The adaptive immune system essentially functions via the production of three key types of effector: antibodies (produced from B cells), cytokines

and cytolytic molecules (produced by T cells) ( Figure 2.6). The first cells to interact with an incoming pathogen are often the phagocytes of the innate immune system, which can engulf and degrade pathogens. However, it is now clearly recognised that professional APCs, typified by DCs, can ingest pathogen-derived proteins, partially digest, process and transport the peptide products to the cell surface, rather than targeting them for complete destruction. These pathogen-derived peptide antigens are bound by a specialised set of receptors known as human leukocyte antigens (HLA) that act as ‘antigen-presenting’ molecules. These molecules are encoded by a gene family called Sorafenib the major histocompatibility complex (MHC). DCs displaying pathogen-derived antigen on the cell surface are Obeticholic Acid in vitro also endowed with migratory properties that allow them to leave the infected site and migrate towards

the nearest lymph node. DCs therefore represent an important cellular messenger, able to transport molecular pathogen fragments to secondary lymphoid organs. Antigen fragments displayed by DCs are destined to activate pathogen-specific T cells residing in the lymph nodes. MHC restriction and T-cell subsets MHC molecules display antigenic peptides to T cells. MHC class I molecules receive endogenous proteins, including those derived from intracellular pathogens,

and are expressed by virtually all nucleated Cediranib (AZD2171) cells of the body. MHC class I peptides are recognised by the T-cell receptor (TCR) expressed by CD8+ T cells. MHC class II molecules are usually expressed by a restricted set of cells such as macrophages, DCs and B cells. They present peptides derived from exogenous antigens, taken up via mechanisms such as endocytosis and phagocytosis. Antigenic peptides presented by MHC class II molecules are bound by TCRs expressed by CD4+ T cells. T cells represent a subset of lymphocytes that differentiate within the thymus, a small bi-lobular organ situated in the anterior mediastinum. Each T cell expresses a unique antigen-specific receptor (the TCR) with a unique recognition capacity. T cells do not directly recognise whole pathogens, but are only specifically activated by DCs transformed into APCs which present molecular fragments (mostly peptides derived from limited digestion of protein antigens) in association with MHC molecules at the cell surface. Naïve lymphocytes are therefore ‘blind’ to live microorganisms and need the help of APCs to adequately react to an invading pathogen. An individual naïve T cell can only be activated by a protein antigen for which it has a specific receptor, and which has been processed and presented by an APC. Cells activated by antigen-bearing DCs express the cluster of differentiation (CD)4 cell-surface protein, and are thus referred to as CD4+ T cells.