Lec7-8 Immunopathology/Amyloids Flashcards Preview

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Flashcards in Lec7-8 Immunopathology/Amyloids Deck (52):

4 main types of hypersensitivity reactions and examples

1. Immediate [allergic], IgE mediated degranulation of mast cell
Ex. Asthma

2. Antibody dependent, IgG autoantibodies
Ex. Goodpasture syndrome

3. Immune complex, IgG/C3/Antigen mediated
Ex. Postinfectous GN, SLE, Vasculitis

4. Cell mediates, T cell mediated
Ex. Type I DM, Sarcoid


Two mech of immunologically-mediated disease

- hypersensitivity disease: react to foreign antigens via hyperreactive inflammatory response
- autoimmune disease: react to self antigens via normal inflammatory response


Bronchial asthma - what is it? What pathology?

- Type I hypersensitivity reaction
- Hypertrophy of bronchus smooth muscle
- Edema
- Leukocyte infiltration [eosinophils!]
- glandular hyperplasia and increased mucus secretion into bronchus lumen
- epithelial damage and sloughing


3 Subtypes of Type II Hypersentivitiy Rxns

Opsonization and phagocytosis
- may not have inflammation

Complement and Fc mediated inflammation
- neutrophil activation, inflammation, tissue injury

Abnormal physiological response
- no inflammation
- ex. receptors, myasthenia gravis [blocks acetylcholine receptors]


Goodpasture syndrome

Type II Hypersensitivity
- react to collagen IV in basement membrane
- complement and Fc receptor mediated
inflammation causes neutrophil activation
- glomeruler necrosis and acute inflammation
- leads to renal dysfunction

clinical: dark brown urine, high serum creatinine, coughing up blood, hematuria, hypertension, decreased glomerular filtration


Post-Streptococcal Glomerulonephritis

Type III hypersensitivity
- renal dysfunction, edema of eyelids, high BP, brown urine
- subepithelial immune complex deposits [granular deposits]
- may resolve on its own


Systemic Lupus Erythematosus [SLE]

Type III hypersensitivity
Reaction to nuclear antigens
- involves skin, joints, kidney, serosal membranes
- cannot resolve on its own, requires immunosuppressive therapy


5 most frequent sites immune complex deposition

skin: sun-exposure injury

glomerulus: high hemodynamic pressures + filtration function

synovium: mech trauma, high hemodynamic pressures + filtration function

endocardium: mechanical trauma, particularly valves

blood vessels: vascular turbulence, high pressure, particularly microvasculature + branch points of large BV


Type I Diabetes Mellitus

Target = Beta islet cells
Type IV hypersensitivity



Type IV hypersensitivity
Causes Granulomas



pathologic accumulation proteinaceous substance deposited in extracellular space

Consists of insoluble aggregates fibrillar proteins, cross B pleated sheet

Diagnosis requires histologic identification



Group of diseases in which amyloids deposited


Amyloid properties

- result of protein misfolding
- self association of cross-B-pleated sheets form protofilament cores
- assembly of protofilaments create amyloid fibrils
- continuous non-branching fibers
- each fiber 4-6 fibrils in parallel array
- physical structure independent of clinical setting or chemical composition


Amyloid in histology

- composed of mostly protein fibrils
- stains blue-black with acidified iodine
- resembles cellulose or starch
- progressive extracellular accumulation
- pressure atrophy, functional disruption
- organs deformed, firm, enlarged
- amorphous, hyaline substance [H&E]
- pink-orange-red [congo red stain]
-red-green birefringence [polarized light]


What does congo red show?

amyloids show up eosinophilic in normal light
show up neony green in polarized light


AL amyloid

- misfolded form of immunoglobulin light chain
- deposits in plasma cells
- stimulus = unknown, possibly carcinogen
- get monoclonal B proliferation --> plasma cells --> lots of Ig light chains
- excess protein and limited proteolysis leads to aggregation
- primary systemic amyloidosis
- ex. multiple myeloma


AA amyloid

- from serum amyloid-associated protein [SAA]
- deposits in liver [acute phase response]
- stimulus = chronic inflammation
- get macrophage activation --> IL-1/6 --> liver cells
- excess SAA protein and limited proteolysis lead to aggregation
- secondary system amyloidosis
ex. chronic inflammatory conditions


B-amyloid [AB] - what disease type?

