Immunopathology II/III Flashcards
What are autoimmune diseases?
Immune reactions against self-antigens causing tissue damage or alteration of physiological response
Systemic, often called CT or collagen vascular diseases, typically target widely distributed intracellular molecules
Single cell or organ, often involve certain systems (endocrine glands)
How is the diagnosis of autoimmune disease made when autoantibodies are found in healthy individuals?
Immunological reaction to a self-Ag or native (self) tissue
Reaction is primary pathogenesis, not secondary to tissue damage
No other well-defined cause or identifiable etiology
How do genes play a part in loss of self tolerance?
Expression of certain MHC alleles (D locus) confers higher susceptibility to loss of self tolerance
Polymorphism in a gene that encodes tyrosine phosphatase, PTPN-22 gene, is most frequently implicated in autoimmunity
How do microbes play a part in autoimmunity?
Act via cross-reactivity, tissue damage, increased expression of APC co-stimulatory molecules non-specific B and T cell stimulation
How does gender play a role in autoimmunity?
Higher incidence in females suggests role of sex hormones
What are the main mechanisms that lead to autoimmune diseases? x8
- Failure of tolerance/immune regulation
- Failure of T cell anergy
- Failure of apoptosis of self-reactive cells
- Failure/dysfunction of regulatory CD4+ T cell
- Molecular mimicry
- Polyclonal lymphocyte (B and T cell) activation
- Emergence of sequestered Ag
- Exposure of cryptic antigenic determinants
What occurs after things like molecular mimicry/reversal anergy/loss of inhibiting cytokines, etc?
Access to professional APC’s
Self-reactive T cell activation
Recirculation of activated T cells to site of tissue damage
Further tissue damage, release of self-antigen, and further T cell activation
What is anti-nuclear antibody testing?
Uses human tissue cell culture nuclei (hep-2 cells) as a substrate for diagnostic screening and other types of nuclei, cell organelles, or soluble nuclear substances as substrates for specificity tests
What antibody is most associated with lupus?
Anti-double stranded DNA
Anti-Sm
What antibody is most associated with drug induced lupus?
antihistone
What antibody is most associated with systemic sclerosis and CREST (less so)?
Nuclear RNP
What antibody is most associated with Sjogren syndrome?
SS-A(Ro)
SS-B(La)
What is the antibody most associated with Systemic Sclerosis?
Scl-70
What is the antibody most associated with CREST?
Anticentromere
What is rim ANA patterning associated with?
dsDNA, SLE active flares
What is homogenous ANA pattern associated with?
RA or drug induced SLE
antihistones
What is speckled ANA patterning associated with?
Least specific
Anti-Smith Ab of SLE but also systemic sclerosis (Scl-70), Sjogren’s syndrome (SS-A, SS-B)
What is the centromere ANA pattern associated with?
Systemic sclerosis
CREST - mostly
What is nuclear ANA pattern associated with?
SLE, systemic sclerosis, CREST
What is systemic lupus erythematosus?
Prototypical multisystem disorder
Clinically acute or insidious with flares and remissions, often febrile
Mainly in females
Occurs between menarche - menopause
What is the ACR diagnostic criteria? x11
- Malar rash
- Discoid rash
- Photosensitivity
- Oral ulcers
- Arthritis
- Serositis
- Renal disorder
- Neurologic disorder
- Hematologic disorder
- Immunologic disorder
- Antinuclear antibodies
What is the hallmark of disease?
Autoantibodies called antinuclear antibodies (ANAs) - reflect loss of tolerance
What 4 categories of nuclear Ag are ANA directed against?
- DNA
- Histones
- Proteins bound to RNA
- Nucleolar Ag
