Chapter 3: Overview Flashcards
The typical inflammatory reaction develops through a series of sequential steps (the 5 Rs). What are these?
Recognition, recruitment, removal, regulation, and repair
When pathogenic microbes invade tissues or tissue cells die, leukocytes are rapidly recruited. What is the order of leukocytes to arrive?
neutrophils, then later monocytes and lymphocytes
What are the major participants in the inflammatory response?
blood vessels and leukocytes
what are the vascular and cellular reactions of inflammation triggered by?
soluble factors that are produced by various cells
What is the main cellular infiltrate for acute inflammation?
mainly neutrophils
what is the main cellular infiltrate for chronic inflammation?
monocytes/macrophages and lymphocytes
What are the 5 cardinal signs of inflammation?
Rubor, Calor, Dolor, Tumor, Loss of function
What are 4 causes of inflammation?
Infection, tissue necrosis, foreign bodies, and immune reactions
What are some examples of endogenous substances that can be harmful if they deposit in tissues?
urate crystals (gout), cholesterol crystals (in atherosclerosis) and lipids
What is the initiating step in inflammatory reactions?
recognition of microbial components or substances released from damaged cells
What is the best defined cellular receptor for microbes?
Toll-like receptors (TLRs)
What is the best example of a cystolic receptor that senses cell damage?
NOD-like receptors (NLRs)
What molecules do NLRs sense?
uric acid, ATP, and reduced intracellular K+ concentrations
When NLRs sense damage to cells, what do they activate?
the inflammasome
what does the inflammasome induce?
the production of the cytokine IL-1
In addition to directly recognizing microbes, what else do many leukocytes express receptors for?
the Fc tails of antibodies and for complement proteins (these receptors recognize opsonized microbes)
What circulating proteins are capable of recognizing microbes and products of cell damage and triggering inflammation?
mannose-binding lectin (MBL) and collectins
What are the cytokine-induced systemic reactions collectively called?
acute-phase response
What cytokines are important mediators of the acute-phase reaction?
TNF, IL-1, and IL-6
The acute-phase response consists of several systemic clinical and pathological changes. What are these three things?
Fever, acute phase reactants, and Leukocytosis
What 2 cytokines are endogenous pyrogens?
IL-1 and TNF
how do IL-1 and TNF function as pyrogens?
when released, they upregulate cyclooxygenases, which is the enzyme that synthesizes prostaglandins
What is the role of prostaglandins in regards to fevers?
prostaglandins (especially PGE2) stimulate the production of NTs by the hypothalamus that reset the body’s steady state temp to a high level by reducing heat loss (via vasoconstriction) and increasing heat generation
What are three of the best known acute-phase reactants?
C-reactive protein (CRP), Fibrinogen, and Serum amyloid associated protein (AA)
What is synthesis of CRP in the liver stimulated by?
cytokines- especially IL-6
What is the role of CRP?
it acts as an opsonin and it aids in clearing necrotic debris
What is the relationship between CRP and MIs?
elevated serum CRP has been proposed as a marker for increased risk of MIs in patients with CAD
what is an established predictor of recurrent cardiovascular events?
hsCRP elevation
What is the synthesis of fibrinogen in the liver stimulated by?
cytokines- especially IL-6
What is the role of fibrinogen?
it binds to red cells and causes them to form stacks (rouleaux)
What is the effect of rouleaux formation?
the red blood cells will sediment more rapidly than individual RBCs
What is an example of a non-specific test for an inflammatory response?
Erythrocyte sedimentation rate- the faster the sedimentation rate the more likely inflammation is present
What is the synthesis of serum amyloid associated protein in the liver stimulated by?
IL-1 and TNF
What is the role of AA?
acts as an opsonin; helps in clearing necrotic cells
What does prolonged production of SAA cause?
secondary amyloidosis
Why does leukocytosis occur initially?
because of the accelerated release of cells from the bone marrow post mitotic reserve pool (caused by cytokines including TNF and IL-1)
What do most bacterial infections cause an increase of?
neutriphils
what do most viral infections, such as infectious mononucleosis, mumps, and German measles, cause an increase in?
the number of lymphocytes
what do allergies and helminth infestations cause an increase in?
eosinophils
What is associated with decreased number of circulating white blood cells?
this is called leukopenia; caused by certain infections like typhoid fever and infections caused by some viruses, rickettsiae, and certain protozoa
What is the clinical triad known as septic shock?
High blood levels of cytokines cause various widespread clinical manifestations such as 1) DIC 2) hypotensive shock and 3) metabolic disturbances (including insulin resistance and hyperglycemia)
