Module 30 - Chronic Inflammation

Question 1

Describe chronic inflammation.

Answer 1

Chronic inflammation is a response of prolonged duration (weeks or months) in which inflammation, tissue injury, and attempts at repair coexist, in varying combinations.

Question 2

Define primary chronic inflammation and give examples.

Answer 2

It refers to an injury that involves chronic inflammation without an initial acute inflammatory response.

• Persistent infections
• Immune-mediated disease
• Prolong exposure to toxic agents
• Primary granulomatous

Question 3

Other than primary chronic inflammation, mention another way that can lead to chronic inflammation.

Answer 3

It can arise as a consequence of unresolved acute inflammation (a progression from the previous bout of inflammation). This may occur due to:

• Persistence of cause (peptic ulcer, chronic abscess)
• Interference with normal healing (bronchiectasis, osteomyelitis)
• Recurrent episodes of acute inflammation

Question 4

Mention the cells involved in chronic inflammation.

Answer 4

• Lymphocytes
• Macrophages (Monocytes)
• Eosinophils: Parasitic infection and allergic reactions - granules release major basic protein toxic to parasites and cause epithelial cell necrosis
• Mast Cells: Acute and chronic inflammation, early vascular change in acute inflammation (histamine, leukotrienes) - Allergic reaction (IgE) }
• Neutrophils: maybe present in some forms of chronic inflammation.

Question 5

Describe monocytes/macrophages activation.

Answer 5

Monocytes (immature mononuclear phagocytes) recruited and differentiate into macrophages in response to inflammation

Tissue macrophages :

• Initiate acute inflammation, but cytokines-prolong inflammatory response leading to chronic inflammation
• Ingest and eliminate microbes and dead tissues (M1)
• Initiate the process of tissue repair (M2)
• Display antigens to T lymphocytes and respond to signals from T cells (feedback loop)

Question 6

How are M1 and M2 macrophages activated?

Answer 6

M1 Classical activation by microbial products and IFN-ϒ:

• Microbicidal processes: ROS, NO, lysosomal proteins
• Promotes inflammation: IL-1, IL-6, IL-12, TNF, chemokines

M2 Alternative activation by other cytokines (IL-4 and IL13):

• Principle role in tissue repair: TGF-β, GF
• Anti-inflammatory: IL-10, TGF-β

Question 7

Describe lymphocytes and their functions.

Answer 7

Amplified ad propagated by immune stimulus (infection) and non-infection mediated inflammation (chemical mediators)

• Recruited into peripheral tissues
• B-lymphocytes develop into plasma cells and secrete antibodies
• CD4+ T lymphocytes become activated, promote inflammation by secreting cytokines

Question 8

Mention the three different types of CD4+ T-lymphocytes and their functions.

Answer 8

T_H1 :

• Secrete IFN-ϒ
• Classical macrophage activation (M1)
• Defense against bacteria, viruses and autoimmune disease

T_H2:

• Secrete IL-4, IL-5, IL-13
• Alternative macrophage activation (M2)
• Defense against helminthic parasites and allergic inflammation (eosinophil)

T_H17 :

• Secrete IL-17
• Leukocyte recruitment (neutrophils and monocytes)

Question 9

Describe the macrophage-lymphocyte interaction in chronic inflammation.

Answer 9

Lymphocytes and macrophages interact in a bidirectional way, and these interactions play an important role in propagating chronic inflammation.

Question 10

Describe the characteristic of granulomatous inflammation.

Answer 10

• Aggregates of activated macrophages
  
  • Epithelioid cells: epithelial-like appearance (large, pink, flat)
  • Giant cells: fusion of macrophages in response to chemical mediators (contain many nuclei)
• Activation of T-lymphocytes (causing chronic macrophage activation) - feedback -> tissue injury
• The rim of fibroblasts and connective tissue & central zone of necrosis

Granuloma formation is a cellular attempt to contain an offending agent that is difficult to eradicate

Question 11

Mention the histological features of chronic inflammation.

Answer 11

• Infiltration of site by mononuclear cells: macrophages, lymphocytes, plasma cells, eosinophils
• Tissue destruction: due to inflammatory mediators & cytokines – produced by inflammatory cells
• Repair: proliferation of fibroblasts and endothelial cells
• Fibrosis

Question 12

Describe the morphology of granulomatous inflammation.

Answer 12

• Could have a central zone of necrosis (caseating or noncaseating)
• Epithelioid cells - pink granular cytoplasm
• Surrounding lymphocytes
• Multinucleated giant cells
• Fibroblasts and collagen

Question 13

Immune-mediated granulomatous inflammation may be caesating or non-caesating. Define caesating and differ between them.

Answer 13

Caseation is defined as necrosis with the conversion of damaged tissue into a soft cheesy substance.

Caseating granuloma occurs in Tuberculosis (infection - M. tuberculosis). It’s characterized by small nodule lesions (tubercle), with a central mass of necrotic tissue surrounded by giant and epithelioid cells.

Non-caseating granuloma occurs in Sarcoidosis (unknown cause). Granuloma filled with a collection of epitheloid and giant cells derived from macrophages cells, rimmed by T-cells, fibroblasts

Question 14

Describe foreign body granuloma.

Answer 14

It is incited by inert foreign material, such as talc, suture, silica, breast implants, etc. These materials are too large to phagocytosed and do not illicit any inflammatory or specific immune response. Hnece, the granuloma forms around it.

Question 15

What are the sequelae (pathological condition) resulting from chronic inflammation?

Answer 15

• Contraction of fibrous tissue
  
  • mitral stenosis - chronic rheumatic fever
  • stricture of small bowel - Crohn’s disease
• Loss of parenchyma & function of organ:
  
  • liver - cirrhosis
• Metaplasia: change from one normal, mature cell type to another
• Neoplasia (new growth = cancer)
  
  • hepatocellular carcinoma in cirrhotic liver