1. Autoimmune Diseases Presented by: Ms. Ahood Alammari (Female)
Mr. Abdullah Mohamed (Male)

2. Learning Objectives:
Upon completing this lecture students should be able to:
Know that the inflammatory processes in auto immune diseases are mediated by hypersensitivity reactions (type II, III and IV).
Know that autoimmune diseases can be either organ specific or may be generalized involving many organs or tissues.
Understand that the manifestations of autoimmune diseases depend upon the organ and the degree of damage inflicted on the target tissues.

3. Autoimmune Diseases
Autoimmune diseases is a condition that results because the immune system mistakenly attacks the body and lose the ability to distinguish between self and non-self.
This process is able to generate autoantibodies that attack healthy or normal cells.
Some autoimmune diseases can target single organ like Type 1 diabetes. Other diseases can affect the whole body like lupus.
Some autoimmune diseases are more common in certain ethnic groups. For example, lupus affects more African-American and Hispanic people than Caucasians.
Autoimmune diseases can result because of genetic disorder or environment.
Autoimmune disorders are able to effect a single organ involvement to a systemic disease.
The disease process is usually prolonged and is generally associated with significant morbidity and mortality.
The mainstay of the treatment is to maintain immunosuppression.

4. Autoimmune Diseases

5. Autoimmune Diseases
- Disease processes and tissue damage are due to hypersensitivity reactions:
Type II (IgG Ab to tissue antigens).
Type III (IgG Immune Complexes),
Type IV (Cell Mediated Immunity).
- All of the hypersensitivity reactions can play a role in autoimmune diseases except type I hypersensitivity. (( Why? ))
- Not all autoimmune diseases are caused by a known hypersensitivity reaction.

6. Autoimmune Diseases The most 8 common autoimmune diseases:
Type 1 diabetes: the immune system attacks and destroys insulin-producing cells in the pancreas. (localized)
Rheumatoid arthritis (RA): the immune system attacks the joints. (Systematic)
Multiple sclerosis (MS): the immune system damages the myelin sheath. (localized)
Systemic lupus erythematosus (SLE): affects many organs, including the joints, kidneys, brain, and heart. (Systematic)
Addison’s disease: the immune system affects the adrenal glands. (localized)
Graves’ disease: the immune system attacks the thyroid gland in the neck. (localized)
Hashimoto’s thyroiditis: thyroid hormone production slows.
Celiac disease: the immune system attacks the intestine and causes inflammation.
** What is the different between celiac disease and gluten sensitivity??

7. Autoimmune Diseases
Autoimmune diseases are classified into two groups:
1- The organ-specific autoimmune diseases where the target antigens and the tissue disorders are localized in one organ.
Ex: Addison disease, autoantibodies attack the adrenal cortex. Type 1 diabetes
2- The systemic autoimmune diseases where the response to a certain type of antigens that are expressed widely in the body, such as an intranuclear antigen and multiple organs are involved.
Ex:  Systemic lupus erythematosus, characterized by inflammation of the skin, joints, and kidneys.
However, there are several autoimmune diseases that stand between these two groups. It remains unclear whether these two groups of autoimmune diseases result from the same or substantially different mechanisms.

8. Organ-Specific Autoimmune Diseases
Mediated by
Antibodies
Stimulating Antibodies (Graves' disease)
Blocking Antibodies (Myasthenia Gravis)
Direct cellular damage
Hashimoto's Thyroiditis

9. Graves' disease
It is an organ-specific autoimmune disease in which the immune system attacks the thyroid gland in the neck.
It is known as Thyrotoxicosis and Toxic diffuse goiter.
Normally, production of thyroid hormones is regulated by thyroid-stimulating hormones (TSH).
The binding of TSH to a receptor on thyroid cells stimulates the synthesis of two thyroid hormones:
Thyroxine
Triiodothyronine

10. Graves' disease
A person with Graves’ Disease makes autoantibodies to the receptor for TSH.
the antibody associated with Graves' disease, which is known as thyrotropin receptor antibody (TRAb), acts like the regulatory pituitary hormone.
Binding of these autoantibodies (TRAb) to the receptor mimics the normal action of TSH leading to overstimulation and overproduction of the thyroid hormones (hyperthyroidism).

11. Graves' disease Symptoms: Hand tremors Weight loss Bulging eyes
Trouble sleeping
Hyperthyroidisms
Anxiety and irritability
Note: Most people with Graves' disease have symptoms of an overactive thyroid.
Note: It is more common in women.

