Acute Inflammation Mechanisms

Acute Inflammation

• Rapid response of living tissue to any injury, characterized by redness, swelling, heat, pain, and loss of function

Mechanisms of Disease

• Vascular dilatation, exudate leaks into tissues, and neutrophils emigrate
• Changes controlled by many short-lived chemical mediators that can be manipulated by drugs
• Neutrophils: fast-acting, short-lived phagocytes that engulf and degrade bacteria, dead tissue, etc.

Phagocytosis

• Enhanced by opsonisation of particles, e.g. antibody or complement on surface
• Bacterial killing largely oxygen-dependent

Defects in the System

• Lead to severe susceptibility to infection

Chronic Inflammation

• May take over from acute inflammation if damage is too severe to be resolved within a few days
• May arise de novo in some autoimmune conditions, chronic infections, or chronic low-level irritation
• May develop alongside acute inflammation in severe persistent or repeated irritation

Characteristics of Chronic Inflammation

• Microscopic appearances, with the type of cell present being the most important characteristic
• Macrophages are the primary cells present, derived from blood monocytes
• Macrophages accumulate due to recruitment from blood, mitotic division, and immobilization by cytokines

Macrophage Function

• Phagocytosis of debris and bacteria, including recognition, engulfment, and killing
• Activation once extravasated, with secretion of interferon gamma (IFN-γ) by sensitized T-cells, bacterial endotoxins, and others

Examples of Chronic Inflammation

• Repeated obstruction by gallstones, leading to fibrosis of the gallbladder wall
• Acute gastritis (alcohol, drugs), and chronic gastritis (Helicobacter pylori)
• Ulceration occurs due to an imbalance of acid production and mucosal defense
• Impaired function in inflammatory bowel disease, including ulcerative colitis and Crohn's disease
• Impaired function in rheumatoid arthritis, an autoimmune disease with localized and systemic immune response

Chronic Inflammation and Immune Response

• Overlap between chronic inflammation and immune responses
• Immune diseases cause pathology by chronic inflammation, and chronic inflammatory processes can stimulate immune responses

Granulomatous Inflammation

• Chronic inflammation with granulomas, characterized by persistent, low-grade antigenic stimulation and hypersensitivity
• Main causes include mildly irritant foreign material, Mycobacteria, syphilis, and unknown causes (e.g. sarcoid, Wegener's granulomatosis, Crohn's disease)

Tuberculosis

• Caused by Mycobacteria, especially M. tuberculosis, which is difficult and slow to culture
• Produces no toxins or lytic enzymes, but causes disease by persistence and induction of cell-mediated immunity
• Destruction of tissues by caseating granulomas, with patterns of disease including primary, secondary, and tertiary forms

Cell Types in Chronic Inflammation

• Lymphocytes, sometimes called 'chronic inflammatory cells', with complex, mainly immunological functions
• Plasma cells, differentiated antibody-producing B lymphocytes, indicating considerable chronicity
• Eosinophils, involved in allergic reactions, parasite infestations, and some tumors
• Fibroblasts/myofibroblasts, recruited by macrophages, making collagen
• 'Giant' cells, multinucleate cells made by fusion of macrophages, including Langhans type giant cells in tuberculosis and foreign body type giant cells

Effects of Chronic Inflammation

• Fibrosis, e.g. in gall bladder, chronic ulcers, and chronic inflammatory bowel disease
• Impaired function, e.g. in chronic inflammatory bowel disease
• Rarely increased function, e.g. mucus secretion, thyrotoxicosis in Graves disease
• Atrophy, e.g. gastric mucosa, adrenal glands
• Stimulation of immune response, including macrophage-lymphocyte interactions