Hypersensitivity Flashcards
what is hypersensitivity?
Hypersensitivity is a group of disorders where the normally beneficial components of the immune response act in an exaggerated or inappropriate fashion to environmental antigens which do not normally cause tissue damage. The exaggerated response directed at the antigen rather than the antigen itself is responsible for the tissue damage which results.
type 1 hypersensitivity =
allergy
immunoglobulin in type 1 hypersensitivity
IgE
phases of type 1 hypersensitivity
sensitisation
reaction
treatment of type 1 hypersensitivity
antihistamines
corticosteroids
adrenaline
allergen avoidance
atophy triad
eczema
asthma
hayfever
what is atopy?
genetic tendency to develop allergic diseases
describe atopic dermatitis
- Common in children
- Exposed and flexor surfaces
- Degranulation of basophils and mast cells in response to sensitised IgE
- “Leaky” skin allows more allergen in and water out
- Dry and itchy
- Itch leads to further infection/inflammation
- Itch worse at night
type 2 hypersensitivity
cytoxic
type 3 hypersensitivity
immune mediated
type 4 hypersensitivity
cell mediated
what is contact dermatitis
- Haptens cross stratum corneum
- Langerhans cells present to TH1 cells
- Langerhans cells are APC that site on cell surfaces
- TNF alfa and IL 1, 13 and 18
- LCs become differentiated Dendritic cells presenting allergenic epitope and multiply
- More aggressive response 2nd time
- Reexposure will not result in anaphylaxis
- Acquired immune response not innate
effector mechanism in type 1 hypersensitivity
mast cell activation
eosinophil activation
antibody in type 11 hypersensitivity
IgG
type 2 hypersensitivity effector mechanism
cell or matrix associated complement
FcR+ cells
cell surface receptor
Ab alters signalling
example of type 2 hypersensitivity
drugs
chronic urticaria
immunoglobulin in type 3 hypersensitivity
IgG
effector mechanism in type 3 hypersensitivity
complement
phagocytes
example of type 3 hypersensitivity
arthus reaction
type 4 hypersensitivity immune reactant
Th1 cells
effector mechanism in type 4 hypersensitivity
macrophage activation
example of type 4 hypersensitivity
contact dermatitis
tuberculin reaction
describe the production of IgE
• IgE produced by plasma B cells in lymph nodes, or
locally at site of inflammation
• IgE located mostly in tissue (hence low serum
concentration), bound to Mast Cell surface
through high affinity IgE receptor Fc!RI
• Certain antigens and routes of delivery appear to
favour IgE production. Transmucosal at low doses
is often a common route.
• CD4+ T cells of the Th2 phenotype that produce
IL4 cytokines favour IgE responses
• Th2 T cells also force B cells to switch the
isotype of the Ig they secrete from IgM to IgE
what do CD8 cytotoxic cells produce?
IFNgamma
TNF-a
what are the functions of the things CD8 cells produce?
target cell lysis
what do CD4 Th1 cells produce?
IFN-g
GM-CSF
TNF-a
what are the functions of the things Th1 cells produce?
macrophage activation
what do CD4 Th2 cells produce
IL4
IL5
what are the functions of the things Th2 cells produce?
b cell activation
features of allergic asthma
• Bronchial constriction • Increased secretion of fluid and mucus, trapping inhaled air • Chronic inflammation may ensue with continued presence of Th2 T cells, eosinophils, neutrophils. • Chronic asthma driven originally by specific allergen, but may then result in hyperreactive airways to other irritants such as cigarette smoke and other pollutants
describe the effects of ingested allergens
• Ingested allergens leads to two main symptoms
• Activation of GI Mast cells results in
transepithelial fluid loss and smooth muscle
contraction: diarrhea and vomiting
• If allergen enters bloodstream, generalised
disseminated rash, Urticaria, (hives).
• In severe cases of food allergy, eg nuts and
shellfish, life threatening generalised anaphylaxis
and cardiovascular collapse may occur
chemical mediators of allergic responses
• Mast cells granules contain a wide range of inflammatory mediators • Lipids • Toxic mediators • Cytokines • enzymes
lipids in allergic response
• Prostaglandins, increase vascular permeability, increase body temperature. Platelet activating Factor, increase adhesion between endothelium and neutrophils. Leukotrienes, attract and activate neutrophils, increase vasc permeability
toxic mediators in allergic response
Histamine, increase vascular permeability, and promotes movement of fluid from the vasculature by constricting vascular smooth muscle.
cytokines in allergic respoonse
• IL-4, IL-13; amplify Th2 response • IL-3, IL-5, GM-CSF; promote eosinophil activation and production • TNF-#; pro-inflammatory, activates endothelium Chemokine MIP-1#; attracts macrophages and neutrophils
enzymes in allergic response
- Tryptase
- Chymase
- Cathepsin G
- Carbopeptidase
- Remodel connective tissue matrix
describe type 2 hypersensitivity
- Type II reactions are the result of antibodies, usually IgG, binding to components of cell membranes or extracellular matrix.
- Can be self-components, or exogenous components
give examples of type 2 hypersensitivty endogenous
• Self: Goodpasture’s syndrome, antibodies bind to basement membrane collagen type IV, glomerulonephritis in kidney, pulmonary haemorrhage in lung
describe type 3 hypersensitivity
- As with Type II, Type III are caused by antibody, usually IgG, but also sometimes IgM.
- Type III antibodies directed to soluble antigens
- Formation of antibody-antigen complexes is a normal part of immune response.
- Usually cleared by reticuloendothelial system (RES): macrophages, neutrophils in liver spleen and bone marrow that ingest and degrade immune complexes
- Excess immune complex deposition in tissues leads to pathology
sites of immune complex deposition in type 3 hypersensitivity
- Sites of immune complex (IC) deposition are not necessarily the sites from where the antigen is derived.
- Glomeruli : kidney, filtration process makes it very common site in IC deposition, damage driven by complement activation
- Blood vessel walls: IC accumulate on veins and arteries, causes vasculitis, often seen as skin lesions if close to surface
- Synovial membranes: Rheumatoid arthritis, in which the IgG of the immune complexes can become an antigen itself, and IgM Rheumatoid Factor antibodies develop.
- Skin: common site for IC deposition, causes rashes.
- Systemic sites: in case of Systemic Lupus Erythematosus (SLE) IC deposits in kidney, joints, skin, vasculature, muscle and other organs.
describe type 4 hypersensitivity
- Unlike I, II & III, Type IV reactions are entirely cell-mediated
- Complement does not play a role in Type IV.
- Most Type IV reactions are caused by CD4+ delayed type hypersensitivity (DTH) reactions. ‘Delayed’ refers to reaction occurring 2 to 4 days after antigen exposure
- Macrophages that cause damage are not specific, harm infected and non-infected tissue
