mellitus-immunology

Sunday, February 7, 2010

~Introduction~

Question 4: Women outlive men and have a more aggressive immune system than males; this is probably the reason for the greater occurrence of Systemic Lupus Erythematosus (SLE) in females. Discuss the following:
a. SLE and its implications for health
b. Causation of autoimmune type 1 Diabetes Mellitus

Why Women Have a More Aggressive Immune System Than Men?
Out of 9 million individuals with autoimmune disease in US, around 6.7millions are women. This shows that inclinations towards autoimmunity is more visible in some disease than others. For instance, the female-to-male ratio of individuals who suffered from disease such as Rheumatoid Arthritis is about 2-3 females to 1 male. In other words, there are 9 women for every man afflicted with Systemic Lupus Erythematosus (SLE). The reason behind why women were more prone to autoimmune diseases was not explained. However, there are some considerable evidence that suggests that there is significant gender differences in immune response between both human and mices.

Studies suggest that females produces a higher titre of anti-bodies than males. Thus, females tend to mount more vigorous immune response. This is particularly apparent in young females. Women tend to have higher level of CD4+ cells and serum IgM. In mice, the studies suggest that female mice are more likely to develop TH1 responses and, in infections for which inflammatory TH1 responses are beneficial.

Estradiol or testoterone can alter the outcome of infection by CV-3 (coxsackie virus type B-3: an etiological agent of immume myocarditis). Estrogen plays an important role in SLE. It was suggested that estrogen can stimulate anti-body production in SLE-prone mice and effects can be regulated by an anti-estrogenic compound. In another words, estrogen is capable of triggering SLE-like-autoimmunity.

Reference
[Thomas J.Kindt, Richard A.Aoldsby & Barbara A. Osborne. (2007) Kuby Immunology 6th edition. US: Wt. Freeman and company.]

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~Whats are the effect of estrogen on immunological functions?~

Females have higher levels of "cell-mediated immunity" (CMI) than males. Steriod is being described as depressing CMI. On the other hand, estrogen is reported to amplify humoral immunity. Females have higher immunoglobulin titres, as well as increased primary and secondary immunological responses to a number of pathogens. These pathogens causes rise in getting hepatitis B and rubella. The increased immune responses in females is reflected on the high incidence of autoimmune diseases like SLE.

Individuals with SLE produces high level of 16 α- hydroxyestrone. This steriod binds with high affinity to estrogen receptors. In SLE, the increased level of 16 α- hydroxyestrone further impairs lymphocyte suppressor function, and thus, enhances auto-antibody production . Besides this, estrogen also increases synthesis of anti-bodies by controlling regulation of T cells.

In females, during their menstrual cycle, the changes in estrogen and progesterone levels are correlated with alterations in the severity of SLE. The worst symptoms of the disease is during luteal phase. (Luteal phase - from ovulation to the beginning of the next menstrual flow.) In addition, SLE is aggravated by estrogen/progestin containing oral contraceptives. This is evident when patients take in Tamofixen, is a competitive estrogen antagonist. Thus, it is ineffective in alleviating disease symptoms.

Reference
[ppornelubio.(2007, May 04) Cell Mediated Immune Response [Video File] Retrieved from http://www.youtube.com/watch?v=1tBOmG0QMbA&feature=player_embedded]

[James A. Marsh & Marion D.Kendall (1996) The Physiology of Immunity. United State of America: CRC Press]

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~Sex steriods and immune responses~

Why do sex steroids affect immune responses?

Hormone cytoplasmic receptor

Hormones circulating throughout the body can alter immune responses by altering the patterns of genes expression. Hormones, being lipophilic, can pass through cell membrane and bind to cytoplasmic receptor. Each hormone has a specific cognate receptor. The binding of hormone receptors leads to the activation of repression of gene expression. Estrogen enters the cell and binds to its receptor. This induces the binding of estrogen receptor to specific DNA sequence which result in modulation of transcription.

