Chronic Inflammation

Question 1

What is chronic inflammation?

Answer 1

• 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

Question 2

Causes of chronic inflammation?

Answer 2

• persistent infection
• persistent toxins
• autoimmune disease
• can result in scarring

Question 3

Histologic features of chronic inflammation?

Answer 3

1. infiltration of mononuclear cells
   - macrophages, lymphocytes, plasma cells, mast cells, eosinophils
2. tissue destruction
   - hallmark of chronic
3. attempts at healing
   - connective tissue replacement, angiogenesis, fibrosis

Question 4

what happens within 48 hours after acute inflammation?

Answer 4

1. within 48 hours, monocyte predominates
2. monocyte migration similar to PMNs
3. monocyte transforms in tissues to macrophages
4. macrophage is central player in chronic inflammation b/c it produces a large variety of substances

Question 5

Describe the maturation of mononucelar phagocytes?

Answer 5

see picture

Question 6

what are the macrophages in the liver?

Answer 6

kupffer cells

Question 7

What are the three mechanisms for macrophage accumulation and persistence in chronic inflammation?

Answer 7

1. recruitment- chemotactic mediators (MCP1), differentiates
2. Division- IL-6 production, macrophages in tissues start dividing
3. IL-6 causes migration, immobilization

Question 8

Products released by macrophages?

Answer 8

• 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

Question 9

what are the actions of chemokines?

Answer 9

• 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

Question 10

what are the major features of chronic inflammatory response?

Answer 10

1. injurious agent persists in tissue for weeks, months, years
2. cell response to persistent injury generally consists of macrophages and lymphocytes
3. granuloma formation occurs upon prolonged macrophage stimulation
4. tissue necrosis within growth of fibrovascular granuulation tissue results in scar formation
   - persistent neutrophilic exudation is occasionally present in chronic inflammation

Question 11

what are the two stimuli for macrophage activation? what are the outcomes?

Answer 11

1. activated T cell- complementary interaction, macrophage activates T cell
2. non immune activation- endotoxin, fibronectin, chemical mediators
   - outcomes: tissue injury or fibrosis

Question 12

what is the complementary interaction of macrophage-lymphocyte?

Answer 12

activated lymphocytes can activate macrophages and vice versa through cytokines

Question 13

common causes of reactive monocytosis?

Answer 13

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

Question 14

when would granuloma form?

Answer 14

delayed (type 4) hypersensitivity

-lymphocytes make a cup around macrophages, epithelioid

Question 15

TB chest xray?

Answer 15

difference in bone density, ciruclar areas are where granulomas are seen

Question 16

Langhans giant cells in TB granulomas?

Answer 16

• 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)

Question 18

acid fast mycobacterium bacilli?

Answer 18

if wanted to make a diagnosis of TB, look for this in samples

Question 19

Interaction between M. tuberculosis and host macrophages?

Answer 19

• 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)

Question 20

leprosy cause?

Answer 20

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

Question 21

foreign body and methyl methacrylate?

Answer 21

• bone reabsorbed and implant (hip) loosened
• granulomas form

Question 22

granulomatous diseases?

Answer 22

-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

Question 23

sarcoidosis?

Answer 23

• similar to TB
• no caseating necrosis
• granulomas with cupping surface

Question 24

Crohns disease?

Answer 24

• sluffing of colon
• granulomas in wall of muscle layer
• massive inflammation
• epithelial surface insulted by cytokines

Question 25

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

Answer 25

d. mycobacterium tuberculosis

Question 26

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

Answer 26

d. abscess formation

Question 27

antiinflammatory effects of glucocorticoids (therapy)?

Answer 27

- 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

Question 28

influence of TGF-beta on inflammatory response?

Answer 28

-antagonist to IL-1beta, TNF-alpha, IFN-gamma

Question 29

Newer therapies for inflammation?

Answer 29

- 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