Acute Inflammation Flashcards
What are the 3 aims of inflammation?
To get rid of damaged/ necrotic tissue
To remove microorganisms or foreign material
To set the scene for regeneration or repair of tissues
What are the five cardinal rules of inflammation
Redness, Swelling, Heat Pain and Loss of Function
What are the three components of a rapid response to stimuli?
- Increased blood flow
- Increased vascular permeability
- Leukocyte emigration
What is the stimuli for acute inflammation?
Microorganisms, Necrosis, Hypoxia, Foreign bodies, Hypersensitivity reactions
What is the release of excess fluid into tissue for body cavities called?
oedema
What are some microorganisms that cause acute inflammation?
Parasites, fungi, bacteria, viruses, microbial toxins
What is the release of fluid and cells from circulation called?
exudation
What is exudate rich in?
Proteins, it has a high specific gravity
What is purulent exudate otherwise known as?
Pus, it is rich in leukocytes and debris of dead cells
What does ultraflitration of plasma create?
a transudate with low protein content and little to no cellular material/ low specific gravity
Why does vasocnstriction occur immediately after insult to the tissue occurs?
To limit the blood loss
What two things does vasodilation do during inflammation?
Allows increased blood flow to the tissue
Causes Erythema (heat and redness) at the site
What two substances induce vasodilation in the smooth muscle of the vessels
Histamine and nitric oxide
What three mechanisms promote the increase in vascular permeability
Contraction of endothelial cells (increasing interendothelial spaces)
Endothelial injury (necrosis and detachment)
Increased transport through the endothelial cells (transcytosis)
What is the most common mechanism of increasing vascular permeability?
Contraction of endothelial cells
When does the contraction of endothelial cells occur?
It occurs immeditaely after exposure to the mediator and is short lived (around 15-30 minutes)
What are some examples of chemical mediators?
histamine. bradykinin, leukotrienes, neuropeptide P
What are some examples of situations that would delay contraction of endothelial cells
forms of mild injury, e.g burns/ ultraviolet radition and exposure to bacterial toxins
vascular leakage can then begin after a delay of 2 to 12 hours and last for several hours or even days
What is endothelial damage?
Direct damage leads to necrosis and detachment from the basement membrane
this occurs in severe injuries such as burns or by the action of microbes that target endothelial cells (endotheliotropic)
What is transyctosis?
Where fluids and proteins are transported through endothelial cells
What is a vesiculovacuolar organelle?
a channel created by vesicles and vacuoles
What effect do mediators have on transyctosis?
They promote transport by increasing the number and size of the channels
What is the effect of plasma leaving the vessel?
acts to dilute the stimulus of acute inflammation
What occurs to fibrinogen during increased vascular permeability?
Its one of the proteins that leaves vessels in exudates
What does fibrinogen polymerise to become?
It polymerises to become fibrin
What are the functions of fibrin?
It stops the stimulus spreading to another tissue
Allows the leukocytes to target the inciting cause of inflammation
Assists in blood clotting
Acts as a scaffold for endothelial migration during wound healing
What is stasis?
vascular congestion (slower blood loss and increased viscosity)
What is the purpose of stasis?
allows leukocytes to accumulate on the vascular endothelium
endothelial cells are activated by mediators of inflammation so they express increased levels of adhesion molecules
Leukocytes can then adhere to the endothelium and migrate through the vessel wall
What is the role of lymphocytes?
Lymphatics normally drain the extravascular fluid (lymph) and take it to the lymph nodes
What is lymphangitis?
Secondary inflammation of the lymphatic vessels can occur
What is it called when a drained lymph node becomes inflamed?
lymphadenitis
What is it called when lymph nodes increase in size due to hyperplasia of lymphoid follicles/
reactive/inflammatory lymphadenitis
How are leukocytes recruited?
- Adhesion to the endothelium
- Migration across the vessel wall
- Migration to the stimulus
How does adhesion between the leukocyte and endothelial cell occur?
Via complimentary adhesion molecules
What can enhance the expression of adhesion molecules?
Cytokines
What are selectins?
Proteins that mediate rolling e.g
L-selectin is expressed on leukocytes
E-selectin is expressed on endothelial cells
P-selectin is expressed on platelets and endothelial cells
What do the selectins bind to?
Selectins bind to ligands
they are expressed in response to cytokines
What is the consequence of the interaction between selectins and their ligands being low-affinity?
They can bind, detach and re-attach quickly which allows rolling along the endothelium
What are two examples of integrins?
ICAM-1
VCAM-1
What do ICAM-1 and VCAM-1 bind to?
ICAM-1 binds to B2 integrins on neutrophils, monocytes and lymphocytes
VCAM-1 binds to B1 integrins on eoisinophils monocytes and lymphocytes
What is diapedesis/ transmigration?
Once the leukocytes have adhered to the endothelial cell they need to move through the endothelium
this occcurs predominatently in post-capillary venules
What molecules mediate transmigration?
PECAM-1 or CD31
What are leukocyte adhesion deficiencies characterised by?
recurrent bacterial infections due to the inability of leukocytes to perform recruitment
What are some examples of molecular defects in animals and humans?
Canine and Bovine leukocyte adhesion deficiency
effecs adhesion and their ability to reach the site of inflammation
What is Chemotaxis?
The migration of cells along a chemical gradient
What are some examples of exogenous chemotaxis?
Bacterial products, such as lipids and peptides
What are some chemotactic agents that move endogenously
Cytokines, Arachidonic acid metabolites, Complement system
What does downstream signalling alter?
