Chapter 10 Immunology vol.3

Chapter10 今日のメモ☆

Immunology第三回目はAutoimmunity（自己免疫）に関して。

Womenのほうが罹患率が高い
e.g.)myasthenia gravis（重症筋無力症）2倍、 SLE 10倍　ただし、
Sjögren's disease（シェーグレン症候群）, Goodpasture syndromeは男性の方が罹患率が高い

Type II hypersensitivity : Antibody-mediated & Complement-mediated cytotoxicity
Type IV hypersensitivity : Cell-mediated cytotoxicity

Organ-specific autoimmunities
 - Rheumatic fever（リウマチ熱）

 - Antithyroid autoimmunities（抗甲状腺自己免疫疾患）
  * Primary autoimmune myxedema（粘膜水腫）
     Antibodies against the thyroid-stimulating hormone(TSH) receptor act as antagonist（拮抗剤）。
     The result is thyroid atrophy（甲状腺萎縮） with hypothyroidism（甲状腺機能低下症）
  *Hashimoto's thyroiditis（橋本病）
    Antibodies against thyroid peroxidase
  *Grave's disease（バセドウ病）
    Antibodies act as agonists（作動薬） of TSH to stimulate hypersecretion of thyroid hormon
    The result is hyperthyroidism（甲状腺機能亢進症）

 - Myasthenia gravis（重症筋無力症）
  Antibodies against the nicotinic acethylcholine receptor on skeletal muscle（骨格筋）
  This activity causes weakness and fatigue in skeletal muscles
  Caused by drugs (penicillamine, aminoglycosides, procainamide etc)
  Therapy : anticholinesterase therapy (neostigmine), corticosteroid in severe cases, plasmapheresis

 - Autoimmune pernicious amenia（自己免疫悪性貧血）
  Antibodies against intrinsic factor(for VB₁₂) decrease absorption of VB₁₂
  Therapy : intramuscular injection of cyanocobalamin or oral administration of intrinsic factor

 - Goodpasture's syndrome
  Antibodies against glomerular capillary basement membrane (GBM)（糸球体基底膜）
  The result is glomerulonephritis（糸球体腎炎）
  Therapy: immunosuppressive (corticosteroids, plasmapheresis)

 - Autoimmune hemolytic anemia (red blood cell)（自己免疫溶血性貧血）
 - thrombocytopenia (plate)（血小板減少症）
 - neutropenia (neutrophil)（好中球減少症）
 - lymphopenia (lymphocyte)（リンパ球減少症）
  Antibodies against each blood cells
  Therapy(when it's chronic): corticosteroids, additionaly cyclophosphamide, chlorambucilm, immune globulin(IVIG)

 - Insulin-dependent diabetes mellitus(IDDM)
  Therapy : cyclosporine(ネオーラル)

 - Multiple sclerosis (MS)（多発性硬化症）
  T cells & macrophages attack the basis protein of myelin in central nervous system(CNS)
  One of CNS demyelination disease（中枢性脱髄疾患）
  Therapy : spasticity（痙攣）- baclofen, peripheral skeletal muscle relaxant (dantrolene)
            Adrenocorticotropic hormone (ACTH)（副腎皮質ホルモン） >> corticosteroids
            IFN-β-1b (betaseron), IFN-β-a, glatiramer acetate

Non-organ-specific autoimmunities
 - Sjögren's disease（シェーグレン症候群）
  inhibition of exocrine gland secretion（外分泌腺分泌阻害）
  Symptom : dryness of the eyes, mouth, gastrointestinal, respiratory, vaginal mucous membranes
   pain and edema in the salivary glands（唾液腺）
  Therapy : artificial tears, drinking water, similar to that for SLE (systemic corticosteroids)

 - SLE (Systemic Lupus Erythematosus)
  type III hypersensitivity (hypereactivity of B cells)
  Drugs-induced SLE [procainamide（抗不整脈薬）, hydralazine（高血圧）, quinidine, methyldopa,
   isoniazid, phenytoin, chlorpromazine]
  *Symptoms
     Mild arthritis, feber, rash and fatigue
     Progressive necrotizing vasculitis（壊死性血管炎）, glomerulonephritis
     Hypertension
     Hemolytic anemia, thrombocytopenia
  *Criteria
     = high concentration of antinuclear antibodies directed against double-stranded DNA
     = Smith (Sm) nuclear antigen
     a discoid erythematous facial rash（円盤状の紅斑）, photosensitivity, oral ulcers, arthritis, persistent proteinuria, anticardiolipin, antierythrocyte, antileukocyte antibodies
  Therapy : nonsteroidal anti-inflammatory drugs(NSAIDs) for mild disease, cyclophosphamide, plasmapheresis. 


Today's question
- Autoimmune disorder(自己免疫疾患)の問題
Q: In which autoimmune disorder is the mechanism of pathogenesis classified as type II hypersensitivity?
(A) Systemic lupus erythematosus (SLE)
(B) Insulin-dependent diabetes mellitus (IDDM)
(C) Grave's disease
(D) Hashimoto's thyroditis







A: (C) Grave's disease
In Grave's disease, an antibody acting as a TSH agonist hyperstimulates the thyroid.
In SLE(TypeIII), persistent circulating immune complexes are responsible for much of the pathogenesis
In IDDM(type IV), T cell cytotoxicity to beta islet cells is probably responsible for the major pathogenesis
In Hashimoto's thyroiditis(type IV), antibodies to thyroid peroxidase may initiate inflammation but TH1 cells and macrophages infiltrate the organ