Immune system

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Human Immune System

The human immune system is made up of different components that allow labelling and elimination of foreign substances, as well as the regulation of these processes. It can be innate or adaptive (specific).

The functioning or malfunctioning of this system is therefore of vital importance to health and disease. Not only does it constitute the body's defensive system against foreign antigens, but a malfunctioning of its regulatory processes can result in conditions such as autoimmune disease. A major area of interest is also the role of its different components in treatments to conditions such as leukaemia, where Graft vs Host Disease due to an inflammatory response launched against the donor's haematopoeitic transplant is a hurdle still to overcome[1]. An understanding of the human immune response is also vital in relation to the study and production of vaccines as the basis behind their function is to stimulate the innate immune response and cause the creation of memory cells without actually giving someone a serious or fatal strain of the disease.

Cell of the Immune System

Leukocytes, more commonly called White Blood Cells, are the cells that are responsible for the body's defensive mechanims and all originate in the bone marrow as Haematopoeitic stem cells. However, their different properties and development let them be divided into three different groups[2].

Lymphocytes

Monocytes

Granulocytes

Components of the Immune System

Physical Barriers

The first line of defence are physical barriers that prevent the pathogen or foreign substance from entering the body or, once entered, from harming it.

The skin is one of the most obvious exmaples. Not only does it provide physical protection from invasion, but the presence of antimicrobial substances[3] and a low pH prevents pathogenic bacterial colonisation for example. As well as on the skin, the large intestine for example contains colonies of normal flora, non-pathogenic bacteria that provide a competitive environment for pathogenic strains.

Epithelial lining of the respiratory and digestive tracts is the physical barrier found in these systems protecting the host from infection spreading into the blood, from where it would circulate throughout the body and lead to septicaemia (blood poisoning).

Mucociliary clearance is another example of the body's ability to combat invading foreign substances, which are trapped in the mucus transported along by the cilia found on respiratory epithelial cells[4].

Lysozyme in tears helps defend the eye, which constitutes a gateway to the paranasal sinuses, from bacterial invasion.

Innate Immune Response

The human immune response can be categorised into the Innate and Specific Immune Responses.

On initial contact with a pathogen or other foreign substance, the body's Innate Immune Response is launched, which can again be subdivided into Humoral and Cell-Mediated Immunity.

The first discribes all the components of the Immune System that are found in the serum and their mechanisms. These include cytokines, low molecular weight proteins that are released by cells of the immune system to interact with other cells to produce an inflammatory response and therefore contribute greatly to regulation of the same. An example of a cytokine involved in the innate immune response is IL-6 (Interleukin-6), which is secreted by macrophages after phagocytosis of a bacteria for example[5].

Complement is another major component of the body's Humoral Innate Immunity. When a foreign antigen binds to a freely circulating antibody in the blood, such as IgM, a cascade of reactions is initiated involving serum and membrane proteins leading to the attraction of immune cells to the site of infection, as well as opsonization of the pathogen with complement proteins, which prepares the cell for phagocytosis[6].

Cell Mediated Innate Immunity is comprised of the body's cellular response to infection. As already mentioned, phagocytes such as macrophages and neutrophils engulf foreign substances and destroy them intracellularly, displaying the foreign antigens on the cell-surface[7] for recognition by T-cells for example and the initiation of events leading to Acquired Immunity. The release of cytokines by phagocytes leads to an amplification of the immune response and attraction of other, more specialised immune cells, such as B-lymphocytes. Binding to the displayed antigen results in activation of the B-cell and the production of antibodies specific to that antigen, which, as the name suggests, leads us to the...

Specific Immune Response

Whereas the Innate Immunity provides a general response to invading pathogens, Specific Immunity is a more specialised array of defense mechanisms that the body deploys to ensure that the infection is targeted specifically according its properties and an "immune memory" is established. The specific response to bacterial infections will be different to that of a viral infection for example. Again, the humoral and cell-mediated components play slightly different roles in achieving this.

Humoral Specific Immunity is largely constituted by the action of antibodies in the serum. These are released from mature B-cells that have bound to an antigen-presenting cell (APC), such as a macrophage, and have been activated and developed into plasma cells[8]. The released immunoglobulins, as antibodies are also called, are all of the same specificity and bind to the invading pathogen, opsonizing it and thereby labelling it for phagocytosis[9]. The longterm effect of this mechanism is the creation of memory B-cells, which can be very quickly activated on recurring contact with the same antigen (if the pathogenic infection is repeated at a later time) and lead to the body's Secondary Immune Response, which is built up much more quickly than the Primary Immune Response on initial infection[10].

Cell-mediated Specific Immunity can be seen mainly in the action of a different type of lymphocyte, the T-cell. These can be divided into two major groups, Helper T-cells (Th) and Cytotoxic T-cells (CTL)[11]. The first are involved in regulation of the specific immune response. They bind to an APC and release specific cytokines that in turn activate other leukocytes to elicit the right type of response[12]. A sub-group of T-helper cells are the so-called T-regulatory cells (T-regs or Th3), which play an important part in controlling the immune response by upregulating some processes and downregulating others. For this reason they have been implicated in autoimmune diseases such as asthma or Type I diabetes melllitus[13]. Cytotoxic T-cells specifically target invading viruses and are activated by the cytokines released by Th-cells. As their name suggests, they destroy the infected host cells by creating a pore in the plasma membrane, which leads to apoptosis of the host cell[14].

References

  1. Dickinson, A.M. et al. (2004) "Genetic Polymorphisms prediciting the outcome of bone marrow transplants" in British Journal of Haematology, 127, 479-490
  2. Alberts et al. (2008) "Molecular Biology of the Cell" 5th ed., Garland Science Publishing, pp. 1450-1454
  3. Alberts et al. (2008) "Molecular Biology of the Cell" 5th ed., Garland Science Publishing, pp. 1524-1527
  4. Alberts et al. (2008) "Molecular Biology of the Cell" 5th ed., Garland Science Publishing, pp. 1524-1527
  5. Cytokines & Cells Online Pathfinder Encyclopedia http://www.copewithcytokines.org/cope.cgi?key=IL6
  6. Alberts et al. (2008) "Molecular Biology of the Cell" 5th ed., Garland Science Publishing, pp. 1528-1529
  7. Alberts et al. (2008) "Molecular Biology of the Cell" 5th ed., Garland Science Publishing, pp. 1531-1534
  8. Alberts et al. (2008) "Molecular Biology of the Cell" 5th ed., Garland Science Publishing, pp. 1551-1552
  9. Alberts et al (2008) "Molecular Biology of the Cell" 5th ed., Garland Science Publishing, Figure 25-24 p. 1555
  10. Alberts et al (2008) "Molecular Biology of the Cell" 5th ed., Garland Science Publishing, pp. 1545-1547
  11. Alberts et al. (2008) "Molecular Biology of the Cell" 5th ed., Garland Science Publishing, pp. 1569-1570
  12. Alberts et al. (2008) "Molecular Biology of the Cell" 5th ed., Garland Science Publishing, pp. 1573-1575
  13. Yazdanbakhsh, M. et al. (2002): "Allergy, Parasites, and the Hygiene Hypothesis" in Science, 296, 490-494
  14. Alberts et al (2008) "Molecular Biology of the Cell" 5th ed., Garland Science Publishing, pp. 1572-1573
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