B & I - Allergy and Hypersensitivity Flashcards
What are the four classifications of hypersensitivity
type I, type II, type III, type IV
what is Type I, what is it mediated by and speed of response?
atopic allergy
IgE mediated
Immediate
what is Type II mediated by and speed of response?
Complement mediated
medium
what is Type III, what is it mediated by and speed of response?
Serum sickness
Immune complexes
Medium
what is type IV and response rate?
delayed type (DTH) slow response
what is the most common form of immune disorder
allergy
what is one of the most serious consequences of allergy
anaphylaxis or anaphylactic shock
what happens in anaphylaxis or anaphylactic shock
oedema and swelling occurs at multiple anatomical sites that are distant from the original site of allergen challenge.
what does anaphylaxis most commonly affect
lips, eyes and throat swell, can extend to airways and gut
treatment for anaphylaxis
immediate injection of epinephrine (adrenalin)
Mast cells in skin possess a _______ for IgE called the _______
receptor
FceR (Fc epsilon receptor)
FceR has an exceptionally _______ ______ toward ____:______ _____
has an exceptionally high affinity toward IgE:antigen complexes
what happens when IgE binds large complex antigens (like pollen)
it triggers local mast cells to rupture and empty their granules
what is released to cause allergic reaction
powerful inflammatory mediators
what does the release of powerful inflammatory mediators, which creates allergic reaction, also create
immediate type (type I) hypersensitivity
what does the body do when first exposed to an allergen
the body mounts an inappropriate B cell response that produces IgE
when next challenged, the allergen cross-links ___-__________ ___ ______ ____ _____ which causes _______________ releasing histamine and other compounds
pre-sensitized IgE coated mast cells
degranulation
chemicals released are highly toxic which causes what to happen ?
local inflammatory response, smooth muscle, vascular and blood vessel constriction
what is the most important compound released
histamine
what does histamine most commonly cause
tissue oedema or swelling
what doe anti-histamines do
block action of histamine with its receptor
what are the two most important components that type I atopic allergy depends on
mast cells and Fc receptor
what drives the inapporpriate response of B cells making IgE instead of IgG
Th1 or Th2
summarise how inflammatory response occurs
after triggered to make IgE instead of IgG you end up with memory cells that reside in lymph nodes which are IgE producing instead of IgG producing and generate plasma cells which produce more IgE - these bind onto the sensitised mast cells waiting for allergen again. When it sees the allergen again degranulation is triggered which releases small molecules that cause inflammatory response
what does Type II hypersensitivity involve
FcR, complement and neutrophils
when does RhD occur
when there is an antibody present in the newborn baby that reacts to the protein on the surface of their red blood cells - the basement membrane of blood cells will attract neutrophils and complement is deposited, neutrophils become frustrated cause lysis of red blood cells
what does RhD cause
haemolytic anemia which is a condition called rhesus
in summary, what is acute hemolytic anemia caused by
a blood group antigen RhD on the surface of red blood cells
what causes lysis of newborn RBCs
maternal antibodies developed to fetal RhD
what are the three steps or normal phagocytosis, what are the three steps of auto-phagocytosis (due to anti-RhD)
phagocytosis:
1) neutrophil adherence
2) phagocytosis
3) lysosome fusion
auto phagocytosis:
1) neutrophil adherence
2) ‘frustrated phagocytosis’
3) extracellular enzyme release
rhesus baby will die unless
it gets a blood transplant
to have a rhesus baby the mother needs to be?
rhesus negative, meaning her blood cells don’t have the rhesus antigen
to have a rhesus baby the father needs to be?
rhesus positive (and genes dominate)
it is not as bad for first born, as the placenta hasn’t leaked fetal cells into mothers blood stream, but why is it bad for second born
the mother will have those B cells producing that anti-RhD in her blood (the one that causes frustrated phagocytosis) and thus when next child is born, the anti-RhD IgG passes across placenta into baby and at birth the baby succumbs to haemophiliac anemia as the antibody triggers type II hypersensitivity
what does treatment or allergy by densistisation consist of
making high affinity IgG that competes with IgE
scratch test identifies
allergens
by giving small doses of allergen, you are…
slowly driving B cells that are producing IgE to produce IgG for that same allergen - IgG binds to allergen before IgE can (due to higher affinity)
what did kohler do to make monoclonal antibodies
took out spleen of mice and immortalized each B cell and then cloned them out and stored them and grew them in large amounts so that he could take the genes out and sequence them and look at their gene sequences etc to compare w/ other B cells to see if there were mutations
through this process, what did kohler realise
this was a technique to produce new types of reagents - very specific antibodies so serum in blood has thousands of antibodies with all different specificities
with monoclonal however, they are single _______ and single ________ ________ so they can be _______ _______ and used for all sorts of things
specificity
binding affinity
highly specific
this was done in mice but now it is done in bacteria and humans… how are these monoclonal antibodies made (long version) (9 steps)
1) inject a mouse with an antigen
2) boost after 2-3 weeks to ensure strong IgG response
3) take out spleen which is full of B lymphocytes that produce the antibody
4) mush up the splenocytes and mix them with the mouse myeloma line
5) mix together in test tube with chemical PEG (polyethylene glycol) which fuses cell membranes together
6) 1:1 ratio fusion between 1 B cell and 1 myeloma cell produces hybridoma which produces antibody that B cells are producing
7) do screening by adding selective chemical so myeloma line cells don’t grow out
8) after about 2 weeks you will have hybridomas growing out of single cells - each of these clones produce a monoclonal antibody
9) take monoclonal and put in microtiter plate to see if you have antibody + extract
how do you make monoclonal antibodies (short version)
1) immunize
2) boost
3) remove spleen
4) splenocytes + mouse myeloma line
5) splenocytes + mouse myeloma line into test tube with PEG
6) hybridoma formation
7) elisa screen
8) A mAb plate
pros of mab as therapeutic agents
- highly specific for the intended target so no “off target” effects
- can be tailor-made with just the right affinity
- humanised so they stay in the blood stream for months
- no adverse reactions or toxicity to the antibody
- can be modified to be “bi- specific” for even greater potency
cons of mab as therapuetic agents
- expensive to develop and make commercially
- side effects of their function can be serious
MAIN POINT (that might not be covered above): Type I hypersensitivity is ___________ and is mediated by _____ with a high affinity ___ __________.
immediate
IgE
Fc receptor
MAIN POINT (that might not be covered above): anaphylaxis is a serious complication when ?
mast cell activation occurs throughout the body
MAIN POINT (that might not be covered above): rhesus haemolytic anaemia is an example of type ___ hypersensitivity cause by…
II
caused by maternal antibodies the RhD antigen expressed on foetal red blood cells
MAIN POINT (that might not be covered above): what is used to explain why allergies and autoimmune diseases are more prevalent in industrialised countries
Th1 and Th2 paradigm
MAIN POINT (that might not be covered above): what does the hygiene hypothesis say
that children are not challenged appropriately with old germs and develop an imbalanced Th2 mediated antibody response with fewer regulatory T cells
MAIN POINT (that might not be covered above): what is the hygiene hypothesis partly proven by
the use of parasitic worm to treat chronic autoimmune diseases of the gut
MAIN POINT (that might not be covered above): what are monoclonal antibodies
single specificity antibodies that are now used as powerful new drugs to treat a range of conditions
