AUTOIMMUNITY RUBINS 140-147 Flashcards
Cytotoxic (Type II mediated) autoimmune reactions
Are mostly organ specific.
Autoimmune diseases: Immune response against Self(Loss of immune tolerance).
May be organ specific or generalized.
So how exactly does this occur?
Normally: antibodies (anti-idiotype Antibodies) bind the antigen binding sites that immunoglobulins wld bind –> therefore controlling the immune response.
When this fails, Immunoglobulins bind self antigens n disease ensues.
Types of reactions?
Type I hypersensitive rxn:
Type I: Immediate-type hypersensitivity reactions. IgE binds Mast cells and or basophils –> subsquently binds antigen–> Antigen xlinking with IgE –> histamine release by mast cells –> Asthma, anaphylaxis, urticaria
SLE: Systematic Lupus Erythematous prototype Systemic Immune complex disease.
Diagnostic autoantibodies: most important ones are the ones against (anti) nuclear antigens(ANAs) esp: ABs to dsDNA and to solublenuclear antigen Complex, Sm (Smith)antigen.
- Chronic Inflammatory disease, autoimmune, multi-system. 80% of cases are women of child bearing age. (Estrogen involved??)
- Prototype of Type III hypersensitivity rxn. Antigen-AB complexes deposit in tissues–> vasculitis, synovitis & glomerulonephritis.
Xteristically: affects the skin, joints, serous membranes and kidneys.
Systemic Lupus
The variety of ABs produced suggests that there is a general disturbance in the immune tolerance.
Evidence suggests that most damage is from the deposition of circulating immune complexes against self antigens, esp DNA.
More evidence suggests that under special circumstances, these immune complexes form in situ- ie in tissues, rather than in circulation
Type II reactions are also implicated in Lupus since cytotoxic ABs against Leukoccytes, erythrocytes and platelets have bn described.
Type II reaction
Hypersensitivity reaction:
IgG or IgM is formed against an antigen, usually a protein (surface antigen). [Less commonly to an intrinsic structural comp. of the ECM, eg basement membrane]
Such antigen-AB coupling–> activates complement –>cell lysis or damage ECM.
Type III
IgG or IgM are the culprits here too, like Type II.
Antigen in circulation binds to an AB.–> Antigen-AB complex is deposited in the tissues –> complement is activated at the site of the Antigen-AB complex –> Leukocytes (neutrophils and macrophages)recruited to the site –>tissue injury!
Type IV hypersensitivity reaction. o cell mediated or delayed type hypersensitivity.
Dont involve Antibodies
Antigen, w/ the help of marophages activates T cells –> release of T lymphocyte components –> Tissue injury.
SLE affiliated complications.
Note: Patients with severe renal or CNS disease or with systolic hypertension have the worst prognosis.
Joint disease in 90%.
An inflammation synovitis occurs, but there is no joint destruction like in Rheumatoid arthritis.
Skin:Erythematous rash in sun exposed areas., a malar “Butterfly rash” is xteristic.
Kidney: IgG- dsDNA Immune complexes deposit in glomeruli –> glomerulonephritis. Interstitial nephritis is also seen.
serous membranes: >1/3 have pleuritis and
pleural effusion
Respiratory: Immune complexes in alveolar septa –>pneumonitis
Cardiac: affects all layers of the heart, esp causing pericarditis.
Libman -Sacks Endocarditis: small nonbacterial vegetations on valve leaflets, confined to the line of valve closure.
CNS disease: life threatening.Vasculitis can –> hemorrhage –infarction of the brain.
Antiphospholipid antibodies: assoc. w/thromboemboli complications, eg stroke, PE, DVT, Spontaneous abortions and Portal Vein Thrombosis.
Drug Induced Lupus
- Also involves immune complexes.
precipitated by:
a) Slow drug-acetylator status and
b) A daily dose of any of these drugs.
- Procainamides (for arythmias)
- Hydralazine(for hypertension in HL4-DR4 genotype patients.)
- Isoniazid (for TB)
1.Ranges from asymptomatic lab abnormalities (+ve ANA) test to being clinically similar to SLE.
- Shows no sex dominance unlike SLE.
- Pts usually > 50 yrs
Drug Induced Lupus
presentation:
constitutional signs, pleuritis, polyarthritis, Antinuclear ABs.
May develop Rheumatoid factor, a false +syphillis test, and a positive Coombs test( ie. a +ve direct antiglobulin test).
RENAL & CNS involvement IS RARE.
ABs to ds DNA and Sm antigen are uncommon.
** ABs to histones account for the +ve ANA test and are typical for drug induced Lupus**
Symptoms resolve when the offending drug is discontinued.
Chronic Discoid Lupus:
Pathogen: Immunoglobulins+complement deposit at the dermal-epidermal interface.
This skin disorder is the most common variety of localized lupus erythematous.
presentation:
Erythematous, depigmented and telangiectatic plaques occur most commonly on the face and the scalp.
Uninvolved skin has no immune complexes, unlike SLE
+ve ANA in ~1/3 of pts, but ABs against dsDNA and Sm are unseen.
Subacute Cutaneous Lupus
Pathogenesis: ABs to ribonucleoprotein complex (SS-A or Ro antigen) and an association with HLA-DR3 genotype are xteristic.
xteristic: Papular and annular lesions, principally on the trunk.
Lesions aggravated by UV light and sunlight.
Lesions heal w/o scarring
Sjogren Syndrome
Pathogenesis: Intense Lymphocytic infiltrate in the Lacrimal gland and the salivary gland.
2nd most common CT disorder after SLE & occurs mostly in women (30-65 y.o)
Presentation of primary vs Secondary ss?
xteristics:
- Dry mouth(xerostomia)
- Dry Eyes (Keratoconjuctivitis
(1&2)without other CT disease –> primary SS.(involves the kidney, thyroid & lung)
(1&2)+other CT disseases –> secondary Sjogren Syndrome
Antibody markers for Sjogren
Common antibodies:
1) SS-A(Ro) & SS-B(La) 2) ANA against DNA and non Histone proteins.
Rare antibodies:
1. Organ specific ABs eg against salivary gland antigen 2. Autoantbodies against DNA or histones ***These suggest Secondary SS assoc . w/SLE***
