The Adaptive Immune System
The adaptive immune system is mobilized by cues from the innate response when the innate processes are incapable of coping with an infection. The adaptive immune system has a number of characteristics that contribute to its success in eliminating pathogens. These include the ability to (1) respond to a variety of antigens, each in a specific manner; (2) discriminate between foreign (“nonself”) antigens (pathogens) and self antigens of the host; and (3) respond to a previously encountered antigen in a learned way by initiating a vigorous memory response. This adaptive response culminates in the production of antibodies, which are the effectors of humoral immunity; and the activation of T lymphocytes, which are the effectors of cell-mediated immunity.
The induction of specific adaptive immunity requires the participation of professional antigen-presenting cells (APCs), which include dendritic cells (DCs), macrophages, and B lymphocytes. These cells play pivotal roles in the induction of an adaptive immune response because of their capacity to phagocytize particulate antigens (eg, pathogens) or endocytose protein antigens, and enzymatically digest them to generate peptides, which are then loaded onto class I or class II MHC proteins and “presented” to the cell surface T-cell receptor (TCR) (Figure 55–2). CD8 T cells recognize class I–MHC peptide complexes while CD4 T cells recognize class II–MHC peptide complexes. At least two signals are necessary for the activation of T cells. The first signal is delivered following engagement of the TCR with peptide-bound MHC molecules. In the absence of a second signal, the T cells become
FIGURE 55–2 T-cell activation by an antigen-presenting cell requires engagement of the T-cell receptor by the MHC-peptide complex (signal 1) and binding of the costimulatory molecules (CD80, CD86) on the dendritic cell to CD28 on the T cell (signal 2). The activation signals are strengthened by CD40/CD40L and ICAM-1/ LFA-1 interactions. In a normal immune response, T-cell activation is regulated by T-cell–derived CTLA-4 and PD-1. CTLA-4 binds to CD80 or CD86 with higher affinity than CD28 and sends inhibitory signals to the nucleus of the T cell, while ligation of PD-1 by PD-L1 or -L2 also inhibits T cell proliferation.