Tx Immunology - Professor Richard Kirk 2023

Professor Richard Kirk
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The immune system consists of several components to protect the body from foreign and malignant substances, including the physical barrier such as skin, and cellular and humoral responses. The cellular response has two lines of defence - the first line, known as the innate immune response, is designed to respond quickly to contain and limit the spread of microorganisms and viruses, whilst the second line, known as the adaptive immune response, targets specifically to eliminate the threat.

Most cells of the innate system are derived from myeloid precursors (coloured green in Fig 1). They include phagocytes which are subdivided into monocytes (found mainly in the blood), granulocytes (found in blood but can migrate to tissues), macrophages (found in tissues) and dendritic cells (which are tissue bound but can also be found in the blood in immature state and can also derive from lymphoid progenitor cells). Phagocytes ingest and kill microorganisms. Granulocytes have small granules in their cytoplasm that release toxic enzymes.
Figure 1
Granulocytes can be subdivided in neutrophils, which are typically the first responders at the site of an infection, eosinophils, which secrete substances to kill parasitic infections e.g. intestinal worms, and basophils and mast cells, which release histamine leading to the inflammatory response. Natural killer (NK) cells are also part of the innate immune system, but are derived from lymphoid, not myeloid, progenitor cells. They can directly attack microorganisms. Cells of the innate system have pattern recognition receptors (PRR), such as toll-like receptors (TLRs), which enable them to recognise pathogen-associated molecular patterns (PAMPs) present on microorganism or viruses, but not on human cell membranes. Innate cells can also recognise damage-associated molecular patterns (DAMPs) which are molecules released upon cellular stress or tissue injury.

Molecules of the innate system include the complement system, acute phase proteins and interferons. The innate system identifies microorganisms by differences in the type of molecules forming 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. Whilst slower to activate compared to the innate system, it has a more specific and sophisticated weaponry. Importantly, it has memory ability so that if a subsequent encounter occurs the response can be more rapid. The adaptive 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). For example, 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+.
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

Authors: Richard Kirk (1), Nathanya Baez Hernandez (2) & Esmé Dijke (3)
Updated: 20 June 2023
  1. Program Consultant, Ospedale Paediatrico Bambino Gesù, Rome, Italy
  2. Haart Failure & Transplant Cardiologist, Associate Professor, University of Texas Southwestern, Dallas USA
  3. Associate Director, Histocompatibility Laboratory & Assistant Professor - Lab. Medicine and Pathology. University of Alberta Hospital, Alberta, Canada
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