12. Myasthenia Gravis
It is a chronic autoimmune neuromuscular disease that causes weakness in the skeletal muscles.
It is caused by a defect in the transmission of nerve impulses to muscles.
The antibodies in MG attack a normal the nicotinic acetylcholine receptor (AchR)., or a related protein called (MusK) a muscle-specific kinase.
IgG Ab interact with the postsynaptic AChR at the nicotinic neuromuscular junction (NMJ).
There is reduction in the number of functional AChR receptors by increasing complement mediated degradation of receptors.

13. Myasthenia Gravis Symptoms: Weakness Fatigability with effort
Drooping eyelids
Trouble talking
Problems walking up stairs or lifting objects
Note: It is a disease that affects the nervous system.

14. Hashimoto's Thyroiditis
Large amounts of damaged immune cells invade the thyroid.
When these lymphocytes enter the thyroid, they destroy the cells, tissue, and blood vessels within the gland.
Because the thyroid is mostly coming under attack from invading, it isn't able to produce as much thyroid hormone as it normally would. 
TSH binds to receptors on the cell membrane of the thyroid gland causing break down of thyroglobulin into T3 and T4AutoAbs may interfere with this process and cause under or over activity of the thyroid.
known as chronic lymphocytic thyroiditis, often leads to an underactive thyroid gland (hypothyroidism).

15. Hashimoto's Thyroiditis
Symptoms:
Feeling cold 
Depression
Dry skin
Constipation 
Fatigue
Sleepiness 
Weight gain
Note: Hashimoto’s thyroiditis is most often seen in women between the ages of 30 and 40 years.

16. Systemic Autoimmune Diseases
Multiple Organ Systems
Systemic Lupus Erythematosus (SLE)
Rheumatoid Arthritis

17. Systemic Lupus Erythematosus (SLE)
Systemic Lupus Erythematosus is the most common autoimmune disease that is known as a chronic systemic inflammatory disease.
The most common characteristic is “butterfly rash”, and it is made worse by exposure to sunlight.
SLE is associated with more than 28 autoantibodies.
Lupus patients appear to have overactive B cells especially the subset with the CD5 marker which increase in number.
Immune responses against endogenous nuclear antigens are characteristic of SLE.
Autoantigens released by apoptotic cells are presented by dendritic cells to T cells leading to their activation.
Activated T cells in turn help B cells to produce antibodies to these self-constituents by secreting cytokines such as interleukin 10 (IL10) and IL23 and by cell surface molecules such as CD40L and CTLA-4.

18. Systemic Lupus Erythematosus (SLE)
Increased amounts of apoptosis-related endogenous nucleic acids stimulate the production of IFN-α and promote autoimmunity by breaking self-tolerance through activation of antigen-presenting cells
Once initiated, immune reactants such as immune complexes amplify and sustain the inflammatory response.
Approximately 1 in every 2000 individuals are affected age of onset is usually between 20 and 40 years of age. Women are much more likely than men to be stricken by a margin of 13 to 1.
Note:
It is a true multi-system disease, it can affect any part of the body. It is unpredictable.
There is no cure for SLE. The goal of treatment is to control symptoms.

19. Systemic Lupus Erythematosus (SLE)

20. Systemic Lupus Erythematosus (SLE)

21. Rheumatoid Arthritis
It is an autoimmune disease in which the normal immune response is directed against an individual's own tissue, including joints, tendons, and bones.
Women are more likely to be affected than men and usually strikes between the ages of 20 and 40.
It has been associated with certain of the HLA class II molecules.
Rheumatoid factor (RF) is the autoantibody (antibody directed against an organism's own tissues.
It is defined as an antibody against the Fc portion of IgG (an antibody against an antibody) and different RFs can recognize different parts of the IgG-Fc.

22. Rheumatoid Arthritis
Antibodies react with determinants in the FC region of IgG (Self-antigen is IgG).
The classic rheumatoid factor is an IgM antibody with this kind of reactivity.
The Ab is not specific for RA as it is found in other diseases such as SLE.
The main difference between rheumatoid and osteoarthritis is that osteoarthritis is a degenerative disease.

23. Rheumatoid Arthritis

24. Recommended books: Prescribed textbook:
Delves PJ, Martin SJ, Burton DR, Riott IM (2006). Riott‟s Essential Immunology. Eleventh Edition. Blackwell Publishing, UK.
Recommended textbooks:
Male D, Brostoff J, Roth DB, and Roitt I. (2006). Immunology. 7th ed. Edinburgh: Mosby.
Murphy - Janeway’s Immunobiology 9th Edition (2017)