Stress and the Immune System

Stress and the Immune System

Stress is defined as a specific response by the body to a stimulus that disturbs or interferes with the normal physiological equilibrium of an organism.¹ Stress is shown to alter the effect of the immune system by inhibiting its actions, resulting in a number of potential physiological and psychological setbacks, which include obesity, cardiovascular and gastrointestinal disease among others. Additionally, there is a strong relationship between the central nervous system and immune system. Homeostasis and hormonal regulation by CNS and specifically neuroendocrine responses to stress, which are mediated by hypothalamic CRF, could result in “increased levels of corticosteroids, catecholamines, and certain opiates, substances which are generally immunosuppressive.²”

1: Effects of Stress

Studies on obesity have found evidence that Leptin is produced and regulated by neurons. Leptin is an appetite and body weight regulator, which also regulates Th1. The neural influence affects the immune system through leptin. There are Leptin receptors on CD4+ T cells (Th-1 immunity) and their lack of leptin gene showed a high thymocyte apoptosis. During starvation, or low leptin period, the immune system will be suppressed. Thus, for microbial infections, limiting stress and adequate nutrition is absolutely necessary for the healing process; however, for autoimmune diseases, stress and starvation can be beneficial.³

Studies on mice have shown that the stress response has a negative effect on the gastrointestinal system. The enteric nervous system (gastrointestinal system) is closely related to the brain by the parasympathetic and sympathetic pathways. This is known as the “brain-gut” axis.⁴ Corticotropin Releasing Hormone (CRH) is released in response to stress.⁵ CRH is responsible for increasing colonic activity, as well as decreasing gastric emptying time, gastric acid secretion and small bowel transit time.⁵ Studies have also shown that the stress response increases the permeability of the intestine to large antigenic molecules, which leads to mast cell activation, degranulation and colonic mucin depletion.⁵ The colon develops an increased susceptibility to colonic inflammation. The stress response has also been related to various gastrointestinal diseases, including functional bowel disorders, inflammatory bowel disease, peptic ulcer disease and gastroesophageal reflux disease. Furthermore, CRH causes the release of ACTH from the pituitary which results in the increase of cortisol in the bloodstream. Cortisol acts as an immunosuppressant by inhibiting the T-cell growth factor production.

Figure 2: Stress

The effects of stress on heart function and development of coronary artery disease (CAD) have also been shown. Stress can lead to inflammation from T lymphocytes, monocytes, macrophages and inflammatory cytokines (IL-1 and IL-6), as well as increased fibrinogen proteins for thrombus development.⁶ These factors can cause vascular inflammation, leading to atherosclerosis, which is the leading cause of CAD. IL-1 and IL-6 levels can be used clinically to test for depressed or anxious patients who might need early prevention of cardiovascular disease.⁶

Psychological stress has been recognized as a contributor to immune deficient responses. Studies have shown that chronic psychological stress leads to a less effective immune response to hormonal fluctuations that occur with infection.⁷ This means that a person under severe emotional stress would not be able to mount a sufficient immune response as compared to an individual with a normal state or at least free of such a stress factor.

Finally, overall happiness or sadness have been studied as contributing variables in the ability of an individual to fight off the common cold.⁸ An overall positive attitude or mental state is directly associated with a shorter period of recovery, whereas a negative state would present with a longer illness time.

Discussion Questions:

1. What is stress?

2. What is the role of T lymphocytes, monocytes, macrophages and inflammatory cytokines in Coronary Artery Disease?

3. What is the role of Leptin and stress in the immune system?

Multiple Choice Questions:

1. Which hormone is released during the stress response?

a. CRH

b. ADH

c. ACTH

d. Leptin

e. All of the above

2. In which of the following disease(s) would stress be beneficial in the treatment of the patient?

a. Obesity due to increased Leptin

b. Autoimmune disease

c. Hypogonadotropism

d. Atherosclerosis

3.The release of what can lead to vascular inflammation

a. IL-1 and IL-6

b. Estrogen

c. Thyroid Hormone

d. ATP

References

1. Stress: Available at: http://dictionary.reference.com/browse/stress. Accessed April 11, 2010.

2. Black PH. Central Nervous System-Immune System Interactions: Psychoneuroendocrinology of Stress and Its Immune Consequences. American Society of Microbiologist. 1994. Vol 38, Pg.1-6. Available at: http://aac.asm.org/cgi/reprint/38/1/1.pdf. Accessed: April 29, 2010.

3. Steinman, L., et al. The intricate interplay among body weight, stress, and the immune response to friend or 1 foe. Journal of Clinical Investigation. 111(2):183-185, January 2003. Available at:http://www.jci.org/articles/view/17622/files/pdf Accessed: April 11, 2010.

4. Hedrich HJ, Bullock GR. The laboratory mouse. London: Academic Press; 2004

5. Bhativa V, Tandon RK. Stress and the Gastrointestinal tract. J Gastroenterol Hepatol. 2005 Mar;20(3):332-9.

6.Roger CM Ho et al. Research on Psychoneuroimmunology: Does stress influence Immunity and Cause Coronary Aftery Disease? Annals Academy of Medicine. 2010 Mar;39(3).

7. Miller, Cohen, & Ritchey, 2002. Beaton, David. Effects of Stress and Psychological Disorders on the Immune System. Rochester Institute of Technology http://www.personalityresearch.org/papers/beaton.html

8. Jones, J. (2003). Stress responses, pressure ulcer development and adaptation. British Journal of Nursing, 12, 17-23

Figures:

1.Sonrieka. The Effects of Stress. Last visited April, 11th 2010. http://sonireka.files.wordpress.com/2009/04/topic_effects-1.jpg

2. Stress. Last visited April 11th 2010.

http://spaceresearch.nasa.gov/research_projects/images/immune_12-2002_1.jpg