Introduction
What is leprosy?
Leprosy is a chronic disease caused by Mycobacterium leprae (M. leprae).1 It spreads from person to person through droplets from the nose and mouth, usually after extended periods of close contact with someone infected but untreated. 1,2 M. leprae is a slow-growing bacterium, so symptoms of leprosy can take a long time to show up.1 The World Health Organisation (WHO) says that the average time between initial infection and the first appearance of disease symptoms is five years.2
Leprosy affects the skin, the nerves of the extremities, the eyes, and the mucosal lining of the nose.2 This causes dermatological and neurodegenerative symptoms such as discoloured skin patches (lesions), numbness and muscle weakness. If left untreated, leprosy can cause serious disability.1
Who does leprosy affect?
M. leprae can infect anyone, but only a small number (around 5%) of people are at risk of developing leprosy.3,4 This is because the way that our immune systems react to the bacteria varies from person to person due to genetic differences, so some people are better at fighting the disease than others.4
How is leprosy treated?
Leprosy is a curable disease. Leprosy is treated by multidrug therapy.2 Accessible leprosy treatment has been very important in preventing leprosy from becoming an international public health problem, but new cases still arise globally.5 New cases of leprosy are more common in countries where leprosy is endemic. However, accessible international travel allows leprosy to spread from endemic regions to non-endemic regions.5 This means that despite advances in the treatment of leprosy, many people still suffer the long-term complications of the disease.
The role of the immune system in leprosy
What is the immune system?
The immune system is our body's defence system against infection and disease. It is a complex network of cells, tissues and molecules that orchestrates a strong defensive response against invading foreign bodies and germs.6 The immune system can be split into ‘innate’ and ‘adaptive’ systems, which differ by their specificity to the germ.6
The innate immune system is the body’s first defence against germs and other harmful intruders. It is a general response, reacting the same way to every foreign substance.6 The cells of the innate immune system prevent the spread of M. leprae and alert the adaptive immune system that the body is infected. This all acts to stop infections from becoming more severe.6
The adaptive immune system is the part of the body’s immune system that utilises an array of defences designed specifically to eliminate the particular invading foreign body it is targeting.6 It precisely recognises the invaders, and it is more accurate in its response than the innate system is. Resultantly, the adaptive response is slower than the innate response. It can also remember the foreign body, leading to a quicker and stronger response if the invader comes back to prevent us from getting unwell again.6 This is known as gaining ‘immunity’ to an infection or disease.6
What are T-cells, and why are they important in the immune system?
Part of the adaptive response is reliant on T-cells, a type of white blood cell that helps the body to fight infections.6 When someone is infected with M. leprae, T-cells are directed to the infected tissues and are activated. Here, they play a big role in how the body reacts as they help to eliminate the bacteria.1,6,7
Th1 vs Th2 T-cells: what’s the difference?
A T-cell’s job is distinguished by the different molecules that it displays on its surface. T-cells with CD4 proteins on their cell surface are known as ‘helper’ T-cells.8 Helper T-cells are then further subdivided into Type 1 helper T-cells (Th1) and Type 2 helper T-cells (Th2).8 These cells are characterised by the different chemical messengers that they can produce, known as cytokines. Cytokines are used by T-cells to communicate with the other cells of the immune system and direct how they behave.8
Immune responses to M. leprae can be Th1 or Th2 dominant, meaning that some responses use more Th1 cells, and others use more Th2 cells to fight infection. Th1 cells produce cytokines that activate the immune system, whereas Th2 cells produce cytokines that calm down the immune system.9 This difference in cytokine production makes Th1 dominant immune responses the ‘good’ response in leprosy, as the cytokines activate killer immune cells that can destroy M. leprae and prevent its spread. The Th2 dominant response does not do this. Instead, the killer immune cells are suppressed, and the disease gets worse as M. leprae can multiply and spread. This is why Th1 dominant responses cause less severe forms of leprosy than Th2 responses. This phenomenon is known as the Th1/Th2 paradigm.9
Leprosy as a spectrum disease
Variations in people’s immune responses to M. leprae mean that leprosy looks different in every infected person and that it can range from mild to very severe.1 Because of this, leprosy is considered a ‘spectrum disease’.2 In 1966, two scientists named Ridley and Jopling created a system to categorise leprosy into five classes based on how it appears on an infected person’s body.10 The table below details this class system.
