Inflammation Flashcards
3 types of inflammation and key differences
acute: neutrophil-mediated, regeneration of normal tissue architecture
chronic: mononuclear cell-mediated, tissue cell death and architecture destruction, repair includes new blood vessels/connective tissue (scars)
granulomatous: mediated by specialized macrophages, circumscribed chronic inflammation, when causative agent can’t be removed so it is sequestered instead
granulomatous inflammation
mediated by specialized macrophages, circumscribed chronic inflammation, when causative agent can’t be removed so it is sequestered instead
describe what occurs during acute inflammation
macrophages release histamine, serotonin —> vascular dilation, plasma leakage to interstitium
later - neutrophil emigration (diapedesis) and phagocytosis, recruitment of macrophages which clean up neutrophil lysis
resolution: macrophages transition to anti-inflammatory (IL-10, TGF-b) and leave the field
what occurs during “red hepatization” of the lung?
due to inflammation of the lung from lobar pneumonia
lung has heavy and dark red appearance - neutrophils have filled in the alveolar spaces
what typically occurs in viral pneumonia presenting with pulmonary inflammation?
mononuclear inflammatory infiltrate, characteristically seen in interstitium
upon activation, mast cells release effector molecules in a time-dependent fashion. describe this (and what is released)
within second: degranulation - histamines, TNF-a, amines
within minutes: eicosanoids - luekotrienes and prostaglandins
within hours: cytokines, chemokines, growth factors
result: vasodilation, vascular leakage, inflammatory cel activation
contrast histamine release from mast cells to cytokines and eicosanoiods release
histamine: already present in granules, released in response to injury/immune reaction/C3a and C5a complement (anaphylatoxins)
cytokines and eicosanoids: synthesized de novo, secreted in response to viruses/bacterial LPS/TLR activation/immune reaction
_____ cytokine mediates an increase in endothelial transcytosis during microvascular leakage in inflammation
VEGF: vascular endothelial growth factor
T/F: histamine- mediated vascular leakage follows a stereotypic time course
TRUE: histamine mediated leakage is gated
what is the major mechanism of inter-endothelial leakage during inflammation, induced by histamine
endothelial shape change, induced by histamine
results in opening of inter-endothelial junctions, allowing for leakage
how is inflammatory edema different than general edema
inflammatory edema has fluid that is localized and has a high protein concentration (exudate)
general edema occurs form imbalance of hydrostatic and osmotic pressures
stasis
as fluid leaves vascular use, blood in microcirculation has increased hematocrit (ratio of RBC volume to total blood volume)
as a result, blood flow slows down (stasis)
what are the roles of each of these endothelial molecules in leukocyte infiltration?
a. P-selectin
b. E-selectin
c. GlyCam-1, CD34
d. ICAM-1
e. VCAM
a. P-selectin: rolling
b. E-selectin: rolling/adhesion
c. GlyCam-1, CD34: rolling (CAM = cell adhesion molecule)
d. ICAM-1: adhesion
e. VCAM: adhesion
two main groups of opsonization factors
- IgG (heat stable): recognized by Fc receptors
- C3b complement proteins (heat labile): recognized by complement receptors (CR)
how do cells produce more energy for phagocytosis, an energy-requiring process accompanied by a burst of metabolic activity and oxygen consumption?
What is the outcome of this process?
glucose metabolized via the hexose monophosphate shunt (HMS): converts glucose phosphate to ribulose 5-phosphate and oxygen
—> generates NADH, NADPH
NADH oxidase converts oxygen to hydrogen peroxidase (required for bacterial killing)
NADPH oxidase generates superoxidase
chronic granulomatous disease
X-linked or AR, affects males mostly - recurrent infections with granulomas
lack of NADPH oxidase activity —> leukocytes do not show burst of metabolic activity that occurs with phagocytosis
remember that NADPH oxidase generates superoxide
Chediak-Higashi syndrome
decreased leukocyte functions because of mutations affecting proteins involved in lysosomal membrane traffic
causes increased CNS infections
pt presents with recurrent CNS infections. PMH includes genetic testing that showed mutation in a protein involved in lysosomal memrbane trafficking. FHx includes a grand-parent who suffered similar recurrent infections
what is your diagnosis
Chediak-Higashi syndrome (AR): decreased leukocyte function due to mutations affecting proteins involved in lysosomal membrane trafficking
name the effect of each:
a. histamine
b. serotonin
c. NO
d. prostaglandins
e. IL-1
a. histamine: vasodilation and increased vascular permeability
b. serotonin: increased vascular permeability
c. NO: vasodilation
d. prostaglandins: vasodilation, fever (pyrogenic), and pain
e. IL-1: leukocyte activation and fever (pyrogenic)
what is the effect of C-reactive protein (CRP), serum amyloid A (SAA), serum amyloid P (SAP), fibrinogen, and haptoglobin?
