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8. Autoimmune Diseases
autoimmune diseases
60
Immunology
Professional
11/12/2014

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Term
Name 6 autoimmune diseases
Definition
1. Diabetes
2. Systemic Lupus
3. Multiple Sclerosis
4. Rheumatoid Arthritis
5. Graves Disease
6. Myasthenia Gravis
Term
What are autoimmune diseases characterized by?
Definition
non-protective immunopathology
Term
What are the two theories of development of autoimmune diseases?
Definition
1. The release of sequestered antigens
2. Molecular mimicry
Term
Development of Autoimmune Disease:
1. Release of sequestered antigens
Definition
- Response to antigens that aren't normally seen by the immune system are released
- (if an antigen is produced in a particular area of the body and doesn't go into circulation, the immune system doesn't have to learn to respond to it)
Term
If you have a ___ amount of antigen (that is not normally seen) released it's not a problem, but if you have a ___ released this causes disease.
Definition
small, bolus
Term
After T cells have matured in the thymus, what 2 characteristics are important to have?
Definition
- want them to respond to MHC
- don't want to respond to self antigens (no negative selection)
Term
What is negative selection?
Where do we see this?
Definition
t cells responding to self antigens

In the thymus
Term
What is an example of something that could cause a release of antigen?
Definition
a traumatic event
Term
If you release antigen that hasn't been seen before, in a reasonable amount, in a site of inflammation what will happen?
Definition
get danger signals and an immune response
Term
Explain theory 2. Molecular Mimicry
Definition
immune system responds to antigen of a pathogen, but we have self-antigens that have very similar molecular structure
--> so the immune system fights the pathogen, and it cross reacts with self antigens
Term
In the molecular mimicry theory, what is the most common shared molecular structure?
Definition
a viral peptide
Term
What is the main function of the pancreas?
Definition
It secretes digestive enzymes into the digestive tract
Term
What type of cells are in the islet of langerhans in the pancreas?
Definition
alpha and beta cells
Term
What is the function of the alpha and beta cells?
Definition
alpha - mainly structural
beta cells - secrete insulin in response to high glucose levels in the blood (which will take it out and sequester it in cells)
Term
Beta cells interact with ___, they don't secrete anything into the gut.
Definition
blood
Term
In type 1 diabetes, how are islet beta cells destroyed?
Definition
by CD4+ T cell mediated immunity and activated macrophages

and also a bit by CTL killing
Term
Explain the evidence that viral infection may provide a trigger for diabetes.
Definition
A researcher in Calgary says some viruses have antigens on their surface that are similar to ones on beta cells -- when immune system produces antibodies to the viruses, you'll get killing of beta cells.
Term
Type 1 Diabetes susceptibility is linked to _ _ _ genotype
Definition
HLA
Term
What does HLA mean?
Definition
human leukocyte antigens
Term
What are the 3 regions for MHC Class II
Definition
DP
DQ
DR
Term
What are the 3 regions for Class I MHC?
Definition
B, C and A
Term
Because you get one DP (for example) from your mom, one from your dad... in total how many do you have?
Definition
6 regions so...
12 in total!
Term
Which region of HLA is the main culprit for Type 1 Diabetes?
Definition
DR! of the Class II MHC
Term
Which types of DR in particular are associated with elevated risk of diabetes?
Definition
DR3 and DR4
Term
True or false: If your dad is DR3, DR7 and your mom is DR4, DR5 all children will get diabetes.
Definition
NO!!
- first of all, not every child will be DR3. DR4
- second, you can be DR3, DR4 and not get diabetes --> it just makes you have higher susceptibility
Term
What other types of HLA may bed linked to risk of Diabetes but to a lesser extent than DR
Definition
HLA-DQ, HLA-B and HLA-C
Term
Where are differences between DR3 and DR4?
Definition
in the AA sequence --> in the alpha helices and beta pleated sheets
Term
Why does everyone have slightly different alpha helices and beta pleated sheets?
Definition
Because as a population, we want to be able to respond to any kind of antigens
Term
Where do islet cells go when you put them into the portal vein?
Definition
Into the liver! (not the pancreas)
there they lodge into the liver sinusoids and produce insulin
Term
What is the problem with Islet cell transplantion?
Definition
The immune response that killed the original islet cells will kill these ones too. --> have to be on life long immunosuppression
Term
Explain a kidney pancreas transplant.
Definition
One result of diabetes may be diabetic nephropathy - so need to get a kidney transplant. Since they will have to be on immunosuppression for their whole life, they can also transplant a pancreas!!

