What is the pathophysiology of alloimmunization?

Updated: Sep 08, 2017
  • Author: Douglas Blackall, MD, MPH; Chief Editor: Michael A Kaliner, MD  more...
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Answer

The immunologic mechanism for alloimmunization to antigens present in transfused cells involves presentation of the donor antigens by donor antigen–presenting cells (APCs), ie, monocytes, macrophages, dendritic cells, B cells, to recipient T cells. Recognition of the MHC class II alloantigens by CD4+ recipient T cells and their subsequent activation requires a co-stimulatory signal from either the donor or recipient APCs. The TH 2 subset of CD4+ T helper cells secretes interleukin (IL)–4, IL-5, IL-6, and IL-10, which activates B cells and initiates the antibody response. [2]

Leukocyte reduction of transfused platelets virtually eliminates donor APCs, but patients may still develop alloimmunization. Alloimmunization from leukocyte-reduced cellular blood products requires recognition of the alloantigen by recipient APCs and activation of recipient CD4+ T cells. This process also involves the initial recognition of alloantigens by natural killer cells, which secrete interferon-gamma. This cytokine, in turn, is involved in the activation of CD4+ TH 2 cells.

After initial activation and development of the primary immune response, T cells become memory cells. Memory T cells do not need co-stimulatory signals to become activated and can recognize signals in the absence of class II HLA molecules. Thus, donor RBCs, platelets, and inactivated APCs can induce restimulation of the immune response. Interestingly, blood transfusion (mainly through the TH 2 subset) can actively suppress the host immune response and induce tolerance to donor antigens. Another mechanism of immunosuppression involves stimulation of CD8+ suppressor T cells, which can recognize MHC class I alloantigens in platelets as well as donor APCs. Primary immunization with blood transfusion thus reflects a balance between clonal expansion and tolerogenic mechanisms. A secondary immune response depends on the restimulation of memory cells. Repeated immunization eventually results in sustained clonal expansion and clinically significant antibody production.


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