Autoimmune Disorders Flashcards
Define autoimmunity
an adaptive immune response against self antigen that is directed toward healthy tissue and leads to impaired tissue
What are the 4 factors that contribute to a persons risk for developing autoimmune diseases
- Genetic
- Race
- Sex/Gender
- Environment
What are the main genetic determinants for autoimmune diseases?
MHC I and MHC II loci
Why do females tend to have a higher risk for autoimmune diseases?
presence of estrogen, progesterone and a different microbiome than men
T reg cells are also known as
CD25
T reg cells suppress
auto reactive CD4 T cells
What 2 possible genetic mutations can lead to autoimmune disease
- The absence of Autoimmune Regulator Protein (AIRE)
2. FoxP3 Mutations
What does AIRE play a role in?
Negative selection
Autoimmune polyglandular disease is a result of the absence of
Autoimmune regulator protein (AIRE)
List 4 clinical presentations of autoimmune polyglandular disease (APD)
- begins in infancy
- hypoparathyroidism
- nail dystrophy
- adrenal failure
- ovarian failure
- type 1 diabetes
- candidiasis
APD clinical association involves what areas (6)
endocrine glands, skin, hair, nails, ovaries, teeth
What does FoxP3 play a role in?
Treg cell differentiation
IPEX is a result of _____ mutation
FoxP3 mutation
What cells are elevated in IPEX
Th17 cells
When does IPEX begin to present
early in life
List the presentations of IPEX (3)
- eczema
- diarrhea
- Type 1 diabetes
What are the 5 ways that infection can trigger autoimmune disease
- Disruption of cell or tissue barrier
- Binding of pathogen carrier to be recognized
- Molecular mimicry
- Superantigen
- Bystander effect
What trigger event can avoid co-stimulaiton
Superantigen
What is the effect of the disruption of cell or tissue barrier?
The release of self antigen
How does binding of a pathogen to self protein trigger immune disease?
pathogen can act as a carrier to allow self antigen response
______ gives microbes the ability to nonspecifically activate T cells
Superantigen
Describe the bystander effect
A T cell can bind self antigen on MHC but will not receive second signal from that cell but if there is an infection nearby that cell can give the T cell the co-stimulatory signal
What is the target of Graves Disease?
Thyroid; TSH receptor
What is the Target in Myasthenia Gravis
Acetylcholine receptor
What is the target in Autoimmune Hemolytic Anemia?
RBC antigens
What is the target in Goodpasture’s Syndrome
Type IV collagen ECM
What is the target in Rheumatic Fever
Antibody against S. pyogens that cross reacts with myosin
What is the target in Rheumatoid Arthritis?
Antibodies against self IgG
What is the target in Systemic Lupus Erythematous (SLE)
antibodies against parts of cytoplasm and nucleus
What is the target in Hashimoto’s Thyroiditis
Thyroid antigens
What is the target in Type 1 Diabetes?
Insulin and glutamate decarboxylase
What is the target in Celiac Disease
gluten metabolites
What is the mechanism for Graves Disease
IgG antibodies directed against the Thyroid stimulating hormone receptor act as an agonist so that the receptor acts as if it was receiving TSH this leads to an increased production of Thyroid Hormone
What is the mechanism for Myasthenia Gravis
IgG antibodies are made against the acetylcholine receptor acting as an antagonist, triggering the ACh receptor to be endocytose and degraded
What is the mechanism for Autoimmune Hemolytic Anemia (warm and cold)
Warm: IgG antibodies are made against self Rh factor trigger destruction by opsonization or complement
Cold: IgM antibodies are made against glycophorin (I antigen)
What is the mechanism for Goodpasture’s Syndrome
IgG autoantibodies directed against type IV collagen of glomerulus basement membrane resulting in the activation complement causing inflammatory damage
What is the mechanism for Rheumatic Fever
The antibodies IgM against S. pyrogens cross react with myosin found in the heart, joints, and kidneys causing inflammation in these organs
What is the mechanism for Rheumatoid Arthritis
Production of IgG antibodies (rheumatoid factor) against self IgG which forms an immune complex that deposits in joints leading to complement activation and inflammation.
Antibodies can also be made against epitopes of self proteins (peptidlyl arginine deaminase)
What is the mechanism for Systemic Lupus Erythematous
Autoantibodes are formed against antinuclear antigens such as ribonucleic proteins, DS DNA and lipoporteins to form immune complexes that deposit in tissues
What is the mechanism for Hashimoto’s Thyroiditis
Th1 cells induce an inflammatory response that cause a change in architecture of the thyroid, forming ectopic lymphoid tissue causing an underactive thyroid
What is the mechanism for Type 1 Diabetes
T cells and antibodies are formed against insulin and glutamate decarboxylase and proteins of beta islet cels causing destruction preventing the production of insulin
What is the mechanism for Celiac Disease
Tissue transglutaminase converts glutamine to glutamic acid–>glutamic acid has higher affinity to bind to MHC–> presentation of glutamic acid to CD4 T cells–>inflammatory response
What are the clinical features of Graves Disease (7)
- Hyperthyroidism
- Weight loss
- Irritability
- Enlarged Thyroid
- Bulging Eyes
- Nervousness
- Heat Tolerance
What are the clinical features of Myasthenia Gravis
- muscle weakness
- ptosis
- diplopia (double vision)
- Weakening of chest muscles
What are the clinical features of Autoimmune Hemolytic Anemia *not discussed
What are the clinical features of Goodpasteur’s Syndrome (3)
*2 occur in smokers
- glomerlonephritis
- pneumonitis
- pulmonary hemmorage
What are the clinical features of Rheumatic Fever
-inflammation and heart damage
What are the clinical features of Rheumatoid Arthritis (2)
- Arthiritis
- damage to cartilage, ligaments, tendons, bones
What are the clinical features of SLE (4)
- glomerulonephritis
- arthiritis
- Vasculitis
- Rash
What are the clinical features of Hashimoto’s Thyroiditis (5)
- Hypothyroidism
- fatigue
- weight gain
- sensitivity to cold
- weakness
What are the clinical features of Type 1 Diabetes
-inability to control blood sugar levels
What are the clinical features of Celiac Disease
-reduced absorption capacity in jejunum
What are the treatment options for Hashimoto’s Thyroiditis
replacement therapy with thyroid hormones
The rheumatoid factor is directed against the _____ receptor
Fc
What is the infection association in Type 1 Diabetes
T cells are produced against cosakie virus and they cross react with insulin.
What enzyme in those with celiac disease converts glutamine to glutamic acid?
Tissue transglutaminase
What is the result of the conversion of glutamine to glutamic acid in the case of Celiac Disease
Glutamate has a more negative charge making it have a higher affinity to bind with MHC resulting in the activation of CD4 T cells that result in cytokine release and reactive oxygen species destruction