KP transplant --> both organs survive and so do the islet cells
Term
Because the main function of the pancreas is to secrete stuff into the bowel, when doing KP transplant, you must also transplant some ___.
Definition
duodenum (as an out for the digestive enzymes)

hook it up either to the bladder (pee out) or the bowel, small intestine (secreted into the bowel and go out in normal way)
Term
What is one clinical presentation of Systemic Lupus Erythematosus
Definition
A butterfly rash!!
Term
What are the main complications of Systemic Lupus?
Definition
- problems with:
- lungs
- lupus arthritis (painful, debilitating)
- lupus nephritis (can be fatal)
- rashes
Term
Why was lupus called the great imposter?
Definition
because it was difficult to diagnose
Term
What is the female to male ratio for lupus?
Definition
10:1 female to male
Term
What causes lupus?
Definition
production of auto-antibodies that are mostly directed at the nucleus
--> anti-histone antibodies are made
Term
In lupus, where do you get immune complex deposition?
Definition
kidney (glomerulonephritis)
inflamed joints (lupus arthritis)
deposition in the skin and lungs
Term
Where does filtration occur in the kidney?
Definition
glomeruli which are in the cortex
Term
Why is the artery entering the glomeruli much bigger than the tubules that come out?
Definition
it increases pressure!! want that b/c you want to push fluid out
Term
Multiple sclerosis is a disease of the __ __.
Definition
myelin sheath
Term
What is the result of having damaged myelin sheath?
Definition
myelin helps signals to propagate more quickly
and protects... so without it can get damage to the nerve
Term
Where in the body can you get MS damage?
Definition
in the brain or spinal cord
Term
What immune cells are involved in MS?
Definition
- Th1 cells
- macrophages mediate tissue damage
- major antigen is myelin basic protein
Term
What drugs are used for treatment of MS?
Definition
- Anti-proliferatives
- Corticosteroids
- Immunosuppression
- Neuropathic pain
- anti-depressives
- Vein liberation (but this doesn't actually work)
Term
Rheumatoid arthritis is characterized by... (2)
Definition
bone destruction and bone displacement
Term
Briefly describe the differences in presentation of rheumatoid arthritis vs osteoarthritis
Definition
Rheumatoid -- sitffness in the morning but improvements on use of the joints, bilateral

Osteo--> using joint makes it worse, often unilateral
Term
Is rheumatoid arthritis more common in men or women?
Definition
women
Term
What causes Rheumatoid Arthritis?
Definition
- Production of auto-antibodies
- get immune complex deposition in the joints causing inflammation
Term
What causes inflammation in rheumatoid arthritis?
Definition
-Th1 mediated macrophage activation
-in the late stages -- osteoclasts
- TNF plays a critical role in maintaining the inflammation
Term
Explain rheumatoid factor.
Definition
Not everyone with rheumatoid factor has rheumatoid arthritis and vice versa
Term
How do we treat rheumatoid arthritis?
Definition
NSAIDS
Corticosteroids
immunosuppressive drugs
Immune modulation
Term
Graves disease is characterized by ___ ___.
Definition
bulging eyes
Term
What leads to Grave's disease?
Definition
a problem with thyroid hormone production
Term
Explain how thyroid hormone is produced and regulated.
Definition
- The pituitary gland secretes thyroid stimulating hormone which acts on the thyroid to induce the release of thyroid hormone
- the pituitary sense the amount of thyroid hormone, and if there is too much it'll stop producing TSH
Term
What goes wrong in the production of thyroid hormone with Grave's disease?
Definition
Autoimmune B cells make agonist antibodies to the TSH receptors that act like TSH and stimulate the production of thyroid hormone. --> get continuous excess thyroid hormone
Term
Myasthenia Gravis is the opposite to ___.
Definition
Grave's disease
Term
Myasthenia gravis is characterized by
Definition
Ptosis - drooping of one eyelid
Term
Grave's disease is an ___ antibody disease whereas Myasthenia Gravis is an ___ antibody disease
Definition
agonist, antagonist
Term
Normally, ACh binds to ACh receptors and produce a response in the muscles. What happens in myasthenia graves?
Definition
antagonist antibodies bind and therefore block ACh from binding to the receptor so can't get the muscle signal
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