Intro to Autoimmunity Flashcards
What is the normal function of the immune system?
-Normally works to defend the body and eliminate infections caused by bacteria, viruses and other invading microbes.
What does the immune system do in autoimmune disease?
-The immune system mistakenly attacks self, targeting the cells, tissues and organs of a persons own body.
There is a break down in tolerance
What are some common autoimmune diseases?
- Graves disease
- Rheumatoid arthritis
- Diabetes type 1
- Hashimotos thyroiditis
What can cause autoimmune disease?
- It is multifactorial
- If you have susceptibilty genes, then environmental/infectious things can trigger them
- This would lead to a breakdown in self tolerance and eventually autoimmunity
What is the fundamental problem in autoimmune disease?
-Imbalance between immune activation and control.
Immune response is innapropriately directed or controlled
What may determine the nature of disease?
-The type of dominant immune response
What doesimmune regulatory failure most likely involve?
- Loss of peripheral tolerance (spleen, lymph nodes)
- Loss of central tolerance (thymic)
- Molecular mimicry
- Innapropriate activation
What role does genetics play in autoimmune disease and give an example of a gene and what it does?
-Certain genes may impact certain aspects of autoimmunity eg.
AIRE; decreased expression of self-antigens in thymus, resulting in defective negative selection of self reactive T cells
What are some other genes that may be involved in autoimmune disease?
- FOXP4
- CTLA4
- FAS
- C1q
- MHC genes
Are most conditions affected by only one gene and give an example?
- No, most conditions are polygenic
- Eg. rheumatoid: DR4, STAT4, PTPN22, CTLA1 and more
When does autoimmunity develop in relation to infectious trigger?
-Develops after infection is eradicated (autoimmune disease is precipitated by infection but not necessarily caused by it).
Give an example of an autoimmune disease that can be prevented by prior infectoin and why is this potentially especially relevant in modern day?
- Type 1 diabetes
- Potentially, stricter hygeine in modern day has lead to children being less exposed to antigens to train immmune system.
What are some examples of organ specific autoimmune disease?
- Hashimoto thyroiditis
- Guillan Barre
- Thyrotoxicosis
- MS
- Type 1 diabetes
- Graves disease
- Addisons disease
What are some examples of non organ specific autoimmune disease?
- RA
- Systemic lupus
- Dermamyositis
- Scleroderma
- Sjogrens syndrome
What are non-organ specific autoimmune conditions?
- Conditions where widespread self antigens become targets for autoimmune attack
- Damage affects such structures such as blood vessels, cell nuclei etc.
What are organ specific autoimmune conditions?
- Conditions where there is autoimmune attack vs. self antigens of a given organ
- Results in damage to organ structure and function
- There is a spectrum of how organ specific an autoimmune condition can be
What is guillan barre syndrome and what is it an example of and what can it commonly cause?
- Autoantibody mediated autoimmune disease of peripheral nerves.
- Eg of molecular mimicry
- Common cause of acute paralysis
Describe the pathogenesis of guillan barre syndrome?
- Triggered by infections, including campylobacter jejuni
- Infection—immune response (antibodies produced)—mostly infection is cleared—antibodies stay around as they have certain half life—if they cross blood nerve barrier they can set off cascades and strip myelin from peripheral nerve resulting in loss of quick nerve action
What are immune mediated inflammatory diseases?
-Chronic diseases with prominent inflammation, often caused by failure of tolerance or regulation
What may immune mediated inflammatory diseases result from?
-Autoimmunity
What are often present in immune mediated inflammatory conditions and what do they often target?
- Autoantibodies
- May target specific things or immune complexes (tissue antigens, soluble antigens).
Describe the pathogenesis of graves disease?
- Thyroid hormones regulated by TSH
- TSH binds to receptor and stimulates synthesis of thyroid hormones.
- Non-regulated activating autoantibodies bind to TSH receptor, leading to overstimulation of the thyroid hormones.
- The autoantibodies are called long acting thyroid stimulating hormones
Describe the pathogenesis of myastenia gravis?
- Normally release of Ach to receptors allows Na influx to muscle.
- Here, autoantibody bind to Ach receptor, can either degrade receptor or block Ach interaction.
- Results in no Na influx so no contraction
