Academic Integrity: tutoring, explanations, and feedback — we don’t complete graded work or submit on a student’s behalf.

IMMUNOLOGY i) A mouse denoted as strain B (H-2b, referred to as “the host”) is i

ID: 163871 • Letter: I

Question

IMMUNOLOGY

i) A mouse denoted as strain B (H-2b, referred to as “the host”) is irradiated (which destroys bone marrow cells and BM derived cells) and transplanted with BM from Strain A mice (H-2k, referred to as “the donor”). These mice, called “chimeric” mice, are vulnerable to infectious illnesses of all kinds and a few of them die before they can be transferred to germ-free housing.

1. Explain the notation of the human MHC phenotypes H-2b and H-2k.

2. Illustrate and explain how thymocytes in the host will rely on MHCs extending from the surface of thymic epithelial cells to be “educated” to what is “self-MHC” and thus, what MHC-expressing cells are “self” and should be “left alone” and what MHC-expressing cells are foreign and should be targeted for rejection. [NOTE: activated CTLs are the major factor in transplant rejection.]

3. Explain this education in the host BEFORE transplant AND AFTER transplant.

B-52 CD8 CD4 K20

Explanation / Answer

MHC-restricted antigen recognition, or MHC restriction, refers to the fact that a given T cell can interact with both the self-major histocompatibility complex molecule and the foreign peptide that is bound to it, but will recognize and respond to the antigen, only when it is bound to a particular MHC molecule.

In organ transplantation, the adaptive immunity is considered the main response exerted to the transplanted tissue, since the principal target of the immune response is the MHC (major histocompatibility complex) molecules expressed on the surface of donor cells. However, we should not forget that the innate and adaptive immunities are closely interrelated and should be viewed as complementary and cooperating. When a human transplant is performed, HLA (human leukocyte antigens) molecules from a donor are recognized by the recipient's immune system triggering an alloimmune response Matching of donor and recipient for MHC antigens has been shown to have a significant positive effect on graft acceptance.

The antigens responsible for rejection of genetically disparate tissues are called histocompatibility antigens; they are products of histocompatibility genes. Histocompatibility antigens are encoded on more than 40 loci, but the loci responsible for the most vigorous allograft rejection reactions are located on the major histocompatibility complex (MHC).