Autoimmunity Flashcards
What is the approximate percentage of the world’s population affected with autoimmune disease?
5 percent
Where does central tolerance occur?
The B-cell and the T-cell
What happens when self tolerance mechanisms fail?
Auto-immune disease
Autoimmune disease involves both B and T cells. True or False?
True
Autoimmunity mechanisms include those for types 1,2,3 and 4. True or False
False, all but type 1
What is epitope spreading?
In response to an original insult, the inflammatory response causes damage, unveils a new epitope against which an immune reaction can be mounted
Autoimmunity is caused mainly be genetic factor, True or false
False, autoimmunity is caused by environmental factors as well
An example of an autoimmune disease with strong genetic component is _
Diabetes Mellitus type 1
The strongest genetic association with autoimmune disease are with _. Genes that predispose to autoimmune disease are usually involved with _
MHC genes
Establishing self tolerance
Majority of autoimmune diseases are caused by a single gene defect. True or false
False. These are the minority
What is the function of AIRE?
Required to express and present self antigens in the thymus. No AIRE, no self presentation
What disease results from defective AIRE?
APECED. Autoimmune PolyEndocrinopathy, Candidiasis, Ectodermal Dystropy
What are the symptoms of AIRE?
Hypoparathyroidism
Adrenal Insufficiency
Hypogonadism
(i.e. Multiple endocrine disorders)
The major function of FoxP3 is _
Major transcription factor for regulatory T-cells
Non-functional FoxP3 leads to _. What are the symptoms?
IPEX (Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked)
- Neonatal diabetes 1, throiditis, diarrhea, dermatitis
- Fatal in year 1
What is FAS?
The major apoptosis ligand
What disease occurs if FAS is mutated?
ALPS (Autoimmune Lymphoproliferative Syndome)
- Can turn on immune system fine, but can not turn off when no longer sick - Lymphadenopathy
What is bystander effect?
APCs activate T-cells in the vicinity of the immune reaction. These T cells can cause disease if specific to self
What is molecular mimicry?
Where an antibody to a pathogen ends up recognizing self because of similarity between the 2 proteins
SLE is a type _ autoimmune disease? It is most prevalent in what population?
Type III (antibody - antigen deposition all over) More common in females
What genetic factor are implicated in SLE?
Several, including
Complement deficiencies
HLA - DR2/DR3
The disease mechanism for SLE is _? What organs are affected?
Ab/Ag deposition all over the body
Virtually all organs are affected
2 specific type of Abs are observed in lupus. They are?
Anti-nuclear Ab
Anti-dsDNA Ab (correlates with disease severity)
Rash, arthritis, glomerulonephritis, vasculitis, hemolytic anemia, thrombocytopenia, CNS involvement are all associated with _
Lupus
Treatment of lupus involves _
Immuno-suppressive medications
There are 11 diagnostic criteria related to Lupus. How many have to be met for diagnosis?
4/11
RA is the most common inflammatory arthritis. What are 2 risk factors?
Cigarette smoking
HLA DR4
The disease mechanism of RA involves _
T-cells and antibodies
Arginine residues converted to citrulline
What are the cytokines involved in RA?
IL17, TNA, IL1
The clinical features of RA include _ (2)
Symmetrical inflammation of small and large joints
Synovitis
Diagnostic tests for RA include _ (2)
Rheumatoid factor (IgM against patients IgG) Anti-cyclic citrulline (Anti-CCP)
Treatment of RA involves? (2)
Glucocorticoids
DMARDs (Disease Modifying Anti-Rheumatic Drugs)
Diabetes Mellitus Type 1 is a multisystem metabolic disease. It is characterized by _ distribution
Bimodal (4-6 and 10-14)
The disease mechanism of DM type 1 is _. This is mediated by what?
Destruction of pancreatic islet cells
CD4 TH1 cells
Why are anti-inflammatory drugs not used for DM type 1?
The damage is already done. No inflammation to treat
What are the clinical features of DM type 1? (3)
Hyperglycemia / Ketoacidosis Macrovascular complications (atherosclerosis, ischemic necrosis) Microvascular complications (retina, glomeruli)
The most common disease of neuromuscular transmission is _
Myesthesia Gravis disease
The disease mechanism if Myesthesia Gravis is _
Abs against the AchR in the neuromuscular junction. Act as antagonists, cause muscles weakness
What type of hypersensitivity is Myesthesia Gravis?
Type 2
What type of tumor is usually found along with Myesthesia Gravis? What usually happens when these tumors are removed?
Thymoma
Patients get better
Myesthesia Gravis is associated with these clinical features _
Muscle weakness, fatiguability with muscle use
What is myesthenic crisis?
When the muscle weakness extends to respiratory muscles, leading to respiratory failure
How is myesthenia gravis treated? (4)
Anticholinesterase agents
Immunosuppression
Immunotherapy (plasma exchange)
Thymectomy
What is Graves disease?
Thyroid stimulated by anti-TSH receptor (agonists)
An aspect of Graves disease that makes it dissimilar from other autoimmune disease is absence of _
Inflammation
Graves disease is characterized by Hyperthyroidism. Symptoms include _ (6)
Anxiety Tremor Palpitation Heat intolerance Weight loss Proptosis and periorbital swelling
What is Hashimoto’s thyroiditis?
An autoimmune destruction of the thyroid gland, leading to hypothyroidism
Symptoms are opposite of hyperthyroidism in graves disease.
Yes
Treatment of hypothyroidism is _
Thyroid hormone replacement
Why don’t the anti-AchR receptors in the Graves disease affect the AchRs in the CNS?
Different subtypes in both locations.
