Chronic Inflammation Flashcards
What is chronic inflammation?
- inflammation of prolonged duration
- active inflammation -> tissue destruction -> attempts at repair processed simultaneously
- may follow acute
- often begins insidiously as low grade, smoldering, asymptomatic response
Causes of chronic inflammation?
- persistent infection
- persistent toxins
- autoimmune disease
- can result in scarring
Histologic features of chronic inflammation?
- infiltration of mononuclear cells
- macrophages, lymphocytes, plasma cells, mast cells, eosinophils - tissue destruction
- hallmark of chronic - attempts at healing
- connective tissue replacement, angiogenesis, fibrosis
what happens within 48 hours after acute inflammation?
- within 48 hours, monocyte predominates
- monocyte migration similar to PMNs
- monocyte transforms in tissues to macrophages
- macrophage is central player in chronic inflammation b/c it produces a large variety of substances
Describe the maturation of mononucelar phagocytes?
see picture
what are the macrophages in the liver?
kupffer cells
What are the three mechanisms for macrophage accumulation and persistence in chronic inflammation?
- recruitment- chemotactic mediators (MCP1), differentiates
- Division- IL-6 production, macrophages in tissues start dividing
- IL-6 causes migration, immobilization
Products released by macrophages?
- enzymes
- neutral proteases
- elastase
- collagenase
- plasminogen activator
- acid hydrolases
- phosphatases
- lipases
- plasma proteins
- complement components
- coagulation factors
- reactive metabolites of oxygen
- eicosanoids
- cytokines, chemokines
- growth factors
- nitric oxide
what are the actions of chemokines?
- activate adhesion molecules
- act through G protein coupled transmembrane receptors and cause calcium influx (actin effect)
- induce haplotaxis (cell migration along surface gradients)
- bind to proteoglycans and ECM
- induce oxygen burst and release of PMN proteinases
what are the major features of chronic inflammatory response?
- injurious agent persists in tissue for weeks, months, years
- cell response to persistent injury generally consists of macrophages and lymphocytes
- granuloma formation occurs upon prolonged macrophage stimulation
- tissue necrosis within growth of fibrovascular granuulation tissue results in scar formation
- persistent neutrophilic exudation is occasionally present in chronic inflammation
what are the two stimuli for macrophage activation? what are the outcomes?
- activated T cell- complementary interaction, macrophage activates T cell
- non immune activation- endotoxin, fibronectin, chemical mediators
- outcomes: tissue injury or fibrosis
what is the complementary interaction of macrophage-lymphocyte?
activated lymphocytes can activate macrophages and vice versa through cytokines
common causes of reactive monocytosis?
infectious agents:
Tuberculosis
Subacute bacterial endocarditis
Rickettsial diseases
Syphilis
Brucellosis
Typhoid fever
Leishmaniasis
Following acute infections
Associated with malignant disease:
Preleukemia & Leukemias
Myeloproliferative syndrome
Hodgkin’s disease & Lymphomas
Multiple Myeloma
Non-hematologic malignant disease
Associated with other conditions:
Neutropenia and anemias
Systemic lupus Erythematosus
Rheumatoid arthritis
Sarcoidosis
Drug reaction
when would granuloma form?
delayed (type 4) hypersensitivity
-lymphocytes make a cup around macrophages, epithelioid
TB chest xray?
difference in bone density, ciruclar areas are where granulomas are seen
Langhans giant cells in TB granulomas?
- caseating necrosis
- fibrotic material in lung, not normal
- cells in middle are giant langhans, horseshoe arrangement of nuclei, group of fused cells, seen in TB granulomas (not langerhans dendritic)
acid fast mycobacterium bacilli?
if wanted to make a diagnosis of TB, look for this in samples
Interaction between M. tuberculosis and host macrophages?
- surface binding of organism by complement and mannose receptors and CD14
- phagosome-lysosome fusion
- killing or inhibition of organism predominantly by ONOO
- recruitment by macrophage release of cytokines (TNF, IL-1) and chemokines (IL-8)
leprosy cause?
mycobacterium leprii
- granulomas under skin
- not caseating
- still have macrophages in center with cupping around
- show up on skin because of temperature difference from internal organs
foreign body and methyl methacrylate?
- bone reabsorbed and implant (hip) loosened
- granulomas form
granulomatous diseases?
-can be chronically inflamed but no granulomas
Bacterial origin:
Tuberculosis
Leprosy
Salmonellosis
Brucellosis
Fungal origin:
Histoplasmosis
Blastomycosis
Coccidioidomycosis
Helminthic orgin:
Schistosomiasis
Metal induced (foreign body): Berylliosis
Unknown etiology:
Sarcoidosis
Crohn’s disease
Wegener’s granulomatosis
sarcoidosis?
- similar to TB
- no caseating necrosis
- granulomas with cupping surface
Crohns disease?
- sluffing of colon
- granulomas in wall of muscle layer
- massive inflammation
- epithelial surface insulted by cytokines
A 32-year-old woman has had a chronic cough with fever for the past month. On physical examination, she has a temperature of 37.5°C, and on auscultation of the chest, crackles are heard in all lung fields. A chest radiograph shows many small, ill-defined nodular opacities in all lung fields. A transbronchial biopsy specimen shows interstitial infiltrates with lymphocytes, plasma cells, and epithelioid macrophages. Which of the following infectious agents is the most likely cause of this appearance?
a. Staphylococcus aureus
b. Plasmodium falciparum
c. Candida albicans
d. Mycobacterium tuberculosis
e. Klebsiella pneumoniae
d. mycobacterium tuberculosis
A 90-year-old woman is diagnosed with Staphylococcus aureus pneumonia and receives a course of antibiotic therapy. Two weeks later, she no longer has a productive cough, but a 3-cm rounded density in the right lower lobe of the lung whose liquefied contents form a central air-fluid level. There are no surrounding infiltrates. Which of the following terms best describes the outcome of the patient’s pneumonia?
a. Complete resolution
b. Regeneration
c. Fibrosis
d. Abscess formation
e. Progression to chronic inflammation
d. abscess formation
antiinflammatory effects of glucocorticoids (therapy)?
- suppress CD4 cells
- stimulate apoptosis of eosinophils
- inhibit expression of adhesion molecules and receptors
- decrease transcription rates for IL-6 and IL-1beta
- suppress phospholipase A2, cycloxygenase 2 and NO synthase
influence of TGF-beta on inflammatory response?
-antagonist to IL-1beta, TNF-alpha, IFN-gamma
Newer therapies for inflammation?
- pentoxifylline and thalidomide suppress the release of TNF-alpha from phagocytes
- infliximab, a monoclonal antibody to TNF-alpha blocks proteins activity
- etanercept- a TNFR:Ig fusion protein that binds TNF
