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study notes for lecture five: autoimmunity

6 Pages
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Department
Immunology
Course Code
IMM250H1
Professor
Dana Philpott

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Lecture FIVE: AUTOIMMUNITY
sepsis
Æwhole-body inflammatory state
(systemic inflammatory response syndrome SIRS)
Æmay be caused as a response to microbes in the blood, urine, lungs, skin or
other tissues
septic shock
Ædecreased tissue perfusion and oxygen delivery as a result of infection and
sepsis
Æcause multiple organ dysfunction syndrome (multiple organ failure)
Æcommon victims are children, the elderly and immunocompromised
patients
Æmortality is ~50%
SARS (severe acute respiratory syndrome)
Æcaused by a coronavirus
Ænear pandemic
Æspread from China to 37 countries in weeks
Æone of the largest outbreaks was in Toronto 2003
transmission of SARS
Æbats were the reservoir
Æbats transmitted it to civets/cats which transmitted it to humans
symptoms of SARS
Æflu-like (fever, sore throat, myalgia/muscle soreness)
Æshortness of breath
Ædeath due to lung failure caused by pneumonia
Æmortality rate ~10%
avian flu
Æcaused by a bird-specific influenza virus: H5N1
*H = hemagglutinin *N = neuraminidase
transmission of avian flu
Æbirds could be infected
Æhighly pathogenic for birds but transmission to humans was inefficient
symptoms of avian flu
Æflu-like (fever, sore throat, myalgia/muscle soreness)
Ædeath due to lung failure
Æmortality rate could be as high as ~60%
cytokine storm
Æpositive feed-back loop that amplifies cytokine production
Æ71).,/-,/-6 and IL-8 are key mediators
* IL-SURGXFWRILQIODPPDVRPHDFWLYDWLRQ
*IL-8 = chemokine that recruits neutrophils
Æmoves from a local response to a systemic response
www.notesolution.com
initiation of septic shock
Æduring a local infection, some of the bacterial products (LPS, peptidoglycan) cannot be removed so they remain in the blood
Æbacteria activate thHERG\VFHOOVDWWKHVDPHWLPHUHVXOWLQJLQDPDVV-production of cytokines activating epithelial cells, neutrophils and monocytes
CONSEQUENCE OF SEPTIC SHOCH
Activated cell
Effect
endothelium cells
- increased TF, adhesion molecules, PAI-1
- increased expression of adhesion proteins on all cells within the different blood vessels
- leads to microvascular occlusion
- leads to coagulation of blood vessels and they can no longer perfuse the tissue with nutrients and oxygen
- leads to fever, vasodilation, capillary leak
- leads to sepsis and multiple organ failure
neutrophils
- forms ROS and nitrogen species
- leads to microvascular occlusion
- leads to coagulation, fever, vasodilation, capillary leak
- leads to sepsis and multiple organ failure
monocytes
- forms prostaglandins
- leads to vascular instability
- leads to sepsis and multiple organ failure
endothelium cells
+
neutrophils
+
monocytes
- formation of ROS and nitrogen species
- leads to microvascular occlusion and vascular instability
- formation cytokines
- leads to increased TF, adhesion molecules, PAI-1, which lead to microvascular occlusion
- leads to increased ROS and nitrogen species production which leads to microvascular occlusion and vascular
instability
- leads to increased prostaglandins which leads to microvascular instability
- leads to increased complement and kinin recruitment
- leads to increased chemotaxis and lysosomal enzymes which leads to vascular instability
- formation of prostaglandins which leads to microvascular instability
- molecular instability and microvascular occlusion both lead to coagulation, fever, vasodilation and capillary
leak
- these lead to sepsis and multiple organ failure
direct response from complement and kinins
- produces a massive inflammatory response
- leads to chemotaxis and lysozomal enzymes
- leads to vascular instability
- leads to coagulation, fever, vasodilation, capillary leak
- leads to sepsis and multiple organ failure
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Description
Lecture FIVE: AUTOIMMUNITY sepsis septic shock whole-body inflammatory state decreased tissue perfusion and oxygen delivery as a result of infection and (systemic inflammatory response syndrome SIRS) sepsis may be caused as a response to microbes in the blood, urine, lungs, skin or cause multiple organ dysfunction syndrome (multiple organ failure) other tissues common victims are children, the elderly and immunocompromised patients mortality is ~50% SARS (severe acute respiratory syndrome) caused by a coronavirus near pandemic spread from China to 37 countries in weeks one of the largest outbreaks was in Toronto 2003 transmission of SARS symptoms of SARS bats were the reservoir flu-like (fever, sore throat, myalgiamuscle soreness) bats transmitted it to civetscats which transmitted it to humans shortness of breath death due to lung failure caused by pneumonia mortality rate ~10% avian flu caused by a bird-specific influenza virus: H5N1 *H = hemagglutinin *N = neuraminidase transmission of avian flu symptoms of avian flu birds could be infected flu-like (fever, sore throat, myalgiamuscle soreness) highly pathogenic for birds but transmission to humans was inefficient death due to lung failure mortality rate could be as high as ~60% cytokine storm positive feed-back loop that amplifies cytokine production %.,-,-6 and IL-8 are key mediators * IL-574:.941L31O,22,8420,.9L;,9L43 *IL-8 = chemokine that recruits neutrophils moves from a local response to a systemic response www.notesolution.com
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