Jump to content

Draft:Immune System Cell Cycle Control

From Wikipedia, the free encyclopedia


The cell cycle, or cell division cycle, in eukaryotic cells is a series of systematic events where the cell grows, replicates DNA, and then divides into two daughter cells in a process called cell division. The cell cycle has several phases and is controlled with cell cycle checkpoints after each key step to ensure that cells duplicate and function properly. Many different factors can impact the cell cycle and how a cell progresses through these checkpoints, such as DNA damage, environmental stresses, and cell differentiation. One area of interest within the study of the cell cycle is how the immune system impacts the cell cycle and cell cycle controls. [1][2]

Immune System Cell Cycle Control

[edit]

The immune system is made up of a complex network of cells, organs, and proteins that fight antigens, microbes, and infections. The immune system is mainly built of white blood cells including lymphocytes (B-cells, T-cells, and killer cells). These white blood cells keep a record of past infections and antigens so the immune system can effectively fight future threats.[1][2]

Similar to other cell types, these immune cells experience the cell cycle and cell cycle controls by regulating how immune system specific cells will proliferate and differentiate. How and when immune cells divide and activate in the presence of threats like bacteria and viruses is regulated by key cell cycle regulators like cyclins and cyclin-dependent kinases (CDKs). When existing immune cells encounter an antigen, it will become active.[2] This activation then triggers a series of cascading events which allow cells to rapidly proliferate to form a large number of antigen-specific cells to attack and destroy the antigen/threat.[2] During the acute infection or immune response, a small number of pathogen-specific lymphocytes are selected, activated, and multiplied by cell division to create a large number of immune cells to clear pathogens.[1][2][3] As a result of this mechanism, the control of cell division is critical to robust and effective immune system function.[1][3] During these periods of high cell proliferation, checkpoints on the cell cycle are very important since they will ensure DNA is properly replicated and the immune system is healthy.

These regulations are important to fight infections and maintain tissue health and homeostasis. Abnormal immune responses, auto-immune diseases, and cancer can develop when there are disruptions or dysregulations of these cell cycle control systems. If these cell cycle controls are not functioning properly, damaged or dysfunctional immune cells might be replicated which will impact the integrity of the immune system. [2][3][4]

Immune Cell Senescence

[edit]

Immunosenescence refers to aging-related changes to the immune system and is what causes the immune system to lose efficacy to attack new pathogens over time.[5][6] This immunosenescence is the result of an accumulation of damage to different parts of the immune system.[5][6] As a result of this damage or other factors impairing the immune system, immune cells stop dividing but don’t die (cellular senescent) and this dysregulation of the cell cycle can cause damage to other tissue or systems.[7]

T cell activation

[edit]

T cells (also called T lymphocytes and thymocyte) are a specialized type of cell in the immune system that come from stem cells and bone marrow.[8] In the presence of recognized antigens, T cells leave dormancy and enter the cell cycle resulting in growth, rapid proliferation, and differentiation into cytotoxic T lymphocytes.[4] T cells need to both recognize the antigen and get stimulatory signals from the antigen-presenting cells (APCs) to fully initiate the cell cycle process.[9] Cyclin D2 is the first to be induced in this process in T cells to transition the cell from G0 to G1. This is then followed by cyclin D3 and CDK4/6 activation. [10][11] After this process, a portion of the T cell will exit the cell cycle and return to a dominant state but now as memory T cells.[4]

B cell differentiation

[edit]

B cells (also called B lymphocytes) are white blood cells that produce antibodies as part of the immune system.[12][13] When B cells encounter specific antigens it is activated through the B cell receptor (BCR) cascade.[13][14] After activation the cells differentiate into plasma cells that produce antigen specific antibodies or memory cells that go dormant for future infections.[14]

NK cell cytotoxicity

[edit]

Natural killer cells (NK cells) are white blood cells that destroy infected cells and cancer cells.[15] These killer cells function by disrupting the cell cycle in target cells which express recognized molecules that activate the killer cells. [16][17] NK cells kill target cells by releasing cytotoxic granules with perforin and granzymes that lyse the target cell.[17] Additionally, NK cells secrete cytokines such as FNγ and TNFα which activate other immune cells like macrophages and promote their entrance into the cell cycle.[17] NK cells are deactivated by MHC I which inhibits NK receptors. This acts as a check on NK cells so that they do not attack cells that are native and not infected.[17]

Clinical implications

[edit]

Disruption of the mechanisms that control the cell cycle and cell cycle controls in immune cells can lead to unregulated cell proliferation and uncontrolled activation of the immune system. This can result in autoimmune diseases, immunodeficiency, and in some cases death immune reactions known as cytokine storm caused by immune cell hyper-activation.[18] Research geared toward understanding the cell cycle control mechanism specific to immune cells could help prevent or treat these conditions.[19][20][21]

Medicines that impact or modulate the immune system have become increasingly popular over the years, especially for new therapeutics for treatment resistant cancers. Some new cancer therapies that act on cell division can interact with the already dysregulated cell cycle of cancer cells and make them more susceptible to immune system attacks. Specifically, CDK4/6 inhibitors can help aid immune cells to attack and kill treated cancer cells.[22][23]

