Immunopathology I - lecture notes - julia Flashcards
what are the possible disorders arising from excessive or inappropriate activity of the immune system? (3)
- mediated by antibodies
- lymphocyte mediated immune responses
- mixed antibody and lymphocyte disorders
what are some examples of immune disorders mediated by antibodies? what type of hypersensitivity is each disorder?
- anaphalactic or atopic reactions (type I)
- cytotoxic, anti-tissue antibody reactions (type II)
- immune complex deposition responses (type III)
what are some examples of lymphocyte mediated immune responses?
- delayed type hypersensitivity (type IV)
- granulomatosis disease
what are the possible types of disorders due to absense or hypofunction of some elements of hte immune system or its tissues? (2)
- endogenous/genetic
- acquired
- iatrogenic
- infectious
what are the two categories of acquired disorders of the immune system due to absense or hypofunction of they system or tissues?
- iatrogenic
- infectious
what are the two basic mechanisms that can cause immunologically based diseases?
- disorders arising from excessive or inappropriate activity of the immune system
- disorders due to absense or hypofunction of some elements of the immune system or its tissues
what are the four types of hypersensitivity reactions? what mediates each type? (summary card)
- type I: mediated by IgE and products of mast cells, eosinophils, and/or basophils
- type II: mediated by direct antibody binding to cells or tissue components
- type III: mediated by deposition of antigen-antibody complexes and activation of complement and neutrophils
- type IV: mediated by T-lymphocytes and macrophages
what mediates type I hypersensitivity reactions?
- IgE
- the products of mast cells, eosinophils and/or basophils
what mediates type II hypersensitivity reactions?
- direct antibody binding to cells or tissue components
what mediates type III hypersensitivity reactions?
- deposition of antigen-antibody complexes
- activation of complement and neutrophils
what mediates type IV hypersenitivity reactions?
- T-lymphocytes
- macrophages
what type of reactions are caused by type I hypersensitivity?
anaphalactic / atopic reactions
describe the process of the activation of a type I hypersensitivity reaction
- antigen is processed by dendritic cells
- dendritic cell stimulates Th2 cells
- T cell help induces B cells to be activated
- b cells develop into plasma cells
- these plasma cells make IgE
- IgE stimulates mast cells stimulated
- mast cells release vasoactive and spasmogenic substances (degranulation)
- these act on endothelial cells and smooth muscle cells locally or systemically
what are some examples of localized anaphalactic/atopic reactions? (3)
- asthma
- hay fever
- insect bites
what are some examples of systemic causes of anaphalactic/atopic reactions? (5)
- insect stings
- drug allergies
- hives
- some food allergies
- anaphalxsis (the syndrome)
why are multiple antigens requred to create an allergic reaction? (ie why won’t just one antigen particle work?)
IgE must be “loaded up” - it must cross-link to be activated so there must be multiple IgE molecules that bind to antigen or the IgE won’t cross-link and there won’t be an immune response
will you get an allergic response during the first exposure to antigen?
- likely not
- the first time you are exposed to a lot of antigen, you basically have a primary immune response, which will result in the generation of antibodies to that antigen (sensitization to this antigen)
- on the next exposure, you’ll get a response
- could be sensitized to something similar that will create a reaction when exposed to the antigen you have an allergy to
what is the most common mechanism for degranulation of mast cells?
can happen by many mechanisms but IgE is most common
look over this table (don’t memorize)
- the physical stimuli mechanism not fully known but can cause mast cells to degranulate
- you don’t form an antibody against cold or heat, but do get a response
- if you have anaphylatoxins in an area, these can cause mast cells to degranulate even if you don’t have an immune response in that area
what are the two stages of type I (anaphylactic) reactions?
- immediate - IgE on mast cell surface binds its specific antigen and the mast cell degranulates => release of preformed mediators into the area
- delayed - once triggered, mast cell begins synthesis of other soluable mediators
as a result of the delayed stage, you can have days of coughing, chest tightness, and mucus after the original exposure
why does tissue undergoing an allergic reaction get puffy?
edema as a consequence of mast cell degranulation
what are the clincal symptoms that occur during the initial (4) and secondary (4) response in a type I hypersensitivity reaction? in what time frame would you expect to see these symptoms?
- initial: in 5 minutes to 1 hour
- vasodilation
- vascular leakage
- smooth muscle contraction
- glandular secretion - secondary: in 2 hours to days
- tissue infilatration by eosinophils, basophils, neutrophils and some T cells
- tissue injury
- mucosal damage
- remodeling
what are the primary mediators of the type I hypersensitivity reaction? (4)
- biogenic amines
- chemotactic mediators
- enzymes
- proteoglycans
what are some examples of preformed mediators released by mast cells?
- don’t memorize this chart!
- just review what’s actually released as preformed mediators
what is severe urticaria? what causes it? what type of reaction is it?
- immune reaction to heat or cold
- localized type I hypersensivity
- get massive degranulation in response to temperature
what is atopic keratoconjunctivitis? what causes it? what type of reaction is it?
