immunopathology II - lecture notes - julia Flashcards
what is the cause of type III immune reactions?
- disease is due to deposition of antigen-antibody complexes
- can be localized or systemic
describe the process of type III immune reactions
- sensitization of the immune system results in production of antibodies
- continuous or repeated antigen exposure results in ag/ab complexes being formed and deposited in tissue
- complement cascade activated (C3a, C3b, C5 frags, MAC)
- neutrophils and macrophages are attracted and activated
- focal acute inflammation causes tissue destruction
note: no direct attack on any tissue or organ or structure
what cell type is mostly involved in type III immune reactions?
mostly the neutrophils that cause tissue damage
but there’s also macrophages involved
what determines the type and location of tissue damage in type III reactions?
where and how the complexes are deposited
can be systemic or localized
what are some examples of systemic type III hypersensitivity reaction? (3)
- serum sickness
- SLE
- drug reactions
what are some examples of localized type III hypersensitivity reactions? (5)
- arthus reaction
- vasculitis
- glomerulonephritis
- arthritis
- pneumonitis
describe the pathogenesis of type III hypersensitivity reactions
- Fc receptor engagement and chemotactic factors released due to complement activation recruit neutrophils and monocytes => activation of phagocytes => release of lysosomal enzymes => necrosis
- complement activation also generates anaphylatoxin => release of vasoactive amines => vasodilation and edema
- platelet aggregation and activation of hageman factor => microthrombi formation => ischemia => necrosis
- activation of hageman factor => release of kinins => vasodilation and edema

what determines where antigen/antibody complexes localize?
- size:
- if little, can be removed by phagocytes in spleen
- if very large, may not get out of tissue at all
- hemodynamic and structural factors
- if flow not enough or chragd, may not be removed
- vascular permeability
- IgE mediated vascular permeability => blood vessel starts leaking and complexes inside lumen of vessel will be flushed into the tissue
what are the consequences/actions of the various complement components involved in type III hypersensitivity reactions?
- C3b => phagocytosis
- C3a + C5a => increased vascular permeability
- C3, C5 fragments, C5,6,7 complex => chemotaxis
- C5-9 => lysis
overall cause:
- vasculitis
- glomerulonephritis
- arthritis
- endocarditis
review the things released into tissue in a type III reaction (don’t memorize the table!)
note: you can zoom in on the computer

what type of immune reaction is post-streptococcal glomerulonephritis?
- localized type III hypersensitivity
what is the process by which post-streptococcal glomerulonephritis causes an immune reaction?
- individual gets an infection with a particular type of streptococcus (not the kind associated wtih rheumatic fever)
- this infection is usually infected with a particular phage
- results in antigen/antibody complex formation - circulate
- these complex are tiny and have a specific charge associated with them - allows them to cross the vascular membrane and enter the blood vessel lumen
- form large nodules of aggregated antigen antibody compelx
- deposited in glomerulus
what will post-streptococcal glomerulonephritis look like histologically (H&E stain)?
- neutrophils in glomerular tufts
- basement membranes thicker

what will post-streptococcal glomerulonephritis look like histologically with a immunoflorescent stain?
- granular “lumpy-bumpy” basement membrane staining due to IgG antigen deposits
- nonlinear localization of antibody
- aggregated antibody

what causes vasculitis (describe pathological process)? what type of reacton is it?
- type of type III hypersensitivity reaction
- occurs when antibody/antigen complexes are deposited in wall of blood vessels and then compliment is activated
- attracts neutrophils
- the combination of neutrophils and compliment results in destruction/disolution/digestion of the vessel wall
- results in hemorrhages, large infarctions, processes in adjacent tissue that cause that tissue to die
what types of arteries are affected in vasculitis? what determines where the tissue damage is located?
- affects medium to small sized arteries - the ones visible to the naked eye
- damage depends on where the complexes are deposited
what will vasculitis look like histologically?
- in this image, this is a muscular blood vessel
- the internal elastic lamina is the squiggly dark pink line
- there’s no smooth muscle left on the left side of the blood vessel
- thrombus formation in lumen

what will the necrotic phase of vasculitis look like histologically?
- hard to even tell it was a blood vessel
- few smooth muscle cells on bottom right corner of vessel, but otherwise muscle layer destroyed
- thrombosis in vessel lumen

what will vasculitis in the very small vessels look like histologically (as opposed the the medium/small vessels that are visible to the naked eye)?
- same pathological picture, but nto as dramatic
- this image is of lung
- note that this is often drug induced

what is the difference between vasculitis in really small vessels and in larger vessels? what is each condition called? how do the processes differ?
- the difference is in the phases of the disease and what likely causes it
- if it’s in small vessels, it’s likely caused by a drug induced/associated type III hypersensitivity response
- if its in the large vessels its still a type III hypersenstivity response, but not associated with drugs (they didn’t say what it is associated with…)
- the processes are the same for both
- for small vessels, called “microangitis” or “microvasculitis”
- for large vessels, called “polyarteritis nerdosa” (PAN)
what type of immune response is serum sickness?
- systemic type III hypersensitivity
describe the progression/pathology of serum sickness. (ie what occurs to create disease?)
- in this graph, the dark line is antigen, horse IgG in this case
- it’s being normally eliminated from the circulation by the same mechanisms by which all antibodies are removed (so the line is droping)
- however, at 6-7 days, the body begins to make antibodies against the horse antibodies (human, anti-horse)
- these human anti-horse antibodies will make antibody/antigen (or really antibody/antibody) compexes with the horse antibodies
- complexes will fix compliment (the line made of round dots at the top of the graph is the complement level - this drops because the complement is being used up)
- the hazy area on the graph depicts the deposition of these complexes in tissues
- will get a type III hypersensitivity response whereever these complexes deposit (in this case, the reaction caused heart, joint, and kidney lesions)

what clinical problems will serum sickness cause? (ie what tissues will it damage, and how?)
- vasculitis
- glomerulonephritis because of deposition of complexes in basement membranes
- activation of compliment => vascular constriction and constriction of bronchioles so trouble breathing
- arthritis
- tissue will likely scar
how long will serum sickness last? will episodes reoccur?
- monophasic so it won’t come back unless you give another dose
- however, there will be scarring of the tissues







