Antigen recognition by T cells is accomplished by a mechanism similar to that employed by immunoglobulin. Essentially, a limited set of gene segments can recombine to encode a highly diverse set of receptor specificities; however, unlike B cells, the receptor is not released. The T-cell receptor (TCR) is on the surface of all thymus-derived lymphocytes. It comprises two transmembrane glycoprotein chains, termed α and β (αβ cells) (although analogous structures named γ and δ (γδ cells) can be found on some immature T cells). The αβ cells play a role in adaptive immune responses, whereas the γδ cells are involved in epithelial defence. As with antibody, the polypetide chains have both a variable (V) and a constant region (C) of amino acid residues. In the β chain the variable region is encoded by V-, D- and J-like elements. The α chain is made up of V- and J-like elements (Fig. 4.6). The polypeptide chains of the receptor are linked by disulphide bridges. The molecule is arranged on the T-cell membrane as a complex with another structure known as CD3. This association is necessary for the antigen receptor to be expressed at the cell surface. The receptor also has a transmembrane tail. When an antigenic peptide is received by the receptor, either in association with MHC class 1 for cytotoxic T cell activation or MHC class II for T-helper cell activation, a signal, manifesting as a series of enzyme phosphorylation reactions, is transmitted to the nucleus and the cell then responds accordingly by becoming activated, releasing cytokines and/or proliferating.

CYTOPLASM

03/12/09

This is the fluid component inside the cell membrane and contains many specialized organelles. It contains a scaffolding or cytoskeleton that regulates the passage and direction in which the interior solutes and storage granules flow. The cytoplasm contains:

  • Endoplasmic reticulum (ER). This consists of interconnecting tubules or flattened sacs (cisternae) of lipid bilayer membrane. It may contain ribosomes on the surface (termed rough endoplasmic reticulum (RER) when present, or smooth endoplasmic reticulum (SER) when absent). The ER is involved in the processing of proteins: the ribosomes translate mRNA into a primary sequence of amino acids of a protein peptide chain. This chain is synthesized into the ER where it is first folded and modified into mature peptides. ER is the major site of drug metabolism.
  • Golgi apparatus. This consists of flattened cisternae similar to the ER. It is characterized as a stack of cisternae from which vesicles bud off from the thickened ends. The primary processed peptides of the ER are exported to the Golgi apparatus for maturation into functional proteins (e.g. glycosylation of proteins which are to be excreted occurs here) before packaging into secretory granules and cellular vesicles that bud off the end.
  • Lysosomes. These are dense cellular vesicles containing acidic digestive enzymes. They fuse with phagocytotic vesicles from the outer cell membrane, digesting the contents into small biomolecules that can cross the lysosomal lipid bilayer into the cell cytoplasm. Lysosomal enzymes can also be released outside the cell by fusion of the lysosome with the plasma membrane. Lysosomal action is crucial to the function of macrophages and polymorphs in killing and digesting infective agents, tissue remodelling during development and osteoclast remodelling of bone. Not surprisingly, many metabolic disorders result from impaired lysosomal function.
  • Peroxisomes. These are dense cellular vesicles so named because they contain enzymes that catalyse the breakdown of hydrogen peroxide. They are involved in the metabolism of bile and fatty acids, and are primarily concerned with detoxification, e.g. d-amino acid oxidase and H2O2 catalase. The inability of the peroxisomes to function correctly can lead to rare metabolic disorders such as Zellweger’s syndrome and rhizomelic dwarfism.
  • Mitochondria. These organelles are the powerhouse of the cell. Each mitochondrion comprises two lipid bilayer membranes and a central matrix. It also possesses several copies of its own DNA in a circular genome. The outer membrane contains many gated receptors responsible for the import of raw materials like pyruvate and ADP, and the export of products such as oxaloacetate (precursor of amino acids and sugars) and ATP. An interesting caveat to our symbiotic relationship is that proteins of the Bcl-2/Bax family are incorporated in this outer membrane and can release mitochondrial enzymes that trigger apoptosis. The inner membrane is often highly infolded to form cristae to increase its effective surface area. It contains transmembrane enzyme complexes of the electron transport chain, which generate an H+ ion gradient. This gradient then drives the adjacent transmembrane ATPase complex to form ATP from ADP and Pi. The inner matrix contains the enzymes of the Krebs cycle that generate the substrates of both the electron transport chain (FADH2 and NADH) and central metabolism.

The causative agents of infectious diseases can be divided into four groups.

Prions are the most recently recognized and the simplest infectious agents, consisting of a single protein molecule. They contain no nucleic acid and therefore no genetic information: their ability to propagate within a host relies on inducing the conversion of endogenous prion protein PrPc into a protease resistant isoform PrPres.

Viruses contain both protein and nucleic acid, and so carry the genetic information for their own reproduction. However, they lack the apparatus to replicate autonomously, relying instead on ‘hijacking’ the cellular machinery of the host. They are small (usually less than 200 nanometres in diameter) and each virus possesses only one species of nucleic acid (either RNA or DNA).
Bacteria are usually, though not always, larger than viruses. Unlike the latter they have both DNA and RNA, with the genome encoded by DNA. They are enclosed by a cell membrane, and even bacteria which have adopted an intracellular existence remain enclosed within their own cell wall. Bacteria are capable of fully autonomous reproduction, and the majority are not dependent on host cells.

Eukaryotes are the most sophisticated infectious organisms, displaying subcellular compartmentalization. Different cellular functions are restricted to specific organelles, e.g. photosynthesis takes place in the chloroplasts, DNA transcription in the nucleus and respiration in the mitochondria. Eukaryotic pathogens include unicellular protozoa, fungi (which can be unicellular or filamentous), and multicellular parasitic worms.

Other higher classes, notably the insects and the arachnids, also contain species which can parasitize man and cause disease: these will be discussed in more detail later on.