However, hormonal effects on immune responses may not be restricted to sterodial sex hormone. Prolactin is not a memeber of the steriod family. Women has higher levels of prolactin as compared to Men. However, prolactin secretion is stimulated by estrogen, thus, it explains why women has higher level of prolactin. Prolactin was found to have profound influence on immune responses. The presence of prolactin receptors on peripheral T and B cells in humans plays an important role in regulating immune responses.

Reference

[GettyImages(2010)Woman Thinking. Retrieved from http://www.gettyimages.com/]

[Student reader (no date) Endocrinology Introduction. Retrieved from http://studentreader.com/category/anatomy-physiology/hormones/ on 4 Feb 2010]

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~Classification of Autoimmune Disease~

Autoimmune responses are similar to normal immune responses and pathogens in that they are specifically activated by antigens. In this case, self antigens or auto-antigens. The type of autoimmune disease stimulated when self-reactive lymphocytes are activated depends on their particular targets. Autoimmune diseases are divided into organ-specific & systemic.

For Type I Insulin-Dependent Diabetes Mellitus (IDDM), which is a organ specific type, it is caused by the immune attack on insulin-producing pancreatic beta cells, auto-antigens from one or a few organs are targeted & disease is therefore confined to those organs.

As for Systemic Lupus Erythematosus (SLE), it is a systemic type where chromatin is a major target. Hence, systemic autoimmune diseases affects multiple organs & have a tendency to become chronic, as the auto-antigens can never be removed from the body as it is present everywhere.

Reference
[Charles A. Janeway, Jr., Paul Travers, Mark Walport, Mark J. Shlomchik. (2005) Immuno Biology 6th Ed. New Yolk & London: Garland Science Publishing]

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Saturday, February 6, 2010

~Causation of Autoimmune Disease~

Autoimmune diseases occur when some aspect of self-tolerance is lost by the self antigens & an adaptive immune response is directed towards normal components of the healthy human body leading to inflammation. This results to the production of more self antigens.

The response strives to rid the target antigens from the body and until that is achieved or the patient dies, a chronic state of information & lymphocyte infiltration exists in tissues where the target antigens are expressed. This severely damages & affect the function of the tissue.

Although the regulatory mechanisms of the immune system respond to the situation & can provide temporary relieve between episodes of disease, autoimmune diseases can rarely be cured. They are chronic diseases in which the immune response remains suspended in its destructive phase & never reaches reconstruction.

[Peter Parham. (2009). The Immune System 3rd Ed. London & New York: Garland Science Publishing; Charles A. Janeway, Jr., Paul Travers, Mark Walport, Mark J. Shlomchik. (2005) Immuno Biology 6th Ed. New Yolk & London: Garland Science Publishing]

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~Part (a) Introduction to Systemic Lupus Erythematosus~

Lupus is an autoimmune disease characterized by acute and chronic inflammation of various tissues of the body. Autoimmune diseases are illnesses that occur when the body's tissues are attacked by its own immune system. Lupus can cause disease of the skin, heart, lungs, kidneys, joints, and/or nervous system. When only the skin is involved, the condition is called Lupus dermatitis or Cutaneous lupus erythematosus. A form of lupus dermatitis that can be isolated to the skin, without internal disease, is called discoid lupus. When internal organs are involved, the condition is referred to as Systemic Lupus Erythematosus (SLE).The disease can affect all ages but most commonly begins from 20 to 45 years of age.

What are the signs and symptoms of lupus?

Patients with SLE can develop different symptoms such as: fatigue, low-grade fever, loss of appetite, muscle aches, arthritis, ulcers of the mouth and nose, facial rash ("butterfly rash"), unusual sensitivity to sunlight (photosensitivity), inflammation of the lining that surrounds the lungs (pleuritis) and the heart (pericarditis), and poor circulation to the fingers and toes with cold exposure (Raynaud's phenomenon). Complications of organ involvement can lead to further symptoms that depend on the organ affected and severity of the disease.

