Acute inflammation Flashcards
Define acute inflammation
Reaction of vascularized tissue to injury
Inappropriate inflammatory response with no foreign substances to remove is the basis of . . .
Autoimmune inflammation
What four things are involved in the formation and clearing of acute inflammation?
- Pathogen/injury
- Host inflammatory cells
- Complement and coagulation cascades
- Chemokines and cytokines
Three things involved in immediate tissue reaction
- Fluid
- Plasma proteins
- Innate immune cells
Intensity of immune response dictated by these four things
- Stimulus
- Duration of the stimulus
- Genetics of the host local factors
- Medical interventions
Four causes of inflammation
- Infections
- Tissue necrosis
- Foreign bodies
- Immune reactions
Recognition by the innate immune system
DAMPs/PAMPs activate TLRs and other recognition receptors on monocytes
Inflammasome
Multi-protein complex characterized by activation of caspase 1; cleaves IL-1 to active form that sets the inflammatory cytokines in action
Nitric oxide in the inflammatory response
Mediates vasodilation that increases flow and vascular permeability
Three main events of inflammation
- Vascular dilation and increased blood flow (erythema and warmth)
- Extravasation of plasma fluid and proteins (edema)
- Leukocyte (mainly neutrophil) emigration and accumulation
Movement of the leukocytes into the extravascular space
TNF alpha and IL-1 beta signal for the leukocytes to move out of laminar flow and roll along vascular wall until they attach and move through the cell space through diapedesis
Chemotaxis
Unidirectional movement along a chemical gradient used by
- Bacterial peptides
- Complement proteins, especially C5a
- Proinflammatory cytokine tetrad
How does chemotaxis work?
Chemoattractants activate membrane receptors on the innate cells that then activate cytoskeleton, particularly actin, changes that move the cell along the gradient
Three phases of leukocyte activity in inflammation
- Moving out of the blood vessel using diapedesis
- Releasing acute inflammatory mediators; immediately undergoing checkpoint mechanism to stop acute inflammation
- Degranulation and quick cleanup moderated by the monocyte/macrophage system
Where are extra neutrophils derived during acute inflammation?
More blood can be dumped out from the spleen, which has more neutrophils in it (cannot actually produce more neutrophils)
What do neutrophils look like histologically?
They have a lot of different lopes to each nucleus, but has ONLY ONE nucleus
What do macrophages look like morphologically?
Have one single, solid, round nucleus
Describe the name changes of monocytes.
In the cavity: macrophage
Into a tissue: histocyte
Which cells are present at the site of inflammation first, neutrophils or macrophages?
Neutrophils and THEN macrophages
Rheologic
Increased delivery of cells per unit time increases the chance that a leukocyte can respond to a signal
Most numerous leukocyte in circulation
Neutrophils (“PMNs”)
Half lives of neutrophils
12 hours in the blood, 1-2 minutes at the site of inflammation
Left shift
Bone marrow pushes immature neutrophils out earlier to deal with acute inflammation
Five features of neutrophils at the site of injury
-Phagocytosis
-recognition/attachment of complement
-engulfment/degranulation
killing/degradation by oxidative burst
-NETS
Phagolysosome
Part of membrane breaks off to form a bubble with the pathogen in it, which then fuses with the lysosome inside the cell and kills the pathogen
What is the most important ROS, and how is it formed?
Myeloperoxidase (MPO) combines with a halide and forms HOCl, which is the most important ROS
What is a NET?
Neutrophil extracellular trap: sacrifices its nucleus by casting its chromatin laden with killer granules out of the cell as a net to trap bacteria and fungi
Half life of monocytes
Circulate for 16 hours (largest leukocyte in the blood)
Interleukins involved in “cleanup” of the inflammatory response
IL-10 and TGF-beta; establish the correct milieu for appropriate healing and wound repair
Control of acute inflammation
- Controlled mostly by macrophages
- Also by decreased activation of TLRs
Least severe form of acute inflammation
Serous - protein-poor transudate from capillary to a space: peritoneal, pericardial, or pleural
Intermediate morphology of acute inflammation
Fibrinous - fluid with larger molecules dominated by fibrinogen which converts to fibrin and potential scarring
Severe morphology of acute inflammation
Suppurative/abscess - protein-rich fluid with inflammatory cell, alive and dead necrotic debris
Example of serous inflammation
Blister
Example of fibrinous inflammation
Pericarditis; deposits fibrin on the pericardium
Example of suppurative inflammation
Bacterial abscesses in the lung in bronchopneumonia
Ulcerative inflammation
Underlying inflammation causes excavation of a mucosal or skin surface
