Immune Attack on Tissues: Hypersensitivity and Allergy

Question 1

What are the potential results from detection of a foreign body?

Answer 1

1. foreign material damaged -> immunity

2. self material damaged -> allergy/hypersensitivity

Question 2

What is the potential result from detection of self as foreign?

Answer 2

self material damaged -> autoimmunity/hypersensitivity

Question 3

What are the types of hypersensitivity?

Answer 3

1. allergy (IgE)
2. antibody sensitivity (IgM, IgG)
3. immune complex sensitivity
4. cell mediated sensitivity
   2-4 allergy and autoimmunity

Question 4

What is hypersensitivity?

Answer 4

exaggerated activated immune response which causes tissue damage

Question 5

Type 1 hypersensitivity key components

Answer 5

ie. atopic allergy
mast cells - generate inflammatory response
allergens - harmless unless IgE antibodies recognise them
IgE

Question 6

Examples of type 1 hypersensitivity

Answer 6

hayfever, allergic asthma, acute urticaria, eczma, food allergies, anaphylaxis

Question 7

What happens in type 1 hypersensitivity?

Answer 7

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

Question 8

What is needed before type 1 hypersensitivity occurs?

Answer 8

priming of immune response, first exposure to allergen

allergic sensitisation

Question 9

What occurs in the first exposure to an allergen?

Answer 9

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

Question 10

What type of T helper cell promotes type 1 hypersensitivity?

Answer 10

TH2

Question 11

How do TH2 cells promote type 1 hypersensitivity

Answer 11

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

Question 12

What does it mean if someone produces high levels of IgE?

Answer 12

atopic
genetically predisposed to produce more
more likely to have atopic eczema

Question 13

How is the structure of IgE differece to IgG and IgA?

Answer 13

IgE has an extra domain in the heavy chain whcih allows movement

Question 14

Why do the majority of people have low levels of IgE?

Answer 14

very short half life of IgE

Question 15

Why does IgE have a very short half life?

Answer 15

endocytosis of plasma - engulfment of plasma
IgG are protected when pH changes by binding to receptors
IgE engulfed and broken down

Question 16

Inflammatory mediators released by mast cell

Answer 16

preformed granule mediators: histamine, heparin, tryptase - immediate
newly generated: arachidonic acid - LKT, PGDs, cytokines - longer term

Question 17

Give the common allergens for systemic anaphylaxis

Answer 17

drugs, serum, venoms, peanuts

Question 18

Give the route of entry for systemic anaphylaxis

Answer 18

intravenous either directly or following oral absorption into the blood

Question 19

Give the response due to systemic anaphylaxis

Answer 19

edema 
increased vascular permeability
tracheal occlusion
circulatory collapse
death

Question 20

Give the common allergens for acute urticaria

Answer 20

insect bites

allergy testing

Question 21

Give the route of entry for acute urticaria

Answer 21

subcutaneous

Question 22

Give the response due to acute urticaria

Answer 22

local increase in blood flow and vascular permeability

Question 23

Give the common allergens for allergic rhinitis

Answer 23

pollens (ragweed, birch)

dust-mite faeces

Question 24

Give the response due to allergic rhinitis

Answer 24

edema and irritation of nasal mucosa

not far

Question 25

Give the response due to food allergy

Answer 25

``` vomiting diarrhea pruritis urticaria anaphylaxis ```

Question 26

Why are there different responses to allergens?

Answer 26

depends on the route of entry

Question 27

Give the common allergens for asthma

Answer 27

danders (cat) pollens dust-mite faeces

Question 28

Give the response due to asthma

Answer 28

bronchial contriction increased mucus production airway inflammation further than hayfever - lungs

Question 29

Give a test to see what someone is allergic to

Answer 29

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

Question 30

If urticaria remains after allergen is removed what does this mean?

Answer 30

autoimmune and not allergy

Question 31

Examples of type 2 hypersensitivity allergy response

Answer 31

allergic hemolytic anemia blood transfusion reactions haemolytic disease of the newborn

Question 32

What happens in type 2 hypersensitivity allergy response?

Answer 32

IgG, IgA, IgM bind to neutrophils which cause tissue damage

Question 33

Describe what occurs in rhesus haemolytic disease of the newborn

Answer 33

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)

Question 34

How is type 2 hypersensitivity exemplified by haemolytic anaemia?

Answer 34

autoantibodies produced against self-antigens on the surface of RBCs bind and complement activated RBC lysed/taken up by phagocytosis

Question 35

Examples of type 3 hypersensitivity response

Answer 35

dermatitis herpetiformis allergic alveolitis

Question 36

What happens in type 3 hypersensitivity response

Answer 36

IgG IgA and IgM immune complex sensitivity - immune system overrun by large number of complexes and not cleared Deposited in tissue where damage occurs

Question 37

Allergic alveolitis

Answer 37

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)

Question 38

Examples of type 4 hypersensitivity

Answer 38

contact dermatitis acute graft rejection (TB, leprosy)

Question 39

What is type 4 hypersensitivity different to the others?

Answer 39

driven by cells - cell-mediated

Question 40

What happens in type 4 hypersensitivity response?

Answer 40

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

Question 41

Contact dermatitis

Answer 41

metal (nickel, chromate) or plant products (poison ivy)

Question 42

Pulmonary tuberculosis

Answer 42

type 4 lungs - activated macriphages in lungs trying to clear infection chronically stimulated extensive fibrosis, lesions, difficulty breathing

Question 43

Leprosy

Answer 43

type of leprosy depends on type of immune response | cell-mediated (type 4) - tuberculus leprosy