References

[edit]
  1. ^ a b c d "Immune system". Better Health Channel. Department of Health & Human Services. 12 October 1999. Retrieved 14 December 2024.
  2. ^ a b c d e f Laphanuwat, Phatthamon; Jirawatnotai, S (2019). "Immunomodulatory Roles of Cell Cycle Regulators". Frontiers in Cell and Developmental Biology. 7 (23): 23. doi:10.3389/fcell.2019.00023. PMC 6399147. PMID 30863749.
  3. ^ a b c Kan, Andrey; Hodgkin, Philip (29 April 2014). "Mechanisms of cell division as regulators of acute immune response". Systems and Synthetic Biology. 9 (September 2014): 215–221. doi:10.1007/s11693-014-9149-3. PMC 4127173. PMID 25136383.
  4. ^ a b c Lewis, David; Ly, Tony (6 October 2021). "Cell cycle entry control in naïve and memory CD8+ T cells". Cell Growth and Division. 9. doi:10.3389/fcell.2021.727441. PMC 8526999. PMID 34692683.
  5. ^ a b Liu, Zaoqu; Liang, Qimeng; Ren, Yuqing; Ge, Xiaoyong; Wang, Libo (2023). "Immunosenescence: molecular mechanisms and diseases". Nature: Signal Transduction and Targeted Therapy Volume. 8 (1): 200. doi:10.1038/s41392-023-01451-2. PMC 10182360. PMID 37179335.
  6. ^ a b "Immunosenescence Overview". Immunosenescence. ScienceDirect. Retrieved 15 December 2024.
  7. ^ "Senescent immune cells spread damage throughout the aging body". National Institute on Aging. National Institute of Health. 25 August 2021. Retrieved 15 December 2024.
  8. ^ "NCI Dictionary of Cancer terms". Comprehensive Cancer Information. NCI. 25 August 2021. Retrieved 15 December 2024.
  9. ^ "T cell activation". T Cell Activation - an overview. ScienceDirect Topics. Retrieved 15 December 2024.
  10. ^ Shi, Min; Lin, Tsung; Appell, Kenneth; Berg, Leslie (1 Oct 2009). "Cell Cycle Progression following Naive T Cell Activation Is Independent of Jak3/Common γ-Chain Cytokine Signals". Journal of Immunology. 7 (184): 4493–4901. doi:10.4049/jimmunol.0804339. PMC 2768578. PMID 19734221. Retrieved 15 December 2024.
  11. ^ Chapman, Nicole; Chi, Hongbo (1 May 2018). "Hallmarks of T-cell Exit from Quiescence. Cancer Immunol". Cancer Immunology Research. 6 (5). doi:10.1158/2326-6066.CIR-17-0605. Retrieved 14 December 2024.
  12. ^ "NCI Dictionary of Cancer terms". Comprehensive Cancer Information. National Cancer Institute. Retrieved 15 December 2024.
  13. ^ a b "B cell". ScienceDirect Topics. ScienceDirect. Retrieved 15 December 2024.
  14. ^ a b "B cells: Types and function". Cleveland Clinic. Retrieved 9 September 2024.
  15. ^ "What are natural killer cells (NK cells)?". Cleveland Clinic. Retrieved 15 December 2024.
  16. ^ Brenner, Ellen; Schorg, Barbara; Ahmetlic, Fatima; Wieder, Thomas (12 March 2020). "Cancer immune control needs senescence induction by interferon-dependent cell cycle regulator pathways in tumours". Nature Communications. 11 (11): 1335. Bibcode:2020NatCo..11.1335B. doi:10.1038/s41467-020-14987-6. PMC 7067802. PMID 32165639.
  17. ^ a b c d Eissmann, Philipp. "Natural Killer Cells". British Society for immunology. Imperial College London UK. Retrieved 15 December 2024.
  18. ^ Fajgenbaum, David; June, Carl (2 December 2020). "Cytokine Storm". The New England Journal of Medicine. 383 (23): 2255–2273. doi:10.1056/NEJMra2026131. PMC 7727315. PMID 33264547.
  19. ^ Kinjyo, Ichiko; Weninger, Wolfgang; Hodgkin, Philip (2015). "Shedding light on cell cycle control by T and B lymphocytes". Cell Cycle. 14 (15): 2381–2382. doi:10.1080/15384101.2015.1063291. PMC 4612679. PMID 26133027.
  20. ^ Balomenos, Dimitrios; Martinea-A, Carlos (November 2000). "Cell-cycle regulation in immunity, tolerance and autoimmunity". Immunology Today. 21 (11): 551–555. doi:10.1016/S0167-5699(00)01748-5. PMID 11094258. Retrieved 15 December 2024.
  21. ^ Pandey, Pratibha; Khan, Fahad; Upadhyay, Tarum; Sharangi, Amit (20 January 2023). "Deciphering the Immunomodulatory Role of Cyclin-Dependent Kinase 4/6 Inhibitors in the Tumor Microenvironment". Int. J. Mol. Sci. 24 (3): 2236. doi:10.3390/ijms24032236. PMC 9916547. PMID 36768557.
  22. ^ "Cell cycle-blocking drugs can shrink tumors by enlisting immune system in attack on cancer, study finds". Dana-Farber Cancer Institue. Retrieved 15 December 2024.
  23. ^ Liu, Lingling; Lu, Yun; Martinez, Jennifer; Wang, Ruoning (9 February 2016). "Proinflammatory signal suppresses proliferation and shifts macrophage metabolism from Myc-dependent to HIF1α-dependent". PNAS. 113 (6): 1564–1569. Bibcode:2016PNAS..113.1564L. doi:10.1073/pnas.1518000113. PMC 4760828. PMID 26811453.
Retrieved from "https://en.wikipedia.org/w/index.php?title=Draft:Immune_System_Cell_Cycle_Control&oldid=1263362677"