Hypersensitivity Flashcards
Type I
Immediate/anaphylatic hypersensitivity
An allergic reaction provoked by re exposure to allergens
Asthma,allergic rhinitis,atopic dermatitis
A,e antibodies against common antigens however non allergic individuals only make IgE
Multivalent antigen
An antigen with multiple binding sites for antibodies
Allergens
- Food
- Plants
- Animal dander
- Drugs
- Insect products
What type of antibodies are allergens mediated by
IgE antibodies
Non allergic people make this in response to parasitic infection
Which 3 factors influence the initial sensitisation of the immune response to allergens?
Genetics
Age
Environment
Process of type I hypersensitivity
Generation of CD4 T cells and B cell helper follicular CD4 T cells which produce the type 2 cytokines IL-4 and IL-13
When these act on B cells they can promote B cell to switch to producing antigen specific IgE
IgE bind to IgE receptor on mast cells & basophils (innate immune cells)
Allergen binds to IgE molecules on mast cells, crosslinking of IgE, which triggers degranulation of the mast cell (or basophil)
Release of histamine (preformed chemical mediations), cytokines that can recruit other cells and promote further Th2 differentiation, prostaglandins and highly active smooth muscle contracting molecules like leukotrienes
3 phases of type I hypersensitivity
Early phase-bioactive small molecules made by mast cells occurs within minutes of allergen exposure
Later response-seen within a few hours early recruitment of neutrophils
Late response-peaks 3-4 days after where high frequencies of eosinophil are recruited and Th2 cells are present
Type II
antibody mediated cytotoxic hypersensitivity
Destruction of IgG or IgM antibodies bound to antigens present of surface of cells
Examples of type II hypersensitivity
Mismatched blood transfusion
Immune thrombocytopenia (antibodies develop against platelet surface proteins)
Graves’ disease (thyroid stimulating antibodies develop that bind thyrotropin receptors causing secretion of thyroid hormones)
Haemolytic disease of fetus
What 2 ways of getting type 2 hypersensitivity are there?
Exposure to foreign antigen (e.g. some drugs can bind to surface of blood cells or non-self antigens blood transfusions)
Aberrant response to a self-antigen resulting in IgGs or IgMs that recognise cell surface structures
What are 3 mechanisms through which IgG and IgM antibodies can cause disease?
- Anti-receptor activity- blocking or activating its function
- Antibody dependent cell-mediated cytotoxicity (ADCC)- where immune cells destroy target cells
-classical activation of complement
How does type 2 hypersensitivity cause tissue damage?
- Local or systemic inflammation
- Cell depletion leading to loss of function
- Imbalance in organ function
Type III
Immune complex driven
Accumulation of immune complexes
When immune complexes can’t be cleared efficiently e.g. if they are result of antibodies reacting against self-antigens like nuclear DNA, the complexes are deposited in blood vessel walls and tissues and promote inflammation and tissue damage
Immune complexes
Non-cell bound antigen-antibody complexes which are normally cleared through activity of immune system
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What issues can type III hypersensitivity lead to?
- Fever, rashes, joint pain, protein in urine
- Vasculitis if deposited in blood vesslels
- Glomerulonephritis if in kidneys
- Arthritis if in joints
What happens in systemic lupus erythematosus (SLE)?
Patients develop IgGs against DNA or proteins present in nucleus of cells (nucleoproteins) which form persistent immune-complex deposits and a variety of pathologies
Why would rapid inflammation occur if a person were to be bitten by a venomous snake the second time around even if they were given anti-serum?
The first time a person is bitten by a snake, anti-serum would be given to the victim to neutralise the venom
However these are foreign bodies and the body will react against them to produce antibodies that recognise anti-venom antibodies
Process takes several weeks so by time of first bite, the anti-serum and venom would be cleared so there is no reaction
But by second bite, antibodies recognise anti-serum and drive rapid inflammation
Why do immune complexes not initiate complement cascade?
The classical pathway activation results in formation of membrane attack complex which occurs in cell wall
Whereas immune complexes are free-floating
Type IV
T cell mediated hypersensitivity/delayed type
Caused by T cells
Sensitization phase where antigen is presented to naive T cells resulting in antigen specific memory cells
- When is memory T cell response shown and why?
2-3 days after inflammation because the memory T cell response is slightly slower than antibody mediated memory (because of recruitment and expansion)
Common type of IV
Contact dermatitis caused by exposure to poison ivy where a small molecule urushiol acts as a hapten (and binds to proteins in skin), driving T helper 1 response but rarely results in antibodies production as it’s so small
What happens on re exposure of ivy
The memory cells produces cytokines like IFN-gamma which promote the pro-inflammatory activation of macrophages resulting in swelling and oedema and formation of blister like lesions
What other antigens can cause type IV hypersensitivity?
Nickel salts or hair dyes that can also drive Th1 based inflammation
Intracellular pathogens like measles virus and tuberculosis bacteria
Give an example where T helper 2 cells cause type IV hypersensitivity?
In asthma, allergens cause overreaction of Th2 cells which produce soluble mediators that promote bronchoconstriction
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