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Sentinel cells refer to cells in the body's first line of defense, which embed themselves in tissues such as skin. [1] Sentinel cells represent diverse array of cell types with the capability to monitor the presence of exogenous or potentially harmful particles and play a crucial role in recognizing and sampling signs of infection or abnormal cellular activity and/or death. Encountering such stimuli is initiating the innate immune response [2] . Their ability to recognize injurious or dangerous material is mediated by specialized pattern recognition receptors (PRR) and possess specialized function to prime naive T cells upon pathogen recognition [3] .
Sentinel cells can refer to specific antigen-presenting cells, such as:
Sentinel cells can also refer to cells that are normally not specialized antigen-presenting cells such as: [1]
Sometimes tissue cells not part of the immune system such as are also referred to as Sentinel cells: [1]
Typically, dendritic cells (DCs) and macrophages serve this function by being strategically distributed throughout diverse tissues within host environment particularly in those regions exposed to the contact with the external environment such as mucosal tissues and skin [4] .
In elucidating the intricate network of phenotypic markers characterizing sentinel cells residing in skin there is a recent study offering an in-depth exploration whereas stimulus-specific gene expression and functions are described in the summarized article [5] .
Interestingly, novel function has been discovered by designing sentinel bacteria Bacillus subtilis combining the living organism with evolutionary function of sentinels resulting in surveillance of specific DNA sequences and reporting single nucleotide polymorphism associated with facial features through the mechanism by which these sentinel cells take up and record target DNA sequences, using CRISPR interference for SNP differentiation and expression of target gene. This technology demonstrates potential applications in areas like forensics, ecology, and epidemiology, by enabling the detection of specific DNA sequences in various environments. Application of such DNA-specific surveillance can be designed in detection of an anomaly and targeting the localized treatment to identified tissue such as tumor [6] .
A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that include B and T cells. Lymph nodes are important for the proper functioning of the immune system, acting as filters for foreign particles including cancer cells, but have no detoxification function.
An immune response is a physiological reaction which occurs within an organism in the context of inflammation for the purpose of defending against exogenous factors. These include a wide variety of different toxins, viruses, intra- and extracellular bacteria, protozoa, helminths, and fungi which could cause serious problems to the health of the host organism if not cleared from the body.
A dendritic cell (DC) is an antigen-presenting cell of the mammalian immune system. A DC's main function is to process antigen material and present it on the cell surface to the T cells of the immune system. They act as messengers between the innate and adaptive immune systems.
Phagocytes are cells that protect the body by ingesting harmful foreign particles, bacteria, and dead or dying cells. Their name comes from the Greek phagein, "to eat" or "devour", and "-cyte", the suffix in biology denoting "cell", from the Greek kutos, "hollow vessel". They are essential for fighting infections and for subsequent immunity. Phagocytes are important throughout the animal kingdom and are highly developed within vertebrates. One litre of human blood contains about six billion phagocytes. They were discovered in 1882 by Ilya Ilyich Mechnikov while he was studying starfish larvae. Mechnikov was awarded the 1908 Nobel Prize in Physiology or Medicine for his discovery. Phagocytes occur in many species; some amoebae behave like macrophage phagocytes, which suggests that phagocytes appeared early in the evolution of life.
A histiocyte is a vertebrate cell that is part of the mononuclear phagocyte system. The mononuclear phagocytic system is part of the organism's immune system. The histiocyte is a tissue macrophage or a dendritic cell. Part of their job is to clear out neutrophils once they've reached the end of their lifespan.
An antigen-presenting cell (APC) or accessory cell is a cell that displays antigen bound by major histocompatibility complex (MHC) proteins on its surface; this process is known as antigen presentation. T cells may recognize these complexes using their T cell receptors (TCRs). APCs process antigens and present them to T-cells.
Cross-presentation is the ability of certain professional antigen-presenting cells (mostly dendritic cells) to take up, process and present extracellular antigens with MHC class I molecules to CD8 T cells (cytotoxic T cells). Cross-priming, the result of this process, describes the stimulation of naive cytotoxic CD8+ T cells into activated cytotoxic CD8+ T cells. This process is necessary for immunity against most tumors and against viruses that infect dendritic cells and sabotage their presentation of virus antigens. Cross presentation is also required for the induction of cytotoxic immunity by vaccination with protein antigens, for example, tumour vaccination.
Gut-associated lymphoid tissue (GALT) is a component of the mucosa-associated lymphoid tissue (MALT) which works in the immune system to protect the body from invasion in the gut.
The innate, or nonspecific, immune system is one of the two main immunity strategies in vertebrates. The innate immune system is an alternate defense strategy and is the dominant immune system response found in plants, fungi, prokaryotes, and invertebrates.
