Flashcards in lecture 6- inflammation (acute and chronic) Deck (22):
When injury happens, what initiates the inflammatory process?
Chemical mediators- these can be produced by the damaged cells itself or from the blood plasma. These mediators, like cytokines determine which type of response occurs and then organises it by alerting the immune system.
Why does acute inflammation occur?
Damage minimisation and prevention of further injury. Acute inflammation also alerts the adaptive immune system of the new threat to the body and also prepares the tissue for healing.
What is step one of acute inflammation?
Vasodilation- the blood vessels in the injured area dilate, increasing blood flow to the region and intravascular pressure. This increased pressure leads to transudate (protein poor) leaking into the extracellular matrix.
What is step two of acute inflammation?
Increased vascular permeability- chemical mediators order the endothelial cells of the blood vessels to contract, creating holes in the blood vessels. This allows exudate (protein rich) to leave the capillaries and dilute the interstitial spaces of toxins.
what other processes may take place in step 2 of acute inflammation, increased vascular permeability?
Endothelial damage, either as as direct result of the injury or from extensive contraction can require repair later.
Transcytosis- certain chemical mediators may cause macromolecules to move from one side of the blood vessel to the other.
What other cells can cause endothelial injury as a result of increased vascular permeability?
The immune cells, like leukocytes, neutrophils and macrophages can cause endothelial damage when they produce oxygen radicals and proteolytic enzymes.
Leukocytes want to migrate out of the blood vessel and into the site of injury. What is leukocyte rolling?
Leukocyte rolling is when the leukocytes are pulled out of the main stream of blood and stick to the blood vessel endothelial lining close to the site of injury. The leukocytes's integrins bind to the E and P Selectins that chemical mediators cause the endothelium to express.
Leukocytes want to migrate out of the blood vessel and into the site of injury. What is leukocyte adhesion?
This is when the leukocytes have rolled to the site of injury and need to stop. To adhere to the endothelium, the leukocytes express either ICAM-1 or VCAM-1 receptors that will bind to the endothelial cells' LFA-1 and VLA-4 receptors respectively.
Leukocytes want to migrate out of the blood vessel and into the site of injury. What is leukocyte transmigration?
The leukocytes once firmly adhered to the endothelium will squeeze through the holes and enter the interstitial spaces. The leukocytes use chemotaxis, and follow the chemical gradient of bacterial chemicals or cytokines to reach the site of injury.
Name five of the cell-derived chemical mediators.
Histamine, serotonin, prostaglandins, leukotrienes and cytokines.
Name some of the plasma derived chemical mediators.
The complement system proteins- C3a, C5a, C3b, the clotting system proteins (Factor 5,7 etc),
What is the clotting cascade?
It is a cascade of plasma proteases, starting with factor 7 being converted to the active factor 7a by activated platelets. Factor 7a activates thrombin, but also activates fibrinolytic system so that the clot does not grow out of control.
what is the kinin system?
The kinin system is the pathway that produces the cell derived chemical mediator, bradykinin. It is responsible for vascular permeability, pain, arteriolar dilation and non vascular smooth muscle contraction. Bradykinin can be inactivated by kininases.
what part of the complement system is responsible for inflammation?
The C3b protein binds to the pathogen, and then a small section of the protein will dislodge and travel to the leukocytes- this is the C3a protein. The C3a will activate the leukocyte and cause it to initiate inflammation by the C5a protein, migrate to the injury site and kill the pathogens there.
what does histamine do as a chemical mediator?
Histamine is described as a vasoactive amine, because it causes increased vascular permeability by stimulating endothelial cells to contract. They are produced in the mast cells and platelets.
what does nitric oxide do as a chemical mediator?
It is a short-acting, soluble, free radical gas that is produced by endothelial cells and macrophages. It is a vasodilator/relaxer, it is a microbicidal and it inhibits platelet adhesion/aggregation.
what does the arachodonic acid pathway chemical mediator, prostacyclin do?
Prostacyclin is responsible for vasodilation.
what does the arachodonic acid pathway chemical mediator, thromboxane do?
Thromboxane is responsible for vasoconstriction.
what does the arachodonic acid pathway chemical mediator family leukotrienes do?
The leukotrienes are vasoconstrictors, chemotaxins, and cause increased vascular permeability.
what are some important cytokines?
The TNF (tumour necrotic factor), IL (inter-leukin) and IFN (interferon) proteins.
what is the symptom felt as a result of increased cytokines in the blood during infection?
Fever, and loss of appetite are caused by cytokines.