Lecture 22: Hypersensitivity disorders

Question 1

Type I, II, III hypersensitivity general

Answer 1

Antibody mediated effector mechanisms

Correspond to defenses against extracellular pathogens

Question 2

Type IV hypersensitivity general

Answer 2

Cell mediated effector mechanisms

Corresponds to defense against intracellular pathogens

Question 3

Type I hypersensitivity

Answer 3

Result from actions of mediators secreted by mast cells

Question 4

Type II hypersensitivity

Answer 4

Abs against cell and tissue Ags may cause tissue injury and disease

Question 5

Type III hypersensitivity

Answer 5

Immune complex diseases
Abs bind to circulating Ags to form complexes, which deposit in vessels, leading to inflammation in vessel walls (Soluble Ab-Ag complexes formed in circulation)

Question 6

Type IV hypersensitivity

Answer 6

T cell mediated diseases which result from inflammation caused by cytokines produced by CD4+ Th1 and Th17 cells, or killing of host cells by CD8+ CTLs

Question 7

Type I hypersensitivity is most often triggered by production of

Answer 7

IgE Ab against environmental Ags, and the binding of IgE to FceR1 on mast cells in various tissues

Question 8

Sequence of events in Type I hypersensitivity

Answer 8

• Production of IgE after activation of Th2 cells by primary exposure to allergen
• Binding of IgE to Fc receptors of mast cells
• Release of mediators by mast cell after secondary exposure to the Ag and cross linking of the membrane bound IgE by Ags

Question 9

What are the hallmarks of immediate hypersensitivity in Type I

Answer 9

Acute vascular dilation, prolonged smooth muscle contraction and inflammation

Question 10

What is characteristic of the late phase reaction in type I hypersensitivity

Answer 10

Inflammatory infiltrate rich in eosinophils, neutrophils and T cells

Question 11

Steps in Type II hypersensitivity

Answer 11

• Abs (IgM and IgG) activate the complement system classical pathway, resulting in recruitment of leukocytes which induce inflammation
• IgG Abs bind neutrophil/macrophage Fc receptors and activate them causing pro-inflammatory response
• ROS and lysosomal enzymes are released which damage the adjacent tissue

Question 12

Steps in Type III hypersensitivity

Answer 12

Ab-Ag complexes form in circulation and are deposited in blood vessels and other sites, causing vascular inflammation and ischemic damage
-Major mechanism triggering damage is classical activation of complement

Question 13

Type IV hypersensitivity is caused by

Answer 13

Activated Th1 cells, upon re-encounter with Ag, the Th1 clones undergo further clonal expansion and secretion of IFN-g, TNF-b, which activate macrophages and cause macrophage dependent tissue damage

Question 14

Difference between Type I-III and Type IV

Answer 14

Type I-III reactions can be transferred by serum containing Abs, while passive transfer of type IV requires the transfer of antigen-specific Th1 clones that orchestrate the macrophage response

Question 15

The inflammation associated with T-cell mediated diseases is typically _____

Answer 15

Chronic

Question 16

What is the most frequent auto-antibody found in systemic lupus erythematosus

Answer 16

Anti-DNA Abs

Question 17

Mechanism of SLE

Answer 17

• Presentation of unknown Ags by MHC molecules leads to priming of CD4+ T cells
• These CD4+ T cells then help B cells undergo affinity maturation etc.. and secrete IgG autoantibodies
• These autoantibodies bind autoantigens and form immunocomplexes, and fix complement or engage Fcy receptors on several cell types- this causes inflammation and tissue destruction through recruitment of inflammatory cells
• Apoptotic cells can also be taken up and novel autoantigens can be presented by the macrophages, further supporting priming and autoreactivity

Question 18

RA is mediated by what type of hypersensitivity reactions

Answer 18

Type II/III mixed reactions

Question 19

What cells are involved in RA

Answer 19

Th1, Th17, activated B cells, plasma cells and macrophages

Question 20

Mechanism of RA

Answer 20

Patients frequently have circulating IgM or IgG that react with the Fc of own IgG (non-immune) molecules
-These auto-Abs are called rheumatoid factors