Question

Chronic rejection mechanism in host vs graft is caused by (Host vs Graft implies transplant rejection)

• A. CD4+ T cells
• B. Antibody
• C. CD8+ T cells
• D. Macrophages

Hint:

• Chronic Graft Rejection Slow, progressive loss of graft function over months/years.
• Involves both cellular (T cells, macrophages) and humoral (antibodies) immune mechanisms.
• Characterized by fibrosis, vascular damage (graft arteriosclerosis), and chronic inflammation.
• CD4+ T cells are critical in initiating and sustaining the alloimmune responses leading to chronic rejection.

Answer 1

The Correct Option is A

Transplant rejection is an immune response by the recipient (host) against the transplanted organ or tissue (graft). Rejection can be classified based on timing and mechanisms:

• Hyperacute Rejection: Occurs within minutes to hours. Mediated by pre-existing recipient antibodies against donor antigens (e.g., ABO blood group antigens, HLA antigens).
• Acute Rejection: Occurs within days to weeks (or later if immunosuppression is inadequate). Primarily mediated by T cells (both CD4+ helper T cells and CD8+ cytotoxic T cells) recognizing donor MHC molecules (alloantigens). Antibodies can also contribute (acute humoral rejection).
• Chronic Rejection: Develops slowly over months to years. It is a complex process involving both cell-mediated immunity (T cells, macrophages) and humoral immunity (antibodies against donor HLA or other antigens, complement activation). It leads to gradual fibrosis, vascular damage (arteriosclerosis), and loss of graft function.

The question asks about the "Chronic rejection mechanism". (a) CD4+ T cells (Helper T cells): Play a crucial role in orchestrating both cellular and humoral immune responses. They help activate CD8+ T cells and B cells. In chronic rejection, CD4+ T cells recognizing donor antigens (often via the indirect pathway of allorecognition) contribute to inflammation, cytokine production, and help for antibody production. They are central to the chronic inflammatory process. (b) Antibody: Alloantibodies (antibodies against donor HLA or non-HLA antigens) play a significant role in chronic humoral rejection, leading to endothelial damage, complement activation, and chronic inflammation in graft vasculature. (c) CD8+ T cells (Cytotoxic T cells): Can directly kill graft cells expressing foreign MHC class I molecules. They are major effectors in acute cellular rejection and can contribute to chronic rejection. (d) Macrophages: Involved in both acute and chronic rejection as effector cells and by producing cytokines and growth factors that contribute to inflammation and tissue remodeling (fibrosis). Chronic rejection is multifactorial, involving T cells (CD4+ and CD8+), B cells/antibodies, and macrophages. However, CD4+ T cells are key initiators and orchestrators of the alloimmune response that drives chronic damage. They provide help for B cell antibody production and activate macrophages and CD8+ T cells. Given the options, and considering the central coordinating role: If only one primary cause is to be selected from the list for "mechanism", the options are all involved. The checkmark is on (a) CD4+ T cells. This highlights their central role in driving the chronic immune response, including help for antibody production and activation of other effector cells. While antibodies are also key effectors in chronic humoral rejection, the T cell response, particularly CD4+ T cell-mediated inflammation and help, is fundamental. \[ \boxed{\text{CD4+ T cells (play a central role in orchestrating chronic rejection)}} \]