Anatomy And Physiology

Cells of the Immune System



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It is helpful to divide the immune system into three divisions: non-specific, innate, and adaptive.

First, non-specific immune defenses include intact skin, body fluids with an acidic pH (esp. sweat, gastric juice, and urine), and complement proteins in the bloodstream.  Many potentially infectious pathogens are foiled at this level of immunity.

The bulk of this article will address the cellular components of the immune system, which can be subdivided into innate and adaptive immunity.

Most of a person's circulating white blood cells (50 -65%) fall into the category of innate immunity, meaning they possess no recognition capacity and respond the exact same way regardless of the nature of the microbial invader. Innate immune cells include granulocytes (neutrophils, eosinophils, basophils, and mast cells) along with monocytes (as well as their tissue counterparts the macrophages), and NK (natural killer) cells.

Collectively, these cells can be thought of as the shock troops of the immune system. Except for monocytes and NK cells, the other cells of the innate immune system tend to be short lived. When they confront foreign cells or antigens, they release a host of chemicals designed to a) combat the invaders directly b) promote inflammation and c) blow the proverbial whistle and attract other white blood cells to the site of infection.

These cells are listed in descending order of abundance in the immune system, and their specific functions are described.

1) Neutrophils contain granules with contents like lysozyme and lactoferrin. These proteins attack bacterial cell walls and sequester iron, respectively. Neutrophils also contain enzymes such as myeloperoxidase which produces hypochlorite ions (a.k.a. bleach) as well as other enzymes that produce oxygen radicals (nitric oxide, superoxide anions, etc.). These chemicals damage bacteria and surrounding tissue indiscriminately. 

Neutrophils respond to cytokines and chemotactic factors such as Interleukin-8, Leukotriene B4, and many other inflammatory mediators.

2) Monocytes/Macrophages  are larger than most other white blood cells. They have a distinctive horseshoe shaped nucleus. These cells are also called phagocytes, meaning they can engulf and destroy bacteria. Macrophages also act as antigen presenting cells to certain T lymphocytes called T helper cells. This will be discussed in further detail.

3) NK cells, formerly called large granular lymphocytes, are believed to be the main cell responsible for immune surveilance. This amounts to patrolling the body looking for virally infected cells as well as tumor cells and pre-cancerous cells.

4) Eosinophils have bilobular nuclei and pink staining granules. They produce major basic protein and other mediators believed to be important in containing parasitic infections, esp. worms. Hyperreactive eosinophils are believed to contribute to airway damage seen in people with chronic asthma.

5) Basophils and Mast cells figure prominently in allergic reactions, e.g. to pollen and bee stings. These cells contain an abundance of purple staining granules as well as an antibody called IgE on their surface. When an allergen crosslinks two IgE proteins, it triggers a chain of events culminating in the release of histamine, platelet activating factor (PAF) and other inflammatory molecules from the granules within these cells. Out of control histamine release can lead to death from anaphylactic shock. 

In contrast to the innate immune system, cells of the adaptive immune system, the lymphocytes, are capable of specific antigen recognition and possess the ability to respond more quickly and efficiently if they encounter the same antigen again. The adaptive immune system is traditionally divided into two arms: humoral immunity, dominated by B lymphocytes; and cell mediated immunity, dominated by T lymphocytes.   

Unlike neutrophils or monocytes, lymphocytes cannot be distinguished as B cells or T cells using a microscope. Instead, a flow cytometer is required to sort lymphocytes based on differences in their surface proteins.

B lymphocytes originate and mature in the bone marrow. These cells produce immunoglobulins, better known as antibodies. Antibody proteins may be soluble, as with gamma globulin or antibodies in breast milk; or may be surface bound like IgE. B cells can generate hundreds of thousands of different antibodies. The basis of this tremendous diversity, a mechanism called gene rearrangement, was not discovered until 1976.

In the aftermath of an infection, a subset of B cells that produced the most effective antibodies persist in the spleen and lymph nodes as memory B cells.  

T cells originate in the bone marrow then migrate to the thymus gland where they undergo maturation and selection. Rather than secrete antibodies, T cells produce a diverse array of surface proteins called T cell receptors (TCR). As with B cells, the mechanism underlying TCR diversity involves gene rearrangement.  

Several categories of T cells exist, including T helper cells (CD4 positive T cells), cytotoxic T cells (CD8 positive T cells), and suppressor T cells.

T helper cells process reports from antigen presenting cells, which include macrophages, B cells, and dendritic cells. TH1 cells interact with macrophages whereas TH2 cells mainly interact with B cells. In general, T helper cells  communicate with antigen presenting cells, cytotxic T cells and each other by means of cytokines, esp. Interleukin-2.

Cytotoxic T cells (CTL) specialize in destroying virally infected cells by direct cell to cell killing. The mechanism of cell killing remains obscure but probably includes production of oxygen radicals, release of inflammatory mediators, and induction of apoptosis (programmed cell death).   

Suppressor T cells are believed to contain inflammation at the site of infection and shut down the immune response once the invaders have been repelled. Several cytokines appear to be involved in turning off inflammation, esp. Interleukin-10.  


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