Week 3 (Part 3): Autoimmune Disorders

Question 1

What do autoimmune disorders represent?

Answer 1

Autoimmune disorders represent a group of disorders that are caused by a breakdown in the ability of the immune system to differentiate between self and non-self antigens

Question 2

What are autoimmune disorders caused by?

- Results in?

Answer 2

Caused by an inappropriate B cell (antibody) and/or T cell immune responses
- Results in destruction of your own cells/organs.

Question 3

What do autoimmune disorders affect?

Answer 3

Autoimmune Diseases can affect almost any cell of tissue in the body and affect 5-10% of the population

Question 4

Are autoimmune disorders:

• Acute or chronic?
• Have relapse or remission?

Answer 4

Tend to be chronic, sometimes with relapses and remissions, and the damage is often progressive

Question 5

Define Self antigen/Autoantigen

Answer 5

an antigen expressed on your own cells

Question 6

define an antigen expressed on your own cells

Answer 6

T or B cells that bind to a self antigen

Question 7

Autoantibody

Answer 7

antibody that binds to a self antigen

Question 8

Define self tolerance:

- Results from?

Answer 8

To function properly the immune system must be able to differentiate foreign antigens from self-antigens: this is called self tolerance
- It results from central and peripheral mechanism that delete self-reactive immune cells that cause autoimmunity or render their response ineffective in destroying self-cells and self tissue

Question 9

Define Central Tolerance:

• Where are T vs. B-cells eliminated?

- Mechanism?

Answer 9

Central Tolerance derives from the deletion or inactivation of self-reactive T and B cells.

• Self reactive T cells are eliminated in the Thymus, Self reactive B cells in the bone marrow
• The mechanisms involves processes such as receptor editing, absence of necessary costimulatory signals, production of immunologic ignorance by separating self-reactive immune cells from target tissues.
• Thinks of central tolerance as a process where autoreactive cells (cells that attack self) are eliminated; and peripheral tolerance as an immunological response that deal with autoreactive cells that escaped central tolerance*
• So these tolerances are what are supposed to happen in order for our immune system to not attack self cells.
• It is the failure of these tolerances that results in immune reactions against self-antigens

Question 10

Define Peripheral Tolerance

- Processes?

Answer 10

Peripheral Tolerance maintenance of tolerance in secondary lymphoid tissue such as the spleen and lymph nodes.
- Peripheral tolerance processes work through deletion or killing of autoreactive cells (apoptosis), anergy (which is a state where cells become unresponsive to antigen stimulation and suppression of effector T cell activation

Question 11

It is obvious that autoimmunity results from loss of self-tolerance… how does this happen?

Answer 11

How this happens is largely unknown, but both inheritance of susceptibility genes that contribute to the maintenance of self tolerance and environmental factors that promote the activation of self-reactive lymphocyte

• Gender may also play a role, as a disproportionate number of autoimmune diseases occur in women, and overall the female to male ratio is 5:
• Genetic factors can increase the incidence and severity of autoimmune diseases, as shown by the familial clustering of several autoimmune diseases.
• The gene showing the strongest genetic association is Human Leukocyte Antigen (HLA) genes of which there are many different types

Question 12

Because autoimmunity does not develop in all persons with genetic predisposition it appears that other factors such as trigger event” interact to precipitate the altered immune state, what does the trigger include?

Answer 12

It has been suggested that the “trigger” could include this like a virus or other microorganism, or even a chemical substance

Once such example is with molecular mimicry: in which a microbe shares and immunologic eptitope with the host

• In Group A strep, which causes strep throat – the cell wall of the streptococci have considerable similarity with antigens in heart and kidney tissue.
• After infection, antibodies directed against the microorganism cause a classic case of mistaken identity, which leads to inflammation of the heart or kidney

Question 13

What is an Organ-specific Autoimmune Disease?

- Examples

Answer 13

autoimmune response targets an antigen present in a specific organ

• Insulin-Dependent Diabetes Mellitus (pancreas - beta cells)
• Graves Disease (thyroid – thyroid-stimulating hormone receptors)

Question 14

What are Systemic Autoimmune Diseases?

- Examples

Answer 14

autoimmune response targets an antigen present at many different sites; can involve multiple organs
- Systemic Lupus Erythematosis (many cell types)

Question 15

What is graves disease?

• What does the immune system attack?
• What is TSI?
• What does TSI do?

Answer 15

Graves’ disease is anautoimmune disorderthat causeshyperthyroidism, or overactive thyroid.

• With this disease, theimmune systemattacks the thyroid and causes it to make more thyroidhormonethan your body needs.
• With Graves’ disease, the immune system makes anantibodycalled thyroid-stimulating immunoglobulin (TSI) that attaches to thyroid cells.
• TSI acts like thyroid-stimulating hormone (TSH), a hormone made in thepituitary glandthat tells the thyroid how much thyroid hormone to make.
• TSI causes the thyroid to make too much thyroid hormone.

Question 16

What is Type 1diabetesmellitus?

• What do T-cells kill? Resulting in?
• Triggers?

Answer 16

Type 1diabetesmellitus (T1DM) is a disorder resulting from a chronic autoimmune destruction of the insulin-producing pancreatic beta cells

• Autoreactive t cells kill insulin-producing beta cells in the pancreas, specifically the islets of Langerhans which results in reduced insulin production that leads to hypergylcemia as seen in diabetes
• It is not known what triggers the inflammatory process, there have been some theories that suggest there is a trigger even, such as a viral illness that triggers the immune response in the host, and interestingly diagnoses of insulin dependent diabetes tend to cluster at specific times of the year, notably the spring and fall

Steps:

• autoreactive CTLs kill insulin-producing b-cells in the pancreas
• results in reduced insulin production → hyperglycemia
• unknown what triggers inflammation in the pancreas

Question 17

What is attacked in MS?

• What does it cause?
• Core process?

Answer 17

InMS, the immune system attacks the protective sheath (myelin) that covers nerve fibers and causes communication problems between the brain and the rest of the body.

• Eventually, the disease can cause permanent damage or deterioration of the nerves.
• The core process in MS is inflammatory, with T cells and their mediators triggering injury of axons and their myelin sheaths through a complex sequence of events.
• The T- cell–mediated inflammation is driven by the autoimmune process, which in turn can trigger a degenerative phase that is immune independent.

Question 18

What trigger myelin damage in MS?

Answer 18

unclear what triggers myelin damage and subsequent CNS inflammation

Question 19

What treatments are there for Autoimmune Diseases?

Answer 19

Immunosuppression (e.g., NSAIDS, prednisone, cyclosporin A)

Plasmapheresis (remove antibodies) – temporary fix

Block MHC with similar peptide (mimic)

Use antibodies that block B cells and/or T cells

Disease-specific treatments – e.g. insulin for IDDM/T1D, joint replacements for rheumatoid arthritis

Question 20

Treatment of autoimmune disease is based on …

• Ideally treatment focuses on?
• What can be used to used to arrest or reverse the downhill course?
• Option in severe cases of autoimmunity?

Answer 20

the tissue or organ that is involved, the effector mechanism involved, and the magnitude and chronicity of the effector processes

• Ideally, treatment should focus on the mechanism underlying the autoimmune disorder.
• Corticosteroids and immunosuppressive drugs may be used to arrest or reverse the downhill course of some autoimmune disorders.
• Purging autoreactive cells from the immune repertoire, through the use of plasmapheresis, is also an option in some severe cases of autoimmunity