Lecture 15- Acute Inflammation and Autoimmune disease Flashcards
How does meningococcal disease progress?
Colonisation of nasopharynx through pili and OMPs, Invasion then passage through the mucosa
The bacteria can then enter the blood where the capsule allows evasion of the immune system and phagocyotsis, it then proliferates and causes damage through LOS
The bacteria then crosses the blood brain barrier and attach via Pili and OMPs, invades, passes through the blood brain barrier and causes more damage through LOS
What causes the most damage in meningococcal disease?
The inflammation response induced by lipid A (LOS)
How does the immune response cause damage in meningococcal disease?
Lipid A is seen as a marker for bacteria, initially cytokines are secreted by lipid A itself, however if the infection is not resolved then greater concentrations of cytokines will be released causing tissue damage
What cytokines cause damage in meningococcal disease?
TNF causes fever and attracts immune cells, as well as increasing vasodilation and capillary leak causing a drop in blood pressure
Excessive cytokines can activate the coagulation pathways leading to intravascular coagulation resulting in damage to blood vessels causing blood to be lost from the circulation resulting in bleeding under the skin causing the rash
Dead phagocytes will release enzymes that cause even more damage
What role does fluid accumulation play in meningococcal disease?
The lose of vascular volume results in an increase in accumulation of fluid in extracellular space leading to multiple organ failure (heart, kidneys, lung etc)
If there has been crossing of the blood brain barrier the inflammation of the meninges causes pressure on the brain which can cause headaches, mental problems or even comas
What is a seqellae
A post infection complication resulting from immue cross reactions
How does S. Pyogenes result in a sequellae?
Initial infection, inflammation and immune responses remove the pathogen, antibodies against M proteins are produced in a few weeks, these antibodies cross react with heart protein and joint epitotes targeting complement and killer T-Cells
This results in inflammation of these sites as well as pain and loss of function
Secondary infections with S.Pyogenes results in the more violent memory response and causes progression of the autoimmune disease
How can rheumatic fever induced by s.Pyogenes be prevented?
Penecillin can be used to clear the infection, resulting in the immune system not being recruited preventing more cross reactive antibodies from forming
