Lecture 11 - Vaccines II

Question 1

What are the stages of the MHCI processing pathway?

Answer 1

1. Degradation of antigen at proteasome into antigenic peptides
2. Transport into tehe ER via TAP transporter protein. Within the ER, peptide binds MHCI via tapsin
3. Further processing occurs at the golgi
4. Vesicle transports final MCHI-peptide complex to CSM
5. Vesicle fuses with CSM displaying MHCI-peptide complex on infected cell. CD8+ cell can bind and initiate immune response

Question 2

What are the stages of the MHCII processing pathway?

Answer 2

1. Antigens endocytosed by APC
2. Degradation of antigen in phagolysosome to form antigenic peptides
3. MHCII molecule bound to invariant chain (Li) in ER. This prevents premature binding of antigenic peptides
4. MHCII + Li move to golgi where Li is degraded into CLIP. CLIP is then displaced allowing antigenic peptide to bind MHCII
5. Vesicle transports final MHCI-peptide complex to CSM
6. Vesicle fuses with CSM displaying MHCII-peptide complex on infected cell. CD4+ cell can bind and initiate immune response.

Question 3

What are polysaccharides on the surface of bacteria composed of?

Answer 3

Repeats of different sugars. The combination of different sugars present give rise to different properties of the polysaccharides

Question 4

What is the difference between the structure of a capsule of gram negative and gram positive bacteria?

Answer 4

Gram negative have LPS whereas gram positive don’t.

Question 5

Give some examples of bacterial pathogens where polysaccharides derived from their surface have been used as vaccines.

Answer 5

Streptococcus pneumoniae - pneumonia

Haemophilus influenzae - pneumonia

Neisseria meningitidis - meningitis

Salmonella typhi – typhoid fever

Burkholderia pseudomallei - melioidosis

Question 6

What is a problem experienced when designing a vaccine based on bacterial surface polysaccharides? How is this overcome?

Answer 6

Different strains have different polysaccharides on their surface, so one vaccination will not protect you from all of the strains.
This can be partially overcome by focusing on the strains that are most likely to cause disease in humans

Question 7

Which group(s) of patients do not respond well to polysaccharide vaccines?

Answer 7

The very young and elderly

Question 8

How is the problem of polysaccharides not being processed by the same conventional pathways as normal antigenic proteins overcome?

Answer 8

Conjugate vaccine- Link polysaccharide to a protein carrier, which enables you to convert the structure of the polysaccharide to look more like a protein antigen. This will cause it to be taken up by the normal MHCI/II processing pathways and elicit a T cell mediated immune response, which is much more effective in the very young or elderly.

Question 9

Which cell types are not involved in the response to polysaccharides?

Answer 9

CD4 and CD8 T cells (it is antigen independent)

Question 10

What is involved in the immune response to polysaccharides?

Answer 10

Indirect interaction with B cells
Clonal proliferation of B cells
Production of IgM antibody
This is a vey immature response and is only sufficient to protect those with normally fully functioning immune systems

Question 11

What is involved in the immune response to polysaccharides?

Answer 11

Indirect interaction with B cells
Clonal proliferation of B cells
Production of IgM antibody
This is a vey immature response and is only sufficient to protect those with normally fully functioning immune systems

Question 12

What is the mechanism of T cell activation by glycoconjuate vaccines?

Answer 12

1. Protein polysaccharide conjugate appears to be processed in same way as a protein would be processed (mhcII presentation pathway)
2. On surface of APC there are peptide fragments linked to polysaccharide on suface
   What this means is that we can elicit t cell help
3. Cytokines produced by CD4 t cells which are essential for the maturation of AB response, so IgG present and higher levels of AB in general produced.

Question 13

Give some examples of diseases where the microbe grows within the host cells

Answer 13

tuberculosis
salmonellosis
melioidosis
yellow fever
influenza
measles

Question 14

What are live attenuated microbes?

Answer 14

Living microbes which are disabled so that they don’t cause disease, they are used to make live attenuated vaccines

Question 15

What two factors must be balanced when designing a live attenuated vaccine?

Answer 15

A balance between over and under attenuation - disabled enough so they don’t cause disease but able to survive long enough to establish an immune response

Question 16

Which MHC processing pathway do subunit vaccines elicit a response via?

Answer 16

They use the phagocytic pathway via MHCII and evoke a CD4+ T cell response

Question 17

Which MHC processing pathway do live attenuated vaccines elicit a response via?

Answer 17

They use a MHCI to elicit a CD8+ T cell response. This kind of response is important when the cell requires killing, for example in cancer cells.

Question 18

Name some examples of live attenuated vaccines

Answer 18

Yellow fever
BCG
Polio

Question 19

How do naked DNA vaccines work?

Answer 19

1. DNA injected
2. Taken up by host cell into cytoplasm
3. Transcription and translation of the protein occur within the host cell
4. Protein presented by MHCI pathway

Question 20

What are the potential problems with naked DNA vaccines?

Answer 20

Protein may be quite long lived, making it difficult to determine how much protein the cell is exposed to, and control any potential side effects of this longevity of exposure

They don’t tend to work as well in humans as animal models, this is not fully understood why

Question 21

How are dendritic cell vaccines produced?

Answer 21

1. Cells harvested from patients
2. Purify APCs
   Make sure theyre differentiated into mature DCs
3. Have antigen you want to raise response against
   Get this into dc
   Infuse cells back into patient
4. Hope that they present to right cells to evoke right response