Hypersensitivity

Question 1

What is an antigen?

Answer 1

An antigen is a molecule which can be recognised by an antibody or the adaptive immune system

Question 2

What is meant by hypersensitivity?

Answer 2

Refers to the undesirable reactions produced by the immune system, including autoimmunity and allergies

Question 3

give some examples of allergens that can cause type 1 reactions

Answer 3

foods (e.g. peanuts), plants (e.g. timothy grass, birch trees), animal dander (e.g. cats, dogs), drugs (e.g. penicillin, sulphonamides) and insect products (e.g. bee venom, house dust mites).

Question 4

What is the name of Type 1 hypersensitivity?

Answer 4

Immediate hypersensitivity / anaphylactic hypersensitivity

Question 5

What is type 1 hypersensitivity triggered by?

Answer 5

The re-exposure to a specific antigen which is referred to as an allergen

Question 6

What type of antibodies are type 1 hypersensitivity reactions mediated by?

Answer 6

IgE antibodies

Question 7

Which cytokines promote the B cell to class switch into an IgE producing cell?

Answer 7

IL-4 and IL-13

Question 8

Which cells does IgE bind to?

Answer 8

Mast cells and basophils

Question 9

What receptor do IgE use to bind to the mast cells?

Answer 9

Fc epsilon receptor 1

Question 10

what happens if an allergen encounters cell bound IgE?

Answer 10

Rapid cross linking and degranulation of the mast cell

Question 11

What is released when the mast cell degranulates?

Answer 11

Histamine, a host of cytokines that can recruit other cells and promote further Th2 differentiation, and highly active smooth muscle contracting molecules such as leukotrienes and prostaglandins.

Question 12

what are leukotrienes?

Answer 12

highly active smooth muscle contracting molecules

Question 13

What affect does histamine have?

Answer 13

it is a vasodilator

Question 14

how can you diagnose allergies?

Answer 14

using a skin prick test (wheal and flare)

Question 15

which reactions create the wheal and flare reaction?

Answer 15

Type 1, seen in the skin prick test

Question 16

What is a multivalent antigen?

Answer 16

Antigen that has multiple sites at which an antibody can attach or antigen can be produced

Question 17

What factors influence the initial sensitisation of the immune response to allergens?

Answer 17

Genetics, age, the environment

Question 18

How do allergies happen immunologically?

Answer 18

First, the body must be sensitised to the allergen.
When the allergen initially enters the body, it results in generation of Th2 cells and Tfh cytokines IL-4 and 13.

When these act on B cells the cells switch to producing allergen (antigen) specific IgE.

Question 19

when do non-allergic people produce IgE?

Answer 19

only against potent venoms or parasitic infections

Question 20

What is the name of Type 2 hypersensitivity?

Answer 20

antibody mediated cytotoxic hypersensitivity

Question 21

what are the 3 phases in type 1 hypersensitivity reactions?

Answer 21

1. early Phase
2. Later Phase
3. Late Phase

Question 22

when does the early phase occur?

Answer 22

few mins following exposure to allergen

Question 23

when does the later phase occur?

Answer 23

within a few hours of exposure to allergen caused by the recruitment of early inflammatory cells such as neutrophils.

Question 24

when does the late phase occur?

Answer 24

3-4 days after exposure where high frequencies of eosinophils are recruited and Th2 cells are present.

Question 25

What does type 2 hypersensitivity involve?

Answer 25

The destruction of cells by IgG or IgM antibodies that are bound to antigens present on the surface of cells - normally healthy cells

Question 26

What are examples of type 2 hypersensitivity reactions?

Answer 26

1. Graves disease - antibodies bind to thyrotrophin receptor resulting in the over production of thyroid hormones 2. Haemolytic disease of newborns - maternal antibodies can cross the placenta and destroy fetal red blood cells 3. Immune thrombocytopenia - antibodies develop gainst platelets

Question 27

What are the three mechanisms by which Type 2 hypersensitivity reactions can occur?

Answer 27

1. Anti-receptor activity - blocking or activating its function 2. Antibody dependant cell mediated cytotoxicity 3. Classical activation of the complement cascade

Question 28

how does the Classical activation of the complement cascade lead to cell death?

Answer 28

antibodies on the surface of cells is recognised by the complement components, ultimately leading to the formation of the membrane attack complex (MAC) in the surface of the cell, and cell death due to loss of osmotic integrity.

Question 29

what are the effects does type 2 hypersensitivity lead to?

Answer 29

- tissue injury including local or systemic inflammation, - cell depletion leading to a loss of function or imbalance in organ function.

Question 30

What happens in type 3 hypersensitivity?

Answer 30

When immune complexes are not cleared. The immune complexes end up being deposited in the blood vessel walls and tissues, promoting inflammation and tissue damage

Question 31

what are the symptoms of type 3 hypersensitivity?

Answer 31

fever, rashes, joint pain or protein in the urine:

Question 32

What happens in systemic lupus erythematosus (SLE)?

Answer 32

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 33

which kind of diseases typically causes type 3 hypersensitivity?

Answer 33

autoimmune conditions

Question 34

What is an immune complex?

Answer 34

non-cell bound antigen-antibody complexes

Question 35

Using snake venom as an example, explain how serum sickness arises?

Answer 35

When a patient is biten by a snake, the venom of the snake enters into the blood stream Patient is given anti-venom, which the patient produces antibodies against Therefore during the second bite, immune complexes may be formed

Question 36

how does type 4 hypersensitivity arise?

Answer 36

- Sensitisation phase occurs where antigen is presented to naive T cells by antigen presenting dendritic cells, resulting in generation of antigen specific memory T cells- takes several weeks - On subsequent exposure these memory T cells respond promoting inflammation at site of exposure

Question 37

what is the other name for type 4 hypersensitivity reactions?

Answer 37

(delayed) T-cell mediated hypersensitivity

Question 38

why is there a delay between exposure and response in type 4 reactions? how long is this lag?

Answer 38

because the memory T cell response (which requires recruitment and expansion) is slightly slower than antibody mediated memory peak responses are seen 2-3 days following re-exposure

Question 39

How does antibody dependent cell-mediated Cytotoxicity work?

Answer 39

When a NK cell binds to the immune complex by recognising the Fc tail Releases perforin which allows for the entry of granzymes and granulysin - results in cell death in an apoptotic way

Question 40

What are the primary cells involved in Type 4 Hypersensitivity reactions?

Answer 40

T cells

Question 41

Name the cytokines released when in contact with poison ivy?

Answer 41

IFN- gamma

Question 42

Explain how contact dermatitis occurs?

Answer 42

- skin is exposed to poison ivy - here a small molecule urushiol acts as a hapten (and binds to proteins in skin), driving T helper 1 response - On re-exposure these memory cells produce cytokines such as IFN-gamma which promote the pro-inflammatory activation of macrophages resulting in swelling and oedema

Question 43

what are the intracellular pathogens that can cause type 4?

Answer 43

measles virus and Mycobacterium tuberculosis

Question 44

The test for what infection is conducted via the means of a type 4 hypersensitivity reaction?

Answer 44

tuberculosis - positive test = raised bump due to oedema / tissue swelling initiated by pro-inflammatory cytokines

Question 45

Are type 4 reactions only limited to Th1 cells?

Answer 45

No, any T memory cell can cause type 4 reactions

Question 46

Can one disease initiate multiple different types of hypersensitivity reactions?

Answer 46

Yes! in many diseases more than one type of hypersensitivity reaction may be contributing to pathology at the same times.