Type IV Immunopathology (T-cell mediated)

Question 1

1. Define Type IV immunopathology.

Answer 1

T cell mediated, don’t require Ab

Question 2

2. Describe the cellular and molecular events following intradermal injection of tuberculin antigen into a person who has cell-mediated immunity to it. Justify calling the process ‘delayed hypersensitivity’. Characterize the cells that would be seen in a 48-hour biopsy of the site with regard to whether T cells or macrophages predominate.

Answer 2

Ag taken up by macs/DCs, presented on MHCII
Anti-TB Th1 memory cells become stimulated
Th1 produces IFNg, attract macs
MACS would be present 48h later

(Th1 can recruit 1000 macs!!)

Question 3

3. Explain why a person usually has no observed symptoms when first exposed to poison ivy.

Answer 3

Urushiol penetrates intact skin and associates with MHC on DCs (directly, or to protein that is then loaded)

DC travels to LN, presents urushiol to Th0 –> Th1, Th17

Th divide in the usual way, but by the time increased numbers of them are in the circulation, the antigen has been washed or worn off the skin, and there is no reaction

Question 4

4. Discuss how a chemical or small peptide might not need to be processed through an antigen- presenting cell to be presented by that cell to T cells.

Answer 4

Penetrate across barrier and load directly on or bind to a peptide that then loads directly on

Question 5

5. Discuss in principle how T cell immunity could be measured in the laboratory.

Answer 5

Incubate whole blood or WBC and Ag. Activation occurs.

1. Count cell numbers for proliferation
2. Look at cell size for activation (“blast transformation”)
3. Look at DNA synthesis using radiolabeled precursors.
4. Measure cytokines released into the medium can be quantified.

Question 6

6. Explain why TB skin tests can be administered repeatedly to the same subject.

Answer 6

Dose of PPD needed to elicit a positive reaction in an immune person is far lower that would be required to immunize him or her

Question 7

7. Differentiate between a first-set and second-set graft rejection.

Answer 7

First set: graph takes longer to be rejected because body is simply reacting to foreign MHC which looks like normal MHC + peptide. Recipient develops more T cells (Th1 and CTL) to respond in future

Second set: Rejected faster because now there are memory cells

Question 8

8. Define hyperacute rejection and indicate the mechanism.

Answer 8

Keep putting A onto B, graft will be rejected before it even has a chance to heal in and become perfused due to pre-existing antibody histocompatibility Ag.

Occurs in xenografts too where ubiquitous carbohydrate epitopes which are present in the foreign species but not in the human

Question 9

9. Discuss how autoimmunity can result from environmental exposure to tissues that cross-react with human organs.

Answer 9

Expose immune system to foreign tissue which reacts like normal Ag, but it’s similar enough to human tissue to cause a cross reaction. (pig brain example)

T’s react against self tissue. Over time, immune response becomes more “dialed in” to your tissue

Question 10

10. Discuss the three requirements for graft-versus-host disease to occur.

Answer 10

1. The graft must contain immunocompetent T cells
2. There must be at least one antigen in the host which the graft’s T cells can recognize.
3. The host must be relatively immunoINCOMPETENT or unable for genetic reasons to recognize the graft’s MHC antigens, otherwise the graft would be rejected too rapidly (outnumbered)

Question 11

11. Define the graft-versus-leukemia phenomenon.

Answer 11

Do a BM transplant, but leave some of the donors T cells in there to fight off any of the recipient’s lingering leukemia that was not destroyed by radiation

Question 12

12. Speculate on the role of HLA alleles in autoimmunity and chronic inflammatory diseases.

Answer 12

Certain HLA alleles confer binding specificity for drugs??