Hypersensitivity

Question 1

Type I

Answer 1

Immediate/anaphylatic hypersensitivity
An allergic reaction provoked by re exposure to allergens
Asthma,allergic rhinitis,atopic dermatitis
A,e antibodies against common antigens however non allergic individuals only make IgE

Question 2

Multivalent antigen

Answer 2

An antigen with multiple binding sites for antibodies

Question 3

Allergens

Answer 3

• Food
• Plants
• Animal dander
• Drugs
• Insect products

Question 4

What type of antibodies are allergens mediated by

Answer 4

IgE antibodies
Non allergic people make this in response to parasitic infection

Question 5

Which 3 factors influence the initial sensitisation of the immune response to allergens?

Answer 5

Genetics
Age
Environment

Question 6

Process of type I hypersensitivity

Answer 6

Generation of CD4 T cells and B cell helper follicular CD4 T cells which produce the type 2 cytokines IL-4 and IL-13

When these act on B cells they can promote B cell to switch to producing antigen specific IgE

IgE bind to IgE receptor on mast cells & basophils (innate immune cells)

Allergen binds to IgE molecules on mast cells, crosslinking of IgE, which triggers degranulation of the mast cell (or basophil)

Release of histamine (preformed chemical mediations), cytokines that can recruit other cells and promote further Th2 differentiation, prostaglandins and highly active smooth muscle contracting molecules like leukotrienes

Question 7

3 phases of type I hypersensitivity

Answer 7

Early phase-bioactive small molecules made by mast cells occurs within minutes of allergen exposure
Later response-seen within a few hours early recruitment of neutrophils
Late response-peaks 3-4 days after where high frequencies of eosinophil are recruited and Th2 cells are present

Question 8

Type II

Answer 8

antibody mediated cytotoxic hypersensitivity
Destruction of IgG or IgM antibodies bound to antigens present of surface of cells

Question 9

Examples of type II hypersensitivity

Answer 9

Mismatched blood transfusion
Immune thrombocytopenia (antibodies develop against platelet surface proteins)
Graves’ disease (thyroid stimulating antibodies develop that bind thyrotropin receptors causing secretion of thyroid hormones)
Haemolytic disease of fetus

Question 10

What 2 ways of getting type 2 hypersensitivity are there?

Answer 10

Exposure to foreign antigen (e.g. some drugs can bind to surface of blood cells or non-self antigens blood transfusions)

Aberrant response to a self-antigen resulting in IgGs or IgMs that recognise cell surface structures

Question 11

What are 3 mechanisms through which IgG and IgM antibodies can cause disease?

Answer 11

• Anti-receptor activity- blocking or activating its function
• Antibody dependent cell-mediated cytotoxicity (ADCC)- where immune cells destroy target cells

-classical activation of complement

Question 12

How does type 2 hypersensitivity cause tissue damage?

Answer 12

• Local or systemic inflammation
• Cell depletion leading to loss of function
• Imbalance in organ function

Question 13

Type III

Answer 13

Immune complex driven
Accumulation of immune complexes

When immune complexes can’t be cleared efficiently e.g. if they are result of antibodies reacting against self-antigens like nuclear DNA, the complexes are deposited in blood vessel walls and tissues and promote inflammation and tissue damage

Question 14

Immune complexes

Answer 14

Non-cell bound antigen-antibody complexes which are normally cleared through activity of immune system

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Question 15

What issues can type III hypersensitivity lead to?

Answer 15

• Fever, rashes, joint pain, protein in urine
• Vasculitis if deposited in blood vesslels
• Glomerulonephritis if in kidneys
• Arthritis if in joints

Question 16

What happens in systemic lupus erythematosus (SLE)?

Answer 16

Patients develop IgGs against DNA or proteins present in nucleus of cells (nucleoproteins) which form persistent immune-complex deposits and a variety of pathologies

Question 17

Why would rapid inflammation occur if a person were to be bitten by a venomous snake the second time around even if they were given anti-serum?

Answer 17

The first time a person is bitten by a snake, anti-serum would be given to the victim to neutralise the venom

However these are foreign bodies and the body will react against them to produce antibodies that recognise anti-venom antibodies

Process takes several weeks so by time of first bite, the anti-serum and venom would be cleared so there is no reaction

But by second bite, antibodies recognise anti-serum and drive rapid inflammation

Question 18

Why do immune complexes not initiate complement cascade?

Answer 18

The classical pathway activation results in formation of membrane attack complex which occurs in cell wall

Whereas immune complexes are free-floating

Question 19

Type IV

Answer 19

T cell mediated hypersensitivity/delayed type
Caused by T cells
Sensitization phase where antigen is presented to naive T cells resulting in antigen specific memory cells

Question 20

• When is memory T cell response shown and why?

Answer 20

2-3 days after inflammation because the memory T cell response is slightly slower than antibody mediated memory (because of recruitment and expansion)

Question 21

Common type of IV

Answer 21

Contact dermatitis caused by exposure to poison ivy where a small molecule urushiol acts as a hapten (and binds to proteins in skin), driving T helper 1 response but rarely results in antibodies production as it’s so small

Question 22

What happens on re exposure of ivy

Answer 22

The memory cells produces cytokines like IFN-gamma which promote the pro-inflammatory activation of macrophages resulting in swelling and oedema and formation of blister like lesions

Question 23

What other antigens can cause type IV hypersensitivity?

Answer 23

Nickel salts or hair dyes that can also drive Th1 based inflammation

Intracellular pathogens like measles virus and tuberculosis bacteria

Question 24

Give an example where T helper 2 cells cause type IV hypersensitivity?

Answer 24

In asthma, allergens cause overreaction of Th2 cells which produce soluble mediators that promote bronchoconstriction

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Question 25

Give an example where CD8 T cells cause type IV hypersensitivity?

Answer 25

I Can lead to inflammation and rejection of a tissue graft by directly killing transplanted cells