Skin manifestations are frequent in lupus and can sometimes lead to scarring. In discoid lupus, only the skin is typically involved. The skin rash in discoid lupus often is found on the face and scalp. It is usually red and may have raised borders. Discoid lupus rashes are usually painless and do not itch, but scarring can cause permanent hair loss. Over time, 5%-10% of patients with discoid lupus may develop SLE.
Over half of the patients with SLE develop a characteristic red, flat facial rash over the bridge of their nose. Because of its shape, it is frequently referred to as the "butterfly rash" of SLE. The rash is painless and does not itch. The facial rash, along with inflammation in other organs, can be precipitated or worsened by exposure to sunlight, a condition called photosensitivity. This photosensitivity can be accompanied by worsening of inflammation throughout the body, called a "flare" of the disease.

Reference
[Kathy Davis. Systemic Lupus Erythematosus. Retrieved Date: 5th Feb 2010. Website: http://www.connectedkansaskids.com/Diagnoses/SLE1.aspx ]

[abonzor100.(2009, April 24) 3D Animations of lupus [video file] Retrieved from http://www.youtube.com/watch?v=u-Em472khOY]

2 Comments:

Hey, nice blog you guys have here :)
But i have a few questions, since Lupus is a disease where the immune system attacks body cells and tissues; is the disease fatal? And what is the average lifespan of a person living with Lupus?

Also what lifestyle changes do you recommend for a person suffering from SLE?

Thank you.

By Rusnealz (Grp 3), at February 10, 2010 at 3:47 PM

hi! Thanks for your compliment on our blog =)The seriousness of the disease varies from different people.For some, it is mild for some it is very serious even leading to death.Those who have milder lupus, can sometimes have the same life span as a normal person - depending if there is any complications that arise at the same time e.g. kidney failures A person with lupus is more susceptable to infections, diseases and cancers.

Some of the lifestyle changes:
Avoid Sun Exposure- Sunlight will burn you easily, worsen lupus skin rashes, and may precipitate a flare-up of other symptoms. Use sun block lotion.

Treat All Cuts and Infections Quickly and Vigorously- Lupus is a disease of your immune system. Anything that stimulates the immune system can cause a flare-up of the disease.

Healthful diet- A healthful diet is one that is low in saturated fat and rich in whole grains, fruits, and vegetables which provide nutrients for the body to function properly and to help you manage lupus and its complications.
Limit

Emotional Stress- Feeling stressed can put extra burden on your body, including your immune system.

Get Adequate Rest- Many people with lupus get tired easily. Immune function, may be compromised if you do not get enough quality sleep. Strive for 7-8 hours of sleep per night, and take naps if you need them.

Exercise Moderately- Regular exercise helps keep you in good shape and better able to manage the affects of lupus.

Reference:
1. Ricker Polsdorfer, MD. (2009). Retrieved 12 Feb 2010, from Aurora Health Care. Website: http://www.aurorahealthcare.org/yourhealth/healthgate/getcontent.asp?URLhealthgate=%2219779.html%22

2. Harris ED, Budd RC, Genovese MC, Firestein GS, Sargent JS, Sledge CB. Kelley's Textbook of Rheumatology. 7th ed. St. Louis, Mo: WB Saunders; 2005. Website: http://www.lifespan.org/adam/healthillustratedencyclopedia/1/000435.html

3. Noble J. Textbook of Primary Care Medicine. 3rd ed. St. Louis, Mo: Mosby; 2001. Website: http://www.lifespan.org/adam/healthillustratedencyclopedia/1/000435.html

By mellitus-immunology, at February 12, 2010 at 1:21 AM

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Implication To Health caused by SLE

The Heart

Heart disease is a major complication of lupus and is now a leading cause of death among people with lupus. Blood tests, chest X-rays, an electrocardiogram (EKG), or an echocardiogram is used to find out whether a heart condition caused by lupus.

1)Perocaditis

Lupus affects the heart is through inflammation of the pericardium, the sac that surrounds your heart.The subject may experience are sharp pain in your chest and, occasionally, shortness of breath. Pericar-ditis usually does not damage your heart’s ability to function because it does not directly involve the heart tissue. However, inflammation that is chronic (long-lasting) can scar the heart tissue, which can interfere with the heart’s ability to pump blood.

