Hunter: Acute Phase Response Flashcards
Most responses to pathogens remain (blank), but systemic responses do occur
localized
Some systemic inflammatory responses to pathogens can be positive and protective. Give an example; other systemic responses can be negative and harmful. Give an example
acute phase response and fever; sepsis and septic shock
What is the LPS receptor?
CD14
Cytokines that mediate the acute phase response and fever
IL-6, TNF-alpha, IL-IB
Chemotactic factor that recruits neutrophils and basophils to the site of infection
CXCL8
This cytokine is predominantly involved in the acute phase response in the liver
IL-6
Cytokines involved in induction of fever
IL-1 and TNF-alpha
These are the principle cytokines that mediate the systemic effects of inflammation
IL1
IL6
TNF-alpha
an evolutionarily conserved and highly coordinated systemic reaction to disturbances in homeostasis caused by infection, tissue injury, trauma or surgery, neoplastic growth, or immunological disorders
acute phase response
The acute phase response involves changes in plasma levels of (blank), many produced in the liver in response to (blank)
acute phase proteins *fibrinogen, haptoglobin, serum amyloid protein, C-reactive protein;
IL6
the predominant cytokine produced during an inflammatory response that induces the liver to produce acute phase reactants like C-reactive protein
IL-6
Positive acute phase proteins include:
(blank), which opsonizes and traps microorganisms
(blank) which activates complement
(blank) which causes coagulation and fibrinolysis,
(blank) which scavenges free Hg and iron,
and (blank) which neutralizes enzymes
C-reactive protein; Mannan-binding lectin; Fibrinogen, prothrombin, factor VIII; ferritin; alpha 1-antitrypsin
What does C-reactive protein do?
good diagnostic marker of inflammation
also promotes opsonization by activating the classical complement pathway and generating c3b
an acute phase protein produced in the liver that functions as an opsonin to promote the phagocytosis and killing of this microorganism
C-reactive protein
Inflammation-associated coagulation begins when cytokines, Toll-like receptor (TLR) agonists, or other stimuli induce (blank) expression on the surfaces of monocytes and vascular endothelial cells
tissue factor
hepatic synthesis of these two factors decreases during the acute-phase response
protein C
antithrombin III
The end result of the acute phase reaction is increased (blank) activity and decreased (blank), which promotes fibrin formation and thrombosis
thrombin; fibrinolysis
Local infection causes release of cytokines which communicate with brain centers to affect local cytokine and prostaglandin synthesis and produce (blank) and (blank)
sickness behavior;
fever
What are some ways in which the acute phase response is kept in check
anti-inflammatory molecules:
IL-1 receptor antagonists
neuroendocrine hormones to downregulate immune responses
protease inhibitors or antioxidants
Body temperature is a vital sign that is controlled by the (blank)
hypothalamus
Neurons in the hypothalamus receive two kinds of signals in order to maintain the hypothalamic set point
- signals from peripheral nerves about warmth/cold receptors in the skin
- signals about the temperature of the blood
What is fever?
increase in the hypothalamic set point due to the generation of prostaglandins, leading to an elevation of normal body temperature
What is the first sign of fever?
vasoconstriction in hands and feet, which shunts blood away from periphery to internal organs and makes you feel cold - shivering may occur to generate heat
T/F: For most fevers caused by infections, body temperature only increases by 1°-2°C
True
any substance that causes fever
pyrogen
Name one exogenous pyrogen - substance outside the patient that causes fever
LPS endotoxin produced by all gram-negative bacteria
Endotoxins from bacteria can directly cause fever, but fever can also be caused indirectly through what mechanism?
release of cytokines, like IL1, IL6 and TNFalpha
T/F: Fever is always due to microbial agents.
False; fever can be a manifestation of disease due to inflammation, trauma, tissue necrosis, antigen-antibody complexes; it can even be due to unknown origin
key arachidonic acid metabolite responsible for resetting of the hypothalamic set point
PGE2
What must you lower in order to lower fever?
PGE2
Which enzyme is inhibited by acetaminophen, aspirin, and other non-steroidal anti-inflammatory drugs?
cyclooxygenase
What are some benefits of fever?
many microorganisms grow best w/i a narrow temp range, so hyperthermia benefits the patient;
increases antibody production;
What are some down-sides to fever?
very high temps are harmful;
high rectal temp is called (hyperpyrexia);
heat stroke
