Autoimmunity Flashcards
Factors in Autoimmunity
Important
Evironmental and endogenous
- Female hormones, tissue injury, microbes, epigenetic factors like aging, food, drugs can trigger
Leads to genetic susceptibility
- Then to loss of immunologic tolerance, self reactive T cells and B cells activate in response to self antigens
Role of Genetic Factors
Complex diseases: multiple genetic variants, MHC haplotype is common risk factor
- Some rare diseases caused by single gene mutation
Wrong Place Wrong Time
Special about DNA and MHC?
Autoreactive B + autoreactive T together can cause APC to present to T cell and form autoantibodies
- DNA is sugar, not protein so its not on MHC
Super Antigens
Random or large stimulation, kills whatever wherever, not targeted, releases irrelevant or autoimmune antibodies
Autoantigen Appearance Factor
Antibodies: recognize 3D epitopes
TCRs: recognize peptides
Some human antigens may look similar to foreign antigens
Organ Specific Vs. Systemic Autoimmunity
Organ: chronic inflammatory in specific organ, autoAb specific for Ag of organ, autoAb are species specific
Systemic: widespread, many organs, autoAbs not organ specific or species specific
Autoimmune Thryoid Diseases: Basics
what does AITD lead to
Increased or decreased production of thyroid hormones due to disregulation of endocrine feedback loop
Thyroid Function & Formation
Thyroid has follicles filled with colloid
- Colloid has thyroglobulin
Thyroglobulin modified into T4 and T3
- Thyroid peroxidase synthesizes T3/T4
Hashimoto’s Thyroiditis
Organ specific
Hypothyroidism
Destruction of thyroid glands
Type II and Type IV
Graves Disease
Organ specific
Hyperthyroidism
Thyroid stimulates Abs, excessive releaseand overstimulation of heart
Type II
Thyroid Issues and The Mechanism Behind It
With symptoms!
Low T3/T4
Hashimoto’s: anti-thyroglobulin, anti-thyroid peroxidase
High T3/T4
Low
Type I Diabetes Mellitus
Endocrine disorder, hyperglycemia - Type I destruction of beta cells in pancreas = insulin deficiency
Type IV
Celiac Disease
Gluten triggered
AutoAbs form in HLA-DQ2/DQ8 positive people to:
- Gliadin peptides
- Tissue transglutaminase, IgA
- Endomysium (tissue around intestinal muscles
Multiple Sclerosis
CNS AI disorder
- Abs against myelin basic membrane
- Demyelination
- T cell disease, Th17 myelin specific CD4 cells
Lab Diagnostic of Multiple Sclerosis
Important
Oligoclonal banding
Distinct bands in patients in Ms
Myasthenia Gravis
Neuromuscular junction
- Abs to acetylcholine receptors = weak muscles
Goodpasture’s Syndrome
Abs to basement membranes of renal glomeruli, can also affect lungs
Type II
Systemic Lupus Erythematosus SLE: Basics
Chronic inflammatory disease
- Numerous AutoAbs
- Immune complexes form, trigger C activation and inflammation
- Involves kidneys, renal failure
Type III
Drug induced: stops once drug stops
Discoid: cutaneous but progresses into SLE
Anti-Nuclear Abs
Not specific
- Vivo: react with free nuclear material of disrupted cells
- Vitro: react with nuclei of different species
ANA Target Classification
- Ab to DNA
- Ab to histones
- Ab to extractable nuclear antigens
- Ab to nucleolar material
Homogenous Pattern
anti what, seen in what
Anti: DNA, histones, nucleosomes
Seen in: RA, SLE, others
Peripheral/Rim
anti what, seen in what
Anti: dsDNA
Seen in: SLE specific
Speckled Pattern
anti what, seen in
Anti: extractable nuclear Ag-SnRNPs
Seen in: SLE, Sjorgren’s syndrome, scleroderma, rheumatic
Nucleolar Pattern
Anti: nucleolus
Seen in: SLE, progressive systemic sclerosis
Centromere Pattern
seen in
Seen in: CREST syndrome
SLE: Lab Diagnosis
ANA positive
- dsDNA Abs + low C3 levels = SLE diagnosis
You can also test anti-histone/rim pattern, speckles pattern is SPECIFIC to SLE
Using Crithidia Luciliae For IFF
Kinetoplast in C. luciliae high in dsDNA
Rheumatoid Arthridis: Basics
anti what
Rehumatoid factor: autoAb against Fc of IgG
Type III
RA: Diagnostics
Agglutination test: cells with IgG
- Does not rule out!
IgA/IgG isotype RF: more specific, nephelometry or EIA
A-CCP Abs: lead marker for RA, much more specific, detected by ELISA
ANA
Granulomatosis with Polyangiitis (Wegner’s Granulomatosis)
Inflammation of blood vessels in respir. tract
- Becomes systemic
Abs to: neutrophil cytoplasmic antigens
- Can be type II, III, or IV
Sjogren’s Syndrome
Moisture glands attacked
- Can be secondary to other AI disease
Lab Diagnostics: nonspecific by ANA, so confirm by doing Ab to Ro and La by ELISA
Progressive Systemic Sclerosis/Scleroderma
Ab to ENA, nucleolus, centromere, Scl-70
- Speckled and nucleolar
AI Liver Diseases
AI hepatitis: SMA (smooth muscle), ANAs
Primary Biliary cirrhosis: mitocondral Abs
