Tx Immunology - Professor Richard Kirk 2023

Professor Richard Kirk
MA FRCP FRCPCH
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Overview
The immune system is composed of several components. These include the physical barrier such as skin and the cellular and inflammatory responses. The immune system has developed two layers of cellular response - the first (innate) is designed to contain and limit the spread of microorganisms whilst waiting for the second (adaptive) to target specifically and eliminate it.

The innate system is the first line of defence. Cells of the innate system are principally derived from myeloid precursors (coloured green in Fig 1). They include phagocytes which are subdivided into monocytes (found exclusively in the blood), neutrophils (found in blood but can migrate to tissues), macrophages (found in tissues) and dendrites (which are also tissue bound). Phagocytes ingest and kill microorganisms. Other cell types also occur; eosinophils secrete substances to kill parasitic infections e.g. intestinal worms, basophils and mast cells release histamine leading to the inflammatory response (vasodilatation brings increased blood flow and hence more phagocytes to the area whilst increased capillary permeability enables plasma proteins to leave the circulation which amongst other functions wall off the infected area). NK Cells (natural killer) are also part of the innate immune system, although are unusual as they are derived from lymphoid, not myeloid, progenitor cells. They are able to directly attack microorganisms.
Cells of the innate system have toll-like receptors (TLRs) which enable them to recognise molecules on microorganism cell membrane which are not present on human cell membranes. For example bacterial cell membranes are composed of carbohydrate molecules whereas human cells are comprised of glycoproteins. The innate immune system will therefore not attack cells with a membrane comprised of glycoproteins.

Molecules of the innate system include the complement system, acute phase proteins and interferons. Whereas the innate system identifies microorganisms by differences in the type of molecules forming the cell membrane, T cells recognise foreign antigens presented to them by HLA glycoproteins on the cell membrane. There is no innate system mechanism for memorising previous encounters - this is one of the main differences between it and the adaptive system.

The adaptive system is the second line of defence. It has memory ability and whilst slower to activate has a more specific and sophisticated weaponry. These cells are derived from the lymphoid cell line (coloured blue in Fig 1) produced by stem cells in the bone marrow. They include B lymphocytes (antibody mediated immunity) and T lymphocytes (cell mediated immunity). The immune cell surface displays proteins that can sense and respond to their surroundings. These proteins include receptors and membrane transponders. They allow communication between cells enabling them to work synergistically. The specific protein pattern on the cell surface enables them to be identified using monoclonal antibody techniques. Such proteins are called cluster determinants (CD). Thus all B lymphocytes are identified by CD19+, T lymphocytes by CD3+ and macrophages by CD68+. Subsets can also be identified e.g. cytotoxic T cells are identified both by CD3+ and CD8+.
 
Unlike the innate system once T or B cells have been activated by binding to an antigen, memory cells are created so that if a subsequent encounter occurs the response can be more rapid.
References & Further Reading

  • Janeway’s Immunobiology, Seventh Edition, Garland Science 2008
  • Cancers 2016;8:36; doi:10.3390/cancers8030036
  • Chen & Flies. Nature Reviews Immunology 2013;13:227
  • Samelson. Cold Spring Harb Perspect Biol. 2011;3:a011510, doi: 10.1101/cshperspect.a011510
  • CD Maps. Kalina et al. Frontiers in Immunlogy 2019; 10:2434 doi: 10.3389/fimmu.2019.02434

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