Immune tolerance in the context of Immunodysregulation polyendocrinopathy enteropathy X-linked syndrome

The regulatory T cells (Tregs /ˈtiːrɛɡ/ or T_reg cells), formerly known as suppressor T cells, are a subpopulation of T cells that modulate the immune system, maintain tolerance to self-antigens, and prevent autoimmune disease. T_reg cells are immunosuppressive and generally suppress or downregulate induction and proliferation of effector T cells. T_reg cells express the biomarkers CD4, FOXP3, and CD25 and are thought to be derived from the same lineage as naïve CD4 cells. Because effector T cells also express CD4 and CD25, T_reg cells are very difficult to effectively discern from effector CD4, making them difficult to study. Research has found that the cytokine transforming growth factor beta (TGF-β) is essential for T_reg cells to differentiate from naïve CD4 cells and is important in maintaining T_reg cell homeostasis.

Mouse models have suggested that modulation of T_reg cells can treat autoimmune disease and cancer and can facilitate organ transplantation and wound healing. Their implications for cancer are complicated. T_reg cells tend to be upregulated in individuals with cancer, and they seem to be recruited to the site of many tumors. Studies in both humans and animal models have implicated that high numbers of T_reg cells in the tumor microenvironment is indicative of a poor prognosis, and T_reg cells are thought to suppress tumor immunity, thus hindering the body's innate ability to control the growth of cancerous cells. Immunotherapy research is studying how regulation of T cells could possibly be utilized in the treatment of cancer.

In medicine, the hygiene hypothesis states that early childhood exposure to particular microorganisms (such as the gut flora and helminth parasites) protects against allergies by properly tuning the immune system. In particular, a lack of such exposure is thought to lead to poor immune tolerance. The time period for exposure begins before birth and ends at school age.

While early versions of the hypothesis referred to microorganism exposure in general, later versions apply to a specific set of microbes that have co-evolved with humans. The updates have been given various names, including the microbiome depletion hypothesis, the microflora hypothesis, and the "old friends" hypothesis. There is a significant amount of evidence supporting the idea that lack of exposure to these microbes is linked to allergies or other conditions, although it is still rejected by many scientists.

A mast cell (also known as a mastocyte or a labrocyte) is a resident cell of connective tissue that contains many granules rich in histamine and heparin. Specifically, it is a type of granulocyte derived from the myeloid stem cell that is a part of the immune and neuroimmune systems. Mast cells were discovered by Friedrich von Recklinghausen and later rediscovered by Paul Ehrlich in 1877. Although best known for their role in allergy and anaphylaxis, mast cells play an important protective role as well, being intimately involved in wound healing, angiogenesis, immune tolerance, defense against pathogens, and vascular permeability in brain tumors.

The mast cell is very similar in both appearance and function to the basophil, a type of white blood cell. Although mast cells were once thought to be tissue-resident basophils, it has been shown that the two cells develop from different hematopoietic lineages and thus cannot be the same cells.

A paraneoplastic syndrome is a syndrome (a set of signs and symptoms) that is the consequence of a tumor in the body (usually a cancerous one). It is specifically due to the production of chemical signaling molecules (such as hormones or cytokines) by tumor cells or by an immune response against the tumor. Unlike a mass effect, it is not due to the local presence of cancer cells.

Paraneoplastic syndromes are typical among middle-aged to older people, and they most commonly occur with cancers of the lung, breast, ovaries or lymphatic system (a lymphoma). Sometimes, the symptoms of paraneoplastic syndromes show before the diagnosis of a malignancy, which has been hypothesized to relate to the disease pathogenesis. In this paradigm, tumor cells express tissue-restricted antigens (e.g., neuronal proteins), triggering an anti-tumor immune response which may be partially or, rarely, completely effective in suppressing tumor growth and symptoms. Patients then come to clinical attention when this tumor immune response breaks immune tolerance and begins to attack the normal tissue expressing that (e.g., neuronal) protein.

The tumor microenvironment is a complex ecosystem surrounding a tumor, composed of cancer cells, stromal tissue (including blood vessels, immune cells, fibroblasts and signaling molecules) and the extracellular matrix. Mutual interaction between cancer cells and the different components of the tumor microenvironment support its growth and invasion in healthy tissues which correlates with tumor resistance to current treatments and poor prognosis. The tumor microenvironment is in constant change because of the tumor's ability to influence the microenvironment by releasing extracellular signals, promoting tumor angiogenesis and inducing peripheral immune tolerance, while the immune cells in the microenvironment can affect the growth and evolution of cancerous cells.