ALS5: Hypersensitivity

Question 1

Hypersensitivity occurs when the immune system…?

Answer 1

over-or inappropriately reacts

Question 2

Name the 5 classes of antibodies

Answer 2

IgG
IgD
IgE
IgA
IgM

Question 3

What structure does IgA have?

Answer 3

It’s a dimer (2 antibodies joined by a J chain)

Question 4

What structure does IgM have?

Answer 4

It’s a pentamer (5 antibodies in a cyclical structure with a J chain)

Question 5

Very briefly outline T cell responses

Answer 5

Encounter specific antigen
Results in clonal expansion
Results in both effector cells and memory cells

Question 6

What is Type I hypersensitivity?

Answer 6

Allergic reaction provoked by re-exposure to specific antigen called allergen

Question 7

What does type I hypersensitivity include?

Answer 7

asthma, allergic rhinitis, atopic dermatitis

Question 8

What is type I hypersensitivity mediated by?

Answer 8

antigen specific IgE antibodies

Question 9

What do people with allergies produce?

Answer 9

Antibodies against common multivalent environmental pathogens

Question 10

What are skin prick tests?

Answer 10

tests where skin is exposed to small amounts of allergen, often used to diagnose allergies

Question 11

How can type I hypersensitivity occur?

Answer 11

Generation of type 2 helper CD4 T Cells and B cell helper follicular CD4 T cells.
These produce 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

Question 12

What happens to IgE once it’s produced in type I hypersensitivity?

Answer 12

IgE is rapidly bound to surface of innate immune cells, especially mast cells and basophils. These granulocytic cells express a high affinity IgE receptor, Fc epsilon receptor I.

Question 13

What happens if an allergen is encountered by cell bound IgE?

Answer 13

Results in rapid cross-linking and degranulation of mast cell or basophil

Question 14

What is the end product of these type I hypersensitivity reactions?

Answer 14

Release of histamine, a host of cytokines that recruit other cells and promote further Th2 (T helper cell type 2) differentiation, and highly active smooth muscle contracting molecules such as leukotrienes and prostaglandins.

Question 15

What are the ‘phases’ of type I hypersensitivity response?

Answer 15

Early phase = result of bioactive small molecules produced directly by mast cells, occurs within mins of allergen exposure
Within few hours = recruitment of early inflammatory cells such as neutrophils
Late response = peaking at 3-4 days after exposure where high frequency of eosinophils are recruited and Th2 cells are present

Question 16

What is Type II hypersensitivity?

Answer 16

antibody-mediated cytotoxic hypersensitivity - involves destruction of cells by IgG or IgM antibody bound to antigens present on cell surfaces.

Question 17

What examples are there of type II hypersensitivity?

Answer 17

• Mismatched blood in blood transfusion –> antibodies recognise non-self antigens in transfused blood resulting in immune induced destruction of RBCs, inflammation and tissue damage.
• Haemolytic disease of newborn
• Immune thromobocytopenia
• Graves’ disease

Question 18

What can type II sensitization involve?

Answer 18

Either exposure to a foreign antigen or aberrant response to self-antigen resulting in IgGs or IgMs that recognise cell surface structures.

Question 19

How can IgGs and IgMs lead to disease?

Answer 19

1. Anti-receptor activity - blocking or activating its function
2. Antibody dependent cell-mediated cytotoxicity (ADCC)
3. Classical activation of complement cascade

Question 20

What is the complement cascade?

Answer 20

A complex process which antibody on the surface of cells is recognised by complement components, ultimately leading to formation of membrane attack complex in surface of cell and cell death due to loss of osmotic integrity.

Question 21

What else can activation of the complement cascade result in?

Answer 21

Inflammation
Opsonisation
Recruitment and activation of immune cells

Question 22

What happens in antibody dependent cell-mediated cytotoxicity?

Answer 22

Antibody-antigen complexes on surface of cells are bound by Fc receptors (which bind constant tail regions of IgM and IgG antibodies) expressed by cells such as granulocytes and NK cells lead to direct lysis of target cell, but also release of inflammatory mediators, chemokines and cytokines.

Question 23

What multiple mechanisms of tissue injury can type II hypersensitivity result in?

Answer 23

Local or systemic inflammation

Cell depletion leading to loss of function or imbalance in organ function

Question 24

What is type III hypersensitivity sometimes known as?

Answer 24

immune complex driven diseases

Question 25

What are immune complexes?

Answer 25

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

Question 26

What can happen if immune complexes are not efficiently cleared?

Answer 26

They end up being deposited in blood vessel walls and tissues, promoting inflammation and tissue damage.

Question 27

What symptoms can arise from type III hypersensitivity reactions?

Answer 27

fever, rashes, joint pain, protein in urine, vasculitis (if in blood vessel), glomerulonephritis (if in kidneys) or arthritis (if in joints)

Question 28

What autoimmune diseases involve type III reactions?

Answer 28

rheumatoid arthritis
multiple sclerosis
system lupus erythematosus (SLE)

Question 29

Other than just auto-immune origins, what else can result in type III hypersensitivity?

Answer 29

Encounters with foreign antigens e.g. persistent infections like hepatitis
Freely circulating foreign antigens such as drugs

Question 30

What is Type IV hypersensitivity primarily initiated by?

Answer 30

T cells

Question 31

How does type IV hypersensitivity occur?

Answer 31

• antigen presented to naïve T cells by APCs (antigen-presenting dendritic cells)
• results in generation of antigen specific memory T cells –> sensitization takes several weeks
• subsequent exposure, memory T cells respond promoting inflammation at site of exposure but response normally peaks 2-3 days after inflammation due to delay

Question 32

What are can cause of type IV hypersensitivity?

Answer 32

Contact dermatitis - caused by poison ivy (urushiol drives Th1 response)
Nickel salts (Th1 inflammation)
Hair dyes(Th1 inflammation)
Measles
TB