Autoimmune Disease Flashcards
Mechanism of Type I Hypersensitivity/Anaphylaxis
Immediate response produced to an allergen (e.g. pollen).
1) Sensitization- initial exposure to allergen- presented on APC to CD4+ T-cells –> B-cell activation
2) Plasma cells produce IgE antiboides, which bind to basophils and mast cells in the respiratory epithelium and GIT
3) Subsequent exposure, allergen attaches to sensitised mast cells and basophils –> crosslinking of IgE antibodies causing rapid degranulation
Degranulation (Type I Hypersensitivity)
-what are the mediators and what are their effects?
Degranulation= release of inflammatory mediators
1) Histamine- vasodilation, increase permeability of capillary beds, bronchoconstriction, increased mucus secretion, pain and itching
2) Prostaglandins and leukotrienes- inflammation and tissue damage. Attract eosinophils
Examples of Type I Hypersensitivity
Allergic Asthma
Anaphylaxis
Hayfever
Mechanism of Type II Hypersensitivity
Antigen on plasma membrane deemed foreign
B-cell sensitisation (via CD4+ T-cells)
Subsequent exposure- antibody production and activation of complement via classical pathway and phagocytosis by macrophages and neutrophils
Examples of Type II Hypersensitivity
Autoimmune Haemolytic Anaemia Immune Thrombocytopenia Mismatched blood transfusion Haemolytic disease of the newborn Myasthenia gravis Goodpasture's Syndrome Pemphigus vulgaris Bullous pemphigoid
Mechanism of Type III Hypersensitivity and Examples
Sensitisation
Subsequent exposure leads to production of antigen-antibody complexes
IgG antibodies combine w/ antigen in the blood and form immune complex and activate complement
Ex. vasculitis, rheumatoid arthritis
Mechanisms of Type IV Hypersensitivity (Delayed Hypersensitivity)
First exposure- antigens bind APCs leading to antigen presentation to CD4+ T-cells
Subsequent exposure, T-cells release cytokines e.g. interferron-gamme, migration inhibiting factor (MIF)
CD8+ T-cells recrutited for direct cell cytotoxicity
Examples of Type IV Hypersensitivity
Contact dermatitis (Nickel)
Graft vs. Host Disease
PPD Test for Tuberculin (Mantoux test)
Mechanism of Type V Hypersensitivity and Example
Mediated by antibodies like Type II but instead of destroying target, antibodies stimulate target.
Ex. Graves’ Disease
Myasthenia Gravis
- Pathophysiology
- Presentation
- Assoc.
A neuromuscular junction disorder in which their are autoantibodies to post-synaptic ACh receptor. This impairs muscle contraction.
Presentation:
Ptosis, diplopia, proximal muscle weakness (myasthenia), respiratory muscle inv. (dyspnoea), bulbar muscle inv. (dysphagia and difficulty chewing), reflexes spared and worsens w/ muscle use
Assoc. w. thymoma and thymic hyperplasia
Assoc. w/ HLA-DR3
Eaton-Lambert Syndrome
- Pathophysiology
- Presentation
- Assoc.
A NMJ disorder where there are autoantibodies to presynaptic Ca2+ channels leading to impaired/reduced ACh secretion.
Presentation:
Myasthenia, autonomic symptoms (dry mouth, constipation and impotence), hyporeflexia and improves w/ muscle use
Assoc. w/ small cell lung cancer
Graves’ Disease
- Pathophysiology
- Assoc.
IgG autoantibody to TSH receptor. Stimulation leads to hypertrophy (diffuse goitre) and increased secretion of T3/4 (hyperthyroidism)
Pretibial myxoedema, proptosis and diplopia
Assoc. w/ HLA-DR3 and -B8
Autoimmune Haemolytic Anaemia (AIHA)
- Pathophysiology (Warm and Cold)
- Causes
Autoantibodies to RBCs leading to destruction by complement and/or phagocytosis
IgG in warm agglutinin and IgM in cold agglutinin
Coombs +ve
Causes: Idiopathic, infections (syphyllis, mycoplasma, EBV), autoimmune (SLE, RA, UC), drugs (penicilin, alpha methyl dopa) and neoplasms (esp. CLL)
Idiopathic Thrombocytopenia Purpura (ITP)
- Pathophysiology
- Assoc.
