Autoimmunity

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immune system response to self components

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autoimmunity

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-mechanisms of self tolerance protect from self-reactive lymphocytes
-evidence=mature, self-reactive B & T lymphocytes recirculating
-normally regulated by clonal anergy, or clonal suppression

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Normal status

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activation of self-reactive clones of T-cells, B-cells, resulting in organ specific autoimmune disease &/or systemic autoimmune disease

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Breakdown in regulation

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may result in
-direct cellular damage 2nd to lymphocytes or Ab's binding to cell membrane Ag's
>> can cause cell lysis &/or
>> inflammatory responses in target organ
>> cellular structures replaced by connective tissues &
>>function decreases
>>> organ function may be stimulated, or blocked by auto Ab's

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immune respone> Ag unique to single organ or gland

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-most common in middle aged females
-autoantibodies & sensitized Tdh cells specific for thyroid Ag's
-intense infiltration of thyroid by lymphocytes, macrophages, & plasma cells>> lymphocytic follicles & germinal centers

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direct cellular damage examples: Hashimoto's Thyroiditis

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-develop goiter
- Abs to thyroglobulin & thyroid peroxidase> involved in iodine uptake
-is prevented by Ab's binding to these proteins
-decreased thyroid hormones> hypothyroidism

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direct cellular damage examples: Hashimoto's Thyroiditis

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-auto-ab's to membrane bound protein> intrinsic factor> facilitates uptake of vit B12
-needed for hematopoiesis>> # of mature RBC's decrease

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direct cellular damage examples: Pernicious Anemia

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-autoAb specific for basement membrane Ag's of glomeruli & lungs
-complement can be activated> cell damage & neutraphil activation
-increased kidney damage & pulmonary hemorrhage
-death often withing months of onset
-kidney biopsy shows deposits of IgG & C3b

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direct cellular damage examples: Goodpasture's syndrome

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-attacks beta cells>islets of langerhans
>>production of insulin decreased & blood glucose levels increase

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direct cellular damage examples:
Insulin Dependent Diabetes Mellitus

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-develop insulitis
>>Tdth cells infiltrate islets & activate macrophages >>> cytokine mediated destruction of more beta cells & activated macrophages release lytic enzymes causing more destruction, Ab dependent cell-mediated cytotoxicity may be involved

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direct cellular damage examples:
Insulin Dependent Diabetes Mellitus

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bind to hormone receptos> stimulate overproduction

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stimulating or blocking AutoAb diseases: Agonist

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block receptor function>> causes gradual atrophy of organ

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stimulating or blocking AutoAb diseases: Antagonist

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-thyroid hormone production regulated by thyroid stimulating hormone (TSH) from pituitary gland
-produce autoAb to TSH receptors, mimicing normal action of TSH> cause production of thyroid hormones>> stimulating thyroid so called long acting thyroid-stimulating (LATS) Ab's

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Grave's Disease

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-autoAb's to acetylcholine receptors on motor end-plates of muscles (C activation may destroy receptors)
-prevents binding of acetylcholine, so
-inhibits muscle activation

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Myasthenia Gravis>> Ex of blocking Ab

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-increased # of autoreactive Tcells
-inflammatory lesions of myelin sheath of nerves are produced causes loss of nerve fiber insulation
-oligoclonal gammopathy in cerebral spinal fluid is definitive for MS, absence of it does not rule out the disease

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multiple sclerosis

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-sclerosis of myelin can be detected on

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MRI or CAT scan

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generalized hyperactive T & B cells
-tissue damage widespread
-involves immune complexes

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systemic autoimmune diseases

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-typical case> female 20 to 40
-signs & symptoms> fever, weakness, arthritis, skin rash, pleurisy, renal dysfunction

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systemic lupus erythematosus (SLE)

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-autoAb's to
--nDNA, histones>> form immune complexes>>deposut on blood vessel walls, GBM
--RBC & platelets>> C'mediated lysis>> increased circulating C3a & C5a (anaphylotoxins)
-increased complement receptor 3(CR3's) on neutraphils
-neautraphils aggregate & attach to vascular endothelium >>> neutropenia, occlude small vessles>>>> vasculitis
-clotting factors

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systemic lupus erythematosus (SLE)

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-symmetrical inflammation of joints, frequently beginning in the hands (later tends to involve large weight bearing joints)
-also affects the tendons surrounding these joints, resulting in the pulling/drawing of the joints
-commonly causes inflammation of small blood vessels following deposit of imumune complexes on vessel surface, then activation of C', the activation of neutraphills
-anemia

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Rheumatoid Arthritis (RA)

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-lab results not definitive, can see low titers of RF test in other autoimmune diseases & can see neg in RA

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Rheumatoid Arthritis (RA)

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-produce AB most commonly to the Fc portion of IgG but can also be directed against IgM
>>this autoAb is of the class IgM
>>in the circulation as well as the synovial fluid of the Pt
>> this Ab is known as the Rheumatoid factor (RF) it is the UNK in the RF test
-significant titer is usually >1:20

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Rheumatoid Arthritis (RA)