Autoimmune Basics Flashcards
What is an Autoimmune Disease?
Immune reaction directed against a self antigen that is responsible for the pathologic condition
Autoimmune diseases can be caused by what type of things?
Genetics
Environment
- Infection = Molecular mimicry
- Damaged tissues = Epitope spreading
What are the autoimmune diseases we discussed?
Systemic Lupus Erythematosus
Sjogren Syndrome
Systemic Sclerosis
IgG4-related disease
What is normal immunologic tolerance?
Tolerating self antigens
When is central tolerance learned and where does it take place?
It is learned before lymphocyte release from the generative organs - at the thymus and bone marrow
If T cells cross-react with self antigens in the thymus, what happens to them?
Apoptosis
If B cells recognize self antigens in the bone marrow, what happens to them?
Receptor editing OR Apoptosis
What 2 things control peripheral tolerance?
T regulatory cell suppression
Anergy
What receptors on the T cell are engaged to induce T cell anergy (no response)?
PD-1
CTLA
What is anergy?
Failure/downregulation of T cell response when their inhibitory ligands (CTLA and PD-1) are engaged
What autoimmune disease is associated with HLA-B27?
Ankylosing Spondylitis
What are the symptoms with Ankylosing Spondylitis and what gene is it associated with?
- Associated with HLA-B27
= Spinal inflammatory condition that causes degeneration and fusion of the vertebra
Degeneration and fusion of the vertebrae?
Ankylosing Spondylitis
What autoimmune disease is associated with PTPN22 variants?
Rheumatoid Arthritis
Rheumatoid Arthritis is associated with variants of what gene?
PTPN22
PTPN22 stands for?
Protein Tyrosine Phosphatase
Variants of PTPN22 (rheumatoid arthritis) directly cause?
Decreased B cell and T cell self tolerance!
What autoimmune disease is associated with NOD-2 variants?
Crohn’s Disease
Crohn’s Disease is associated with variants of what gene?
NOD-2
What do NOD-2 variants do?
Render intestinal Paneth cells ineffective at microbial killing
= Accumulation of bacteria
This gene variant renders intestinal Paneth cells ineffective, which results in accumulation of bacteria and an exaggerated immune response
NOD-2 – Crohn’s Disease
Describe Molecular Mimicry
Antigenic similarity between true pathogens are native tissues
What is an example of molecular mimicry that leads to an autoimmune disease?
Rheumatic Heart disease
- Streptococcal Ag looks like Myocardial Ag
- Antibodies attack Myocardial Ag
What is an example of Epitope spreading with damaged tissues?
Oral Lichen Planus
Describe Epitope spreading with Oral Lichen Planus
- T cell response leads to lesions in oral mucosa
- Basement membrane disruption exposes more antigens (new)
- B cell response occurs to those antigens
What is an ANA test?
Anti-Nuclear Antibody
- If (+) could indicate a non-specific autoimmune disease
A (+) ANA test will prompt?
More specific testing to figure out which autoimmune disease may be present
Systemic Lupus Erythematous has what Antibodies?
Anti-DS DNA
Anti-Smith
How does SLE stain?
Homogenous
Sjogren has what Antibodies?
Anti-RO/ss-B
Anti-LA/ss-A
How does Sjogren stain?
Speckled
Systemic Sclerosis has what Antibodies?
Anti-DNA Topoisomerase
Anti-Scl-70
How does Systemic Sclerosis stain?
Speckled or Nucleolar
How does CREST syndrome stain?
Centromere
Non-specific test for an Autoimmune disease?
ANA
Anti-Nuclear Ab
