why you randomly become glabrous.

[woman staring into a phone with her hand on her hair] (stock images)

Hair is a stratified keratinized squamous epithelium, it protects and strengthens the hair shaft (Wikipedia, n.d.). It consists of melanocyte stem cells and possesses immune privilege. Hair can be classified into three types based on medullation (Hamilton, 2003): Lanugo — hair present on foetus-; Vellus — that replaces the lanugo hair a month before birth of the foetus -; and Terminal — medullated and highly pigmented, Vellus hair turns into Terminal hair after puberty (Chapter 6, 2016). This essay will discuss the overworking of T-lymphocyte cells and how it causes hair loss by a disease termed Alopecia Areata.

In a normal hair model, the strand of hair possesses a site of immune privilege and the hair bulb on the epithelium does not express major histocompatibility complex [MHC] most likely as the milieu around the bulb is immunoinhibitory created by the presence of numerous immunoinhibitory cytokines and neuropeptides. Some Langerhans cells that are present below the stem cell region, are impaired and do not exhibit major histocompatibility complex Class II (Gilhar, Etzioni and Paus, 2012). An immunological dilemma is created due to the absence of MHC class I molecules as they might activate Natural Killer Cells [NK cells] that produce MHC class-I negative cell to lyse them. This NK-cell mediated cytolysis was seen to be inhibited immediately with the help of macrophage inhibitory factor [MIF] (McElwee et al., 2013). Recent research thereby shows that NK cells influence the reactivity of T-cells. Whether the lack of or excess of NK-cells causes this immune response is still not confirmed.

Since autoimmune diseases are caused in relation with another disease (most likely auto-immune as well,). Alopecia areata is most commonly triggered after the patient has been affected by a previous disease correlated with the pigmented melanocyte tissues in the body.

Hair growth occurs in four phases, namely: anagen, catagen, telogen, and exogen phases. The growth cycle is repetitive and depends on numerous factors such as: age, genetic predisposition, ethnicity, etc.,. The growth of hair depends on the interaction between mesenchymal and epithelial cells. The anagen phase is when hair growth takes place and it is divided into 6 growth phases, almost 85–90% of hair is in this phase. The papilla and the dermis help nourish and grow the strand. The catagen phase is the involuntary controlled phase when blood supply to the hair strand is cut off, it consists of 8 different stages and usually lasts for 2 weeks. The telogen phase consists of 10–15% of the hair strands and lasts for about 2 months. This lasts until the hair follicle can regenerate and re-enter the anagen phase. The exogen phase is a shedding phase that is independent of telogen and anagen phase (Erdoğan, 2017).

When hair cannot enter the anagen phase and directly goes into telogen phase which causes hair shedding, termed as Alopecia. Falling of hair in spontaneous patches around the body sometimes leading to complete baldness. Alopecia areata specifically is an organ-specific, autoimmune disorder that is characterised phenotypically by non-scarring hair loss and changes in the nail matrix. Almost everyone during a short period in their life are affected by this. Hair on the scalp becomes scarce around the crown and the terminal hair is replaced by vellus hair (Ruszczak, 2012). This hair is short and often termed as exclamation mark hair.

Alopecia areata can occur due to numerous factors, all of which have a similar result that leads to the pro-inflammatory reaction of T-lymphocytes in the body (Bharghava, 2020). Commonly, due to some sort of stress in the body that is causing the T-lymphocytes to overwork and introduce confusion among them in differentiating between the body’s natural cells and harmful foreign cells. Usually countered by an anti-inflammatory steroid drug [Corticosteroids]. This inflammation is caused due to the genetical breaking of immune privilege and hyper-attacking of T-lymphocytes on the hair follicles (Xing et al., 2014). CD8+ cytotoxic T-lymphocytes play a huge role in the development of Alopecia areata and are more likely to enter the hair follicles. However, CD8+ cells alone cannot influence hair loss, they act as effector cells in cooperation with helper CD4+ T-cells, and together to cause the onset of Alopecia areata. Now it has also become necessary to look for Human Leukocyte Antigen [HLA] and its association with the disorder (Gilhar et al., 2002).

