Acute Inflammation Flashcards
Cardinal Features of Acute Inflammation
1) Injury: Causative Agent
2) Rubor: Redness
3) Calor: Heat
4) Tumor: Swelling
5) Dolar: Pain
What is Acute Inflammation?
1) The reaction of vascularized tissue to injury.
2) The culmination of a tightly regulated, complex series of interactions b/t: pathogen/injury, host inflammatory cells, complement and coagulation cascades, chemokine and cytokines.
3) End game is neutralizing the injuring agent and allowing for repair
4) Inflammation is a potentially harmful process
Immediate inflamed tissue reaction is characterized by the accumulation of?
1) Fluid
2) Plasma Proteins
3) Innate Immune Cells
Intensity of Inflammatory response is determined by?
1) The Stimulus
2) Duration of the stimulus
3) Genetics of the host local factors
4) Medical interventions
Causes of Inflammation
1) Infection
2) Tissue Necrosis
3) Foreign bodies
4) Immune Reactions
Inflammation Steps
1) Necrotic debris or microbe get through endothelial barrier
2) Resident cells (APCs) beneath the endothelium take up debris/microbe and then present it
3) This leads to the release of mediators (amines, cytokines) which leads to vascular responses
4) Responses Include: Recruitment of leukocytes, release of plasma proteins and vasodilation and increased vascular permeability which leads to edema
Recognition by the Innate Immune System
1) DAMPs/PAMPs activate TLRs and other recognition receptors on monocytes.
2) This forms an INFLAMMASOME (a multi-protein complex) which then activates CASPASE-1. CASPASE-1 then cleaves IL-1 to IL-1beta which is the active form.
3) A multi-phase cellular inflammatory sequence ensues
IL-1 Beta
Active form of IL-1 after it is cleaved by CASPASE-1. It is the MAIN PLAYER in recruiting inflammatory cells
Vascular Role in Inflammation
1) Regulated by cytokines, chemokines, and other inflammatory mediators.
2) Logic: It expedited the innate responses to the offending agent
3) Nitric oxide mediated vasodilation increases flow and increases vascular permeability
4) Plasma proteins like complement and antibodies access the extracellular space
5) Cytokine/chemokine induced endothelial changes allow innate cells access to the inflammatory site
The Inflammatory Site Has?
1) Vasodilation and increased blood flow (erythema and warmth)
2) Extravasation of plasma fluid and proteins (edema)
3) Leukocytes (mainly neutrophil) emigration and accumulation
Antibodies and complement bodies cause endothelial cells to form gaps
Steps of Leukocyte (Neutrophil) Migration through the blood vessel
1) Microbes are recognized by macrophages in tissue which release cytokines and chemokines to get increased number of P-selectins and E-selectins.
2) Rolling occurs by binding to the selectins. Leukocytes “marginate” or move towards the periphery of the vessel instead of flowing in the center.
3) Integrin activation on the leukocytes via chemokine
4) Stable adhesion via integrins and Diapedesis
5) migration through the endothelium
How do PMNs move from a blood vessel to point of injury?
Chemotaxis- unidirectional movement along a chemical gradient. The chemoattractants activate membrane receptors on the innate cells that then active cytoskeleton (ACTIN IS CRITICAL) changes that move the cell along the gradient to the site of inflammatory stimulus.
Sequence of Cell Traffic in Inflammation
1) Edema
2) Neutrophils
3) Monocytes/macrophages/histeocytes
Action of White Cells (neutrophils) During Acute Inflammation
Increased delivery of cells per unit time increases the chance that a leukocyte can respond to a signal.
Cytokine signals form the responding cells at the site induce changes in the endothelium, up regulating families of receptors that coax innate inflammatory cells across the endothelial lining.
Neutrophil Steps to Leave Vessel
1) Margination
2) Adhesion
3) Transmigration
Neutrophils are the vast majority of responding cells
