(L28) Hypersensitivity

Question 1

What are the characteristics of type I hypersensitivity? Timing and mechanism. L28 S4

Answer 1

• Immediate response
• mediated by IgE and results from the action of mediators secreted by mast cells.
• most of the time triggered by enviromental antigens which activate mast cells in an IgE dependent manner

Question 2

What are the mast cell mediators involved in Type I hypersensitivities? L28 S5

Answer 2

Histamine: -vasodilator and increased permeability

Protease: -tissue damage

Prostaglandins -vasodilator

Leukotrienes: -smooth muscle contraction

Cytokines: -inflammation/leukocyte recruitment

(HPPLC)

Question 3

What is Atopy

Answer 3

genetic tendency to develop allergic diseases.

Question 4

What is unique to first and subsequent exposures in type I hypersensitivities? L28 S6-7

Answer 4

1) First exposure to allergen: -causes B cell maturation and production of plasma cells that produce IgE -no hypersensitivity response as allergen is likely gone before IgE is produced
2) Subsequent exposures to allergen: -circulating IgE bind allergen and bind to FcεRII (CD23) -degranulation occurs due to cross-linking of FcεRI

Question 5

What are the different phases of a type I hypersensitivity response? L28 S9

Answer 5

Immediate phase: -occurs within minutes -due to degranulation -vasodilation, congestion, and edema

Late phase: -occurs 2-24 hours later -due to leukocyte infiltration (eosinophils, neutrophils, t cells)

Question 6

Summary of Type 1 Hypersensitivity:

Answer 6

• exposed to allergen
• antigen is then put on B cell and TH2 WILL recognize it and stimulate class switching
• production of IGE is made
• IGE will bind to FCER1 on mast cells
• repeat exposures will cause ag cross linking and activation of mast cells which release inflamatory mediators

Question 7

Asthama

Answer 7

• caused by release of infammatory mediators from mast cells due to allergen
• will cause increase capillary permability and aspamodic contraction
• will decrease size of the bronchial lumen which will cause SOB

Question 8

non immunologic stimuli such as ___ and ____ will also sitmulate airway inflamation and bronchospasms

Answer 8

cold, excersise

Question 9

anaphylaxis (systemic reaction)

Answer 9

exposure to allergen –> mast cell relase of vasoactive substances of amines and cytokines from mast cells and basophils throughout the body resulting in contraction of smooth muslce of the vaslualtory and vasodilation of the capillary endothelim

• blood pressure drops causing vascular shock
• will make breathing difficult

Question 10

allergen test

Answer 10

• test type 1 hypersentivities: either on arm or back
• make a grid and then inject it into the arm
• look for redness and swelling

Question 11

What is allergen-SIT? L28 S13-14

Answer 11

Administration of allergen in increasing doses to cure allergies

Functions:

• induces T cell tolerance (Tregs)
• increase the treshold for mast and basophil actication by allergens
• decreased IgE-mediated histamine release

The generation of ITregs is key for this

Question 12

What are the characteristics of type II hypersensitivity? L28 S16

Answer 12

• IgG/IgM interaction with cell/tissue SURFACE Ags
• those Igs activate complement and production of C3a and C5a anaphylatoxins resulting in leukocyte recruitment/ cause inflamation
• Opsonization of cell via IgG causing neutrophil and macrophage activation by FcR gamma or CR1 receptors
• also FC receptor dependent manner of (ab cellular cytotoxicity) will cause neutropils and macrophages to bind and release inflamatory mediators:
  
  • ros and lysosomal enzymes released damage adjacent tisues and then cause inflamation

Question 13

What are examples of type II hypersensitivity that don’t results in cell damage but instead have other physiological responses? L28 S18

Answer 13

Grave’s disease:

-binding of Ab to TSH receptor in thyroid, activating them -results in hyperthyroidism

Myasthenia gravis:

-binding of Ab to ACh receptor in neuromuscular synapses blocking stimulation

Question 14

DIIHA

Answer 14

DRUG induced immune hemolytic anemia

• PCN: binds to erethrocyte and Ig bind to drug and causes hemolysis (pahgoyctosis or complement)
• QUINIDINE: autoantibodies form immune complexes with drug as the drug binds via c3b (hemolysis by complement)

METHYLODPA: pahgocytosis binds to rbc antigens

Question 15

What are examples of type III hypersensitivity? L28 S25

Answer 15

• systemic lupus erythematosus (DNA)
• polyarteritis nodosa
• post-streptococcal glomerulonephritis
• serum sickness (systemic vasculitis)
• Arthus reaction (local vasculitis)

Question 16

What are the characteristics of type III hypersensitivity? L28 S24

Answer 16

• IgG/IgM interaction with cell/tissue SOLUBLE Ags
• Formation of immune complexes which form in the blood and then are deposited in the tissues/ blood vessels that are the sites of injury
  
  • Especially problematic in lungs and kidneys
• Results in ischemia

Question 17

What occurs in all disorders of type III hypersenitivity?

Answer 17

injury is caused by complement mediated and and recruitment of leukocytes (Fc receptor mediated inflamation).

Question 18

Systemic vs local reaction for type 3 hypersenitivities

Answer 18

Systemic

• FC receptors on endothelium bind to antitoxin that has reacted with a toxoid
• additional antitoxins and toxoid bind to form a larger complex
• which will activate the complement and release c5a c4a and c3a attacting macrophages and neutrophils

Local/arthus reaction:

• ab transported to site of anigen deposition
• will cause stimulation of clasical CP

Question 19

Arthus recaction

Answer 19

induced by subcutaneous administration of a protein ag to a previously immunized animal. This results in the formation of immune complexes at the site of ag injection and local vasculitis.

Question 20

What are the characteristics of type IV hypersensitivity? Timing and mechanism. L28 S27

Answer 20

• Delay-type hypersensitivity (DTH) (24-48 hours). Reacts to exagerated or persistent responses of the enviromental ags and some microbal Ags.
• Caused by inflamation from cytokines that are produced mainly by CD4+ T cells (1 and 17), macrophages or by CD8 CTL.

Question 21

What is the mechanism of reaction to poison ivy? L28 S31

Answer 21

Pentadecacatechol from poison Ivy complexes with skin protein forming a neoantigen.

The pentadecacatechol is too small to form an immune reaction on its own (hapten).

-secondary contact will cause dermatitis to the antigen as the first time the t cells are sensitized.

Question 22

What are examples of type IV hypersensitivity? L28 S29

Answer 22

-multiple sclerosis (myelin) -rheumatoid arthritis -Type 1 DM (pancreatic β cell Ags) -Crohn’s disease -contact sensitivity (poison ivy haptens) -chronic infections (ie. tuberculosis)

Question 23

What are examples of type I hypersensitivity? L28 S4;10–11

Answer 23

Anaphylaxis (systemic) Asthma (local) Acute urticaria (bug bites) Allergic rhinitis (pollen) Food allergies

Question 24

What are the most common contact allergens? L28 S32

Answer 24

(allergic contact dermatitis). Caused by enviromental exposure to external antigens that contact with skin and trigger an inflamatory response.

-it is a result of DTH reactions.

Metals: -nickel -cobalt -chromium

Question 25

DTH TB example

Answer 25

-purified protein deriviate (ppd), a protein antigen of mycobaterium tb, elicits a DTH reaction called the tuberculin reaction.

Question 26

Hypersenitivity is from

Answer 26

uncrontoeled or abnormal response to foreign antigens or anutoimmune responses against self antigens.

Question 27

Summary Slide of Type 1-4

Answer 27