Cancer vaccines

Question 1

How do dendritic cells work?

Answer 1

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

Question 2

What sis the difference between CD8 and CD4?

Answer 2

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

Question 3

T/F

t-cells affinity mature

Answer 3

false

Question 4

How is repertoire of t-cells selected for?

Answer 4

By tolerance through regulatory t-cells and thymic selection

Question 5

What are the names of each MHC class1 and MHC class2 alleles?

Answer 5

HLA-A,B,C

HLA-DR,DP,DQ

Question 6

How is thymic selection done?

Answer 6

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

Question 7

What two are the two types of affinities that are selected for?

Answer 7

Peptide/MHC moderate affinity

TCR-moderate affinity

Question 8

How do regulatory t-cell suppress immune system?

Answer 8

By CD4CD25 binds to the APC cell to CD80/86 and stops the induction of antigen signalling

Question 9

What do you need to stimulate immune response when looking at the full activation of t-cells? What inhibits co-stimulation?

Answer 9

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

Question 10

What cytokine matures the DC?

Answer 10

Il-10

Question 11

How do DC recognize antigens?

Answer 11

Through their TLR that binds to molecular motifs found on pathogens

Question 12

How do tumours escape immune response?

Answer 12

tumour induced Immunesuppression
Low immunogenicity
Antigenic modulation

Question 13

What cytokines dysregulate t-cells?

Answer 13

IL-10,TGB

Question 14

How to target Tumours? What antigens to target?

Answer 14

Finding cancer specifc antigens. maybe ones that overexpress stem cell genes or self peptides or have high affinity, or mutated epitopes

Question 15

What are problems with immunizing against self antigens?

Answer 15

Need to overcome tolerance

Immunosuppression and t-cell regulation

Question 16

What would the ideal vaccine be?

Answer 16

Naturally processed antigens
CD4 or CD8 epitope
HLA phenotype
APC activation
Remove regulatory t-cells
correct conformation for antibody

Question 17

What are the most effective cancer vaccines? And what is good about them?

Answer 17

Proteins- stimulate th rsponse

and DNA or RNA-stimulate CTL response

Question 18

What are the advantages and disadvantages of peptide vaccines?

Answer 18

Can make a lot, cheap,
epitope prediction
Have to know sequence, b/t cell epitope, genetic restriction in immunogenic response, low immunogenicity

Question 19

What is the requirements for CD8 epitope?

Answer 19

MHC class 1, it has to fit 9 amino acids

Question 20

CD4 can accomodate larger epitopes compared to CD8

Answer 20

True

Question 21

What are adjuvants and how do they work? What do they stimulate?

Answer 21

It’s a small agent hat acts nonspecifically that stimulates immune response by sending a signal 2 to t-cells. TH1 and TH2

Question 22

What are some examples of adjuvants?

Answer 22

liposomes, particles, bacterial derived adjuvantd

Question 23

How do DNA vaccnations work? How are they administered?

Answer 23

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

Question 24

What are teh advantages and disadvantages of using DNA vaccinations?

Answer 24

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

Question 25

How does using antibody work when traeting cancer?

Answer 25

Can design an antibody against a tumour associtaed antigen

Question 26

What are other types of vaccines they can use?

Answer 26

Recombinant vaccines
Bacteria
viruses
dentdritic vaccines

Question 27

How do DC vaccinations work? And what are the advantages and disadvantages?

Answer 27

They take an antigen an present it to an immature dendritic cell in vitro, it matures and they inject it inot the patient
It’s highly specific with antigen and have an activated dendritic cell presenting it
It’s hard work, limited to a subset of DC, poor distributionof DC at specific site of injection

Question 28

Give example of an FDA approved dendritic vaccine? WHat does it treat?

Answer 28

Provenge

Prostate cancer