Hunter-Acute Phase Response & Fever Flashcards
The host response to invading microbes begins with what?
microbes begins with recognition of pathogen associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs) on macrophages and other innate immune cells
Microbes can cause tissue damage, eliciting what?
DAMPs: damage associated molecular patterns
What changes do inflammatory mediators, like TNFalpha make to vascular endothelium?
Mediators like TNF-a change the properties of vascular endothelium, prompting an increase in vascular permeability, vasodilation, upregulation of adhesion molecules, and clotting
When a local inflammatory response becomes systemic..is it helpful or harmful?
can be either.
Helpful: acute phase response & fever
Harmful: sepsis & septic shock
What is an example of a highly conserved PAMP?
endotoxin on gram negative bacteria
Give some examples of toll like receptors of various organisms.
f-Met-Leu-Phe receptor (bacteria)
Mannose receptor (bacteria, fungi, viruses)
Scavenger receptors (acetylated lipoproteins on bacteria)
Dectin-1 glucan receptor (fungi)
LPS binding protein and CD14 detected by TLR-4 (bacteria)
T/F Local coagulation in microvessels is a natural part of inflammation.
True!
This helps keep the microorganisms in a local region.
What are some of the pro inflammatory cytokines released by macrophages in an inflammatory response?
IL-6 TNFalpha IL-1beta CXCL8 IL-12
IL-6 has what effects?
Systemic:
fever
induces acute phase protein production by hepatocytes
TNF alpha has what effects?
Local:
activates vascular endothelium & increases vascular permeability
**increased entry of complement & other cells to tissue
**increased fluid drainage to lymph nodes
Systemic:
fever
mobilization of metabolites
shock
IL-1beta has what effects?
Local: activates vascular endothelium activates lymphocytes local tissue destruction increases access to effector cells Systemic: fever IL-6 production
What are the affects of CXCL8?
Local:
chemotactic factor
recruits neutrophils & basophils to site of infection
IL-12 has what affects?
activates NK cells
What are the principle cytokines that mediate the systemic effects of inflammation?
IL-1
IL-6
TNFalpha
What is IL-6 predominantly involved in?
acute phase response in liver
Which 2 cytokines are involved in the induction of fever?
IL-1
TNF alpha
What does the liver produce?
acute phase proteins
like C-reactive protein & mannose-binding lectin
**leads to activation of complement opsonization
A 68-year-old woman presents to the ED with a high fever (38.2° C), malaise, and myalgia of four days duration. You suspect an infectious process and order blood cultures and blood chemistries. She has profoundly elevated C-reactive protein indicating systemic inflammation. Which of the following is the predominant cytokine produced during an inflammatory response that induces the liver to produce acute phase reactants like C-reactive protein? TNF-a IL-6 TGF-b IL-12 IFN-g
IL-6
A 25-year-old man presents with a three day history of cough and fever. He has chest pain and difficulty breathing. A chest films shows right lower lobe consolidation and a blood culture reveals the presence of Streptococcus pneumoniae. In this bacteremic patient, which of the following is an acute phase protein produced in the liver that functions as an opsonin to promote the phagocytosis and killing of this microorganism? Ferritin Plasminogen C-reactive protein A-1 anti-trypsin Transferrin
C-reactive protein
A team of investigators has designed a new drug that lowers fever by blocking the formation of this key arachidonic acid metabolite responsible for resetting of the hypothalamic set point. LTB4 PGE2 Prostacyclin Thromboxane A2 PGD2 5-HPETE
PGE2
A 5-year boy with no history of immunization presents with an exanthematous skin rash. You notice the presence of Koplik spots in the buccal mucosa and make the diagnosis of measles. He has a fever of 38.5° C and is very uncomfortable, so you recommend acetaminophen to lower his fever. Which of the following enzymes is inhibited by acetaminophen, aspirin, and other non-steroidal anti-inflammatory drugs? Lipooxygenase Nitric oxide synthetase Lysosomal peroxidase Cyclooxygenase Phospholipase A2
Cyclooxygenase
What is the acute phase response ?
and highly coordinated systemic reaction to disturbances in homeostasis caused by infection, tissue injury, trauma or surgery, neoplastic growth, or immunological disorders
orchestrated by IL-1, IL-6, TNF alpha released by macrophages etc
What’s the deal with acute phase proteins?
produced by the liver
prompted by IL-6
What is the function of C-reactive protein?
opsonin on microbes
What is the function of mannan-binding lectin?
mannan-binding lectin pathway of complement activation
What is the function of fibrinogen, prothrombin, factor 8, vwf?
coagulation factors
trapping invading microbes in blood clots