| Ridley-Jopling Classification (1966) 10 | Symptoms | Is the disease stable? | Severity | Th1 or Th2 dominant |
| Tuberculoid (TT) | Fewer than five painless, pale skin lesions with clear edges. They are often large and unevenly spread on the face, body or limbs. Nearby nerves may feel swollen or sore.11 | The disease is usually stable, with a good immune response, but it can sometimes persist or get worse.11 | Least severe | Th1 dominant |
| Borderline Tuberculoid (BT) | Skin lesions are similar to those in TT but more numerous. They sometimes have smaller nearby ‘satellite’ lesions. There is greater nerve involvement.11 | The disease is unstable. It may persist, improve or worsen.11 | ||
| Mid-Borderline (BB) | Numerous, asymmetrical skin lesions that are often clearly defined ring-shaped patches. Larger rings may have normal-looking skin spots inside, creating a ‘Swiss cheese’ look. More nerve involvement is seen.12 | The disease is unstable. It may persist, improve or worsen.11 | ||
| Borderline Lepromatous (BL) | Numerous symmetrical small lesions that are restricted to certain areas of the skin. Nerves may be thickened and tender.11 | The disease is unstable. It can persist, improve or worsen.11 | ||
| Lepromatous Leprosy (LL) | Many small, raised, numb skin lesions that are usually spread out symmetrically, often on the face. This can cause eyebrow loss and a thickened, lion-like appearance of the face (‘leonine facies’). Severe nerve damage may lead to sensory issues, motor issues, deformities and disability.11 | The disease is stable, but the immune system cannot respond appropriately to the infection. The disease does not regress.11 | Most Severe | Th2 dominant |
Why do people’s immune systems react differently to M. leprae?
It is estimated that only around 5% of people exposed to M. leprae become successfully infected, with only about 1 in 5 of those infected actually developing leprosy.4 This is because most people’s immune systems can fight the disease. Additionally, scientists have known about a genetic link to leprosy risk since the 1900s, with modern genetic research technology allowing us to see which genes are involved.4 Most genes linked to leprosy risk are immune system-related.4 This genetic risk, paired with a range of other factors like age, gender, socioeconomic factors and environmental factors, all determine how well a person’s immune system can respond to M. leprae infection.3,4
Summary
- Leprosy is a chronic disease caused by Mycobacterium leprae bacteria
- It can be treated with multidrug therapy
- It affects each person differently depending on a person’s genetics and how their immune system reacts to the infection
- A Th1 immune response is a strong and protective response that can keep M. Leprae under control
- A Th2 response is weaker and less effective, so M. Leprae can spread and cause more serious forms of leprosy
- The Th1/Th2 Paradigm explains why leprosy can look different from person to person
- Scientists use the Ridley and Jopling classification system to describe leprosy clinically
- Genetic variations from person to person play a role in the differences between immune responses to leprosy
References
- Yasmin H, Varghese PM, Bhakta S, Kishore U. Pathogenesis and Host Immune Response in Leprosy. In: Kishore U, editor. Microbial Pathogenesis - Infection and Immunity [Internet]. Springer Cham; 2021 [cited 18 June 2025]. p. 155–77. Available from: https://doi.org/10.1007/978-3-030-67452-6
- World Health Organisation. Leprosy [Internet]. Who.int. World Health Organisation: WHO; 2025 [cited 2025 Jun 14]. Available from: https://www.who.int/news-room/fact-sheets/detail/leprosy
- Alrehaili J. Leprosy Classification, Clinical Features, Epidemiology and Host Immunological Responses: Failure of Eradication in 2023. Cureus [Internet]. 2023 Sep 15 [cited 14 Jun]; Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC10557090/
- Mi Z, Liu H, Zhang F. Advances in the Immunology and Genetics of Leprosy. Frontiers [Internet]. 2020 Apr 16 [cited 16 Jun 2025];11. Available from: https://doi.org/10.3389/fimmu.2020.00567
- Masson E. Leprosy: Clinical aspects and diagnostic techniques. EM-Consulte [Internet]. [cited 2025 Aug 24]. Available from: https://www.em-consulte.com/article/1372200/leprosy-clinical-aspects-and-diagnostic-techniques.
- Marshall JS, Warrington R, Watson W, Kim HL. An introduction to immunology and immunopathology. Allergy, Asthma & Clinical Immunology [Internet]. 2018 Sep 12 [cited 18 Jun 2025];14. Available from: https://doi.org/10.1186/s13223-018-0278-1
- Jr CAJ, Travers P, Walport M, Shlomchik MJ, Jr CAJ, Travers P, et al. Immunobiology. 5th ed. Garland Science; 2001.
- Berger A. Th1 and Th2 responses: what are they? British Medical Journal [Internet]. 2000 Aug 12 [cited 14 Jun 2025]; Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC27457/
- Modlin RL. Th1-Th2 Paradigm: Insights from Leprosy. Journal of Investigative Dermatology [Internet]. 1994 [cited 2025 Aug 24]; 102(6):828–32. Available from: https://www.sciencedirect.com/science/article/pii/S0022202X94946140.
- Ridley DS, Jopling WH. Classification of leprosy according to immunity. A five-group system. International Journal of Leprosy. 1966;31(3):255–73.
- Ernst JD. 334- Leprosy (Hansen’s Disease). In: Goldman’s Cecil Medicine [Internet]. 2012 [cited 17 Jun 2025]. p. 1950–4. Available from: https://doi.org/10.1016/B978-1-4377-1604-7.00334-1
- Shenoy SM. Mid-borderline leprosy. Indian Dermatology Online Journal [Internet]. 2013 [cited 17 Jun 2025];4(2):162. Available from: https://journals.lww.com/10.4103/2229-5178.110647.
