Type IV Hypersensitivity and Autoimmunity Flashcards
Autoimmune hemolytic anemia
Ab against cell-surface/matrix antigen (type II)
Autoantigen: Rh blood group antigens, I antigen
Consequence: Destruction of RBCs by complement and phagocytes, anemia
Autoimmune thrombocytopenia purpura
Ab against cell-surface/matrix antigen (type II)
Autoantigen: Platelet integrin gpIIb:IIIa
Consequence: Abnormal bleeding
Increased bleeding time
Goodpasture’s syndrome
Ab against cell-surface/matrix antigen (type II)
Autoantigen: Non-collagenous domain of basement membrane collagen type IV (IgG against alpha3 chain of the collage)
Consequence: Glomerulonephritis, pulmonary hemorrhage, hemoptysis, dyspnea, anemia
Treatment: plasma exchange, immunosuppressive drugs
Pemphigus vulgaris
Ab against cell-surface/matrix antigen (type II)
Autoantigen: Epidermal cadherin
Consequence: Blistering of skin
Pemphigus foliaceus
Ab against cell-surface/matrix antigen (type II)
Autoantigen: Desmoglein
Consequence: Mild blistering of skin
Acute rheumatic fever
Ab against cell-surface/matrix antigen (type II)
Autoantigen: Streptococcal cell wall antigens; antibodies cross-react with cardiac muscle
Consequence: Arthritis, myocarditis, late scarring of heart valves
Graves’ disease
Ab against cell-surface/matrix antigen (type II)
Autoantigen: Thyroid-stimulating hormone receptor (mimic TSH)
Consequence: Hyperthyroidism (anti-TSH receptor autoantibodies)
MHC class II on thyroid cells; HLA-DR3
Myasthenia gravis
Ab against cell-surface/matrix antigen (type II)
Autoantigen: Acetylcholine receptor
Consequence: Progressive weakness
Treatment: Pyridostigmine (acetylcholinesterase inhibitor); Azathioprine (immunosuppressive); Thymectomy
Type 2 diabetes (insulin-resistant diabetes)
Ab against cell-surface/matrix antigen (type II)
Autoantigen: Insulin receptor (antagonist)
Consequence: Hyperglycemia, ketoacidosis
Insulin is bound by antibodies and is not effective
Hypoglycemia
Ab against cell-surface/matrix antigen (type II)
Autoantigen: Insulin receptor (agonist)
Consequence: Hypoglycemia
Subacute bacterial endocarditis
Immune-complex disease (type III)
Autoantigen: Bacterial antigen
Consequence: Glomerulonephritis
Mixed essential cryoglobulinemia
Immune-complex disease (type III)
Autoantigen: Rheumatoid factor IgG complexes (with or without hepatitis C antigens)
Consequence: Systemic vasculitis
Systemic lupus erythematosus
Immune-complex disease (type II and III)
Autoantigen: DNA, histones, ribosomes, snRNP, scRNP
Consequence: Glomerulonephritis, vasculitis, arthritis (deposition of immune complexes)
HLA-DR2, HLA-DR3
Type 1 diabetes (insulin-dependent diabetes mellitus)
T-cell-mediated disease (type II and IV)
Autoantigen: Pancreatic beta-cell antigen
Consequence: Beta-cell destruction by antibodies and T-cells
HLA-DR3, HLA-DR4
Rheumatoid arthritis
T-cell-mediated disease (type II and IV)
Autoantigen: Rheumatoid factor: Synovial joint antigen - Fc region of IgG (create IgM/G/A to it)
Consequence: Joint inflammation and destruction by CD4, CD8, B-cells, neutrophils, macrophages
HLA-DR4
Treatment: Anti-inflammatory / immunosuppressive drugs (anti-TNF-alpha)
Multiple sclerosis
T-cell-mediated disease (type II and IV)
Autoantigen: Myelin basic protein, proteolipid protein
Consequence: Brain degeneration, paralysis (inflammatory demyelination)
Activated T-cells are implicated: IL-17 producing Th17 cells
- also IFN-gamma
Treatment: IFN-beta injection (suppress Th17); immunosuppressive drugs; Natalizumab (anti-VLA4/integrin)
APECED (Autoimmune PolyEndocrinology Candidiasis Ectodermal Dystrophy)
Mutations in AIRE gene
- defective thymic deletion of autoreactive T cells (b/c can’t express peripheral antigens in thymus)
The defective negative selection leads to autoimmunity
IPEX (Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked syndrome)
Mutations in T-cell transcription regulator FOXP3
- FOXP3 necessary for generation of Tregs
–> no immune cell regulation
HLA allotype for ankylosing spondylitis?
B27
HLA allotype for celiac disease?
DQ2 and DQ8
wheat flour gluten peptide-specific CD4+ T-cells
–> auto-antibodies to gut anti-transglutaminase (villi destruction)
HLA allotype for multiple sclerosis?
DQ6
Infections and autoimmunity:
Group A Streptococcus (pyogenes)
HLA: unknown
Consequence: Rheumatic fever (carditis, polyarthritis)
Infections and autoimmunity:
Chlamydia trachomatis
HLA: HLA-B27
Consequence: Reiter’s syndrome (can’t pee, can’t see, can’t climb a tree)
Infections and autoimmunity:
Campylobacter jejuni
HLA: HLA-B27
Consequence: Reactive arthritis (…and Guillain-Barre?)
