Immune Attack on Tissues: Hypersensitivity and Allergy Flashcards
What are the potential results from detection of a foreign body?
- foreign material damaged -> immunity
2. self material damaged -> allergy/hypersensitivity
What is the potential result from detection of self as foreign?
self material damaged -> autoimmunity/hypersensitivity
What are the types of hypersensitivity?
- allergy (IgE)
- antibody sensitivity (IgM, IgG)
- immune complex sensitivity
- cell mediated sensitivity
2-4 allergy and autoimmunity
What is hypersensitivity?
exaggerated activated immune response which causes tissue damage
Type 1 hypersensitivity key components
ie. atopic allergy
mast cells - generate inflammatory response
allergens - harmless unless IgE antibodies recognise them
IgE
Examples of type 1 hypersensitivity
hayfever, allergic asthma, acute urticaria, eczma, food allergies, anaphylaxis
What happens in type 1 hypersensitivity?
IgE binds to IgE receptor on mast cell
allergen binds to at least 2 IgE antibodies (mast cell crosslinks)
mast cell activates and degranulates
physiological consequences: mediators released
in lungs: smooth muscle contraction
systemically/blood: increased vascular permeability and vasodilation
What is needed before type 1 hypersensitivity occurs?
priming of immune response, first exposure to allergen
allergic sensitisation
What occurs in the first exposure to an allergen?
antigen is processed and presented on APC in MHC class 2 interacts with CD4 helper T cell (TH2) cytokines produced (IL 4, 5, 10) - influence other cells in immune system IL 4 and 13 cause class switching of B cell (IgM -> IgE antibodies) IgE antibodies sit on mast cells
What type of T helper cell promotes type 1 hypersensitivity?
TH2
How do TH2 cells promote type 1 hypersensitivity
produces cytokines: IL 4, 5, 10
10 - inhibits TH1 actions, co-stimulate mast cell growth
4 - class-switching B cells (IgM to IgE)
5 - stimulate eosinophils which have receptors for IgE, important in chronic response of type 1 response
What does it mean if someone produces high levels of IgE?
atopic
genetically predisposed to produce more
more likely to have atopic eczema
How is the structure of IgE differece to IgG and IgA?
IgE has an extra domain in the heavy chain whcih allows movement
Why do the majority of people have low levels of IgE?
very short half life of IgE
Why does IgE have a very short half life?
endocytosis of plasma - engulfment of plasma
IgG are protected when pH changes by binding to receptors
IgE engulfed and broken down
Inflammatory mediators released by mast cell
preformed granule mediators: histamine, heparin, tryptase - immediate
newly generated: arachidonic acid - LKT, PGDs, cytokines - longer term
Give the common allergens for systemic anaphylaxis
drugs, serum, venoms, peanuts
Give the route of entry for systemic anaphylaxis
intravenous either directly or following oral absorption into the blood
Give the response due to systemic anaphylaxis
edema increased vascular permeability tracheal occlusion circulatory collapse death
Give the common allergens for acute urticaria
insect bites
allergy testing
Give the route of entry for acute urticaria
subcutaneous
Give the response due to acute urticaria
local increase in blood flow and vascular permeability
Give the common allergens for allergic rhinitis
pollens (ragweed, birch)
dust-mite faeces
Give the response due to allergic rhinitis
edema and irritation of nasal mucosa
not far
Give the response due to food allergy
vomiting diarrhea pruritis urticaria anaphylaxis
Why are there different responses to allergens?
depends on the route of entry
Give the common allergens for asthma
danders (cat)
pollens
dust-mite faeces
Give the response due to asthma
bronchial contriction
increased mucus production
airway inflammation
further than hayfever - lungs
Give a test to see what someone is allergic to
Skin prick test
give 0.02 ml of allergen extrat interdermally into tissue
if allergic: immediate immune response (15-60 mins) swelling and redness
later: swelling increases due to further cellular recruitment
If urticaria remains after allergen is removed what does this mean?
autoimmune and not allergy
Examples of type 2 hypersensitivity allergy response
allergic hemolytic anemia
blood transfusion reactions
haemolytic disease of the newborn
What happens in type 2 hypersensitivity allergy response?
IgG, IgA, IgM bind to neutrophils which cause tissue damage
Describe what occurs in rhesus haemolytic disease of the newborn
RhD- mother
RhD+ antigen expressed on RBCs of fetus of 1st pregnancy
some left behind, mother produces antibody response against
subsequent pregnancy: anti Rh antibody crosses placenta and attacks RBCs of fetus (IgG can cross placenta)
How is type 2 hypersensitivity exemplified by haemolytic anaemia?
autoantibodies produced against self-antigens on the surface of RBCs
bind and complement activated
RBC lysed/taken up by phagocytosis
Examples of type 3 hypersensitivity response
dermatitis
herpetiformis
allergic alveolitis
What happens in type 3 hypersensitivity response
IgG IgA and IgM
immune complex sensitivity - immune system overrun by large number of complexes and not cleared
Deposited in tissue where damage occurs
Allergic alveolitis
exposure to allergen (fungal spores inhalation)
immune response
immune complexes not cleared and deposited in lungs
damage to lungs and difficulty breathing
no wheezing - SoB (inability for gas exchange)
Examples of type 4 hypersensitivity
contact dermatitis
acute graft rejection
(TB, leprosy)
What is type 4 hypersensitivity different to the others?
driven by cells - cell-mediated
What happens in type 4 hypersensitivity response?
APC presents to T helper cell, helping T killer cell and macrophages
T helper cell continuously produces cytokines, chronically stimulating macrophages
fusion of macrohpages into epitheloid cells
these fuse to multinucleated giant cells which cause the tissue damage
Contact dermatitis
metal (nickel, chromate) or plant products (poison ivy)
Pulmonary tuberculosis
type 4
lungs - activated macriphages in lungs trying to clear infection chronically stimulated
extensive fibrosis, lesions, difficulty breathing
Leprosy
type of leprosy depends on type of immune response
cell-mediated (type 4) - tuberculus leprosy
