hypersensitivity and allergy Flashcards
what type pf reaction is happening in allergy
type 1 hypersensitivity reaction (T1 HSR)
the role of Th2 cells in promoting IgE production and eosinophil production
whether TH1 or 2 is dependent on environment during development from immature CD4+ lymphocyte.
activated TH2 lymphocytes produce IL-4, IL-13 and IL-5, which are responsible for IgE production by B cells, eosinophil activation and recruitment and mucus production
mast cells/ basophils
- type of WBC, once thought to be resident basophils, as their structure is so similar.
- both are granulocytes, with granules containing histamine and heparin.
- can bind to Fc portion of IgE
- when IgE binds to specific antigen= degranulation
- mast cells are particularly prominent in areas that would come into contact with the outside world, mouth nose etc.
mast cell activation
1) histamine released causes increased vascular permeability, smooth muscle contraction in lung, dilation in blood vessels
2) release cytokines IL-4, IL-13 [promotes Th2 differentiation, promotes IgE production]. TNF alpha- promotes tissue inflammation.
3) lipid mediators released: leukotrienes and Prostaglandins (PGD^2)- increases vascular permeability, causes smooth muscle contraction
clinical findings of T1HSR [antigenic activation of mast cells/ basophils]
- rhinitis and conjunctivitis
- asthma
- dermatitis
- hives
- vomiting and diarrhoea
- systemic anaphylaxis
- if laryngeal oedema is present; most likely to be associated with bee envenomation, penicillin and peanuts
sequence of events in T1HSR
1) allergens taken up by APC, macrophage or dendritic cell- leads to T cell activation
2) activated Th2 release IL-4 which induces naive cd4+ T cells to become Th2 cells that make more IL4, and IL5
3) IL-4 also causes isotype switching in plasma cells from IgM to IgE
4) IL-5 stimulates the production and activation of eosinophils
eosinophils
- leukocyte with a bilobed nucleus and red-staining cytoplasmic granules, often found at sites of parasitic infections
- production stimulated by IL-5 [lesser extent IL-3] and Granulocyte-Monocyte Colony Stimulating Factor (GM-CSF)
anaphylaxis
- a serious allergic reaction involving specific antigen, mast cells and basophils
- caused by food, venom and medications
- symptoms range from widespread urticaria to cardiovascular collapse, laryngeal oedema, airway obstruction and respiratory arrest
skin prick test
- most effective diagnostic test to detect IgE mediated type I allergic reactions.
-T1HSR are characterised by wheal and flare reactions to skin prick testing with common environmental antigens.
depends on:
1) intact immune system
2) presence pf IgE sensitised mass cells that release mediators when exposed to antigen.
3) skin will respond to histamine
atopy
term used to describe individuals who produce substantial amounts of IgE antigen following trivial exposure to everyday antigens. have an increased tendency to exhibit: - asthma -hay fever - eczema - urticaria - allergic rhinitis
early and late phase responses to TR1HSR
- immediate effects of allergen exposure is due to mast cell degranulation
- late phase response are mediated by TH2 cells recognising peptide epitopes, recruitment of eosinophils is often a prominent feature.
- chronic inflammation, difficult to control, is a feature of LPR. in asthma the LPR gives rise to prolonged wheezing, can be fatal.
- immediate sensitivity is usually responsive to antihistamines but the LPR is not, requiring immune modulators such as corticosteroids
type 2 (cytotoxic) hypersensitivity
- an antibody is directed against antigens on the cell membrane or in the extracellular matrix
- these are compliment-dependent reactions, and are either IgM or IgG mediated.
- IgM mediated generally end with lysis via membrane attack complex (C5-C9)
T2 HSR- antibody-dependent reaction IgM
example: anti-l cold antibodies (IgM) in immune haemolytic anaemia due to Mycoplasma pneumoniae, this is thought to be mediated through Antigen Minicry
T2 HSR- antibody-dependent reaction IgG
IgG attaches to the basement membrane/ matrix, activates the compliment system, C5a is produced (chemotactic factor), recruitment of neutrophils/monocytes recruited to activation site, enzymes, reactive oxygen species released leading to tissue is damaged.
- warm (IgG) immune haemolytic anaemia, in which RBCs coated by IgG and/or C3b are phagocytosed and destroyed by splenic macrophages
examples:
- goodpasture syndrome with IgG antibodies directed against pulmonary and glomerular capillary basement membranes.
- pernicious anaemia, in which IgG antibodies are directed against the proton pump in parietal cells
T3 HSR [immunocomplex]
first exposure of antigen leads to the synthesis of antibodies. second exposure leads to formation of antigen-antibody complexes that circulate the blood; they are usually deposited in vessel walls and extravascular sites e.g. joints, basement membrane of skin.
ICs are cleared from the blood by the reticuloendothelial system usually, but occasionally they persist and deposit in tissues. when deposited in tissue, they activate the compliment system and produce C5a, which attracts neutrophils and ultimately damage the tissue.
