Type IV Hypersensitivity reactions + Transplant Immunology

Question 1

Which type of HSR is mediate by CD4+ T cells?

Answer 1

Delayed type hypersensitivity response – HSR due to the action of CD4+ T cells (sub-category of Type IV HSR)

Question 2

The tuberculosis skin test is an example of which HSR?

Describe the test. How is the reaction different from the “wheel and flare” reaction in Type I HSR?

Answer 2

The tuberculosis skin test (PPD) is a delayed type of Type IV HSR that is mediated by macrophages and CD4+ T cells

Sensitization: exposure to the antigen (either thru primary infection or vaccination)

Note that the reaction is NOT the same is wheel and flare where you’ve injected an allergen into the patient’s skin (making it a Type I HSR, and not a type IV)

This reaction involves injecting bacterial peptide into the patient

Note also that the response takes a couple of days

Question 3

If you biopsy the site where you do the PPD test, what population of cells will be present?

Answer 3

Left side: mononuclear cells (i.e. lymphocytes + macrophages and maybe NK cells with one round nucleus. No granulocytes involved

The lymphocytes are surrounding the blood vessels because they’re leaving this site (because they were circulating in the blood stream) to go to the site of injury

Question 4

Which endothelial adhesion molecules correspond to the following cells:

Neutrophils

Monocytes

T cells

What is the order in which these cells extravasate and arrive at the site of injury?

Answer 4

When E selectin is high, neutrophils are going to be interacting with it. Followed by ICAM-1, the main adhesion molecule for monocytes, and VCAM-1, the main adhesion molecule for T cells

(the order above is the order in which they extravasate generally)

Question 5

How does a granuloma form?

Mycobacterium tuberculosis and laprae cause which diseases?

What are 2 other examples of T cell mediated diseases in which the antigen is foreign (from a bug)?

Answer 5

Formation of a granuloma: T cells and macrophages surround the area with the bacteria in an effort to contain the infection

Some macrophages get hyperactive and some can even fuse such that they look one huge cell with multiple nuclei (recall that this is called a “giant cell”)

Because the immune system is hyperactive in this case, this can result in damage of surrounding cells and fibrosis since fibroblasts are trying to keep up with repairing the damaged tissue. Eventually you’ll have a lot of scar tissue remaining in the area (in the lungs of TB patients in this case)

Tuberculosis (by M. tuberculosis)

Leprosy (by M. leprae)

Leishmaniasis (by Leishmania)

Inflammatory bowel disease (IBD)

Question 6

Why do the 2 patients with the same leprosy infection have two different phenotypes?

Answer 6

The difference between the patient that has lesions all over the body and the one that has only a few lesions is the type of response that was mounted/strength of response. The one lesion person likely has a strong Th1 response that can contain the infection and limit any damage to one area, whereas the multi-lesion person probably has a weaker Th2 response that can’t contain the infection as well so it spreads and the lesions develop all over

Question 7

What are the types of Th cells that play a role in autoimmunity? Which types of bugs does each set target?

What are the immune cells activated by each of the Th cells?

Answer 7

Th1 and Th17 cells are important cell types that play a role in autoimmunity

(see diagram below)

Th1 cells >> macrophages via IFN-y >> autoimmunity + chronic inflammation **target intracellular bugs**

Th17 >> neutrophils via IL17 >> autoimmunity **target extracellular bugs**

Question 8

The growth of Tregs is influenced by the transcription factor ___, a defciency of which results in IPEX disease

Answer 8

For Tregs, know that FoxP3 is important for their growth, and they express CD25 which is important for their function

Question 9

Describe the phenotype of Wegener’s granulomatosis

Answer 9

Wegener’s granulomatosis: vasculitis that involves granulomas around the affected blood vessels

Question 10

What are 3 examples of Type IV HSRs (CD8+ T cell mediated?)

Answer 10

Contact dermatitis (nickel, poison ivy etc)

Graft rejection

Viral hepatitis (Hep B virus)

Question 11

Define a superantigen and explain how it leads to septic shock

What are two examples of superantigens?

Answer 11

Recall that superantigens bind from the side of the MHC and doesn’t interact with the binding pocket (hence the “no specificity” part) and causes a massive cytokine downstream response >> causes septic shock

Bugs to know for this: Staph aureus and Strep pyogenes

Question 12

What are the primary mechanisms through which transplant rejection occurs?

Answer 12

T cell mediated B cell responses

Question 13

Describe the direct pathway of antigen presentation that leads to rejection

Answer 13

Direct: Donor MHC presents donor peptide antigen to the recipient’s T cells

Question 14

Describe the indirect pathway of antigen presentation that leads to rejection

Answer 14

Indirect: debri from the donor (such as circulating dna and other donor derived material) which is typically endocytosed and brought into the recipient’s APC is presented on the recipient’s MHC to the recipient’s T cells

Question 15

Describe the semi-direct pathway of antigen presentation leading to transplant rejection

Answer 15

Semi-direct pathway: you have a small chunk of the cell wall of a donor’s cell (the cell wall has the donor’s MHC and donor antigen) that is presented to the recipient’s T cell

Question 16

The rejection process damages the transplanted organ through ____

Answer 16

The rejection process damages the transplanted organ through antibody mediated complement activation

Question 17

___ rejection happens within minutes; mediated by pre-existing host antibodies to donor antigen (Type II HSR). Not very common in this day and age

Answer 17

Hyperacute reaction: happens within minutes; mediated by pre-existing host antibodies to donor antigen (Type II HSR). Not very common in this day and age.

Question 18

____ several days, weeks to months; may be T cell mediated (CD8+ and or CD4+ T cells activated against donor MHC, Type IV HSR) or antibody mediated (similar to hyperacute except antibodies develop post-transplantation)

Answer 18

Acute rejection: several days, weeks to months; may be T cell mediated (CD8+ and or CD4+ T cells activated against donor MHC, Type IV HSR) or antibody mediated (similar to hyperacute except antibodies develop post-transplantation)

Question 19

____ over months or years; **uses the indirect pathway, so recipient APCs present donor antigen to CD4+ T cells, and both T cell and antibody responses involved (so both Type II and Type IV HSR)

Answer 19

Chronic rejection: over months or years; **uses the indirect pathway, so recipient APCs present donor antigen to CD4+ T cells, and both T cell and antibody responses involved (so both Type II and Type IV HSR)

Question 20

The most common drug given for maintenance following transplantation is ____, which works via T cell suppression by inhibiting calcineurin

Answer 20

The most common drug given for maintenance following transplantation is pro-graft/tacrolimus, which works via T cell suppression by inhibiting calcineurin