The pathologic mechanisms of transplant rejection are complex, and they can be hard to get a grip on. Here are some questions that may help you understand these processes a little better.

Q. What are mononuclear cells?
A. Mononuclear cells are lymphocytes, plasma cells (which are just a specialized kind of B lymphocyte, really) and macrophages (a specialized form of monocytes). The term “mononuclear cells” is used to differentiate an inflammatory infiltrate composed of these cells (lymphocytes, plasma cells, macrophages) from one composed of neutrophils. Acute inflammation is usually composed of neutrophils; after about 48 hours, mononuclear cells start to predominate.

Q. What do “CD4+” and “CD8+” mean?
A. CD4 and CD8 are “markers” on the surface of lymphocytes. There are lots of markers on lymphocytes – and on other cells, for that matter. The + signifies that the cell in question is positive for that marker; a CD4+ cell has the CD4 marker on its surface. Helper T cells are CD4+ (positive) and CD8- (negative), whereas cytotoxic (killer) T cells are CD4- and CD8+. A simplified (but useful) way to look at these cells in the context of transplant rejection is this: CD4+ T cells recognize the cells to be killed, and CD8+ T cells do the killing.

Q. I’m confused by all the different kinds of rejection.
A. There are basically three types of rejection.

1) Hyperacute rejection – occurs within minutes/hours after transplantation (sometimes right on the table). The patient already has antibodies against the graft – so it’s usually a result of a technical error, like giving the patient the wrong blood-type organ. It’s really rare now, with all our testing, but it does occasionally happen.

2) Acute rejection – this can happen within months of transplant, or sometimes years later (after immunosuppressive therapy is stopped). It can involve both antibodies and T cells.

3) Chronic rejection – this one can happen at any time; it evolves over a period of several months. T cells (not antibodies) are the main damage-causers in this type of rejection.

That’s it in a nutshell in terms of mechanisms. The other thing to remember about rejection is that sometimes people talk about it in terms of “cellular” vs. “vascular” rejection. “Cellular” rejection usually happens in an acute fashion (the graft fails shortly after transplantation). The parenchyma of the graft (for example, the renal tubules, if it’s a kidney graft) gets invaded by lymphocytes. “Vascular” rejection can happen either in an acute fashion, or in a chronic fashion. In vascular rejection the vessels get attacked and there’s a vasculitis, so the organ gets damaged because of lack of blood supply. So acute rejection can show cellular changes and/or vascular changes, whereas chronic rejection shows mostly vascular changes.