inflammation

• Chronic inflammation is an inflammatory response of prolonged duration - weeks, months, or even indefinitely
• Chronic inflammation


  The extended time course is provoked by persistence of the causative stimulus to inflammation in the tissue
• Chronic inflammation


  Inevitably causes tissue damage (destruction) and is accompanied by simultaneous attempts at healing and repair
• Acute inflammation


  • Rapid onset
  • Brief duration
  • Stereotyped
  • Exudation & PMN emigration
  • Neutrophils
• Chronic inflammation


  • Slow onset
  • Prolonged
  • Modulated
  • Inflammation & Injury & Repair
  • Varied cell response
• Predisposing causes of chronic inflammation

  • As a progression from acute inflammation
  • If the original stimulus persists, after repeated episodes of acute inflammation
  • De novo if the causative agent produces only a mild acute response
• Aetiological agents of chronic inflammation

  • Infectious organisms that can avoid or resist host defenses and so persist in the tissue for a prolonged period
  • Infectious organisms that are not innately resistant but persist in damaged regions where they are protected from host defences
  • Irritant non-living foreign material that cannot be removed by enzymic breakdown or phagocytosis
  • A "normal" tissue component in autoimmune diseases
  • Unknown causes for some diseases like Crohn's disease
• Histological appearances in chronic inflammation

  • Macrophage
  • Lymphocyte
  • Plasma cell
  • Eosinophil
  • Neutrophil
• Macrophages


  • They contribute to the reaction by secreting cytokines and growth factors that act on various cells, by destroying foreign invaders and tissues, and by activating other cells, notably T lymphocytes
  • They are professional phagocytes that act as filters for particulate matter, microbes, and senescent cells
• Macrophage natural history


  There are two major pathways of macrophage activation: classical and alternative
• Classical macrophage activation


  May be induced by microbial products, T cell-derived signals like IFN-γ, or foreign substances
• Alternative macrophage activation


  Is induced by cytokines other than IFN-γ, such as IL-4 and IL-13
• Microbes and other environmental antigens activate T and B lymphocytes, which amplify and propagate chronic inflammation
• Role of lymphocytes


  • They use various adhesion molecule pairs and chemokines to migrate into inflammatory sites
  • Cytokines from activated macrophages promote leukocyte recruitment, setting the stage for persistence of the inflammatory response
• CD4+ T lymphocyte subsets

  • TH1 cells produce IFN-γ, which activate macrophages by the classical pathway
  • TH2 cells secrete IL-4, IL-5, and IL-13, which recruit and activate eosinophils
  • TH17 cells secrete IL-17 and other cytokines, which induce the secretion of chemokines responsible for recruiting neutrophils (and monocytes)
• Lymphocytes and macrophages


  Interact in a bidirectional way, and these interactions play an important role in propagating chronic inflammation
• Activated B lymphocytes and antibody-producing plasma cells


  Are often present at sites of chronic inflammation, but their specificity and importance are unclear
• Tertiary lymphoid organs


  Lymphoid tissues resembling lymph nodes that form in some chronic inflammatory reactions, which may perpetuate the immune reaction
• Eosinophils


  Are abundant in immune reactions mediated by IgE and in parasitic infections, and their recruitment is driven by adhesion molecules and chemokines
• Mast cells


  Participate in both acute and chronic inflammatory reactions, and in immediate hypersensitivity reactions, their degranulation releases mediators like histamine and prostaglandins
• Neutrophils


  Although characteristic of acute inflammation, many forms of chronic inflammation lasting for months continue to show large numbers of neutrophils, induced either by persistent microbes or by mediators produced by activated macrophages
• Chronic inflammation cells


  • Macrophages
  • Lymphocytes
  • Plasma cells
  • Neutrophils
  • Eosinophils
• Cytokines/chemokines


  Low MW peptides with autocrine, paracrine, and endocrine effects, involved in the acute phase reaction, endothelial activation, fibroblast activation, and leukocyte activation
• Functions of cytokines


  • Regulators of lymphocyte function
  • Modulators of natural immunity
  • Activators of inflammatory cells
  • Haemopoietic factors
• Acute inflammation


  The rapid response of a living vascularised mammalian tissue to an injurious agent. It serves to deliver mediators of host defence (Leukocytes and plasma proteins) to the site of injury, in order to eliminate the offending agent.
• Neutrophils


  • Characteristic of acute inflammation
  • Can persist in large numbers in chronic inflammation
• Acute inflammation


  • It is characterized by extracellular fluid and leukocyte accumulation
  • It is a complex dynamic process intended by nature as a protective response, which eliminates noxious agents and paves way for repair of damaged tissues
  • It results from a delicate interplay between several protagonists and antagonists, and therefore trivial to life-threatening effects may result from excessive or inadequate inflammatory reactions
• Without inflammation, infections would go unchecked, wounds would never heal, and injured tissues might remain permanent.
• Chronic inflammation


  • Lasts for months
  • Shows large numbers of neutrophils
  • Induced by persistent microbes or mediators produced by activated macrophages
• Clinical features of inflammation were described in an Egyptian papyrus

  2700 BC
• Cells of chronic inflammation

  • Macrophages
  • Lymphocytes
  • Plasma cells
  • Neutrophils (minor component)
  • Eosinophils (minor component)
• Cardinal signs of inflammation (described by Celsus in 1st century AD)

  • Rubor (redness)
  • Tumor (swelling)
  • Calor (heat)
  • Dolor (pain)
• Lymphoid cell response in chronic inflammation

  1. Proliferation at site of inflammation

  2. Proliferation in local lymph nodes

  3. Can give rise to lymphoid follicles with germinal centres
• John Hunter in 1793 noted that inflammation is not a disease.
• Classes of cytokines/chemokines


  • Haemopoietic factors
  • Activators of inflammatory cells
  • Modulators of natural immunity
  • Regulators of lymphocyte function
  • Chemokines
• Chemokines


  Low MW peptides with autocrine, paracrine, and endocrine effects
• Julius Cohnheim (1839-1884) described the events of inflammation
• Elie Metchnikoff in 1880 discovered phagocytosis
• Histologic patterns of chronic inflammation

  • Macrophage rich
  • Eosinophil rich
  • Lympho/plasmacytic
  • Mixed cell
  • Granulomatous
• Paul Ehrlich developed the humoral theory of inflammation