AUTOIMMUNITY Flashcards
It is characterized by the presence of an autoantibody to an antigen in the basement membranes of glomeruli and alveoli of the lungs.
good pasture syndrome
70% - 80% of patients carry the HLA-DRB1-15 antigen
good pasture syndrome
Treatment of Good Pasture Syndrome
corticosteroids - to stop inflammation
plasmapheresis
lifetime hemodialysis or kidney transplantation
an autoimmune disease that affects neuromuscular junction characterized by weakness and fatigability of skeletal muscles, causes antibody-mediated damage to acetylcholine receptors in skeletal muscles
myasthenia gravis (MG)
HLA haplotype, A1,B8, DR3 has strong association with _ while HLA antigens B7 & DR2 are more likely to appear in _
Early Onset MG; Late Onset MG
It is a radio-labeled snake venom used to detect antibodies to ACHR in radioimmunoprecipitation (RIPA)
a-bungaro-toxin
an autoimmune disorder involving inflammation and destruction of the CNS
Multiple Sclerosis
Multiple Sclerosis is most closely associated with the inheritance of this particular HLA molecule
HLA-DRB1*1501
these are the environmental factors that appear to be associated with multiple sclerosis
- reduced exposure to sunlight
- vitamin D deficiency
- cigarette smoking
these are alleles associated with a higher risk of developing autoimmune hepatitis (AIH) or chronic active hepatitis
HLA-DRB1 & HLA-DQB1
What are the two types of Autoimmune Hepatitis (AIH) that can be differentiated on the basis of its autoantibody specificity
- AIH-1 - 2/3 of all AIH cases, F:M of 4:1
- AIH 2 - seen mostly in children and has F:M ratio of 10:1
This is necessary to confirm the diagnosis of Autoimmune Hepatitis and to assess the extent of liver damage
liver biopsy
It has a W:M ratio of 10:1 and it is the most common autoimmune liver disease
primary biliary cirrhosis (PBC)
treatment for primary biliary cirrhosis
ursodeoxycholic acid (UDCA) , a bile acid that helps move bile through liver; liver transplant
An autoimmune disorder associated with an environmental trigger - dietary gluten
Celiac Disease
In lab diagnosis of celiac disease, it is a serological method of choice for initial testing which is ELISA based
tissue transglutaminase (tTG)
An autoimmune disease affecting small intestines and other organs, HLA-DQ2 (90-95%) or HLA-DQ8, W:M of 2-3:1
celiac disease
Type 1 Diabetes carries these HLA genes
HLA-DR3 and DR4 genes
an endocrine disorder characterized by hyperglycemia (a high level of glucose in the blood); characterized by a complete or nearly complete deficiency in insulin
Type 1 Diabetes
hyperglycemia does not become evident until ?
80% or more of the beta cells are destroyed
Hashimoto’s thyroiditis is associated with the inheritance of these HLA antigens
HLA antigens DR3, DR4, DR5, and DQ7
Graves dse is associated with this HLA antigen
HLA-DR3
aka chronic lymphocytic thyroiditis; Japan, 1912; Dr. Hakaru Hashimoto, most common autoimmune disease, 8 in evey 1,000; W:M-5-10:1
Hashimoto’s Thyroiditis
autoantibodies that are produced against proteins that are present in the neutrophil granules
Antineutrophil Cytoplasmic Antibodies
strongly associated with three syndromes involving vascular inflammation WG, MPA, EGPA
Antineutrophil Cytoplasmic Antibodies
a rare autoimmune disease involving inflammation of the small- to medium-sized blood vessels, or vasculitis, mainly directed against the PR3 antigen
Granulomatosis With Polyangiitis (Wegener’s Granulomatosis)
what is the antibody that is most often tested to aid in making the initial diagnosis of RA
Rheumatoid Factor (RF)
- affects about 0.5% to 1.0% of the adult population; age:25 and 55; W:M-3:1
- can be characterized as a chronic, symmetric, and erosive arthritis of the peripheral joints that can also affect multiple organs such as the heart and the lungs
∟ HLA-DRB1 alleles or PTPN22 gene polymorphisms
∟ strongest environmental risk factor - cigarette smoking
Rheumatoid Arthritis
- associated with deep-vein and arterial thrombosis and with recurrent pregnancy loss
- found in up to 60% of patients with lupus
- can be identified by their ability to cause false-positive results in nontreponemal tests for syphilis
Antiphospholipid antibodies
autoantibodies that are directed against antigens in the nuclei of mammalian cells
Anti-Nuclear Antibodies
- chronic systemic inflammatory disease
- peak age of onset: 20-40 yo,
- Women:Men – 9:1
- 5 yr survival rate - 90% (today)
∟ genetic defects in genes coding for HLA-A1, B8, and DR3 — increases the chance of developing lupus
Systemic Lupus Erythematosus (SLE)
Immune Response is targeted toward self-antigens resulting in organ and tissue damage
Autoimmune Disease
ability of the immune system to accept self-antigens and not initiate a response against them
self-tolerance
2 levels of Immunologic Tolerance
central & peripheral tolerance
a state of immune unresponsiveness that is directed against a self-antigen
Immunologic Tolerance
more prevalent among family members and among monozygotic (genetically identical) twins than dizygotic (non-identical) twins or siblings
Genetics
Enumerate other Endogenous and Environmental Factors
hormonal influence, tissue trauma and release of cryptic antigens, microbial infections
Enumerate 5 mechanisms of microbes
1) molecular mimicry
2) bystander effect
3) superantigens
4) Epigenetics and Modification of Self-Antigens
5) Interactions between factors
Superantigens that can cause polyclonal activation of B cells
Epstein-Barr virus (EBV) and cytomegalovirus (CMV)
the microorganism can induce a local inflammatory response that recruits leukocytes and stimulates APCs to release cytokines that nonspecifically activate T cells
Bystander Effect
many bacterial or viral agents contain antigens that closely resemble the structure or amino acid sequence of self-antigens, give an example of a bacteria
molecular mimicry, S. pyogenes
proteins produced by various microbes that have the ability to bind to both class II MHC molecules and TCRs, regardless of their antigen specificity
Superantigens
refers to modifications in gene expression that are not caused by changes in the original DNA sequence
Epigenetics
Triggered by exposure to environmental toxins, ingestion of harmful foods or drugs, or the aging process
Epigenetics and Modification of Self-Antigens
citrullination of collagen
Rheumatoid Arthritis
glycosylation of myelin
Multiple Sclerosis
complex interactions between genetic and environmental factors may cause break in immunologic tolerance
Interactions Between Factors
has genetic defects in genes coding for HLA-A1, B8, and DR3
SLE
antibodies to endothelial cells
vasculitis
can cross the placenta and have been associated with neonatal lupus
Antibodies to both SS-A/Ro and SS-B/La
