(04) Allergy and Hypersensitivity Flashcards
Examples of type I allergies
asthma
allergic rhinitis (seasonal hay fever)
dermatitis
insect allergies etc.
what is anaphylaxis
a severe form of allergic reaction
when hypersensitivity spreads from site of atopy and becomes systemic
can be life threatening
(can be treated with adrenalin via epipen)
Name the four types of hypersensitivity and briefly describe them (mediated/speed)
Type I = atopic allergy, IgE mediated, immediate
Type II = complement mediated - medium
Type III = serum sickness, resulting from the production of immune complexes that create unusual response, usually medium-slow
Type IV = delayed type (DTH). also involves adaptive immune response
example of Type IV hypersensitivity
tuberculosis
DTH response measured by injecting a small amount of tuberculin material into the skin and wait a few days - to determine exposure to tuberculosis (ring test)
what immunoglobin is responsible for Type I allergy?
IgE
regulates response against large complex antigens (eg. pollen)
process triggering Type I allergy
the Mast cell is most responsible for allergic response
it has been primed in early life against allergens (IgE would have developed against them)
Fc(epsilon) Receptor on mast cell has very high affinity for the IgE molecule
IgE binds, cross-linking of receptors causes RAPID ACTIVATION of mast cell, releases granules causing inflammatory response
where are mast cells found?
unlike other cells, not found in lymph tissue or blood
sits in the TISSUE, in areas facing the environment (particularly epithelium in throat/gut)
what granules are released by mast cells?
Histamine
Leuoketrienes
Prostaglandins
Free radicals
Substance P
Mechanism for Type I allergic response
early life: allergen stimulates naive B cells with IgM to activate. CD4 helper T cell recognises complex presented in MHC Class II
CD4+ T cell, producing IL-4, causes B cells to rearranges antibodies with IgE domains (instead of IgG), becomes an IgE producing B cell
–> memory cells that produce IgE instead of IgG
–> sensitised mast cell w/ Fc(epsilon)R (to bind to Fc on IgE)
Describe Type II hypersensitivity in one sentence
antibody/complement-mediated hypersensitivity, occurs when the immune system mistakenly targets and attacks healthy cells/tissues in the body
also known as the “frustrated phagocyte”
explain the mechanism involved in Type II hypersensitivity
normal phagocytosis involves an Fc receptor and C3 receptor (triggers complement)
BUT receptors can also be triggered by things OTHER than bacteria, such as when a self-antigen is incorrectly recognised as foreign (expresses antigen that has not been seen before)
Stimulates aberrant antibody, anti-RhD
what is the rhesus condition
where antibodies in a pregnant woman’s blood destroy her baby’s blood cells
phagocytes recognise the RBC and initiate the frustrated phagocyte effect
–> acute haemolytic anaemia
mechanism for rhesus anaemia
mother is RhD- (does not have the antigen), fetus is RhD+ (picked up from father, it’s a dominant gene)
some makes its way into mother’s blood, stimulates antibody response
mother makes Anti-RhD IgG, transfers across placenta
how is rhesus anaemia treated/prevented?
give mother a dose of Anti-Rh
passive immunity - destroys possible foetus RhD+ cells that might exist in the mother’s blood so she never produces this antibody
what is a treatment for allergy
desensitisation
how does desensitisation work?
works well when young
inject with very low doses of allergen weekly for 12-24 weeks
generates IgG instead of IgE, competes with IgE / blocks
works for about 50% of patients
what are monoclonal antibodies?
identical copies of one type of antibody (the proteins produced by lymphocytes)
how are monoclonal antibodies made?
immunise: antiGEN injected into mouse, which produces antibodies specific to the antigen
boost
spleen cells (produce lymphocytes) are removed from the mouse
fused w/ mouse myeloma cells (immortalised) using PEG –> hybridoma cells which divide infinitely, producing millions of monoclonal antibodies specific to the original antigen
plate cells out on ELISA screen and test for reactivity
give one example of where monoclonal antibodies are used as a treatment
Infliximab: anti-TNF (Tumour Necrosis Factor) treatment, blocks the effect of a very potent cytokine (TNF)
treatment for Rheumatoid arthritis
Pros and cons of using monoclonal antibodies as therapeutic agents
pros: highly specific, tailor-made affinity, stay in blood stream for months
cons: expensive to commercially produce, possibly serious side effects