It alters the cytoskeleton of leukocytes, causing filopedia to move the cell in the direction of the stimulus along the chemical gradient
Where are G-protein coupled receptors found and what do they recognise?
They are found on most leukocytes and they recognise short bacterial peptides containing N-formylmethionyl residues
What do Toll-like receptors recognise?
They recognise components of different types of microbes e.g bacterial lipopolysaccharide
What are Cytokine receptors for?
For communication between cells
they are prodcued in response to microbes
What is the function of opsonin receptors?
They are proteins that are used to coat organisms of particles for phagocytosis
the act of coating is called** opsonisation**
the receptors are present on leukocytes
What are the three main stages of phagocytosis?
1- recognition and attachment of the particle via the leukocyte
2- Engulfment and formation of a phagocytic vacuole (phagosome)
which then fuses with a lysosome
3- Killing or degredation of the material by reactive oxygen species or lysosomal enzymes within the phagolysosome
What can mediators be derived from?
They are either cell derived or plasma protein derived
What kind of amines are histamine and Serotonin?
(cell-derived mediators)
They are vasoactive mediators because their main action is on vessels
they are stored pre-formed inside of cells
Where is histamine stored
What is it released in response to
And what receptors does it bind to?
It is stored in mast cell granules
It is released by degranulation in response to *trauma, heat, cold, proteins *
It binds to H1 receptors on microvascular endothelial cells
causes dilation of arterioles and increases the permeability of venules
What is the effect of serotonin?
It acts similiary to histamine
released from platelets when they begin to aggregate
It results in increased aggregation and vascular permeability
Where is PAF derived from?
It is derived from platelets, basophils, mast cells, neutrophils, macrophages…
What does PAF illicit?
It illicits most vascular and cellular reactions of inflammation
e.g platelet aggregation, vasoconstriction, incraesed leukocyte adhesion
at low concentrations it can induce vasodilation and increased venular permeability
When are oxygen derived free radicals released?
They are released extracellularly from leukocytes after exposure to microbes, chemokines
What are the major species produced within cells and what can they form when combined with NO
superoxide anions, hydrogen peroxide, hydroxyl radicals and they can form reactive nitrogen species
What can ROS in leukocytes destroy and why is this a problem?
They can destroy phagocytosed microbes so their release can be damaging to the host
What in the body possesses antioxidant mechanisms that protect against oxygen-derived radicals?
Serum, tissue fluid and host cells
What produces NO and what is its function?
It is produced by endothelial cells and macrophages and it relaxes vascular smooth muscle
also inhibits the cellular component of the inflammatory response
What are the two Cytokines produced by activated macrophages?
TNF and Interleukin 1
What are the local effects of TNF and Interleukin 1?
increased expression of adhesion molecules
increased procoagulant activity
activation of leukocytes
production of further cytokines
proliferation of fibroblasts
What are the systemic effects of TNF and Interleukin 1?
Fever, leukocytosis, increased acute phase proteins, decreased appetite
What is a Cell-Derived Mediator?
Neuropeptide that is secreted by sensory nerves and leukocytes e.g substance P and neurokinin A
What is the function of substance P?
Transmission of pain signals
Regulation of blood pressure
Stimulation of secretion of endocrine cells
Increased vascular permeability
What are plasma protein derived mediators triggered by?
antibody fixation or microbial antigens
What are kinins?
proteins in blood that cause inflammation
What are vasoactive peptides derived from?
They are derived from kininogens by the action of kallikreins (specific proteases)
What are the functions of bradykinin?
Increases vascular permeability, Contraction of smooth muscle, Dilation of blood vessels and pain
How is acute inflammation terminated?
- The half life of the mediators is short and they are rapidly degraded after they have been released
- Neutrophils have short half lives and die via apoptosis within hours after their release from circulation
- They switch from pro to anti-inflammatory mediators
What is the morphological appearance of acute inflammation?
On the nose
The non-haired skin of the nose is covered by a crust resulting from dehydration of the serous exudate
What is the microscopic appearance of acute inflammation?
Moderate expansion of the superficial dermis with oedema, secondary to vascular leakage
What does a catarrhal infection look like in the abomasum of a cow?
The mucousal epithelium is moderately thickened
covered by a glistening layer of clear mucus and has a subtle nodular appearance
What does a catarrhal infection look like in the colon of a cow?
catarrhal colitis with hyperplasia of mucousal epithelial cells and increased accumulation of mucus on the mucousal surface
What does fibrinous inflammation look like?
pleural surfaces are covered by a yellow-grey, thick, friable exudate consisting of fibrin mixed with other plasma proteins
the exudate can easily be pulled apart
What does supparative inflammation look like?
cranioventral areas of the lung are firm and beige/brown
the lesion is caused by neutrophils transmigrating into alveoli in the inflammatory response
What does an acute inflammation abscess look like?
white to grey exudate that bulges from the cut surface
When does endothelial injury occur?
Immediately after injury and is then sustained for several hours until the damaged vessels are thrombosed or repaired
What is the function of VCAM-1 and ICAM-1 ?
They flatten out the cell/ cytoskeleton so that the leukocyte can move through the endothelium
What is the complement system?
Group of plasma proteins triggered by antibody fixation or microbial antigens, causes inflammation, phagocytosis and cell lysis
Name 4 anti-inflammatory mediators
- Anti-inflammatory lipoxins
- Anti-inflammatory cytolines (TGF-beta IL-10)
- Resolvins and Protectins
- Cholinergic discharge that inhibits TNF production
What are some chemotactic agents that move exogenously?
Any bacterial products such as lipids and peptides