Defined by isolated low platelet count w/ normal bone marrow
IgG autoantibodies against platelet surface structures
Assoc. w/ SLE, drugs (co-trimoxazole) and haematological malignancies (CLL)
Autoimmine Neutropenia
-Pathophysiology
Autoantibodies cause neutrophil destruction
Increased susceptibility to infection, most common otitis media in children
Pemphigus Vulgaris
- Pathophysiology
- Presentation
Type II Hypersensitivity reaction caused by IgG antibodies vs. desmoglein- I and/or -3 (component of desmosomes which connect keratinocytes in stratum spinosum)
Presentation:
Flaccid intraepidermal bullae caused by acantholysis
Oral mucosa inv.
Nikolsky’s Sign +ve
Bullous Pemphigoid
- Pathophysiology
- Presentation
Type II Hypersensitivity reaction caused by IgG antibodies vs. hemidesmosomes (epidermal basement membrane)
Presentation:
Tense blisters- less likely to break than pemphigus
Nikolsky’s sign -ve
Goodpasture’s Syndrome
- Pathogenesis
- Presentation
Anti-GBM antibodies, attack collagen type IV in basement membrane. Destroy glomerular BM and alveoli
Presentation:
Nephritic syndrome
Alveolitis (diffuse pulmonary haemorrhage, haemoptysis and resp. failure)
Systemic Lupus Erythematosus
- Pathogenesis
- Presentation
Systemic, remitting and relapsing autoimmune disease
Organ damage- mainly from type III hypersensitivity and to lesser degree, type II hypersensitivity
Autoantibodies: anti-red cell, anti-platelet, anti-cardiolipin, anti-dS and anti-nuclear (ANA)
Assoc. w/ deficiency of early complement proteins reducing immune complex clearance
Presentation:
Fevers, malaise, lymphadenopathy, arthralgia and arthritis, vasculitis, serositis, fibrosing aveolitis, glomerulonephritis and photo-sensitive skin rash
Type 1 Diabetes Mellitus
- Patholgy
- Autoantibodies
Infiltration of islets w/ lymphocytes incl. CD8+ T-cells, which kill the beta cells.
Autoantibodies: anti-islet cell, anti-insulin and anti-glutamic decarboxylase (GAD)
Hashimoto’s Thyroiditis
-Autoantibodies and assoc.
Autoantibodies: anti-TPO and anti-thyroglobulin
Assoc. w/ HLA-DR3, -DR5 and increased risk of non-Hodgkin lymphoma (B-cell)
Pernicious Anaemia (Autoimmune Gastritis) -Pathology
Lymphocytic infiltrate in lamina propria
Autoantibodies against parietal cells, intrinsic factor (Anti-IF diagnostic)
Decreased secretion of IF leading to B12 absorption
Predisposition to stomach malignancy
Coeliac Disease
- Pathophysiology
- Assoc.
Gluten-sensitive enteropathy
Autoimmune mediated intolerance of gliadin leading to malabsorption (distal duodenum, proximal jejunum), and steatorrhoea
Autoantibodies- IgA anti-tissue transglutaminase (IgA tTG), anti-endomysial, anti-reticulin and anti-deamidated gliadin peptide antibodies
Histo: intra-epithelial lymphocytosis, lymphocytic infiltrate in lamina propria, villous atrophy and crypt hyperplasia
Assoc. w/ HLA-DQ2, -DQ8, dermatitis herpetiformis
Increased risk of MALT lymphoma
Chronic Autoimmune Hepatitis
- Autoantibodies
Classically affects young women and if untreated progresses to liver failure
Subtypes, distinguished by autoantibodies: ANA, anti-SMA, anti-liver/kidney microsome, antibodies vs. liver soluble antigen
