B & I - Allergy and Hypersensitivity

Question 1

What are the four classifications of hypersensitivity

Answer 1

type I, type II, type III, type IV

Question 2

what is Type I, what is it mediated by and speed of response?

Answer 2

atopic allergy
IgE mediated
Immediate

Question 3

what is Type II mediated by and speed of response?

Answer 3

Complement mediated

medium

Question 4

what is Type III, what is it mediated by and speed of response?

Answer 4

Serum sickness
Immune complexes
Medium

Question 5

what is type IV and response rate?

Answer 5

delayed type (DTH)
slow response

Question 6

what is the most common form of immune disorder

Answer 6

allergy

Question 7

what is one of the most serious consequences of allergy

Answer 7

anaphylaxis or anaphylactic shock

Question 8

what happens in anaphylaxis or anaphylactic shock

Answer 8

oedema and swelling occurs at multiple anatomical sites that are distant from the original site of allergen challenge.

Question 9

what does anaphylaxis most commonly affect

Answer 9

lips, eyes and throat swell, can extend to airways and gut

Question 10

treatment for anaphylaxis

Answer 10

immediate injection of epinephrine (adrenalin)

Question 11

Mast cells in skin possess a _______ for IgE called the _______

Answer 11

receptor

FceR (Fc epsilon receptor)

Question 12

FceR has an exceptionally _______ ______ toward ____:______ _____

Answer 12

has an exceptionally high affinity toward IgE:antigen complexes

Question 13

what happens when IgE binds large complex antigens (like pollen)

Answer 13

it triggers local mast cells to rupture and empty their granules

Question 14

what is released to cause allergic reaction

Answer 14

powerful inflammatory mediators

Question 15

what does the release of powerful inflammatory mediators, which creates allergic reaction, also create

Answer 15

immediate type (type I) hypersensitivity

Question 16

what does the body do when first exposed to an allergen

Answer 16

the body mounts an inappropriate B cell response that produces IgE

Question 17

when next challenged, the allergen cross-links ___-__________ ___ ______ ____ _____ which causes _______________ releasing histamine and other compounds

Answer 17

pre-sensitized IgE coated mast cells

degranulation

Question 18

chemicals released are highly toxic which causes what to happen ?

Answer 18

local inflammatory response, smooth muscle, vascular and blood vessel constriction

Question 19

what is the most important compound released

Answer 19

histamine

Question 20

what does histamine most commonly cause

Answer 20

tissue oedema or swelling

Question 21

what doe anti-histamines do

Answer 21

block action of histamine with its receptor

Question 22

what are the two most important components that type I atopic allergy depends on

Answer 22

mast cells and Fc receptor

Question 23

what drives the inapporpriate response of B cells making IgE instead of IgG

Answer 23

Th1 or Th2

Question 24

summarise how inflammatory response occurs

Answer 24

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

Question 25

what does Type II hypersensitivity involve

Answer 25

FcR, complement and neutrophils

Question 26

when does RhD occur

Answer 26

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

Question 27

what does RhD cause

Answer 27

haemolytic anemia which is a condition called rhesus

Question 28

in summary, what is acute hemolytic anemia caused by

Answer 28

a blood group antigen RhD on the surface of red blood cells

Question 29

what causes lysis of newborn RBCs

Answer 29

maternal antibodies developed to fetal RhD

Question 30

what are the three steps or normal phagocytosis, what are the three steps of auto-phagocytosis (due to anti-RhD)

Answer 30

phagocytosis: 1) neutrophil adherence 2) phagocytosis 3) lysosome fusion auto phagocytosis: 1) neutrophil adherence 2) 'frustrated phagocytosis' 3) extracellular enzyme release

Question 31

rhesus baby will die unless

Answer 31

it gets a blood transplant

Question 32

to have a rhesus baby the mother needs to be?

Answer 32

rhesus negative, meaning her blood cells don't have the rhesus antigen

Question 33

to have a rhesus baby the father needs to be?

Answer 33

rhesus positive (and genes dominate)

Question 34

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

Answer 34

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

Question 35

what does treatment or allergy by densistisation consist of

Answer 35

making high affinity IgG that competes with IgE

Question 36

scratch test identifies

Answer 36

allergens

Question 37

by giving small doses of allergen, you are...

Answer 37

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)

Question 38

what did kohler do to make monoclonal antibodies

Answer 38

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

Question 39

through this process, what did kohler realise

Answer 39

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

Question 40

with monoclonal however, they are single _______ and single ________ ________ so they can be _______ _______ and used for all sorts of things

Answer 40

specificity binding affinity highly specific

Question 41

this was done in mice but now it is done in bacteria and humans... how are these monoclonal antibodies made (long version) (9 steps)

Answer 41

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

Question 42

how do you make monoclonal antibodies (short version)

Answer 42

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

Question 43

pros of mab as therapeutic agents

Answer 43

- 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

Question 44

cons of mab as therapuetic agents

Answer 44

- expensive to develop and make commercially | - side effects of their function can be serious

Question 45

MAIN POINT (that might not be covered above): Type I hypersensitivity is ___________ and is mediated by _____ with a high affinity ___ __________.

Answer 45

immediate IgE Fc receptor

Question 46

MAIN POINT (that might not be covered above): anaphylaxis is a serious complication when ?

Answer 46

mast cell activation occurs throughout the body

Question 47

MAIN POINT (that might not be covered above): rhesus haemolytic anaemia is an example of type ___ hypersensitivity cause by...

Answer 47

II caused by maternal antibodies the RhD antigen expressed on foetal red blood cells

Question 48

MAIN POINT (that might not be covered above): what is used to explain why allergies and autoimmune diseases are more prevalent in industrialised countries

Answer 48

Th1 and Th2 paradigm

Question 49

MAIN POINT (that might not be covered above): what does the hygiene hypothesis say

Answer 49

that children are not challenged appropriately with old germs and develop an imbalanced Th2 mediated antibody response with fewer regulatory T cells

Question 50

MAIN POINT (that might not be covered above): what is the hygiene hypothesis partly proven by

Answer 50

the use of parasitic worm to treat chronic autoimmune diseases of the gut

Question 51

MAIN POINT (that might not be covered above): what are monoclonal antibodies

Answer 51

single specificity antibodies that are now used as powerful new drugs to treat a range of conditions