Hypersensitivities 3 Flashcards
Type III hypersensitivities
Caused by the formation of Type III immune complexes formed between soluble antigens in the serum or tissues and IgG antibodies
- No cell-associated antigen and antibody complexes formed in this type of hypersensitivity
Steps of immune complex diseases (Type III)
- Immune complexes form
- Fixation or activation of the complement cascade (through classical pathway)
- Complement activation generates chemotaxic and activating substances for neutrophils (C3a, C5a)
- Neutrophil and mast cell degranulation leads to release of free radicals and proteolytic enzymes which destroy tissues
Neutrophils during Type III hypersensitivities
- No phagocytosis
- Only degranulation
Type III hypersensitivity occurrence and
Type III reactions are a normal occurrence, and disease only occurs if there are large amounts or persistence of antigen
- Severity and significance of immune complex reactions depends on the amount and site of the deposition of the complexes
Type III hypersensitivity reaction types
- Local
- Generalized
Local Type III hypersensitivity location
Immune complexes are confined to single site
Arthus Reaction
- Stimulating local type III hypersensitivity
- Antigen injection subcutaneously into an animal with high levels of antibodies
- Peaks in intensity in 6-8 hours
- High numbers of neutrophils, red (hyperemic), edematous (swollen), painful
Pathogenesis of the Arthus Reaction
- Antigen diffuses from the injection site into blood vessel
- Antigen meets antibodies in serum
- Formation of immune complexes between and beneath vascular endothelial cells
- Immune complexes in blood vessel wall
- Mast cell and neutrophil degranulation
- Problematic lesion= vasculitis
Local Type III hypersensitivity examples
- Hypersensitivity Pneumonitis
- Heaves Chronic obstructive pulmonary disease (COPD) In horses
Hypersensitivity Pneumonitis
- Occurs in the lungs of immune animals after inhaling antigens (typically moldy feed)
- Inhaled spores encounter antibody and form immune complexes within the alveolar walls
- Activation of complement and neutrophils
- Can be acutely fatal within hours of a large feeding or chronic condition of coughing/dyspnea
- Similar to farmers lung, librarians lung or pigeon breeders lung
Heaves Chronic obstructive pulmonary disease (COPD) In horses
- Combination of Type I and Type III hypersensitivity reactions
- Occurs 5-10 hours after exposure
- Antigen: molds in hay dust
>Mold spores are small enough to avoid elimination from muco-cillary apparatus so they make it into the alveolus
>Repeated feeding of moldy hay results in high antibody titers and antigen encounter forms complexes in alveolar wall - Results in vasculitis, edema, thickened alveolar walls interfering with air exchange
Generalized Type III hypersensitivity location
Immune complexes are formed in the circulation (intravenous) and damage is widespread
- Normally, these serum immune complexes are removed by binding to either platelets or RBCs (depending on species)
Ex. primates bind to RBCs
What determines immune complex size?
The number of antibodies vs antigens
- If more antibodies than antigens than the antigens will be completely covered in antibodies
- If more antigens than antibodies, then some antigens will have an antibody and others will have none
- If equal amounts of antibodies and antigens, molecules will link together to form large complex
Insoluble vs. soluble immune complexes during generalized Type III
Large insoluble immune complexes have the potential to plug small blood vessels
- Have to be taken up by phagocytes
A lot of small soluble immune complexes that excess the platelets/RBC binding capacity are deposited in the blood vessels
Where does the build up of small soluble complexes often occur?
Medium sized arteries of the glomeruli, synovia, skin, choroid plexus
