Cells of the immune system

White blood cells defend the body against infectious disease, tumours, and foreign materials and are classified by their appearance and function. Some white blood cells recognise specific foreign organisms and can respond more rapidly to those organisms if they encounter them a second time. These specific immune cells are called lymphocytes and include the T- and B-cells.

Other leukocytes are non-specific and will attack all organisms that do not carry the host’s MHC markers. These cells include granulocytes (neutrophils, eosinophils, basophils); monocytes and macrophages; dendritic cells; and mast cells. These non-specific leukocytes are referred to collectively as phagocytes (‘eating cells’) because of their role in engulfing, entrapping, and eliminating pathogens.

Neutrophils, basophils, and eosinophils are called granulocytes because they contain granules (small enzyme-containing sacs) of toxic molecules used to kill bacteria, fungi, and parasites that are released when stimulated by antigens.

Neutrophils circulate in the bloodstream and can migrate into tissue when infection is developing there; they are also attracted to sites of inflammation in the body. Neutrophils are normally the 'first responders' to these areas and are produced by bone marrow in enormous quantities. They are generally more effective against bacteria than they are against fungi and parasites. Their lifespan is up to about three days. The body’s production of neutrophils can be inhibited by drugs. A low neutrophil count is called neutropenia.

Eosinophils are similar to neutrophils in function, but generally kill larger micro-organisms, such as parasites.

Basophils (in response to stimulation such as injury or infection) release histamine to dilate the blood vessels, allowing other immune cells, oxygen, and nutrients to move into the area quickly. Although they do not ingest and destroy foreign material, they attract other immune cells to those sites. Mainly, basophils respond to inhaled material and gut parasites and are responsible for the symptoms of allergy.

Mast cells are a stationary counterpart to basophils and are found in tongue, skin and lung tissue and in the lining of the nose and gastrointestinal tract.

Monocytes are agranular phagocytes and the largest of the white blood cells. Monocytes in the bloodstream develop into macrophages when they enter tissues. They are concentrated in lymph nodes, connective tissue, the digestive tract, lungs, spleen, kidneys, and liver. Monocytes and macrophages filter and eliminate worn-out cells and debris. After destroying foreign organisms, monocytes and macrophages ‘present’ the antigen to T-cells. They also emit strong chemicals called monokines that mediate immune response. These cells are long-lived. Because they carry the CD4 molecule on their surface, they can be infected by HIV.

Dendritic cells are also antigen-presenting cells (APCs) and able to activate naive T-cells and stimulate the growth and differentiation of B-cells. Dendritic cells are concentrated in the lymphatic organs (e.g. lymph nodes and spleen) where they are able to trap foreign material. Dendritic cells can also trap material elsewhere, such as the mucosal linings of the bowel and lung. They then bring these antigens to the lymph nodes to present to lymphocytes. Langerhans cells are a type of dendritic cell that circulate in the skin and move antigens to the lymph nodes. Helper T-cells only become activated when they recognise an APC.

The third group of immune cells are lymphocytes and these include B-cells, T-cells and natural killer (NK) cells. B- and T-cells are the most important immune cells for specific or acquired immunity. In general, B-cells are most effective against bacterial, parasitic, and protozoan infections and T-cells against viral infections.

During their lives, CD4 and CD8 T-cells progress through a range of developmental states identifiable by the expression of various cell surface molecules called ‘markers’. All T-cells start as ‘naive cells’ and activate when encountering the specific antigen they are programmed to recognise with a primary response. After fighting the infection, most T-cells die; however, a proportion become long-lived memory cells, ready for the possible reappearance of the antigen.

Memory T-cells express the marker CD45RO and constitute most of the initial rise in T-cells after initiation of antiretroviral therapy. Naive T-cells express CD45RA and make up the second, slower phase of the CD4 cell count rise during antiretroviral treatment. While a number of other markers exist for naive and memory cells, contention remains about the precise manner of maturation and the appropriateness of individual markers.

CD38 and HLA-DR are expressed when a T-cell is activated. These markers are measured to show the proportion of activated T-cells, as many of these cells will subsequently die. When T-cells activate, they may also express the FAS gene. This gene is member 6 of the tumour necrosis factor receptor superfamily. FAS is officially known as TNFRSF6. This molecule increases the T-cell’s susceptibility to death through the process known as apoptosis (programmed cell death).

In HIV infection, T-cell activation is elevated too much and this elevation is associated with high levels of apoptosis. This is thought to be a major cause of CD4 T-cell loss during HIV infection.

Apart from B- and T-cells, the other type of lymphocyte are natural killer (NK) cells. NKs are small lymphocytes that originate in the bone marrow, but do not mature in the thymus. Like cytotoxic T-cells they are granule filled, but they do not attack a pathogen directly. NKs attack virus-infected cells and tumour cells and can do so without prior sensitisation; they do not need to recognise an antigen before acting. Virus-infected cells secrete interferon and this stimulates NK cells to attack.