Inflammation 1 Flashcards
Why does inflammation occur?
In response to : Infection Trauma Foreign bodies Immune reaction Necrosis of any cause
Why is inflammation both helpful and unhelpful?
Aid recovery from tissue damage but may also contribute to tissue damage
What is the inflammatory response?
Acute inflammation
Chronic inflammation
Acute inflammation and what happens?
Initial response to tissue injury (delivery of cells and mediators to injury):
Vascular phase of increased flow
Exudate formation
Neutorphil polymorph infiltration of tissue
bacterial phagocytosis and killing
Resolution, suppuration, organisation or chronicity
Phases of acute inflammation, in order?
Vascular phase
Cellular phase
Morphological features (signs) of inflammation due to phases?
Calor (heat) Dolor (pain) Rubor (redness) Tumour (swelling) Loss of function
Basic steps of the vascular phase in acute inflammation and what vessels does this affect?
Marked changes in blood flow:
Initially, vasoconstriction followed by prolonged VASODILATION, accompanied by increased vascular PERMEABILITY (slow blood flow)
First occurs in arterioles and then capillary beds.
Leads to formation of protein-rich exudate and tissue oedema
Why does the tissue appear red and warm?
Due to the increased blood flow to the site (vasodilation)
What is vascular permeability?
Results in “leaky” vessels; loss of proteins
Why does the tissue swell?
Vascular permeability leads to changes in osmotic pressure; water follow protein causing swelling (tumour)
Why does vascular permeability occur?
Endothelial contraction - response to inflammatory mediators, like histamine, bradykinin, leukotrienes, nitric oxide
Direct injury - burns or bacterial infection
White cell injury - from leukocytes (release of cytotoxic agents causes endothelial injury)
What does the cellular phase involve? Steps?
Movement of wbcs (particularly neutrophils) from circulation to injured site:
White cell margination
Rolling
Adhesions
Migration
What is white cell margination and why does it occur?
During slowing of blood flow (vascular phase), larger wbcs move towards blood vessel peripheries (near endothelium)
What is rolling of wbcs?
Wbcs roll along endothelial surface of blood vessels due to slow blood flow
What does adhesion of wbcs involve?
During rolling, wbcs adhere to endothelial surface.
Why does adhesion occur?
Endothelial cells express selectins of their surfaces - recognise specific carb groups (ligands) found on macrophage/neutrophil cell surfaces
Intergrins bind to blood vessel walls, specifically to ligands (like VCAM and ICAM)
VCAMs - Vascular Cell Adhesion Molcule (immunoglobins on endothelial cell surface)
ICAMs - Intercellular Cell Adhesion Molecule (immunoglobins on endothelial cell surface)
How is adhesion enhanced and why?
Integrin/selectin interaction with ligands is of low affinity (binding on and off is fast)
HISTAMINE (release by mast cells, basophils and platelets) and thrombin increase selectin expression
Pro-inflammatory cytokines TNF (Tumour Necrosis Factor) and Interleukin 1 (IL-1) increase endothelial cell expression of VCAM AND ICAM
What are cytokines?
Small protein that are involved with cell signalling
What are chemokines?
Cell signalling molecules involves with inducing chemotaxis (movement of a molecule along a chemical gradient)
How is the avidity between adhesive molecules increased?
Chemokines from injury site bind to proteoglycans on endothelial cell surface
Proteoglycans increase affinity of VCAMs and ICAMs for integrins
What occurs after adhesion?
The wbcs pass between adjacent endothelial cells (permeability) out of circulation
Migrate to injured site via chemotaxis (respond to conc. gradient of chemotaxins)
What are the 3 phases of phagocytosis?
Recognition and attachment
Engulfment
Killing and Degradation
Recognition and attachment of neutrophils to injurious agent?
Via opsonins, which coat the e.g: bacteria. Opsonins can be immunoglobins, complements and carb molecules
Via mannose sugars, recognised by car-binding proteins/lectins in plasma which attach. In turn, mannose receptors are recognised by neutrophils
Scavenger receptors on neutrophils recognise LDL (similar mechanism)
What does engulfing of the injurious agent involve?
Pseudopods (cytoplasmic extensions) flow around bacterium and cell membranes fuse, enclosing bacterium in phagosome
Lysosome binds, forming phagolysosome leading to bacterial killing
What types of killing mechanisms exist for neutrophils/macrophages?
Oxygen dependent (more important) Oxygen independent
Mechanism for oxygen-dependent killing?
Reactive oxygen metabolites generated during phagocytosis due to rapid action of NADPH oxidase on NADPH (oxygen gains electron from NADPH and becomes a superoxide)
Conversion into hydrogen peroxide which is converted into killing agents
Also, reactive nitrogen metabolites are formed (nitric oxide synthase combines NO with superoxide and produces ONOO)
Why does pain (dolor) occur due to inflammation?
Mediated by prostaglandins and bradykinin
What are neutrophils and how do they appear?
Short-lived inflammatory wbc that characterises inflammation
Polymorph - many lobes to one nucleus
Granulocyte - has granules (secretory vesicles) in cytoplasm
Has phagocytic and cytotoxic abilities
