Hypersensitivity

Question 1

• What can activation of the immune system lead to?

– Define ‘antigen’

• What does IgG3 potently activate?

Answer 1

Inflammation causing pain and discomfort

Any molecule or molecular structure that can be recognised by an antibody or the adaptive immune system 

Complement 
Fc receptor mediated phagocytosis

Question 2

• Can IgA cross the mucosal epithelium?

- What does IgE induce?

Answer 2

yes

Mast cell degranulation

Question 3

• What is another name for type I hypersensitivity?

- What is type I hypersensitivity?

Answer 3

Immediate or anaphylactic hypersensitivity

Allergic reaction provoked by re-exposure to a specific type of antigen referred to as an allergen

Question 4

• What are type 1 responses mediated by?
• When do non-allergic individuals make IgE?
• When do allergic individuals make antibodies?

Answer 4

Antigen specific IgE antibodies

Response to parasitic infections or very potent venoms

Produce it against common multivalent environmental antigens (known as allergens)

Question 5

• Outline the process of type I hypersensitivity?

Answer 5

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 bound to surface of innate immune cells (mast cells and basophils)

If allergen encountered by cell bound IgE it results in rapid crosslinking and degranulation of the mast cell or basophil.

Question 6

• Which granulocytic cells are involved in type I hypersensitivity?
• What is the name of the high affinity IgE receptor these granulocytic cells express?
• What are the end products of type I hypersensitivity reactions?

Answer 6

Mast cells and basophils

Fc epsilon receptor I

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

Question 7

• Name and explain the 3 phases that occur due to the variety of molecules released during type I responses

Answer 7

Early phase - mast cells producing small bioactive molecules (in minutes)

Later response - early inflammatory cells (neutrophils) recruited (in hours)

Late response - high frequencies of eosinophils are recruited and Th2 cells are present (3-4 days after exposure)

Question 8

• What is another name for type II hypersensitivity?

- Give examples of type II hypersensitivity?

Answer 8

Antibody-mediated cytotoxic hypersensitivity

Immune thrombocytopenia 
Haemolytic diseases of newborns 
Graves disease

Question 9

• What is graves disease?

Answer 9

Patients develop thyroid stimulating antibodies that bind the thyrotropin receptor resulting in secretion of thyroid hormones.

Question 10

• What can type II sensitisation involve?

- what three responses can IgG and IgM result in?

Answer 10

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

1. Anti-receptor activity – blocking or activating its function
2. Antibody Dependent Cell-mediated Cytotoxicity (abbreviated to ADCC)
3. Classical activation of the complement cascade

Question 11

• What is the complement cascade?

- What effects can the complement cascade form?

Answer 11

Process in which antibodies on cell surface are recognised by the complement components
leading to the formation of the membrane attack complex (MAC) on the cell surface
cell death due to loss of osmotic integrity

MAC in surface of the cell, Inflammation, Opsonisation , Recruitment and activation of immune cells

Question 12

• What are Fc receptors expressed by?
• What are antigen-antibody complexes in ADCC bound by?
• What does ADCC lead to?

Answer 12

Granulocytes and NK cells

Fc receptors (the constant tail regions of IgM and IgG antibodies bind to them, causing them to bring about an effect on the body)

Directed lysis of target cell
release of inflammatory mediators, chemokines and cytokines

Question 13

• List some things type II hypersensitivity can result in?

Answer 13

Local/systemic inflammation

Cell depletion leading to a loss of function

Imbalance in organ function

Question 14

• What are immune complexes?
• If immune complexes aren’t efficiently cleared by the immune system where do they go?
• What symptoms can immune complexes not being efficiently cleared lead to?

Answer 14

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

Deposited in blood vessel walls and tissues, promoting inflammation and tissue damage 

Symptoms such as fever, rashes, joint pain or protein in the urine

Question 15

• What are the terms for immune complexes being deposited in the blood vessels, kidneys and joints respectively?
• List 3 auto-immune diseases which involve type III reactions
• In which auto-immune disease do patients develop IgGs against DNA or proteins present in the nucleus (nucleoproteins) forming persistent immune complex deposits and a variety of pathologies?

Answer 15

Vasculitis , Glomerulonephritis, Arthritis

Rheumatoid arthritis, Multiple sclerosis, Systemic lupus erythematosus (SLE)

Systemic lupus erythematosus

Question 16

How does an antibody complex lodged in wall cause swelling

Answer 16

C1 binds to FC region of antibody
C2- C9 recruited
C3a, C4as, C5a in particular
inc permeability of vessels
fluid leaks out so swelling

Question 17

How does a lodged antibody complex cause inflammation

Answer 17

C1 binds to FC region of antibody
C2- C9 recruited
C3a, C4as, C5a in particular
act as chemokines and recruit other cells eg neutrophil
unsuccessful phagocytosis
neutrophil degranulate- release lysosomal enzymes and reactive oxygen species
tissue inflammation

Question 18

• What is type IV hypersensitivity primarily initiated by?
• What needs to occur before T cells can initiate type IV?
• How do memory T cells respond on subsequent exposure?

Answer 18

T cells

Sensitisation phase where antigen is presented to naive T cells by antigen presenting dendritic cells → results in the generation of antigen specific memory T cells

Promote inflammation at site of exposure

Question 19

• What is the most common example of type IV hypersensitivity and explain how it works briefly?

Answer 19

Contact dermatitis

Poison ivy exposure
urushiol acts as a hapten
drives a Th1 response
on re-exposure memory cells produce cytokines eg IFN-gamma
to promote the pro-inflammatory activation of macrophages
resulting in swelling and oedema
formation of blister like lesions

Question 20

• Why do immune complexes not initiate complement cascade?

- What are leukotrienes?

Answer 20

Whilst they can initiate it somewhat
The classical pathway activation results in formation of membrane attack complex which occurs in cell wall
Whereas immune complexes are free-floating

Molecules released by mast cells that trigger contraction of smooth muscle of bronchioles in asthmatics