Cancer vaccines Flashcards
(28 cards)
How do dendritic cells work?
They are immature cells surveying environment when they encounter antigen they uptake it through receptor mediated endocytosis and pinocytosis and then migrate to the lymph node mature and present antigen and gives co-stimulation to the t-cells, which will be activated and leave the lymph node and then the DC will upregulate their MHC2 class and stop processing antigens
What sis the difference between CD8 and CD4?
cd8-endogenous antigens-kill them directly or with helper t-cells, recognize mhc class 1 CD4- exogenous antigens- recognize mhc class2, endocytosis and releases cytokines
T/F
t-cells affinity mature
false
How is repertoire of t-cells selected for?
By tolerance through regulatory t-cells and thymic selection
What are the names of each MHC class1 and MHC class2 alleles?
HLA-A,B,C
HLA-DR,DP,DQ
How is thymic selection done?
There is negative selection of the t-cells that recognize self antigens, they are deleted also t-cells with high affinity(regulatory t-cells) and low affinity(die of neglect) are also deleted.
There is posistive selection of the t-cells that recognize MHC and has moderate affinity when binding to the MHC and peptide
What two are the two types of affinities that are selected for?
Peptide/MHC moderate affinity
TCR-moderate affinity
How do regulatory t-cell suppress immune system?
By CD4CD25 binds to the APC cell to CD80/86 and stops the induction of antigen signalling
What do you need to stimulate immune response when looking at the full activation of t-cells? What inhibits co-stimulation?
1st signal- the mhc+peptide
signal2-costimulation by APC- CD80/86(APC) binds to CD28(t-cells)
CTLA-4 on t-cells bind to CD80/86 and has higher affinity compared to CD28 t inhibits signalling
What cytokine matures the DC?
Il-10
How do DC recognize antigens?
Through their TLR that binds to molecular motifs found on pathogens
How do tumours escape immune response?
tumour induced Immunesuppression
Low immunogenicity
Antigenic modulation
What cytokines dysregulate t-cells?
IL-10,TGB
How to target Tumours? What antigens to target?
Finding cancer specifc antigens. maybe ones that overexpress stem cell genes or self peptides or have high affinity, or mutated epitopes
What are problems with immunizing against self antigens?
Need to overcome tolerance
Immunosuppression and t-cell regulation
What would the ideal vaccine be?
Naturally processed antigens CD4 or CD8 epitope HLA phenotype APC activation Remove regulatory t-cells correct conformation for antibody
What are the most effective cancer vaccines? And what is good about them?
Proteins- stimulate th rsponse
and DNA or RNA-stimulate CTL response
What are the advantages and disadvantages of peptide vaccines?
Can make a lot, cheap,
epitope prediction
Have to know sequence, b/t cell epitope, genetic restriction in immunogenic response, low immunogenicity
What is the requirements for CD8 epitope?
MHC class 1, it has to fit 9 amino acids
CD4 can accomodate larger epitopes compared to CD8
True
What are adjuvants and how do they work? What do they stimulate?
It’s a small agent hat acts nonspecifically that stimulates immune response by sending a signal 2 to t-cells. TH1 and TH2
What are some examples of adjuvants?
liposomes, particles, bacterial derived adjuvantd
How do DNA vaccnations work? How are they administered?
They take naked vectors with strong promoters and code for the antigens that can transcribe certain genes in situ and stimulates the immune response.
Intramuscular injection, interdermal injection, gene gun
What are teh advantages and disadvantages of using DNA vaccinations?
They can put multiple antigens in one injection, doesn’t need an expression system, it is there for the long term
They cant control it’s expression
Limited effectiveness in human trials
