Unit 4 Lec 6 Flashcards
(21 cards)
What are autoantigens?
Antigens that activate autoimmune response
Wheras autoantibodies are antibodies generated by autoimmune responses and autoimmune disease is caused by autoimmune responses
What happens in autoimmunity?
Results from failure of tolerance to self antigens
Can occur at any of the steps of central or peripheral tolerance
What do most autoimmune diseases involve?
Involve both B and T cells
- Antibodies (against tissues, or immune complex formation)
- T cells
Usually chronic and progressive and self perpetuating
- Constant supply of autoantigens that are not cleared from the body
- AMPLIFICATION and EPITOPE SPREADING
What is epitope spreading?
Response initiated against one self antigen that injures tissues that may result in the release and alteration of other tissue antigens and activation of lymphocytes specific to these other antigens (leads to exacerbation of the disease)
What are some amplification mechanisms?
Cytokines that promote activation of autoreactive lymphocytes
What is a strong component of autoimmune disease?
Concordance in diabetes mellitus type I
35-50 monozygotic twins
5-6% dizygotic twins
What has the strongest genetic association with autoimmune disease?
Associated with MHC genes
- HLA B-27 positive individual – 73 relative risk of developing Ankylosing Spondylitis
- Autoantigenic peptides to autoreactive T cells
What is APECED?
Autoimmune PolyEndocrinopathy Candidiasis, Ectodermal dystrophy
- Autoimmune polyglandular syndrome type I (APS1)
- AiRE gene mutations (Autoimmune Regulator )– Failure to delete autoreactive T cells
- Hypoparathyroidism, adrenal insufficiency, hypogonadism
What is IPEX?
Immune dysregulation, Polyendocrinopathy, Enteropathy, X linked
- FOXP3 gene mutations – Impaired regulatory T cells
- Neonatal type I diabetes, thyroiditis, chronic life-threatening diarrhea due to enteropathy, dermatitis
USUALLY FATAL within the first year
What is ALPS?
Autoimmune Lymphoproliferative syndrome
- FAS gene mutations – impaired apoptosis
- Autoimmune disease: hemolytic anemia, thrombocytopenia (ITP) neutropenia
- Glomerulonephritis, autoimmune hepatitis, Guillain-Barré syndrome uveitis
Lymphadenopathy, hepatomegaly, splenomegaly: INCREASED risk of lyphoma
What is bystander activation?
Infections induce local innate immune responses in tissues that recruit leukocytes and result in activation of tissue APCs, these APCs express costimulators and activate bystanders T Cells are not specific for infectious pathogen, result in breakdown of tolerance
What is molecular mimicry?
Microbes may contain antigens that cross-react with self antigens, so immune response to the microbes may result in reactions against self antigens
- Examples include Rheumatic Fever following group A Streptococcus infection
- Hemolytic anemia following mycoplasma infection
What is hashimotos thryoiditis?
Ab against thyroid peroxidase
What is Grave’s disease?
Ab against TSH (thyroid stimulating hormone) receptor
What happens in Type I diabetes?
Insulin producing pancreatic B cells
What are examples of Systemic autoimmune?
Systemic Lupus Erythematous (SLE)– Ab to nuclear antigens (eg chromatin)
- Multiple organs: skins, joints, kidneys, heart, lungs, nervous system
What happens in systemic lupus erythematosus (SLE)
Chronic remitting and relapsing multisystem autoimmune disease Prevalence 20-150 cases per 100,000 - Female to male ratio is 10:1 Age of onset is 15-55 - Genetic factors 50 loci predisposes to SLE - Complement deficiencies (C1q, C4A, C4B, C2 - HLA-DR2, HLA-DR3
What is the pathophysiology?
Immune complex deposition – Glomerulonephritis, arthritis, and vasculitis involving small arteries throughout the body
- Virtually every organ is effeted
Important autoantibodies in SLE
- ANA (anti-nuclear Ab) very sensitive for SLE
- Neg. AN excludes SLE
- Anti-dsDNA is very specific for SLE
What is rheumatoid arthritis?
Most common inflammatory arthritis: 1 percent pop
Risk factors: HLA-DR4 and cigarette smoking
What is the pathophysiology of RA?
T cell and Abs both contribute to joint inflammation
- 7 autoantigens are likely to be involved e.g. type II collagen, citrullinated peptides
- Citrullinate peptides are derived from proteins modified in the inflammatory environment by enzymatic conversion of arginine residues to citruillin
Synovial inflammation perpetuated by proinflammatory cytokines IL-17 and TNF and IL-1
What are some rheumatoid factos?
Circulating IgM against Fc portion of patients own IgG
Antibodies against cyclic citruiillinated peptides (ANTI-CCP)
Treatment:
- Glucocorticoids
DMARDS
Biologic agents: Monoclonal Ab against: TNF, IL-1, IL-6, CD20 (B cells)
