD3δ (delta), CD3ε (epsilon)