- from amyloid precursor protein [APP]
- cerebral deposits [plaques]
senile cerebral localized amyloidosis
ex. alzheimer disease


ATTR amyloid

- from Transthyretin [TTR]
- mutation [genetic syndrome, aging]
- mutant/abnormal protein aggregates
- senile/hereditary amyloidosis
ex. senile systemic/cardiac amyloidosis


Chemical Composition of Amyloid

95% major amyloid fibril protein
- AL, AA, AB, etc

5% minor components
- serum amyloid P component
- proteoglycans, glycosaminoglycans


Pathogeneisis of Amyloidosis

1. Abnormal folding of protein, becomes unstable
2. Self-associates into oligomers/fibrils, becomes insoluble
3. Deposits in extracellular tissue, causes pressure atrophy
4. Disrupts normal tissue function


Why do misfolded proteins turn into amyloids instead of being degraded in some people?

High level normal proteins [misfold when accumulate]
- increased production from aging
- decreased excretion
- decreased proteolysis

Mutation causes misfolding of abnormal proteins
- hereditary [ATTR] or acquire [prion]


Classification of Amyloidosis

Tissue distribution: either localized or systemic

If systemic:
-- primary: due to plasma cell proliferation, clinically unrecognized
-- secondary: due to chronic inflammatory disorder

Also can be hereditary/familial


Prognosis of generalize system amyloidosis

- progressive, unremitting
- median survival 2-5 yrs [primary < secondary]
- cardiac or renal complications


Prognosis localized or familial amyloidosis

15-20 years
longer than generalized


treatment for amyloidosis

- reduce precursor protein synthesis
- inhibit fibrillogenesis
- amyloid can rarely be resorbed


Origins of autopsy

- 18th century
- Giovanni Battista Morgagni
- first great autopsy pathologist
- publicly opposed galileo's theories


19th century autopsy

Marie-Francois Xavier Bichat = father of histology

Rudolph Virchow: said cellular derangement is at basis of disease


Does histamine lead to transudate or exudate? Why?

- Histamine is a vasodilator and increases vascular permeability
- Causes cells and fluid to leave = exudate


Type III hypersenstivity mechanism and pathology?

- circulating immune complex is deposited in kidney
- activated inflammatory pathway in kidney
- causes vasculitis [fibrinoid necrosis]


Type IV hypersensitivity examples, mech, pathology?

examples: type I diabetes, sarcoidosis, contact dermatitis, transplant rejection

mech: CD4 or CD8 T cell activation

pathology: granulomas


Type II hypersensitivity examples, mech, pathology?

examples: goodpastures, autoimmune hemolytic anemia, graves

immune mech: antigen on cell surface or tissue surface

pathology: complement activation or acute inflammation


Definition of polyp

growth protruding above epithelial surface


Clinical signs of bronchial astham

- wheezing, breathlessness, tight chest, cough


clinica sign of systemic analphylaxi

- itching, hives, difficult breathing, diarrhea, shock


What is myasthenia gravis

- type II hypersensitivity
- blocks acetylcholine receptor


what is grave's disease

- stimulates TSH receptor
- type II hypersensitivity


what type of hypersensitivity is autoimmune hemolytic anemia?

- type II
- attacks red cell antigen


What type of hypersensitivity is post-strep glomerulonephritis?

type III


What type of hypersensitivity shows granular immunofluorescence and which linear?

Type III is granular
Type II is linear [goodpasture]


What is multiple myeloma? What amyloidosis associated?

- cancer of plasma cells where overproduce one type of abnormal antibody
- overproduction of antibody can lead to AL amyloidosis


What disease associated with AL amyloid?

multiple myeloma


What disease associated with AA amyloid?

chronic inflammatory conditions [rheumatoid arthritis


If you see subepithelial deposits in glomerulus what should be first thought?

post stre glomerulonephritis


What is heparin?

An anticoagulant


What are schistocytes?

Fragmented RBC
a sign of disseminated intravascular coagulation


Most likely cause arterial thrombus?

Endothelial injury


What inflammatory cell involved primarily in bronchial asthma?



What form of amyloid associated with alzheimers? What precursor?

AB amyloid, from APP


What type of necrosis is associated with type III hypersensitivity

fibrinoid necrosis


How do you tell if a granuloma in lung is sarcoid or TB?

- granulomas of sarcoid have no central necrosis, those of TB do
- sarcoid granulomas often surrounded by fibrosis [scar tissue]


What are 4 diseases that cause granulomas and where?

in lung: sarcoidosis, TB
in intestine: crohns
in skin: leprosy