Phagocytes

Monocytes and Macrophages

Monocytes and macrophages are closely related immune cells. Monocytes are found circulating in the blood. They migrate into tissues in response to infection or inflammation where they differentiate into macrophages. Macrophages are the main phagocytes found in tissues, where most infections occur.

Monocytes

Monocytes circulating in the blood can be recruited into tissues in response to infection or inflammation. They are the largest type of phagocyte, with a kidney bean-shaped nucleus when seen under a microscope.

Monocytes can also differentiate into dendritic cells if certain cytokine signals are present, particularly during inflammation.

By Bobjgalindo (Own work) CC BY-SA 4.0-3.0-2.5-2.0-1.0 (http://creativecommons.org/licenses/by-sa/4.0-3.0-2.5-2.0-1.0)], via Wikimedia Commons

Fig 1
Electron micrograph showing a monocyte surrounded by red blood cells.

Macrophages

Macrophages are long-lived cells that reside in all tissues of the body and are often the first cells to encounter a pathogen.

Upon phagocytosis of microbes, cellular debris or other foreign substances, they:

• release cytokines (IL-1, IL-6, TNF) to initiate inflammation, akin to ‘sounding the alarm’
• release chemokines to recruit neutrophils to the site of infection
• present antigens to T cells in their capacity as antigen-presenting cells (APCs), triggering the adaptive immune response

Macrophages are strategically located throughout the body to patrol and defend against new pathogens. They may take on specialised forms (and names) depending on the tissue they reside in, e.g. the liver (Kupffer cells), lungs (alveolar macrophages) and brain (microglia). This system of macrophages is termed the mononuclear phagocyte system.

By Originally by Frevert U, Engelmann S, Zougbédé S, Stange J, Ng B, et al. Converted to SVG by Viacheslav Vtyurin who was hired to do so by User:Eug. [CC BY 2.5 (http://creativecommons.org/licenses/by/2.5)], via Wikimedia Commons

Fig 2
Diagram showing the location of Kupffer cells within the liver.

Dendritic Cells

Dendritic cells are normally formed in the bone marrow and migrate to tissues throughout the body. However, they can also be derived from monocytes during inflammation. Dendritic cells act as a link between the innate and adaptive immune systems.

Like macrophages, dendritic cells are professional APCs. As immature cells, they act as sentinels, continuously sampling their environment for pathogens by macropinocytosis. They can be activated by encountering a pathogen or the presence of cytokines indicating infection.

Upon activation the dendritic cells mature, process the antigen, migrate to peripheral lymphoid organs (e.g. lymph node, spleen, gut-associated lymphoid tissue) and present the antigens on their surface to T cells, initiating the adaptive immune response.

Dendritic cells are so named because of their long cytoplasmic projections, which resemble the dendrites of neurons. These projections increase the surface area available for interaction with their environment, pathogens and T cells.

By Zhiguo.he (Own work) [CC BY-SA 4.0 (http://creativecommons.org/licenses/by-sa/4.0)], via Wikimedia Commons

Fig 3
Dendritic cells (stained green) located in the corneal epithelium.

Granulocytes

Granulocytes are a group of phagocytes of the myeloid lineage, characterised by dense granules in their cytoplasm and lobulated nuclei. They include neutrophils, eosinophils and basophils.

Neutrophils are the most abundant type of white blood cell overall and are the first cells to respond during the acute phase of infection. They circulate in blood until they are recruited to the site of infection, squeezing through the vessel endothelium (details of this process are discussed here).

Neutrophils are also the most potent at killing pathogens from all the phagocytes. Their granules contain antimicrobial proteins, enzymes and reactive oxygen species, which are released into phagosomes to destroy engulfed pathogens. They also release neutrophil extracellular traps (NETs) – networks of extracellular fibers that trap and kill pathogens.

Partly due to their potent antimicrobial activity, neutrophils are short-lived cells that die shortly after phagocytosis, forming a major component of the purulent exudate (pus) seen with infection.

By Dr Graham Beards (Own work) [CC BY-SA 3.0 (http://creativecommons.org/licenses/by-sa/3.0)], via Wikimedia Commons

Fig 4
Electron micrograph showing neutrophils on a blood smear.

Clinical Relevance

Neutropenia

Neutropenia is a low neutrophil count, normally defined as less than 1.5 x 10⁹/L. Neutropenic patients are at high risk of infections due to a compromised innate immune system. If they become unwell they require urgent broad-spectrum antibiotics due to the risk of this progressing to septic shock.

The causes of neutropenia vary according to duration:

• Acute neutropenia (for less than 2 weeks) – viral infection (HIV, CMV, EBV, influenza), recent chemotherapy
• Chronic neutropenia – autoimmune disorders (SLE), B12/folate deficiency, haematological malignancy, medication, or ethnicity (benign in some people of Afro-Caribbean or Middle Eastern descent)

If patients are well, ethnicity or medication changes could explain the neutropenia. Blood films can help identify infection, autoimmune conditions, or lymphoproliferative disorders. Viral serology and autoantibodies may also be helpful.

Haematological malignancy is a relatively unusual cause for an isolated neutropenia. Patients should be referred if there is suspicion of serious disease, progression, or development of other blood cell abnormalities.

By Roberto J. Galindo (Own Work: Foto tomada por Roberto J. Galindo) CC BY-SA 2.5-2.0-1.0 (http://creativecommons.org/licenses/by-sa/2.5-2.0-1.0)], via Wikimedia Commons

Fig 5
Blood smear from a neutropenic patient showing only one neutrophil.