Several mice models have been used such as C3H/HeJ inbred mouse models that have helped prove the Immune Privilege Theory and also show, in some cases, the phenotypical loss of hair. But these mice — although helpful in proving some theories — also possess their limitations often focused around human specific and inbred mouse genetics. For example, one being that MHC class I are unidentical in the species and identifiable in mice. The more recent humanized AA mice model was discovered about 20 years ago and has proved to be a more viable source in learning about Alopecia areata. It was achieved by the transplanting the lesions of Alopecia areata affected skin into Severe Combined Immunodeficiency [SCID] mice. The latter mouse model can be used to characterize the role of CD8+ T-cells and NK Cells in this disease (Gilhar et al., 2016).

Alopecia areata is a recurring, auto-immune disease characterised by nonscarring hair loss, with the presence of an abnormal number of antibodies in the hair follicle antigen (Tobin, Orentreich, Bystryn and Fenton, 1994). This can be triggered due to numerous factors and be affected by many genes and hence is categorised as a complex disease. The main factors that cause internal depletion is the loss of immune privilege at the hair shaft, and the T-lymphocytes signalling Natural Killer Cells to attack the hair follicles that result in hair falling out. A pattern noticed is a history of pigmented autoimmune melanocyte disease in the subject analysed, although not in everyone. Future research studies should focus on it as a complex disease, focusing on the overworking of T-lymphocytes tracing to what triggers it originally and how the broken immune privilege can be restored (Rodriguez and Duvic, 2008).

References:

1. Bharghava, H., 2020. Is My Hair Loss Due to Alopecia Areata?. [online] WebMD. Available at: [Accessed 23 March 2021].
2. Slideplayer.com. 2016. Chapter 6 Integumentary system= skin & accessory organs (hair, nail, cutaneous glands) Dermatology= scientific study & medical treatment of abnormal appearance. — ppt video online download. [online] Available at: [Accessed 23 March 2021].
3. Erdoğan, B., 2017. Anatomy and Physiology of Hair. Hair and Scalp Disorders,.
4. Gilhar, A., Etzioni, A. and Paus, R., 2012. Alopecia Areata. New England Journal of Medicine, 366(16), pp.1515–1525.
5. Gilhar, A., Landau, M., Assy, B., Shalaginov, R., Serafimovich, S. and Kalish, R., 2002. Mediation of Alopecia Areata by Cooperation Between CD4+ and CD8+ T Lymphocytes. Archives of Dermatology, 138(7).
6. Gilhar, A., Schrum, A., Etzioni, A., Waldmann, H. and Paus, R., 2016. Alopecia areata: Animal models illuminate autoimmune pathogenesis and novel immunotherapeutic strategies. Autoimmunity Reviews, 15(7), pp.726–735.
7. Hamilton, L., 2003. TYPES OF HAİR Lanugo hair: Soft fine hair that covers much of fetus; usually shed before birth Vellus hair: Fine, nonpigmented hair that covers the body. — ppt video online download. [online] Slideplayer.com. Available at: [Accessed 23 March 2021].
8. En.wikipedia.org. n.d. Human hair growth — Wikipedia. [online] Available at: [Accessed 23 March 2021].
9. McElwee, K., Gilhar, A., Tobin, D., Ramot, Y., Sundberg, J., Nakamura, M., Bertolini, M., Inui, S., Tokura, Y., King, L., Duque-Estrada, B., Tosti, A., Keren, A., Itami, S., Shoenfeld, Y., Zlotogorski, A. and Paus, R., 2013. What causes alopecia areata?. Experimental Dermatology, 22(9), pp.609–626.
10. Rodriguez, T. and Duvic, M., 2008. Onset of alopecia areata after Epstein-Barr virus infectious mononucleosis. Journal of the American Academy of Dermatology, 59(1), pp.137–139.
11. Ruszczak, Z., 2012. Hair Disorders and Alopecia. Textbook of Clinical Pediatrics, pp.1489–1508.
12. Tobin, D., Orentreich, N., Bystryn, J. and Fenton, D., 1994. Antibodies to Hair Follicles in Alopecia Areata. Journal of Investigative Dermatology, 102(5), pp.721- 724.
13. Xing, L., Dai, Z., Jabbari, A., Cerise, J., Higgins, C., Gong, W., de Jong, A., Harel, S., DeStefano, G., Rothman, L., Singh, P., Petukhova, L., Mackay-Wiggan, J., Christiano, A. and Clynes, R., 2014. Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition. Nature Medicine, 20(9), pp.1043- 1049