2)Myocarditis

Lupus can cause inflammation of the myocardium, the muscle tissue of your heart. The symptoms are chest pain and an unexplained rapid or irregular heart beat. Myocarditis is often seen when there is inflammation in other muscles in the body.

In addition to that, it can also caused viral, bacterial, and fungal infections. And also, lupus creates an added risk for developing infections, especially if the subject is taking certain immunosuppressive drugs. The subject will have the risk of getting this type of myocarditis.

The Blood

Blood is made up of many different parts, but those that are most often affected by lupus are the red blood cells, the white blood cells, and the platelets.

1) Anemia

Lupus-related anemia occurs because when the body is not producing enough red blood cells. However, antibodies target healthy red blood cells for destruction. This condition is called hemolytic anemia, or simply hemolysis. Hemolysis can cause a yellowish color(caused by bilirubin) in your skin and eyes and is a serious condition.

Anemia may also be caused by aspirin, ibuprofen, and other non-steroidal anti-inflammatory drugs (NSAIDs) used to treat lupus. These drugs can irritate the lining of your stomach, which may lead to bleeding and loss of red blood cells. Feeling very tired is the earliest and most common symptom of anemia.

2) Granulocytopenia

It is due to decrease in white blood cells in the body which granulocytopenia. Both are common in people with active lupus.The reason of low numbers of white blood cells is due to an infection in your body, or due to certain drugs used to control lupus that work by suppressing your immune system.

The Lungs

Inflammation caused by lupus may affect the lungs in many ways, and can involve the membrane lining of the lungs, the lungs themselves, the blood vessels within the lungs, land the diaphragm.

1)Pleuritis

Lupus can affect your lungs is through inflammation of the pleura, the lining that covers the outside of the lungs. The symptom of pleuritis is severe, often sharp, stabbing pain in a specific area or areas of your chest. The pain, which is called pleurisy, is made worse when you take a deep breath, cough, sneeze, or laugh. You may also experience shortness of breath. An abnormal amount of fluid will build up in the space between your lungs and your chest wall; when it leaks out it is called a pleural effusion. Pain from pleurisy, with or without effusions, is found in 40 to 60 percent of people with lupus.

2) Chronic Diffuse Interstitial Lung Disease

It is due to inflammation in the lungs is chronic, it can cause scarring. The scar tissue can prevent oxygen from moving easily from the lungs into the blood and may cause widespread interstitial lung disease. The symptoms experience include a chronic dry cough, chest pain, and difficulty breathing during physical activity.

What are the treatments available?

Treatment can be used to treat the symptoms but not the disease. If the lupus causes only arthritis and rash, the medications can be relatively mild, such as non-steroidal anti-inflammatory drugs (NSAIDs; ex Naprosyn, Ibuprofen, or Celebrex). Disease modifying anti-inflammatory drugs (DMARDs) may also be used. A mild one that helps rash and fatigue especially is Plaquenil. Methotrexate is a DMARD that can be given orally or by injection and requires regular laboratory monitoring. More powerful DMARDs called cytotoxic drugs include Imuran and Cytoxan and can be taken by mouth, injection or infusion. These are reserved for children with severe lupus involvement. One of the more effective drugs for controlling lupus is a steroid or glucocorticoid called Prednisone. The more severe the disease the higher the steroid dose and the more severe the side effects.

Reference
[Lupus Foundation of America(2009). The Cardiopulmonary System. Retrieved 8 Feb 2010. Website:http://www.lupus.org/webmodules/webarticlesnet/templates/new_learnaffects.aspx?articleid=2301&zoneid=526 ]
[Kathy Davis. Systemic Lupus Erythematosus. Retrieved Date: 5th Feb 2010. Website: http://www.connectedkansaskids.com/Diagnoses/SLE1.aspx ]

2 Comments:

The colours used for this post makes reading the content difficult. Ms Verena

By Anonymous, at February 16, 2010 at 5:29 PM

We had made the necessary changes.

