hypersensitivity and autoimmunity Flashcards
type 1
allergy
IgE mediated; allergic or anaphylactic
- IgE bound to mast cells and basophils
- allergen binds to IgE forming cross-links which trigger mast cell degranulation
granules release:
- chemoattractants
- activators (vasodilation, complement, platelets)
- spasmogens (SM contraction & mucus secretion)
what causes type 1 hypersensitivity
- rhinitis (dust mites, pollens, animal dander)
- insect stings
- food allergies
- small molecules
common sites of type 1 hypersensitivity
- respiratory tract
- gut
- skin
- multiple organs = anaphylaxis
treatment of type 1 hypersensitivity
(avoid if possible)
- antihistamines
- corticosteroids, especially in asthma
- adrenaline
- densensitisation
type 2 hypersensitivity
antibodies against cell surface antigens bind leading to ADCC and complement activation by immune complex formation
- membrane attack complex for lysis
- C3b to help neutrophil attachment
what is an example of type 2 hypersensitivity
haemolytic disease of the newborn
- Rh(D) - mother has Rh(D) + child
- baby is born, exposure to Rh(D) + to red cells causes antibody production in mother
- Anti-Rh IgG crosses placenta in sebsequent pregnancy
= complement mediated haemolysis
type 3 hypersensitivity
immune complex-mediated
- in chronic infection, period when antibody to antigen is similar, causing formation of large lattice-like immune complexes
- large complexes lodge in small vessels –> micro-thrombus
- neutrophil and complement recruitment can lead to vascular damage
type 4 hypersensitivity and tests
CD4 TH1 cell-mediated
mantoux test:
- tests immune memory
- small amount of antigen injected under skin
- if immune memory exists, immune response causes swelling, redness over next 24 hours
contact sensitivity
- small molecules diffusing into skin, attach to normal proteins to change shape
- dendritic cells in skin recognises new shape, then present T cells in node
- memory TH1 cells return from node and provoke inflammation
autoimmunity
organ-specific (usually type 2) - antibodies directed against particular tissue
systemic (usually type 3) - antibodies made against soluble antigens
development of autoimmunity
- natural IgM low-affinity autoantibodies are common (disease rare)
- anti-nuclear antibody (ANA) seen in systemic lupus erythematosis (SLE) - elderly
- anti-thyroid antibody seen in thyroid disease
mechanisms of tolerance in autoimmunity
- clonal deletion in bone marrow and thymus (central)
- clonal regulation (peripheral)
- suppression
- ignorance
molecular mimicry mechanism in autoimmunity
- in infection, peptides are presented to immune system. Peptides are similar to self-peptides and therefore response to bacteria attacks tissue and causes autoimmunity phenomenon
treatment of autoimmunity
- replacement of insulin, thyroxin, hormones, vitamin B12 etc
- immunosuppressive drugs
SLE = corticosteroids
rheumatoid arthritis = corticosteroids, NSAIDs, TNF
