Cure Alveolar Soft Part Sarcoma International (iCureASPS)

Simply put. : )

“T-cell activation is critical for the initiation and regulation of the immune response. Activation of T cells leads to the development of cell-mediated immune mechanisms “

https://www.sciencedirect.com/topics/me ... activation

T cell: A type of white blood cell that is of key importance to the immune system and is at the core of adaptive immunity, the system that tailors the body's immune response to specific pathogens. The T cells are like soldiers who search out and destroy the targeted invaders.

Immature T cells (termed T-stem cells) migrate to the thymus gland in the neck, where they mature and differentiate into various types of mature T cells and become active in the immune system in response to a hormone called thymosin and other factors. T-cells that are potentially activated against the body's own tissues are normally killed or changed ("down-regulated") during this maturational process.

There are several different types of mature T cells. Not all of their functions are known. T cells can produce substances called cytokines such as the interleukins which further stimulate the immune response. T-cell activation is measured as a way to assess the health of patients with HIV/AIDS and less frequently in other disorders.”




https://www.medicinenet.com/script/main ... ekey=11300

Humoral and Cell-Mediated Immune Responses

The immune system distinguishes two groups of foreign substances. One group consists of antigens that are freely circulating in the body. These include molecules, viruses, and foreign cells. A second group consists of self cells that display aberrant MHC proteins. Aberrant MHC proteins can originate from antigens that have been engulfed and broken down (exogenous antigens) or from virus‐infected and tumor cells that are actively synthesizing foreign proteins (endogenous antigens). Depending on the kind of foreign invasion, two different immune responses occur:


The humoral response (or antibody‐mediated response) involves B cells that recognize antigens or pathogens that are circulating in the lymph or blood (“humor” is a medieval term for body fluid). The response follows this chain of events:
Antigens bind to B cells.
Interleukins or helper T cells costimulate B cells. In most cases, both an antigen and a costimulator are required to activate a B cell and initiate B cell proliferation.
B cells proliferate and produce plasma cells. The plasma cells bear antibodies with the identical antigen specificity as the antigen receptors of the activated B cells. The antibodies are released and circulate through the body, binding to antigens.
B cells produce memory cells. Memory cells provide future immunity.

The cell‐mediated response involves mostly T cells and responds to any cell that displays aberrant MHC markers, including cells invaded by pathogens, tumor cells, or transplanted cells. The following chain of events describes this immune response:


https://www.cliffsnotes.com/study-guide ... -responses

Chapter Four - A Transendocytosis Perspective on the CD28/CTLA-4 Pathway


Abstract
T cell activation is a key event in the adaptive immune response and vital to the generation of both cellular and humoral immunity. Activation is required not only for effective CD4 T cell responses but also to provide help for B cells and the generation of cytotoxic T cell responses. Unsurprisingly, impaired T cell activation results in infectious pathology, whereas dysregulated activation can result in autoimmunity. The decision to activate is therefore tightly regulated and the CD28/CTLA-4 pathway represents this apical decision point at the molecular level. In particular, CTLA-4 (CD152) is an essential checkpoint control for autoimmunity; however, the molecular mechanism(s) by which CTLA-4 achieves its regulatory function are not well understood, especially how it functionally intersects with the CD28 pathway. In this chapter, we review the established molecular and cellular concepts relating to CD28 and CTLA-4 biology, and attempt to integrate these by discussing the transendocytosis of ligands as a new model of CTLA-4 function.

https://www.sciencedirect.com/science/a ... 1479000042

Study of an extended family with CTLA-4 deficiency suggests a CD28/CTLA-4 independent mechanisresponsible for differences in disease manifestations and severity



Abstract
The CTLA-4 checkpoint regulates the activation of T cells. Individuals with heterozygous mutations in CTLA-4 have a complex phenotype typically characterized by antibody deficiency alongside variable autoimmunity. Despite severe disease in some individuals, others remain largely unaffected with reasons for this variation unknown. We studied a large family carrying a single point mutation in CTLA-4 leading to an amino acid change R75W and compared both unaffected with affected individuals. We measured a variety of features pertaining to T cell and CTLA-4 biology and observed that at the cellular level there was complete penetrance of CTLA-4 mutations. Accordingly, unaffected individuals were indistinguishable from those with disease in terms of level of CTLA-4 expression, percentage of Treg, upregulation of CTLA-4 upon stimulation and proliferation of CD4 T cells. We conclude that the wide variation in disease phenotype is influenced by immune variation outside of CTLA-4 biology.



https://www.sciencedirect.com/science/a ... 1617306228