Autoimmune Diseases Flashcards
What factors are at play that can influence susceptible genes?
1: infection
* increased activation of T cells can cause them to accidentally mistaken self
* virus can add protein to tissue membrane
* microbes may have same amino acid sequence as self proteins
2: injury
* alter display of self antigen
* release of molecules like DNA
The T cells and B cells do not recognize the intercellular self antigens
aka they don’t recognize the inside of the cell as self
CD4 cells activate=B cells activate to produce autoantibodies against the intercellular products
These products are deposited through circulation in skin, kidneys, brain, heart, spleen, lungs, GI and joints=causes inflammation=IFN alpha overproduction=opsonization and phagocytosis of RBC, WBC, platelets
Systemic Lupus Erythematosus
What is ANA?
antinuclear antibodies; created by B cells to target the intracellular components that they do not recognize as self
in the diseases Lupus
What is a diagnostic used to dx Lupus?
antibodies to the double stranded DNA (dsDNA) or the Smith (Sm) antigen
What disease primarily affects the ductal epithelia cells of the lacrimal glands and salivary glands ultimately cause sing dryness of mouth and eyes?
Sjogren’s Syndrome
CD4 T cells do not recognize self lacrimal and salivary glandular cells because loss of tolerance in the CD4 population or the response against known or unknown antigens expressed in the gland
this causes B cells to secrete antibodies against the lacrimal and salivary glands
T and B cells aggregate and blocks glands
activates CD8
=inflammation=induces apoptosis=atrophy, fibrosis, dysfunction
Sjogren’s Syndrome
What is the long term affects of systemic sclerosis (scleroderma)?
fibrosis of the dermis and subcutaneous tissue, macro vascular disease, CREST Syndrome (calcinosis, raynauds, esophageal dysmobility, sclerodactyly, telangiectasia)
What are anticentromere antibodies and DNA toposomerase I antibodies and what do they indicate?
1: anticentromere antibodies indicate limited scleroderma
2: DNA toposomerase I antibodies indicte diffuse scleroderma
CD4 T cells respond to unknown antigens in the skin=cytokines=inflammation=activate mast cells, macrophages, platelets=upregulation of fibroblasts->secrete excessive amounts of collagen=excessive fibrosis
endothelial injury, endothelial proliferation, fibrosis, and narrowing=tissue ischemia
B cell activation
ex: fibrosis of lung, GI, heart, kidney
Systemic Sclerosis (Scleroderma)
membrane attack complex, CD4 T cell, and B cell deposition in microvascular around myocytes
microvascular is damaged by the inflammatory response=myocyte injury and necrosis occurs
=inflammatory and lymphocytic infiltration around blood vessels in muscle
Dermatomyositis
What are the clinical manifestations of dermatomyositis?
proximal muscle weakness, elevated CK from muscle degeneration, IL 1, TNFa constitutional symptoms
What are the B cell constitutional symptoms?
fatigue, fever, night sweats, wt loss
Classic purple rash around the eyelids and periorbital edema is associated with…
dermatomyositis
when the inflammatory and lymphocytic infiltration around blood vessels in muscles occurs
CD4 differentiates into Th1 and Th2
Th2 stimulates activation of CD8 T cells and macrophages
=inflammation, lymphocytic infiltration round muscle fiber=proximal muscle weakness, elevated CK from muscle degeneration, IL 1 and TNFa constitutional symptoms
Polymyositis/Inclusion-Body Myositis (focus is the myocyte)
What autoimmune disease does not have genetic predisposition?
inflammatory myopathies
The genetic predisposition in ankylosing spondylitis is…
HLA-B27
T cell activation against unknown axial antigen=antibodies against axial joint elements primarily sacroiliac joint, apophyseal joint and vertebral ligaments=inflammation=erosion of articular cartilage and bone=repair leads to calcification and ossification with bony outgrowths
symptoms: progressive low back pain, stiffness, decreased spinal mobility, increased kyphosis, diminished normal convex curve of lower spine
Ankylosing Spondylitis
What diagnostics are used for Ankylosing Spondylitis?
radiology: osseous bridging between the vertebrae, calcification of discs
increased sediment rate
disease can extend to peripheral joints and eyes
Antigen Antibody complexes are deposited in the sub endothelium of blood vessels of skin, joints, and kidneys=inflammation=cell injury
autoantibodies are directed against neutrophil cytoplasm=neutrophils release ROS and proteolytic enzymes=injure cel
Non-Infectious Vasculitis
In non-infectious vasculitis, what autoantibody is positive?
ANCA (anti-neutorphil cytoplasmic antibody)
CD4 T cell response to unknown antigen-Th2 activates B cells->antibodies RF
RF target IgG ‘self’
complexes are deposited in the synovial membranes=inflammation=injury to tissue
synovial cell activation and proliferation->secrete cytokines, fibroblasts activate, proliferation and secretion of cytokines, secretion of matrix metalloproteinases
causes IL 1 and TNFa constitutional symptoms
RA
Why are RF antibodies not essential in RA?
Not everyone with RA test positive for RF
What are the cytokines that are secreted by macrophages that are important in RA?
IL 1, IL 6, TNFa, IL 8, IL 17
How does destruction of cartilage and bone occur in RA?
1 cartilage: fibroblasts activation and proliferation cause secretion of protease which destroy cartilage and bone. This forms scar tissue that immobilizes joint. inflammation stimulates synovial-lining cell proliferation=chondrocytes attack cartilage=synovium becomes hyper plastic and grows over cartilage=this causes pannus (fibrovascular growth) that causes further cartilage reabsorption
2 bone: CD4 and synovial cells activate osteoclasts that cause bone destruction
