Chronic Inflammation Notes

Chronic Inflammation Definition

  • Prolonged response involving inflammation, tissue injury, and repair attempts.
  • May follow acute inflammation or begin insidiously.

Causes

  • Persistent infections.
  • Hypersensitivity diseases (autoimmune, allergic).
  • Prolonged exposure to toxic agents (exogenous or endogenous).

Cells Involved

  • Macrophages: Dominant cells that secrete cytokines and growth factors, activating other cells (T lymphocytes).
    • Functions: Phagocytosis, inflammation propagation, tissue repair, antigen presentation to T cells.
    • Activation:
      • Classical (M1): Microbicidal, inflammation (stimulated by microbial products, IFN-γ).
        • ROS, NOS, Lysosomal enzymes.
        • IL1, 12, 23.
      • Alternative (M2): Tissue repair, fibrosis (stimulated by IL 4 & IL 13).
        • Growth factors, TGF-B.
        • IL 10, TGF-B (anti-inflammatory)
  • Lymphocytes:
    • T lymphocytes: Amplify and propagate chronic inflammation; activation leads to memory cells.
      • T CD4+ Lymphocytes promote inflammation.
        • Th1 cells: Secrete IFN-γ, activate macrophages (Classical Pathway).
        • Th2 cells: Secrete IL-4, IL-5, and IL-13, activate macrophages (Alternate Pathway).
        • Th17 cells: Secrete IL-17, recruit neutrophils.
    • B lymphocytes and plasma cells: Produce antibodies against persistent foreign antigens, self-antigens, or altered tissue components.
  • Eosinophils: Mediate IgE reactions and parasitic infections; granules contain major basic protein.
  • Mast cells: Recognize IgE antibodies, release mediators, and induce strong inflammatory responses; associated with allergic reactions.
  • Neutrophils: Present in acute on chronic inflammation, induced by persistent microbes or mediators.

Morphologic Patterns

  • General characteristics: Mononuclear cell infiltration (macrophages, lymphocytes, plasma cells), connective tissue replacement, angiogenesis, and fibrosis.
  • Nonspecific proliferative: Infiltration of mononuclear cells, proliferation of fibroblasts, connective tissue, vessels, and epithelial cells.
  • Granulomatous Inflammation: Collections of activated macrophages, often with T lymphocytes, and sometimes necrosis.

Granulomatous Inflammation

  • Characterized by collections of activated macrophages, often with T lymphocytes, frequently associated with necrosis.
  • Cellular attempt to contain an offending agent that is difficult to eradicate.
  • Composed of aggregates of epithelioid histiocytes, with a peripheral cuff of lymphocytes and plasma cells, and occasionally a necrotic center.

Types of Granulomas

  • Infectious Granulomas:
    • Caseating Granulomas (Necrotizing):
      • Cause: Mycobacterium tuberculosis (TB), histoplasmosis, coccidioidomycosis.
      • Feature: Central caseous necrosis.
      • Histology: Langhans giant cells, epithelioid macrophages, lymphocytic rim.
    • Non-Caseating Granulomas (Non-Necrotizing):
      • Cause: Sarcoidosis, Crohn’s disease, berylliosis, some fungal infections.
      • Feature: Lack of central necrosis.
      • Histology: Compact, well-formed granulomas with multinucleated giant cells.
  • Foreign Body Granulomas:
    • Cause: Inert foreign material (sutures, talc, silica, beryllium, prosthetic implants).
    • Feature: Foreign material visible under polarized light.
    • Histology: Foreign body giant cells with phagocytized material.
  • Immune (Hypersensitivity) Granulomas:
    • Cause: Persistent antigens that trigger T-cell mediated immune responses.
    • Example: Sarcoidosis, Crohn’s disease.
    • Histology: Epithelioid cells, multinucleated giant cells, lymphocyte infiltration.

Tuberculoid Granuloma Structure

  • Epithelioid cells: Activated macrophages with pink granular cytoplasm.
  • Surrounding collar of lymphocytes.
  • Older granulomas may have a rim of fibroblasts and connective tissue.
  • Multinucleated giant cells (Langhans giant cells): Large mass of cytoplasm with many nuclei.
  • Central zone of caseous necrosis: Amorphous, structureless, eosinophilic, granular debris.

Types of Giant Cells

  • Macrophage derived giant cells: *Langhan giant cells- Langhans' giant cells have horse shoe-shaped nuclei arrangement at one pole of cell. It contains more than 15 nuclei. * Seen in Tubercular granuloma, Leprosy, Syphilis, Deep fungal infection, Sarcoidosis, Leishmaniasis, Crohn's disease
    • Foreign body giant cell larger than Langhans' giant cells with nuclei randomly scattered throughout their cytoplasm
      • Seen in foreign body granuloma formed in response to various exogenous or endogenous materials.
        Touton giant cells have a central ring of nuclei while the peripheral cytoplasm is clear due to accumulated lipid
        *Seen in Fat necrosis, Xanthoma, Xanthogranulomas, Dermatofibroma
  • Epidermal cell derived
    *Tzank cells are multi-nucleated giant cell with moulding of the nuclei as they are crowded together
    *Seen in Herpes simplex, Varicella and herpes zoster, Cytomegalovirus
    *Multinucleated epidermal giant cells-than three clumping nuclei has been considered an episodic and exceptional phenomenon in inflammatory skin diseases.
    *Seen in Chronic eczema or prurigo, Lichen amyloidosis, Dermatitis herpetiformis, Erythema multiforme, Pustular psoriasis, Lichen planus, Lupus erythematosus.
    *Melanocyte derived giant cells
    *Starburst giant cells are multi-nucleated melanocytes with a stellate appearance due to its prominent dendritic processes. These are useful indicator for the diagnosis of lentigo maligna
    *Balloon cells may be multi-nucleated and larger than ordinary nevus cells.Seen in baloon cell nevus and baloon cell melanoma
    *Floret like multinucleated giant cell
    *These cells have scanty cytoplasm and peripherally arranged nuclei in the intervening stroma.
    *Seen in: Gynaecomastia, Neurofibroma in NF-1, Giant cell angiofibroma, Pleomorphic lipoma
    *Tumor giant cells
    *Reed-sternberg giant cells in Hodgkins lymphoma and many other hematolymphoid neoplasms
    *Osteoclast like giant cells in giant cell tumour as well as other bone lesions
    *Giant cells in lymph node associated with anaplastic large