- eye becomes puffy and you get corneal edema that extends out into the sclera
- will see dilated blood vessels on sclera
- due to a type I hypersensitivity response secondary to IgE
- due to a large dose of antigen
describe the pathology of asthma (what happens ot the epithelial cells and smooth muscle cells in the respiratory tract?)
- overall, asthma is an abnormal repair response to epithelial injury
- after many cycles of allergic reaction, the epithelial cells will be killed off and have to be replaced
- myofibroblasts will migrate in to help replace these cells
- this will result in a thickening of the basement membrane
- will also get extra-cellular matrix remodelling because theres lots of inflammatory molecules being released –> these will stimulate fibroblasts, which will remodel the ECM
- smooth muscle cells will hypertrophy because the have to constantly squeeze more than normal - they’ll get stronger
- this increased smooth muscle cell strength can also give the mucus glands more secretion power
- plust get gland hyperplasia
what structural changes would you expect to see in the airways of patients with asthma (list - summary card)?
- epithelial shedding
- gland hyperplasia
- matrix remodeling
- basement membrane pseudothickening
- inflammatory infiltrate
- muscle hyperplasia
what would a lung from an asthma patient look like (gross level)?
- overinflated - get air trapping because of mucus in the airways
- most lungs collapse when the chest is opened for autopsy - here it’s full of air
- airways full and oozing with mucus
what would lung from a patient with asthma look like histologically?
- smooth muscle hypertrophy (areas surrounded by white circles)
- thickend basement membrane under epithelium
- lots of peribronchiolar inflammation
- areas where bronial epithelium (dark blue) is thin or almost missing
- ring around bronchiole = chronic inflammation with lymphocytes, macrophages, plasma cells (making IgE), mast cells, and eosinophils
describe the physiological effects of a bee sting in a patient with a severe bee allergy (what would happen to heart rate and respiratory rate?) what can be done to treat such patients?
- this is a graph of an experiment from the 70s - they took a patient with a severe bee allergy an had him stung and then kept resucitating him with epinipherine
- within minutes of sting, both respiratory and heart rate go up, the difference between diastolic and systolic collapse
- by 9 minutes post sting, the patient is essentially dead
- epi resucitates him
- can see from the graph that, even though the initial sting occured only once, he goes into respiratory and cardiac arrest multiple times from the same sting, though the subsequent episodes are less bad than the first episode
- this is all due to a massive release of histamine
review the complement cascade (be familiar with it, but don’t memorize it)
what are some ways the cascade can be activated? (3)
- classic pathway = antibody binds to its target, antibody receptor is engaged => => => c5 activation, MAC complex
- some substances released by mast cells can kick off c3a and c5a
- some enzymes in the coagulation cascade can activate it, such as hageman factor
what is erythroblastosis fetalis? what type of reaction is it? why does it occur? what would it look like?
- condition that involves having a huge number of erythroblasts (last nucleated precursor before erythrocytes)
- type II hypersensitivity reaction
- happens when mother is Rh- and father is Rh+
- after first pregnancy, mother will form antibodies to fetus’s Rh+ blood following birth (since some of the fetal blood will mix with maternal blood in the birth canal)
- during a second pregnancy, the new infant’s Rh+ erythrocytes will be attacked by maternal antibodies (IgGs)
- results in continous ongoing chronic hemolysis in the infant
- infant will be endemous, pink
note that this is rarely seen anymore because pregnant women who are Rh- get a shot to prevent the formation of antibodies to Rh+ blood
what would erythroblastosis fetalis look like histologically? how does this histological presentation relate to the clinical symptoms you would see in these patients?
- liver will have myriad erythroblasts in the sinusoids
- because child is trying to make RBCs with every organ it has
- therefore spleen, bone marrow, wall of gut, kidneys will all be full of erythroblasts, but will still not be able to keep up
- child will have severe anemia and these organs won’t be doing their jobs as well as they should
- also, these organs won’t be getting enough O2 and so will display stunted growth
this image is of liver
how would goodpasture’s disease appear histologically with an immunoflorescent stain?
- if you used an immunoflorescent stain against the IgG antibody, you would see the glomeruli and alveolar walls light up bright green (image is of glomeruli)
- these antibodies are binding in the basement membranes of the glomeruli
how will goodpasture’s disease appear histologically with an H and E stain in the lung?
- will have hemorrhage in alveolar spaces
- can still see where the alveoli were though
what will a heart of a patient with rheumatic fever look like (gross)?
- vegetations (fibrin/platelet aggregates) form on the surface of the valve, often the mitral valave
- chordae tendinae will get sticky, shorten, fuse together => deformaton of valve
- eventually get fish-mouth deformity of aortic valve (edges of valve that should be three leaflets fuse and get a narrow appeture)
what will a heart of a patient with rheumatic fever look like histologically?
- should see aschoff bodies at areas of inflammation (myocarditis)
- inflammatory cells
- aschoff giant cells - small with 5-6 nuclei at most
- anitschkow monocytes - chromatin looks like caterpillar
