BOD - Revision - Michaelmas - Kelly - Immunology Overview Lecture 1: Disease, Cell injury and the Immune System 1 Pathology = study of disease > disturbance in homeostasis whenever there is damage to cells · Aetiology = cause of diseases · Pathogenesis = how diseases develop > immune system has an important role in disease progression . What happens to diseased cells and tissues > Ischaemic heart disease and stroke top cause of death globally 1 Virchow: proposed cell injury is the basis of disease · Cell injury can be caused by: extreme oxygen tension or pH, lack of ATP, exposure to toxins, drugs and chemical agents (xenobiotics), cold and heat, prolonged deficiencies of nutrients, trauma, aging · Cells can also be injured through infection by bacteria, viruses, fungi, parasites * Infection may be direct result of toxins/initiated or accelerated by tissue reaction to infection Acute/Chronic inflammation may injure host cells Stress NORMAL CELL (HOMEOSTASIS) Recovery ADAPTATION Recovery Injury REVERSIBLE INJURY Unable to adapt CELL DAMAGE Severe injury Transient or mild injury IRREVERSIBLE INJURY APOPTOSIS CELL DEATH NECROSIS > Cell responses to stress and injury: · Consequence of loss of homeostasis will depend on type of injury, duration, severity · Also it will depend on type of cell, capacity to adapt, genetic makeup (polymorphisms or variations) . Adaptation of cells is often reversible > cells return to normal when the stimulus is removed * Hypertrophy: increase in size e.g. right ventricular hypertrophy in response to * Hyperplasia: increase in number * Metaplasia: reversible change from one differentiated cell to another (e.g. squamous, glandular epithelium) # Dysplasia: changes that do not necessarily revert to normal when injury is removed e.g. change in shape or size # Atrophy: reducing complexity, diminishing cell volume over several hours or days by digestion of cellular proteins by proteasome system > backed up by autophagy * Autophagy: organelles encapsulated by intracytoplasmic membranes and digested by fusion with lysosomes · Cells that don't adapt may suffer reversible or irreversible damage * Reversible injury: fatty deposits or swelling > commonly caused by Na'K ATPase shut down > influx of Na and water · If injury is too severe > cell will die > by necrosis or apoptosis # Apoptosis: requires cell to retain control of its own energy metabolism
· Common process in tissue development and repair · Intrinsic pathway: cell senses stress so kills itself · Extrinsic pathway: cell is signalled to kill itself by other cells · Cells lose contact with surrounding cells > shrink in volume · Nuclear fragmentation, chromosome condensation, DNA fragmentation · Membranes bleb and bud > cell may fragment into multiple membrane bounded subcellular bodies · Caspases: selectively cleave important proteins > surface of cell exposes signals > immediate phagocytosis by macrophages · Silent death > rarely induces inflammation Necrosis: . Loss of cell volume homeostasis > cellular swelling fl rupture of PM and internal membranes · Intracellular contents leak into extracellular space > reach bloodstream > some are chemotactic for