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In humans, dysfunctional macrophages cause severe diseases such as chronic granulomatous disease that result in frequent infections. Beyond increasing inflammation and stimulating the immune system, macrophages also play an important anti-inflammatory role and can decrease immune reactions through the release of cytokines.
There is uncontrolled activation and proliferation of macrophages, and T lymphocytes, with a marked increase in circulating cytokines, such as IFN-gamma, and GM-CSF. The underlying causative event is unclear, and is the subject of ongoing research. In many cases of MAS, a decreased natural killer cell (NK-cell) function is found.
Lymphohistiocytosis is a similar immune system disease characterized by the inappropriate activation of natural killer cells, CD8+ cytotoxic T-cells, and macrophages, involving principally the liver, spleen and central nervous system and associated with severe lymphoid atrophy. [9] [10]
Through the release of Interleukin 4 (IL-4) and Interleukin 13 (IL-13) by TH2, or T helper cells, and mast cells, these macrophages can fuse to form foreign body giant cells. [1] [4] The macrophages are initially attracted to the injury/infection site through a variety of chemoattractants like growth factors, platelet factors, and interleukins. [4]
Most infections show no symptoms, in which case it is known as latent tuberculosis. [1] Around 10% of latent infections progress to active disease that, if left untreated, kill about half of those affected. [1] Typical symptoms of active TB are chronic cough with blood-containing mucus, fever, night sweats, and weight loss. [1]
A macrophage's location can determine its size and appearance. Macrophages cause inflammation through the production of interleukin-1, interleukin-6, and TNF-alpha. [75] Macrophages are usually only found in tissue and are rarely seen in blood circulation. The life-span of tissue macrophages has been estimated to range from four to fifteen days ...
Upon entry to the human respiratory tract, L. pneumophila is able to infect and reproduce within human alveolar macrophages. [4] This causes the onset of Legionnaires' disease, also known as legionellosis. [4] Infected humans may display symptoms such as fever, delirium, diarrhea, and decreased liver and kidney function. [6]
Giant cells are also known to develop when infections are present. They were first observed as early as the middle of the last century, but it is not fully understood why these reactions occur. In the process of giant cell formation, monocytes or macrophages fuse together, which could cause multiple problems for the immune system. [citation needed]