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Hyperacute rejection is characterized by a rapid and immediate immune response that occurs within minutes to hours after transplantation. This type of rejection is primarily mediated by pre-existing antibodies in the recipient's serum that react against antigenic components present on the endothelial cells of the transplanted organ. These antibodies typically arise from prior sensitization to foreign antigens, possibly from previous transplants, blood transfusions, or pregnancies.

In hyperacute rejection, the binding of these antibodies to the graft leads to complement activation and subsequent destruction of the transplanted tissue, resulting in a swift and severe reaction. This rejection does not involve T cells or delayed-type hypersensitivity mechanisms, which are characteristics of other rejection types, such as acute or chronic rejection. Thus, the hallmark of hyperacute rejection is its humoral nature, highlighting the crucial role that antibodies play in this immediate immune response.