Lecture 2: Inflammation in the Pathogenesis of Disease Flashcards
What are the main functions and characteristics of Leukocytes?
The main function of a Leukocyte is to assist with attacking and removing the pathogens and therefore reducing inflammation.
Leukocytes have a number of functional characteristics . Firstly diapedesis which is the ability to translocate from one capillary to another tissue. Amoeboid motion, this is the leukocytes ability to move through tissue spaces via cytoplasmic extensions and rolling along other cells. Also leukocytes follow positive chemotaxis, this is where the cells can follow chemical trails of inflammatory molecules allowing them to pinpoint the affected area.
What is a pathogen?
A pathogen can be defined as any external organism which attempts to affect the homeostasis and balance of a different organism.
Examples of pathogens:
Viruses, Bacteria, Fungi, Parasites and Injury.
Describe and explain the cardinal signs of inflammation?
The cardinal signs of inflammation are Pain due to sensory nerve endings being stimulated by both chemical mediators and increasing levels of vasodilation. Heat and Redness are another sign of inflammation as a result of vasodilation. Swelling is also a sign due to the vascular permeability resulting in an oedema around the affected area. Loss of function is the final sign, this is often due to increased levels of pain and swelling.
How does a leukocyte travel from the blood stream in to the affected cell?
During the inflammation process there is a release of cytokines which stimulates selectin of cells. This selectin binds to the CHO of the leukocyte cells, this binding slows down the movement of the leukocyte. As the leukocytes are slowing down the rolling of the cells causes a signalling of inflammatory molecules called integrin’s which are adhesion molecules. These molecules (integrin) binds to ICAM1 and VACAM1 which are adhesion molecules of the affected endothelial cell which are released due to oxLDL. This binding stops the movement of the leukocyte, an enzyme called bradykinin then makes the space between the endothelial cells more permeable allowing the entry of the leukocytes.
Which factors dictate the resolution of inflammation?
Healing, this is where the pathogen has been eliminated and the tissue is repaired allowing for the return of normal function.
Abscess formation, this factor increases the duration of inflammation and only subsides when the abscess is removed.
Scarring is often a result of the abscesses, the main problem is that the tissue is repaired however to a lower functional capacity resulting in potential loss of function.
Chronic inflammation where there is an active process of tissue damage and tissue healing.
Would exercise be prescribed to reduce inflammation?
Exercise would be prescribed for individuals suffering with acute inflammation due to the fact it triggers an anti-inflammatory cascade and releases IL-1ra which inhibits the pro-inflammatory mediators.
Define and explain the role of NF-κB?
Nuclear factor kappa Beta cells upregulates the transcription of DNA to mRNA by binding to a DNA sequence. This transcription process results in an increase of pro-inflammatory mediator, or cytokine production.
Define and explain the role of TNF-a?
Tumour Necrosis Factor - alpha is a pro inflammatory molecule however some of its functions are anti-inflammatory also. TNF-a activates the IKK complex which is a key factor in the inflammatory cascade. TNF-a stimulates the phase response to inflammation in the liver. TNF-a is an important cytokine in amplifying the inflammatory response.
What is the role of CRP?
C reactive protein Downstream inflammatory response Acute phase protein synthesised by liver Released in response to IL6 High sensitivity of CRP is more reflective or early stage, low grade inflammation Stable biomarker
