Varying The Strength Of Cell-cell Interactions Or The Concentration Of Soluble Factors Can Influence The Outcomes Of Cell Signalling.

The objective of this essay is to thoroughly explore the effects of various cytokines, including their different types and concentrations, on the activation and differentiation of CD4+ T cells. Moreover, the impact of interactions between the T-cell receptor (TCR) and major histocompatibility complex (MHC) on these cells will also be discussed. In addition to these topics, this essay will also investigate the roles that Bone Morphogenetic Protein (BMP) and Noggin play in the development of the dorsal mesoderm, and how cell migration can influence this process.

CD4+ T lymphocytes play an essential role in the immune system, initially remaining in a naïve state until they come across a complementary antigen that matches their T cell receptor (TCR) (Bhattacharyya and Feng, 2020)(Flies, n.d). This activation process involves other components such as antigen-presenting cells (APCs), which include macrophages, dendritic cells, and B cells (Luckheeram et al., 2012). After the presentation of the antigen, APCs can express either major histocompatibility complex (MHC) class I or II molecules, which subsequently activate T cells and begin an immune response (Bhattacharyya and Feng, 2020). (Szeto et al., 2022).

The production of cytokines is a crucial step in initiating an immune response as they play a vital role in the differentiation of CD4+ cells (Figure 1) through intracellular signalling pathways that can activate or inhibit transcri ption factors (Ether Martinez-Sanchez et al., 2018) (Luckheeram et al., 2012). The resulting changes in epigenetic markers then trigger the production of autocrine cytokines within the cell. (Luckheeram et al., 2012) The concentration of cytokines in the surrounding environment can drive CD4+ cell differentiation as demonstrated in a study by E. Martinez-Sanchez et al. (2018), where varying concentrations of exogenous cytokines were used to differentiate Th0 cells. Different cytokines required different concentrations for the differentiation from Th0 to Th1, Tfh, or Th2 cells. However, IL2e and IL27e themselves proved to be insufficient to induce transitions, indicating that CD4+ T cells are sensitive to changes in the quantities of other cytokines and their polarization requires a threshold concentration of most single cytokines (Ether Martinez-Sanchez et al., 2018). This study proved that the concentration of cytokines required for polarization was lower when numerous cytokines were taken simultaneously, rather than when a single cytokine was used alone, revealing a synergistic effect of cytokines on CD4+ T cell development(Ether Martinez-Sanchez et al., 2018). Therefore, the cytokine milieu plays a critical role in the differentiation and polarization of CD4+ T cells, and their absence or imbalance can significantly affect immune responses (Flies, n.d).

Interlecukin-2 (IL-2) is a crucial cytokine in T-T communication, as it facilitates communication and coordination between different types of T cells in the immune response (Uhl and Gérard, 2020). IL-2 is produced when an antigen is detected, causing CD4+ T cells to produce IL-2 and release it into the extracellular environment, where it binds to IL-2 receptors on the surface of other T cells. This activates intracellular signalling pathways which lead to increased T cell activation, proliferation, and differentiation, resulting in a more powerful immune response that can combat infections (Ross and Cantrell, 2019). IL-2 also stimulates the production of other cytokines and cytokine receptors, which improves T-T communication and regulates the immune response (Ross and Cantrell, 2019). However, diseases like HIV can interfere with IL-2 levels, as the virus can kill CD4+ T cells and compromise IL-2 synthesis and release (Vidya Vijayan et al., 2023) (Zhang et al., 2016 This can lead the body to be vulnerable to disease, due to a weakened immune system. HIV-infected individuals may also have elevated levels of IL-2 in response to the virus (Lang et al., 1988), resulting in disease progression and the development of symptoms associated with AIDS.

To activate CD4+ T cells and initiate an immune response, the interaction between TCR and MHC (Figure 2) must be strong and prolonged (Corse, Gottschalk and Allison, 2011). This interaction can be affected by the quality and quantity of peptide/MHC ligands, which can alter TCR signal strength and avidity (Bhattacharyya and Feng, 2020) (Corse, Gottschalk and Allison, 2011). The strength of the signal delivered by TCR is determined by the number of TCR molecules expressed and the affinity of the TCR for pMHC complexes (Bhattacharyya and Feng, 2020). TCR sequence mutations can modify the TCR`s affinity for pMHC. This can lead to longer interactions between pMHC and TCR (Corse, Gottschalk and Allison, 2011). Similarly, a higher concentration of antigen can result in longer and stronger signals, while lower concentrations can lead to shorter and weaker signals (Au-Yeung et al., 2014). These weak or short signals can be problematic as they may not provide enough activation for T cells to differentiate into effector cells and perform their essential functions in the immune response (Au-Yeung et al., 2014). This may result in a weakened immune response, making individuals more susceptible to infections or abnormal cell growth.