Manipulation of the Immune Response

Question 1

Why are boosters needed for vaccines?

Answer 1

Vaccines are attenuated, meaning that the pathogenic agents that make up the vaccine are less immunogenic. Therefore, multiple injections (boosters) are needed to induce a sufficient protective response.

Question 2

Passive immunotherapies (vaccines) are effective for:

Answer 2

• black widow spider bite
• snake bite
• rabies
• botulism
• diphtheria
• Hep A and B
• measles
• tetanus

Question 3

What is the purpose of vaccine adjuvants?

Answer 3

• improve efficacy of vaccines

- reduce unwanted side effects of vaccines

Question 4

What are the antigen sources for vaccines?

Answer 4

• killed/inactivated pathogen
• toxoid
• viral subunits
• live attenuated virus

Question 5

What are the features of an effective vaccine?

Answer 5

• safe
• protective
• sustained protection
• induces protective T-cells
• induces neutralizing antibody
• low cost per dose
• biological stability
• ease of administration

Question 6

What are tumor antigens?

Answer 6

They are usually “altered self” proteins, meaning they have been modified or selectively over-expressed by a tumor.

Question 7

Are tumor cells highly immunogenic or poorly immunogenic?

Answer 7

They are poorly immunogenic, so their immunogenicity must be increased (if whole-tumor vaccines are to be created, that is) by adjuvants, gene-engineered tumor cells, or co-stimulatory molecules (like B7).

Question 8

Passive (adoptive) immunotherapy is most effective for which types of tumors?

Answer 8

highly immunogenic tumors (like melanoma)

Question 9

What are 2 examples of monoclonal antibodies used in tumor immunotherapy?

Answer 9

1) Rituximab (anti-CD20)

2) Herceptin (anti-HER2)

Question 10

What are 2 examples of adoptive cellular therapy used in tumor immunotherapy?

Answer 10

1) Monoclonal antibodies

2) Effector T-cells (TILs or tumor-specific antigens)

Question 11

What are ways by which tumors escape the immune system?

Answer 11

• immune inhibition via inhibitory cytokines (TGFβ, IL10, VEGF)
• T-cell inactivation
• evading immune checkpoint (tumor cells constantly stimulate the T-cell by tumor antigens, which chronically induces CTLA-4 on T-cell surface; this limits T-cell function, as they are constantly being inhibited)

Question 12

What is passive (adoptive) immunotherapy?

Answer 12

It provides an exogenous source of anti-tumor T-cells. The patient’s own T-cells are activated in vitro and re-transferred. Tumor specificity is generated by using (1) defined tumor-specific antigen or (2) tumor infiltrating lymphocytes (TILs)

Question 13

With regard to CTLA-4, what is helpful in allowing positive signaling from co-stimulatory molecules to T-cells, thus boosting the tumor immune response?

Answer 13

giving antibodies (anti-CTLA4 Abs) that block CTLA-4 and allow T-cell activation to be up-regulated

Question 14

How are tumors related to PD-1 (another immune checkpoint molecule)?

Answer 14

Tumor cells upregulate PDL1/2 on their surface, neutralizing the cytotoxic T-cell tumor attack.