Immunity system complexity: many different cell types (Introduction)

by David Turell , Thursday, June 04, 2020, 23:56 (1632 days ago) @ David Turell

Acting in different ways for as complete infection control as possible:

https://science.sciencemag.org/content/368/6495/1052.full

"One of the most important traits of immune host defense against pathogens is memory, which improves survival if the same pathogen is reencountered. However, immune memory can also be deleterious, driving autoimmune diseases and the rejection of transplanted organs. Memory characteristics have been considered a fundamental property of adaptive immune cells such as T and B lymphocytes. However, innate immune cells such as myeloid cells and natural killer (NK) cells can also adapt to previous encounters with pathogens through epigenetic, transcriptional, and functional reprogramming, called trained immunity. The discovery of this innate immune memory emerged from studies with live vaccines and was described as being largely nonspecific. Dai et al. reveal that monocytes and macrophages acquire specific memory and induce organ rejection in mice, which could be prevented to improve transplantation outcomes.

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"It is important to note that in both vertebrates and invertebrates, the Ig superfamily [immune globulins] of molecules is often the pillar mediating specificity of the innate immune memory responses. Indeed, PIR-A, B cell receptors, immunoglobulins, and T cell receptors share a similar type of structure, which argues for an evolutionary continuum of memory specificity in innate and adaptive immune responses. (my bold)

"Ig-based specific immune responses complement the more primitive nonspecific trained immunity-mediated memory. The increased responsiveness provided by trained immunity after certain infections or vaccinations can induce protection against both specific and heterologous infections. Yet, in conditions characterized by excessive immune responses, such as inflammatory and autoimmune diseases and organ transplant rejection, enhanced innate immune responses can aggravate the pathological consequences of inflammation. It is crucial to know the roles played by innate immune cells in transplant rejection, in order to target it and improve survival.

"The findings of Dai et al. have several implications that go beyond transplantation. If monocytes and macrophages can develop specific memory to MHC-I–presented antigens, this reveals possible therapeutic approaches in organ transplantation, but also autoimmune and inflammatory diseases. In addition, it is intriguing to hypothesize whether specific innate immune memory responses could also form against pathogens, as proposed for NK cells in response to viral infections.

"Macrophages are heterogeneous tissue-resident cells: Yolk sac– and fetal liver monocyte–derived tissue-resident macrophages colonize different tissues during embryonic development. These are long-lived and able to self-renew, so the specific characteristics of these macrophages rely on their niche. For example, lung macrophages are exposed to airway antigens, whereas Kupffer cells in the liver are exposed to gut-derived molecules. The phenotype of a microglial cell in the brain greatly differs from that of a peritoneal macrophage. The potential ability of these and other myeloid cell subsets to develop different types of immunological memory to antigens could offer additional evidence for their different functions across tissues and help to explain the development of different types of memory responses to the same antigens in different locations. (my bold)

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"If monocytes and macrophages develop antigen-specific memory to antigens presented by donor-derived MHC-I molecules, it is likely that these and other myeloid cells can develop immunological memory to self- and nonself antigens of different sources. Given the variety of receptors expressed by the different types of myeloid cells, the implications of these mechanisms could encompass many processes beyond organ transplantation, including the response to pathogens, vaccines, inflammatory and autoimmune diseases, or the development of allergies. Dai et al. identified several families of polymorphic Ig superfamily receptors that could bind to MHC-I molecules. The extension of this search to other receptors that can bind antigens of a different nature could lead to the identification of other structures with the potential to trigger or block antigen-specific memory in myeloid cells, potentially offering a new set of targets for immunotherapy."

Comment: Note my second bold. The immune cells can learn to fight thousands of different antigens depending upon the organs they find themselves placed in. It is all an automatic set of responses, without which organisms would not survive. It has to have been designed early in evolution as the first bold indicates.