20a - Type III Hypersensitivity

Question 1

Type III:

Answer 1

-‘immune complex’ disease
>formed between soluble antigen in the serum or tissues and antibody
(not between cell-associated antigen and antibody as in type II)

Question 2

Immune complex disease due to:

Answer 2

-‘fixation’ or activation of the complement cascade (classical pathway)

Question 3

Complement activation Type III:

Answer 3

-generates chemotaxis and activating substances for neutrophils (C3a, C5a)
*neutrophil and mast cell degranulation leads to release of free radicals and proteolytic enzymes=destroy tissues
>degranulate because they can’t ingest the immune complexes

Question 4

Classification of type III (immune complex reactions) depends on:

Answer 4

-amount and site of deposition of the complexes
*normal occurrence, but get disease when there is LARGE AMOUNTS of antigen and/or PERSISTANCE of the antigen

Question 5

Types of Type III reactions:

Answer 5

-local
-generalized

Question 6

Local Type III reactions:

Answer 6

-immune complexes are confined to single site
Ex. Arthus Reaction and hypersensitivity pneumonitis

Question 7

Arthus Reaction:

Answer 7

-local Type III
-antigen injected subcutaneously into an animal with high levels of antibodies
-within a few hours, site will contain high neutrophils, red, edematous (swollen) and painful
*peaks in intensity in 6-8hrs

Question 8

Pathogenesis of the Arthus-Reaction:

Answer 8

1. Antigen diffuse form injection site into blood vessel
2. Antigen meets Ab in serum
3. Formation of immune complexes between and beneath vascular endothelial cells
4. Immune complexes in blood vessel wall
5. *mast cell and neutrophil degranulation
6. The problematic lesion is the VASCULITIS

Question 9

Vasculitis:

Answer 9

-group of disorders that destroy blood vessels by inflammation

Question 10

Hypersensitivity pneumonitis:

Answer 10

-occurs in lungs of immune animals after inhaling antigens
-inhaled spores encounter Ab and form immune complexes with the alveolar walls (complement activation/neutrophils)

Question 11

Outcome of hypersensitivity pneumonitis:

Answer 11

-can be acutely fatal within hours of a large feed of molding feed OR
-chronic condition characterized by coughing/dyspnea

Question 12

Hypersensitivity pneumonitis in different species:

Answer 12

-“farmers lung” in humans (same antigen)
-pigeon breeders lung (pigeon feces: antigen)
-librarians lung (dust)

Question 13

“Heaves” COPD in horses:

Answer 13

-combination of Type I and Type III hypersensitivity reactions
-antigens: molds in hay dust

Question 14

COPD in horses is due to:

Answer 14

-5-10hrs after feeding moldy hay (dyspnea and coughing)
-small particle size of mold spores inhaled to the alveolus
>large particles are eliminated by muco-ciliary apparatus

Question 15

Repeated feeding of moldy hay results in:

Answer 15

-high antibody titres and interaction with Ag to form immune complexes in alveolar wall
*vasculitis, edema and thickened alveolar walls interfere with air exchange

Question 16

Generalized Type III reactions:

Answer 16

-intravenous antigen/complex formation (in circulation)
>normally they are removed by binding to either platelets or RBCs (species differences)
-damage is WIDESPREAD

Question 17

Primates serum immune complex removed by binding:

Answer 17

-RBCs

Question 18

Other mammals (not primates) serum immune complexes removed by binding:

Answer 18

-platelets

Question 19

‘types’ of generalized Type III reactions:

Answer 19

1. Immune complexes are very large
2. Large numbers of circulating small complexes

Question 20

Immune complexes are very large:

Answer 20

-‘insoluble’
-have the potential to plug small blood vessels
*taken up by phagocytes

Question 21

Large numbers of circulating small complexes:

Answer 21

-‘soluble’
-exceed the platelets/RBC binding capacity and become deposited into blood vessels

Question 22

Where are many ‘soluble’ immune complexes more likely to be deposited?

Answer 22

-medium sized arteries of:
>glomeruli
>synovia
>skin
>choroid plexus

Question 23

What are considered ‘soluble’ immune complexes?

Answer 23

-excess of Ab, each antigen is completely coated with Abs and not accessible for binding into large complexes
-excess of antigens, one or no Ab bind most antigens and not large complexes form

Question 24

When do you get ‘insoluble’ immune complexes?

Answer 24

-Abs and antigens are equal (or close to equal)
>link together to form large complexes

Question 25

‘serum sickness’:

Answer 25

-discovered through the use of horse serum as source of passive antibody for people
Ex. hyper-immune horse serum used to protect people from tetanus exposure
*caused by high numbers of immune complexes due to Ab responses to wide array of ‘foreign/horse’ proteins

Question 26

Systemic Lupus Erythematosus (SLE):

Answer 26

-generalized type III reaction
-auto-antibodies to self-antigens
-immune complex deposition in various areas
-‘butterfly’ rash on face due to immune complexes=looks like wolf face (hence ‘lupus’)

Question 27

Immune complex depositions in systemic lupus erythematosus:

Answer 27

-basement zone of the skin
-glomeruli of kidney
-small vessels

Question 28

Names of immune complexes in small vessels:

Answer 28

-vasculitis
-thrombosis
-tissue ischemia
-necrosis

Question 29

Diagnosis of Systemic Lupus Erythematosus:

Answer 29

-clinical signs
-anti-nuclear antibodies (ANAs)

Question 30

Rheumatoid Arthritis:

Answer 30

-generalized type III reaction
-immune complex deposition in the synovial membrane of the joint
>tissue destruction

Question 31

Immune complex glomerulonephritis occurs in:

Answer 31

-a variety of diseases (in addition to SLE)
>chronic viral diseases
>chronic bacterial diseases (pyometra)
>chronic parasitic infections (heart worm)

Question 32

Immune complex glomerulonephritis:

Answer 32

*persistence of antigen (an ongoing Ab response)
-damage and lesions depend on size of immune complexes and whether complement is fixed/activated
Ex. canine pyometra

Question 33

Canine pyometra:

Answer 33

-uterine infection
-uterus is filled with bacteria, inflammatory cells and purulent (infected) material

Question 34

Example of systemic type III reaction:

Answer 34

-‘idiopathic’ immune mediated polyarthritis
>shows up ‘spontaneously’

Question 35

‘idiopathic’ immune mediated polyarthritis:

Answer 35

*most common manifestation of immune-mediated arthritis in dogs
-sometimes follows know viral or bacterial infections
-not as deforming or erosive as RA
-usually self-limiting as the inciting antigen is removed