The afferent phase of the immune response arc comprises the initial recognition, transport, and presentation of antigenic substances to the adaptive immune system. Recognition starts with antigen-presenting cells (APCs), which are specialized cells that bind antigen at a site. After the APC receives stimulatory signals (ie, complement), phagocytosis of the antigen occurs, as discussed in Chapter 1. Following ingestion of antigen, APCs migrate via afferent lymphatics to lymph nodes. Afferent lymphatic channels, usually simply termed lymphatics, are vein-like structures that drain extracellular fluid (ie, lymph) from a site into a regional lymph node. Lymphatics serve 2 major purposes: to convey immune cells and to carry whole antigen from the site of inoculation to a lymph node. In the APCs, enzymatic digestion of proteins within endocytic vesicles produces short chains of 7–11 amino acids: the antigenic epitopic fragments. Each antigenic fragment is combined with a groove-shaped human leukocyte antigen (HLA) peptide residing on the APC surface, and this surface complex contains a unique epitope. The combination of peptide and HLA protein is recognized by the T-lymphocyte receptors CD4 and CD8. HLA molecules vary in their capacity to bind various antigenic peptide fragments within their groove, and thus the HLA type determines the repertoire of peptide antigens capable of being presented to T lymphocytes. Specific HLA alleles are important risk factors for certain forms of uveitis. See Chapter 4 for further discussion of HLA molecules and disease susceptibility.
Figure 2-1 Comparison between the neural reflex arc and the immune response arc. APCs = antigen-presenting cells.
Major histocompatibility complex (MHC) class I molecules (ie, HLA-A, -B, and -C) serve as the antigen-presenting platform for CD8+ T lymphocytes, which are essentially cytotoxic T cells (Fig 2-2). Class I molecules are present on almost all nucleated cells and generally function to process peptide antigens synthesized by the host cell. If these presented antigens are recognized as self (ie, normal host protein), no immune reaction occurs. However, if there is an alteration of the normal host peptide (termed altered self ), by tumor or viral peptides after host cell invasion, an immune response is initiated. A viral infection, a neoplasm, or simply a genetic mutation that alters protein structure could also induce autoimmunity by stimulating an inappropriate immune response to normal host proteins.
MHC class II molecules (ie, HLA-DR, -DP, and -DQ) serve as the antigen-presenting platform for CD4+, or helper, T lymphocytes (Fig 2–3). The antigen receptor on the helper T lymphocyte can recognize peptide antigens only if the antigens are presented with class II molecules simultaneously. Only certain cell types express MHC class II molecules. Macrophages and dendritic cells are the most important of these types, though B lymphocytes can also function as class II–dependent APCs, especially within a lymph node. Class II–dependent APCs are considered the most efficient APCs for processing extracellular protein antigens; that is, antigens that have been phagocytosed from the external environment (eg, bacterial or fungal antigens).
Excerpted from BCSC 2020-2021 series: Section 9 - Uveitis and Ocular Inflammation. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.