By mellitus-immunology, at February 18, 2010 at 1:31 AM

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Friday, February 5, 2010

~Part (b) Type I Diabetes Mellitus~

Causation of Type I Diabetes Mellitus
Autoimmune response

Type 1 Diabetes, also known as Insulin-Dependent Diabetes Mellitus (IDDM) or Juvenile-onset diabetes. It is caused by the selective autoimmune destruction of the insulin-producing beta cells of the pancreas. Symptoms of disease are shown during childhood or adolescence and they rapidly progress to coma and death in the absence of treatment. Insulin is important for children's growth and development. Therefore, without insulin it may result in stunted growth. Type 1 diabetes usually occurs in individuals under 30 but it can occurs at any age.

In Type 1 diabetes patients, antibody and T-cell responses are made against insulin, glutamic acid decarboxylase and other specialized proteins of the pancreatic beta cell. It is not known which of these responses cause the disease. A healthy person has about 100 million beta cells, thus provides a greater insulin-making capacity than that needed by the body. The excess and the slow rate of beta cell destruction mean that the disease symptoms do not appear until years after the start of the autoimmune response. The disease starts to develop when there are insufficient beta cells to provide the sufficient amount of insulin to control the level of blood glucose.

The islets of Langerhans are scattered within the exocrine tissue of the pancreas. The pancreas contains about half a million islets, each consisting of a few hundred cells. Each islet cell is responsible to make a single hormone: alpha cells make glucagon, beta cells make insulin and delta cells make somatostatin.

Genetic factors
Researchers have found at least 18 genetic locations, that are related to type 1 diabetes. Each labeled IDDM1 - IDDM18. The IDDM1 region contains the HLA genes that affect the immune response. Advances in genetic research are continuing to identify other genetic components of type 1 diabetes.

However, most people who develop type 1 diabetes do not have a family history of the disease. The odds of inheriting the disease is only 10% if a first-degree relative has diabetes. Children are more likely to inherit the disease from a father with type 1 diabetes than from a mother with the disorder.Genetic factors cannot fully explain the development of diabetes.

Viruses
Recent research is providing evidence that the type 1 diabetes is caused due to an infection of the Coxsackie virus. It is a viral infection which attacks the intestinal tract, triggering the disease in genetically susceptible individuals.

How to control it?
People who develop type 1 diabetes need up to four injections of insulin daily for the rest of their life. The insulin is purified from the pancreata of pigs or cattle. However, as human and animal insulin have different amino acid sequences, some patients develop immune response to it. The antibodies they make causes negative effects when binded to insulin - it reduces activity of insulin and form soluble immune complexes causing further tissue damage and serum sickness. Patients who are unable to use animal insulin will have to use recombined human insulin produced in the laboratory from the cloned insulin gene.

There are many long-term complications – for example, type 1 diabetes is the major single cause of adult blindness and kidney disease and an important contributor to cardiovascular disease.

Reference
[Peter Parham. (2009). The Immune System. London & New York: Garland Science Publisher]

[Len Harrison. (n.d.). Autoimmunity: Type 1 Diabetes. Retrieved 5th Feb 2010, from Walter+Eliza Hall: Institute of Medical Research. Website: http://www.wehi.edu.au/faculty/disease_research/autoimmunity_research/]

[Wasdom01. (2009, August 01).Insulin Production and Type1 Diabetes (Etsuko Uno and Drew Berry, wehi, 2009). [Video File]. Retrieved from http://www.youtube.com/watch?v=MLM5418YPGc&feature=player_embedded]

[Harvey Simon. (2009). Diabetes Type 1 Causes. Retrieved 7th February 2010, from University of Maryland Medical Center. Website: http://www.umm.edu/patiented/articles/what_causes_type_1_diabetes_000009_2.htm]

1 Comments:

Very neat and easy to read, except for some parts where the font colour makes it hard to read. Otherwise, good job done.

By Anonymous, at February 16, 2010 at 5:30 PM

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