HYPERSENSITIVITY Flashcards
what is hypersensitivity?
extreme physical sensitivity to particular substances or conditions
how is hypersensitivity classified?
type 1
type 2
type 3
type 4
what is type 1 hypersensitivity?
IgE-mediated, immediate type hypersensitivity
IgE-mediated degranulation of mast cells
what is type 2 hypersensitivity?
Cytotoxic reaction (complement lysis/ADCC)
what is type 3 hypersensitivity?
Immune complex reaction- (complement activation)
what is type 4 hypersensitivity?
T-cell mediated, delayed type hypersensitivity
give an example of type 1 hypersensitivity
allergic rhinitis, allergic asthma, urticaria
give an example of type 2 hypersensitivity
drug allergy
give an example of type 3 hypersensitivity
allergic vasculitis
give an example of type 4 hypersensitivity
allergic contact eczema
how long does type 1 hypersensitivity occur?
30 minutes
how long does type 2 hypersensitivity occur?
days
how long does type 3 hypersensitivity occur?
6 - 8 hours
how long does type 4 hypersensitivity occur?
48 - 72 hours
what is the organ manifestation of type 1 hypersensitivity?
skin/mucosa 45%
resp tract 25%
GI tract 20%
Cardiovascular system 10%
Why is allergy on the increase?
Hygiene hypothesis
Change to a clean environment in developed countries skews the immune response to a Th2 response
Th1/inflammatory immune defects are also on the rise (MS, IBD)
what are the causes of type 1 hypersensitivity?
genetics
environment
what causes Allergic rhinitis / asthma?
IgE mediated reaction to inhaled allergens
what does rhinitis affect?
upper airways
what are symptoms of rhinitis?
nasal itch
Sneeze
Rhinorhoea
nasal obstruction
what does asthma affect?
lower airways
what are symptoms of asthma?
bronchoconstriction, mucus hypersecretion
Wheeze
Breathlessness
Cough
what is a direct/rapid route in to blood stream?
sting
ingestion
what affects the outcome of a reaction?
route
dose
what is anaphylaxis?
Catastrophic lowering of blood pressure, airway constriction, swelling of epiglottis
how is anaphylaxis treated?
Epinephrine relaxes bronchiole smooth muscle
what do eosinophils do?
mainly kill parasites via reacting towards opsonised parasites
what causes degranulation?
large amounts of IL5 / IL3 in allergy cause
what causes atopic dermatitis?
Chronic inflammation (initiated via IgE), apopotosis of keratinocytes Leaky skin (filaggrin defect) binds keratin fibres together (leaky skin-allergens)
what is allergic contact dermatitis?
Important cause of occupational disease
Hapten
what type are Non IgE allergic diseases?
type 2
type 3
what are type 2 Non IgE allergic diseases?
IgG mediated destruction of blood cells/platelets-autoimmune hemolytic anemia.
Hemolytic disease of the newborn Thrombocytopenia. Change in signalling
what are type 3 Non IgE allergic diseases?
IgG immune complex deposition on vessel walls-
Arthus reaction
Serum Sickness, arthritis, vasculitis, nephritis, farmers’ lung
what are type 4 hypersensitivity reactions mediated by?
by antigen-specific effector T cells
what is Allergic contact dermatitis mediated by?
via lipid soluble urushiol oil haptens binding MHCI
what is coeliac disease?
small intestine is hypersensitive
what is tolerance?
describes immune cell non-reactivity to antigens
what are the different types of tolerance?
self
neonatal
acquired
what is self tolerance?
Tolerance to innate antigens
what is neonatal tolerance?
Antigens encountered within hours after birth are tolerated
what is acquired tolerance?
a
what does self tolerance and self recognition allow?
the maturation f both T and B cells
what does the breakdown of immunological tolerance lead to?
to autoimmune disease
what do T cells need to have to function correctly?
recognise self MHCs (self recognition)
they must display self tolerance
can B cells show self tolerance?
yes
what leads to autoimmune disease?
the loss of self tolerance
how do normally pre T cells in the thymus develop self recognition?
via positive selection
how is self tolerance acquired?
by negative selection
what do some of the T cells produced become?
fully mature immunocompetent cells
what can happen to self reactive T cells after they leave the thymus?
can be deleted if they contact an unrecognised self protein.
what is acquired tolerance?
describes a non reactivity to an antigen that should cause an immune response
what are the properties of allergens?
small proteins, soluble, long lasting in environment, mucosal exposure, often proteases
what can protease allergens activate?
PAR receptors
what do antibodies attach to in type 2?
to epitopes on self cells
what do antibodies in type 2 induce?
activation of compliment
what does activation of compliment in type 2 result in?
in vasodilatation and migration of phagocytic cells to the effected tissue
what does activation of compliment in type 2 promote?
activation of membrane attack complex
what do type 2 antibodies refer to?
antibodies that attacked self blood cells, used to describe antibodies that target other tissues
what is type 3 caused by?
by antigen antibody complexes
what are the antigens in type 3?
can be self antigens or non-self antigens such as bacteria
what do antigens in type 3 promote?
inflammatory response
what are the 2 types of type 3 hypersensitivity?
local
systemic
what is Local form Type 3 Hypersensitivity?
If an individual is immunised against an antigen, subcutaneous injection of a high conc of that antigen induces an inflammatory response peaking within 7 hours at that site
what is systemic form Type 3 Hypersensitivity?
Antigen complexes may form systemically - promoting system wide inflammatory responses
what is type 4 related to?
to Helper T cells interacting with activated cytotoxic T cells, NK cells or macrophages
what happens with type 4?
Response is delayed and cannot be transferred in the serum
