IC5 Flashcards
What cells produce MHC class I?
nucleated cells and platelets
What cells produce MHC class II?
APCs, B cells
What types of antigen does MHC class I bind to?
endogeneous: own, virus, neoantigen
What types of antigen does MHC class II bind to?
exogenous: bacteria
Which MHC class binds to CD8+
class I
Explain the process of antigen presentation by MHC I
endogeneous protein already in cytoplasm is broken down into peptides by proteasome.
Explain the process of antigen presentation by MHC II
exogeneous protein is phagocytosed into cell
How have T cells adapted to produce intracellular signals despite a short cytoplasmic tail?
CD3 proteins form dimers- CDey, CDEs, CDzz that contain ITAMs. ITAMs contain tyr which are phosphorylated to initiate signal transduction
How many CDRs are in T cells and antibodies
6 and 12
How, when and where does hypervariability of CDRs occurs in B cells?
In bone marrow, naive B cells undergo genetic rearrangement of variable domain ->clones are different
How, when and where does hypervariability of CDRs occurs in T cells?
Naive T cells in thymus undergo genetic recombination in variable domains. Va undergoes VJ recombination while VB undergoes DJ and then VDJ recombination
Whats the difference between monoclonal and polyclonal antibodies?
Monoclonal ab produced from the same B cell clone and only recognises one epitope.
polyclonal ab is a mixture of monoclonal ab
How are polyclonal antibodies made?
from passive immunisation of animals and collecting their antiserum
What 2 ways is antiserum purified? Which purification method results in the isolation of more antigen-specific antibodies
proteins A/G and
Immunoaffinity column chromatography. The latter
What modification is done in chimeric mabs?
all seq humanised except V domains
What modification is done in humanised mabs?
all seq humanised except CDR domains
Is humanised mabs or recombinant human mabs 100% human?
recombinant human mabs
What is a bispecific antibody derivative?
to different Fab arms
Whats the different between bispecific and triomabs antibody derivatives?
triomab is a bispecific + Fc component
How are Fab2 and Fab antibody derivatives made?
pepsin and papain enzymes to cleave ab
What does defucosylating an antibody do?
enhance affinity for Fc receptor on effector cells to bind to antigen
Which T cell therapeutic doesn’t involve genetic modification?
TIL
Which generation of CAR-T effective against antigen negative tumour cells?
4th gen as it has a transgene that secretes IL2 cytokine after antigen binding to scfv which activates endogeneous T cells which can recognise that antigen CAR-T cannot.
What are the upgrades in the different generations of CAR-T? and what difference does it make?
- CD3z
- CD28
- 4-BB
- transgene
stronger signaling and more potent antitumor activity
- transgene
Is TCR-T or CAR-T more effective in cancer treatment? Why?
TCR complex allows full activation at low antigen concentration and extended killing
Which T cell immunotherapy is used in both solid and hematological tumours?
TCR-T
Which T cell immunotherapy induces more CRS cytokine release syndrome? CAR-T or TCR-T
CAR-T
What do immune checkpoint inhibitors do?
they bind to checkpoint targets so that endogeneous ligand cannot bind to it and immune suppression is prevented
What are the 3 types of cancer vaccines?
cell, protein/peptides, nucleic acid
why are protein/peptide cancer vaccines less effective?
- neoantigens not included in vaccine
- peptides are too small ->non-specific binding + can only bind to MHC I
What is anergy?
lack of immune response
What type of nucleic acid is preferred in cancer vaccines?
RNA as its immediately translated and does not involve insertion into host DNA. so there is no chance of insertional mutation.
