Lecture 20 - Hypersensitivity

Question 1

true or false, hypersensitivity diseases are caused by the immune response

Answer 1

true, and directly damages the host

Question 2

what are the types of hypersensitivity?

Answer 2

Type I -> IgE mediated
Type II -> IgG -> antibody mediated
Type III -> IgG -> immune complex mediated
Type IV -> T cell mediated -> Delayed type hypersensitivity

Question 3

what type of hypersensitivity reaction causes allergies?

Answer 3

Type I IgE mediated

Question 4

Atopic patients are who?

Answer 4

people who suffer with allergies

Question 5

describe the IgE concentration in blood of normal people vs atopic people

Answer 5

much higher in people with allergies

Question 6

why do we even need IgE

Answer 6

to deal with parasitic infections e.g worms

Question 7

how are large parasites killed by IgE

Answer 7

can’t do phagocytosis
- IgE gives a larger range of effector functions
- responses are rapid (immediate IgE/FCeR response in presence of pathogen)

Question 8

how does IgE induce an immune response?

Answer 8

via mast cells
- IgE binds FCepsilonR on the mast cell
- 1 allergen binds two IgE molecules at the hypervariable region and cross-links two FCER
- this causes de-granulation of the mast cell

Question 9

how long does de-granulation take after allergin cross-links?

Answer 9

immediately

Question 10

what are in the mast cell granules

Answer 10

pre-formed chemicals that can immediately cause an immune response against parasites. e.g:
- chemoattractants
- activators (increase blood flow and vasodilation -> enables activation of immune cells)
- spasmogens (smooth muscle contraction and mucus secretion -> body trying to expel pathogen)

Question 11

what happens if mast cells degranulate but there is no parasitic infection?

Answer 11

we get an allergic response/disease

Question 12

what are the two pre-formed mast cell chemicals?

Answer 12

Histamines (vasodilation and vascular link -> enables immune cells to get to site of infection)
enzymes e.g tryptase (break down ECM between cells to reduce parasite attachment to tissue

Question 13

what are the two mast cell chemicals formed after activation?

Answer 13

lipid mediators (bronchoconstriction and intestinal hypermotility)
cytokines (inflammation)

Question 14

what is rhinitis?

Answer 14

hayfever

Question 15

what causes rhinitis?

Answer 15

house dust mite
pollens
animal dander

Question 16

what are the main causes of allergies?

Answer 16

rhinitis (hayfaver)
insect stings
food allergies
small molecules (penicillin, codeine, morphine)

Question 17

how is IgE different to other immunoglobins binding to their antigen?

Answer 17

Normally, antigen binds and then antibody binds to FCR.
IgE can sit on the FCeR without the antigen/allergen bound

Question 18

describe the first and second stages of the allergic response

Answer 18

Sensitisation: 1st exposure, B cells (with help from helper T cells switch class to…) create IgE which ‘arms’ mast cell
Effector: second exposure to allergen causes a stronger hypersensitivity/allergic reaction

Question 19

what are the common sites of allergy?

Answer 19

respiratory tract
skin
gut
multiple organs: anaphylaxis

Question 20

how do we treat allergies?

Answer 20

avoidance: often difficult
antihistamines: mild allergies e.g hayfever
corticosteroids: e.g asthma
Epinephrine
Desensitisation

Question 21

how do corticosteroids work?

Answer 21

dampens down whole immune response

Question 22

how does epinephrine work?

Answer 22

adrenaline in anaphylaxis

Question 23

how does desensitisation work?

Answer 23

gradually increasing allergen dose to induce high affinity IgG, which competes with IgE for the allergen
- doesn’t always work

Question 24

how do we test for allergies?

Answer 24

Immunoassay (seeing if IgE from blood binds to known allergens)
skin prick (allergen on needle prick)

Question 25

what is the benefit and con of using immunoassays to test for allergies?

Answer 25

pro: safe con: IgE is often bound to mast cells and may go undetected

Question 26

which allergen testing method is most commonly used?

Answer 26

skin prick

Question 27

what is a positive result of a skin prick?

Answer 27

skin is red and itchy - localised reaction

Question 28

what is the hygiene hypothesis?

Answer 28

living in a cleaner environment nowadays means people are more predisposed to allergic responses and there is dysregulation of IgE responses

Question 29

what are the four types of helper T cells?

Answer 29

Th1, Th2, Th17 and Treg

Question 30

describe Th1

Answer 30

IgG and IgM responds to CD8+ T cells responds to viral and bacterial infections

Question 31

describe Th2

Answer 31

IgE and more parasitic infections

Question 32

what do Th17 cells do?

Answer 32

promote inflammatory responses

Question 33

true or false, allergies are less common in higher income countries and small families

Answer 33

false, the opposite is the case

Question 34

describe type II hypersensitivity

Answer 34

an IgG or IgM antibody binds host cells and recruits cytotoxic T cells or complement and can cause cell lysis - can cause autoimmunity

Question 35

what is complement mediated lysis on a host cell

Answer 35

a type of type II hypersensitivity reactions

Question 36

what is hemolytic anemia and what type of hypersensitivity reaction is it?

Answer 36

When someone makes antibodies to their own RBCs Type II

Question 37

in hemolytic anemia, what antibody causes RBCs to be phagocytosed?

Answer 37

IgG - Antibody-dependent cellular cytotoxicity

Question 38

in hemolytic anemia, what antibody causes RBCs to be fixed by complement and lysed via the MAC?

Answer 38

IgM - Antibody dependent complement-mediated cytotoxicity

Question 39

what is frustrated phagocytosis in hemolytic anemia?

Answer 39

when a phagocyte releases its vacuole contents directly onto the cell surface

Question 40

what is goodpastures syndrome?

Answer 40

antibodies against type IV collagen (BM) - effects kidney glomeruli and lung alveoli - complement cascades destroy these tissues

Question 41

what happens in a type III hypersensitivity reaction?

Answer 41

antibody complex is not cleared and instead gets lodged (large and insoluble) and provokes an immune response and causes tissue damage

Question 42

what is serum sickness?

Answer 42

develops after injection of foreign antigen that can't be processed e.g antiserum - complex of antigen (antiserum) and antibody form and cause fever-like symptoms - self-limiting (foreign agent disappears, so does this)

Question 43

what type of hypersensitivity reaction is rheumatoid arthritis?

Answer 43

type III - antibodies such as IgG and IgM bind patients own IgG

Question 44

how does a type IV hypersensitivity reaction happen?

Answer 44

- antigen is processed by APC dendritic cells - Th1 effector cell recognises antigen and releases cytokines that act on vascular endothelium - recruitment of plasma and phagocytes cause visible lesion after 24-72 hoursw

Question 45

what type of hypersensitivity reaction is the mantoux test an example of

Answer 45

type IV - tests for M. TB, shows a local T cell inflammatory reaction if positive after 24-72 hours

Question 46

what is contact hypersensitivity

Answer 46

caused by direct contact of small molecules to 'carrier' proteins in the skin, transport to lymph nodes, stimulate T cells, and memory Th1 cells return and cause inflammation and type IV reaction - poison ivy - nickel jewellery symptoms appear after 24-72 hours