The 102nd Difference Between Women and Men

The body's innate aversion to self destruction is called as autoimmunity. This was first noted by Ehrlich and Morgenroth. It was found that the injection of self antigens failed to elicit an immune response in the autologous host. The goats which were immunized failed to recognise and produce their own antibodies. Thus was coined the concept horror autotoxicus. This is the horror of self toxicity. It was thought that this condition itself might lead to a disease. Over the years the concept of autoimmunity came to materialise and it was said that an autoimmune response should be considered the cause of human disease if:

(1) It is regularly associated with the disease;
(2) Immunization in an animal leads to the development of a cell mediated immune response.
(3) There are pathological changes observed in association with the response.
(4) The experimental disease can be transferred to non-immunized animals by serum/Lymphoid cells.

It has recently been proved that even the hormonal, environmental and genetics contribute to the defective immune system in order to produce an autoimmune disease.

It has been documented that some autoimmune diseases are more susceptible in women than in men. This made people come to a notion that sex hormones have a role to play. It is a known fact that these hormones have a direct effect on the immune system cells or indirectly through cells that control growth and development of immune system. In contrast to mice which synthesise more antibodies depending on the gender the humans are impartial. The female mice synthesise more antibodies than the males. Sex hormones have a major effect on the thymus. The sex hormones have many targets like the bone marrow and thymus where the precursors of immunity originate and differentiate. Sex steroids do affect the development and function of immune system.

The four possible reasons why autoimmunity occurs more in females than in males:
(1) Hormone theory
(2) Environmental Factors
(3) Genetic Influences
(4) Whole organism Influences

Theories of Sex predominance:

Hormone Theory: It is a belief that estrogen producing women are more prone to autoimmune diseases than men. In actual the estrogen makes the immune system of the woman over react. These findings help us to prove that the autoimmune diseases actually tend to over react to the immune system and hence they occur more in women than in men. For instance Lupus associated is found in every 9 women for every one man. There is also a problem of severity, the women who develop lupus fall severely ill.

Environmental Factors:
The environment also is said to have a major role to play in the autoimmune responses. The workplace of a person or where he stays can also be one of the deterministic factors for causing autoimmune diseases. Scleroderma is a type of autoimmune disease which is seen more amongst women. This occurs due to the constant contact with contaminated oil. This could occur both in males and in females it is just that the ladies tasted the food while it was being cooked so the contaminants were not destroyed on the other hand the males had it only after the contaminants were eradicated. These examples support the idea that exposure to a toxin determines who will develop the disease, rather than the sex of the patient. Unfortunately, it does not yet help to explain female predominance in a disease like systemic lupus erythematosus.

Genetic Influences: Every cell in man is different from the cell found in the woman. There is also a difference between the DNA and the way the cells associate themselves in the body. Women who are pregnant carry the cells of their babies along with them and this perishes after the baby is born but the women suffering from autoimmune diseases have cells of the babies retained in them for a long time.

Whole organism issues: The chances of a female developing breast cancer maybe due to the number of children she gives birth to. The Alzimers disease is linked with age.
The most striking sex differences are observed in Sjogren's syndrome, SLE, autoimmune thyroid disease (Hashimoto's thyroiditis and well as Graves' disease) and scleroderma, which represent a spectrum of diseases in which the patient population is >80% women. The next relatively common diseases that includes rheumatoid arthritis (RA), multiple sclerosis (MS) and myasthenia gravis, in which the sex distribution is 60-75% women. A final group, which includes sarcoid, the more common inflammatory bowel diseases and immune-mediated (type 1) diabetes (also known as insulin-dependent diabetes mellitus or IDDM), are characterized by a female: male ratio that is approaching 1:1. In addition to a difference in prevalence between women and men, it is also recognized that the two sexes exhibit differences in disease presentation.

The autoimmune diseases have been studied for a long time now. The occurrence of them being more in women than in men has also been a question of debate. It was first thought that the each autoimmune is different and they were treated differently but then it was seen that the mechanism of all the autoimmune diseases are the same. For instance the activation of CD4 helper T cells seemed to be important in RA, MS and IDDM though the antigenic specificities of each are quite different. The increased prevalence of autoimmune diseases in women is due to the sexual dimorphism of the immune response and the modulatory effects of sex steroids on immune function in vitro mainly estrogens, progesterone and testosterone. The fluctuation of the disease during and after pregnancy has been explained by the hormonal environment during pregnancy which favours Th2 response. In MS (Multiple Sclerosis) and RA (Rheumoid Arthritis) there is suppression of Th2 cells seen in contrast to SLE (Systemic Lupus erythematosus) where there is proliferation of Th2 cells. Men having RA have lower levels of testosterone. An alternative hypothesis to explain changes in disease during and after pregnancy has examined the genetic relationship between mother and offspring.

The sex steroids have a direct effect on the immune system, modulating aspects of hypothalamic-pituitary-adrenal, antigen presentation, cytokine gene expression and lymphocyte activation. Sex hormones modulate the stress response which results in decreased concentrations of the cortecosterone whereas orchidectomy enhances the cortecosterone response.

Females of many species including the humans have higher cortecosterone-cortisol concentration than males. The glucocorticoids suppress this activation of sex hormones to a great extent. This helps in the decline of estrogen postpartum. Hence the interaction between the HPA axis, the sex hormone and immune system is complex. Genetics also plays a prominent role in talking about the autoimmune susceptibility and the se hormone expression. The environmental factors, genetics and the sex of the person also determine the autoimmunity. There is a need for the thorough understanding of the differences right from the first stage to the late stage in response to the exogenous and self antigens. Understanding of the fluctuations between the normal immune response and the autoimmune response is also essential.

The contribution of genetics to the sex differences in autoimmune response is still not known. Never has there been such a keen interest in knowing the sex differences in relation to the autoimmune diseases. Many funding organisations are investing their money towards this research. This contribution helps and promotes the research on this particular field.

Reasons put forward so far for the higher prevalence of autoimmune diseases in women are:

(1) Difference in antibody production:
• Females produce more antibodies than males.
• They have more vigorous immune responses in comparison to the males.
(2) Sex hormones play an significant role:
•Studies indicate that the estrogen can encourage auto-antibody production. This was seen in SLE-prone mice.
• Testosterone seems to be acting as a protective gear against many auto immune diseases. E.g.: SLE, Diabetes.
(3) Pregnant women tend to modify their foetus during pregnancy.
(4) The women even after pregnancy tend to retain their foetus cells which lead to the development of auto immune diseases.

There has been a keen interest on the autoimmune diseases and there has been a lot of money invested on the treatment of these diseases. The new treatment methods include TNF inhibitors. Many of the treatments are in the phase 3 stages.

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