Lecture 15 - Hypersensitivity

Question 1

Most allergic IgE responses occur where?
In response to where?

Answer 1

On mucous membrane surfaces in response to allergens that enter the body by either inhalation or ingestion.

Question 2

What are allergens?

Answer 2

Small proteins or protein-bound substances having a molecular weight between 15,000 and 40,000

Question 3

Allergenicity is a consequence of a complex series of interactions involving…

Answer 3

Allergens, dose, the sensitizing route, an adjuvant (most important), and the genetic constitution of the recipient.

Question 4

Where are mast cells found and what do they do?

Answer 4

They line the external mucosal surfaces and serve to alert the immune system to local infection.

Question 5

Mast-cell activation and granule release on the…
1) Gastrointestinal tract causes…
2) Eyes, nasal passages, and airways causes…
3) Blood vessels causes…

Answer 5

1) Increases fluid secretion and increased peristalsis.
2) Decreases diameter and increase mucous secretion.
3) Increases blood flow and permeability.

Question 6

Where is IgE mostly found?

Answer 6

On fixed cells that carry this receptor-mast cells in tissues and basophils in the circulation.

Question 7

What is IgE captured by?

Answer 7

High affinity Fce receptor (FceRI) in the absence of bound antigen.

Question 8

What are the 2 types of IgE-binding Fe receptor?

Answer 8

FceRI - a high affinity receptor of the immunoglobulin superfamily that binds IgE on mast cells and basophils
FceRII - or CD23, is a C-type lectin that binds IgE with low affinity and regulates the intensity of the IgE response

Question 9

What does FceRI receptor interact with?

Answer 9

The CH3/CH3and CH4/CH4 domains of Ig molecule via the 2 Ig-like domains of the chain.

Question 10

What are mast cells?

Answer 10

They are derived from hematopoietic stem cells but mature locally often residing near surface exposed to pathogens and allergens like, mucosal tissues, and connective tissues surrounding the blood vessels.

Question 11

MCT (a type of mast cells) predominately express what? And predominate where?
What about MCcT?

Answer 11

Express tryptase only, and predominate in mucous epithelia.
Express tryptase, chymase, carboxypeptidase A, and cathepsin G, and predominate in the submucosa and other connective tissues.

Question 12

The crosslinking of the FcRI receptors activates what? And causes what? (3)

Answer 12

Activates PTKs.
Resulting in the phosphorylation of tyrosines within ITAMs of the subunit, phosphorylation of residues on the subunit and on phosphorylation C, and second messengers.

Question 13

What is Type II hypersensitivity (involves what)?

Answer 13

IgG or IgM induced damage to self cells (Cell-surface or Matrix Antigen).

Question 14

When is IgG or IgM made in Type II hypersenstivity?

Answer 14

Against normal self-antigens or as a foreign antigen resembling some molecule on the surface of host cells.

Question 15

The immune processes involved in Type II hypersensitivity include…

Answer 15

Classical complement pathway, phagocytosis via FcR complement receptor, and ADCC via NK cells or eosinophils.

Question 16

Explain the process of…
Classical complement pathway.
Phagocytosis via FcR complement receptor.
ADCC via NK cells or eosinophils.

Answer 16

Create pores in the membrane of a foreign cell and cause MAC lysis.
Opsonization of the host cells where phagocytes stick to host cells like IgE, C3b, or C4b and discharge their lysosomes.
NK cells attach to Fc portion of antibodies and release perforins and granzymes which leads to apoptosis of the infected cell.

Question 17

Give examples of type II hypersensitivity.

Answer 17

Ab and Rh blood group reactions autoimmune diseases like…
Rheumatic fever, multiple sclerosis, Goodpasture’s syndrome, idiopathic thrombocytopenia purpura.

Question 18

Are transfusion reactions Type II reactions?

Answer 18

Yes

Question 19

Give an example of an autoimmune disease of Type II hypersensitivity.

Answer 19

Autoimmune hemolytic anemia

Question 20

Large amounts of immune complexes can lead to what?

Answer 20

Tissue-damaging type III hypersensitivity reactions.

Question 21

For type III, complexing of Ag with Ab facilitates what?

Answer 21

The clearance of antigen by phagocytotic cells.

Question 22

What are the immune complexes involved in type II hypersensitivity?

Answer 22

Classical complement pathways, and phagocytic cells

Question 23

Explain the process of Arthus reaction.

Answer 23

Locally injected antigen in immune individual with IgG antibody.
Local immune-complex formation.
Activation of complement releases inflammatory mediators C4a, C5a also induces mast-cell degranulation.
Local inflammation, increase fluid and protein release, phagocytosis, and blood vessel occlusion.

Question 24

What happens during the Arthus reaction?

Answer 24

As the reaction develops, localized tissue and vascular damage results in an accumulation of fluid (edema) and red blood cells (erythema)at the site. Severity can very from mild swelling and redness to tissue necrosis.

Question 25

What is serum sickness?

Answer 25

Where large amounts of Ag enter bloodstream and bind to Ab –> circulating immune complexes.
If Ag is in excess, small complexes form and are not easily cleared by phagocytic cells

Question 26

Give 2 examples of serum sickness.

Answer 26

Horse antitetanus and antiditheria serum

Question 27

Give an example of type III hypersensitivity.

Answer 27

Serum sickness

Question 28

What does the precise manifestation of sickness serum depends on? They accumulate where? And explains the high incidence of what? (3)

Answer 28

The quantity of immune complexes and the size of complexes.
Accumulate in tissues where filtration of plasma occurs and explains the high incidence of glomerulonephritis, vasculitis, and arthritis.

Question 29

When is Type IV or delayed-type hypersensitivity (DTH) used?

Answer 29

When subpopulations of activated TH cells encounter Ag, they secrete cytokines, then localize inflammatory reaction called DTH.

Question 30

What is Type IV hypersensitivity mediated by and list 3 syndromes.

Answer 30

Mediated by antigen-specific effector T-cell.
Delayed-type hypersensitivity, contact hypersensitivity, and gluten-sensitive enteropathy (celiac disease).