The mucosa-associated lymphoid tissue (MALT), also called mucosa-associated lymphatic tissue, is a diffuse system of small concentrations of lymphoid tissue found in various submucosal membrane sites of the body, such as the gastrointestinal tract, nasopharynx, thyroid, breast, lung, salivary glands, eye, and skin. MALT is populated by lymphocytes such as T cells and B cells, as well as plasma cells, dendritic cells and macrophages, each of which is well situated to encounter antigens passing through the mucosal epithelium. In the case of intestinal MALT, M cells are also present, which sample antigen from the lumen and deliver it to the lymphoid tissue. MALT constitute about 50% of the lymphoid tissue in human body. Immune responses that occur at mucous membranes are studied by mucosal immunology.
Malignant histiocytosis is a rare hereditary disease found in the Bernese Mountain Dog and humans, characterized by histiocytic infiltration of the lungs and lymph nodes. The liver, spleen, and central nervous system can also be affected. Histiocytes are a component of the immune system that proliferate abnormally in this disease. In addition to its importance in veterinary medicine, the condition is also important in human pathology.
A histiocytoma in the dog is a benign tumor. It is an abnormal growth in the skin of histiocytes (histiocytosis), a cell that is part of the immune system. A similar disease in humans, Hashimoto-Pritzker disease, is also a Langerhans cell histiocytosis. Dog breeds that may be more at risk for this tumor include Bulldogs, American Pit Bull Terriers, American Staffordshire Terriers, Scottish Terriers, Greyhounds, Boxers, and Boston Terriers. They also rarely occur in goats and cattle.
White pulp is a histological designation for regions of the spleen, that encompasses approximately 25% of splenic tissue. White pulp consists entirely of lymphoid tissue.
Follicular dendritic cells (FDC) are cells of the immune system found in primary and secondary lymph follicles of the B cell areas of the lymphoid tissue. Unlike dendritic cells (DC), FDCs are not derived from the bone-marrow hematopoietic stem cell, but are of mesenchymal origin. Possible functions of FDC include: organizing lymphoid tissue's cells and microarchitecture, capturing antigen to support B cell, promoting debris removal from germinal centers, and protecting against autoimmunity. Disease processes that FDC may contribute include primary FDC-tumor, chronic inflammatory conditions, HIV-1 infection development, and neuroinvasive scrapie.
Ralph Marvin Steinman was a Canadian physician and medical researcher at Rockefeller University, who in 1973 discovered and named dendritic cells while working as a postdoctoral fellow in the laboratory of Zanvil A. Cohn, also at Rockefeller University. Steinman was one of the recipients of the 2011 Nobel Prize in Physiology or Medicine.
Certain sites of the mammalian body have immune privilege, meaning they are able to tolerate the introduction of antigens without eliciting an inflammatory immune response. Tissue grafts are normally recognised as foreign antigens by the body and attacked by the immune system. However, in immune privileged sites, tissue grafts can survive for extended periods of time without rejection occurring. Immunologically privileged sites include:
A non-specific immune cell is an immune cell that responds to many antigens, not just one antigen. Non-specific immune cells function in the first line of defense against infection or injury. The innate immune system is always present at the site of infection and ready to fight the bacteria; it can also be referred to as the "natural" immune system. The cells of the innate immune system do not have specific responses and respond to each foreign invader using the same mechanism.
The pluripotency of biological compounds describes the ability of certain substances to produce several distinct biological responses. Pluripotent is also described as something that has no fixed developmental potential, as in being able to differentiate into different cell types in the case of pluripotent stem cells.
Alloantigen recognition refers to immune system recognition of genetically encoded polymorphisms among the genetically distinguishable members of same species. Post-transplant recognition of alloantigens occurs in secondary lymphoid organs. Donor specific antigens are recognized by recipient’s T lymphocytes and triggers adaptive pro-inflammatory response which consequently leads to rejection of allogenic transplants. Allospecific T lymphocytes may be stimulated by three major pathways: direct recognition, indirect recognition or semidirect recognition. The pathway involved in specific cases is dictated by intrinsic and extrinsic factors of allograft and directly influence nature and magnitude of T lymphocytes mediated immune response. Furthermore, variant tissues and organs such as skin or cornea or solid organ transplants can be recognized in different pathways and therefore are rejected in different fashion.
Dermal macrophages are macrophages in the skin that facilitate skin homeostasis by mediating wound repair, hair growth, and salt balance. Their functional role in these processes is the mediator of inflammation. They can acquire an M1 or M2 phenotype to promote or suppress an inflammatory response, thereby influencing other cells' activity via the production of pro-inflammatory or anti-inflammatory cytokines. Dermal macrophages' ability to acquire pro-inflammatory properties also potentiates them in cancer defence. M1 macrophages can suppress tumour growth in the skin by their pro-inflammatory properties. However, M2 macrophages support tumour growth and invasion by the production of Th2 cytokines such as TGFβ and IL-10. Thus, the exact contribution of each phenotype to cancer defence and the skin's homeostasis is still unclear.