acute phase response of inflammation
released by hepatocytes (liver)
describe process of chronic inflammation
- mononuclear emigration
- angiogenesis and fibroblast invasion
- granulation tissue (precursor to scar) - ingrowth of new capillaries and fibroblasts
process of fibrosis (scar formation)
quiescent fibroblasts become active myofibroblasts which secrete ECM
activated by TGF-b, IL-13, IL-1
as fibrosis progresses, number of microvessels and cells decreases, becoming relatively acellular tissue
acute respiratory distress syndrome (ARDS)
widespread lung injury from pneumonias, sepsis, aspiration, inhaled toxins (high fatality rate)
results in inability of alveoli to gas exchange
inflammatory response, Type II pneumocyte proliferation, necrotic debris accumulates at alveolar/air interface —> hyaline membranes form
formation of hyaline membranes at the alveolar/air interface is a distinctive histological feature of the initial state of _____
ARDS (acute respiratory distress syndrome)
inflammation due to widespread lung injury leads to inability of alveolar to exchange gas
following initial phase is proliferation and fibrotic phase
purulent inflammation
encapsulated accumulation of pus (neutrophilic exudate) with tissue destruction and formation of a cavity
empyema
accumulation of pus in existing body cavity (purulent inflammation that is not walled off)
can be seen following inflammation of pleura or pericardium
type of chronic inflammation that occurs in response to localized inciting agent that can be sequestered by inflammatory tissue, but not easily removed
granulomatous inflammation
macrophages (foamy) are prominent, along with mononuclear cells and giant cells
granuloma surrounded by cuff of B/T cells
which of the following is most suggestive of ARDS?
a. bacterial pneumonia
b. hyaline membranes
c. diffuse collagenous fibrosis
d. organizing pneumonia
b. hyaline membrane
*ARDS = acute respiratory distress syndrome (alveoli can’t gas exchange)
what is the enzyme that generates superoxide from molecular oxygen?
NADPH oxidase
the pain experienced during inflammation is most likely the result of the formation of which of the following two chemical mediators?
a. complement C3b and IgG
b. Interleukin-1 and TNF
c. prostaglandin and bradykinin
d. histamine and serotonin
c. prostaglandin and bradykinin
a. C3B/IgG - opsonization
b. IL-1/TNF - chemotaxis
d. histamine/5HT - vascular permeability
a women with a breast implant that has ruptured experiences a foreign body reaction to the silicone particles. This would lead to what kind of reaction?
a. acute inflammation
b. hypertrophic (raised) scar
c. chronic inflammation
d. granulation
e. granulomatous inflammation
e. granulomatous inflammation - when invading material becomes sequestered in granuloma because the body can’t get rid of it
what types of cell aggregates form multinucleated giant cells seen in granulomas in granulomatous inflammation?
macrophages
which of the following stimulates collagen and fibronectin production in fibrosis?
a. matrix metalloproteinase
b. NO (nitric oxide)
c. TGF-b
d. TNF
e. VEGF
c. TGF-b (transforming growth factor beta)
a. matrix metalloproteinase - ECM degradation
b. NO - vasodilation
d. TNF (tumor necrosis factor) - chemotaxis, fever
e. VEGF (vascular endothelial growth factor) - angiogenesis
local defect of the surface of a tissue or organ caused by sloughing of inflammatory or necrotic tissue
ulcers
can be caused by H. pylori (helicobacter), steroids, NSAIDs
Helicobacter pylori, steroids, and NSAIDs are all possible causes of
ulcers
what is the order of events leading to neutrophil infiltration? order these steps:
rolling, migration across vessel wall, margination, adhesion, migration through tissues
margination
rolling
adhesion
migration across vessel wall
migration through tissues
initial rolling interactions of neutrophils during infiltration are mediated by:
a. arachidonic acid metabolites
b. cadherins
c. integrins
d. selectins
selectins
(selectin phase, then integrin phase)
presence of WBC and epithelial casts, along with bacteria, in urine indicates infection in ____
infection in kidney proper, not just lower urinary tract
autopsy of a lung shows fibrinous exudates over the pleural surfaces, and innumerable small, grey-white nodules, as well as a large caseous tubercle which eroded into a large pulmonary vessel
what is the likely causative organism? diagnosis?
agent: mycobacterium tuberculosis
diagnosis: miliary (disseminated) tuberculosis
serous inflammation
aka blister
outpouring of fluid (effusion) derived for either plasma or secretions of mesothelial cells lining the peritoneal, pleural, and pericardial cavities
fibrinous inflammation
fibrinous exudate is characteristic of inflammation in the lining of the body cavities (ex- meninges, pericardium, pleura)
exudate develops when vascular leakage allows fibrinogen to traverse vascular barrier (appears eosinophilic histologically)
pus is made of mostly
neutrophils
chronic inflammation is characterized by tissue infiltration by ______
mononuclear cells (macrophages and lymphocytes)
acute inflammation - neutrophils
chronic inflammation - macrophages/lymphocytes replace neutrophils
Cachexia (“wasting”) is caused by chronic inflammation, which induces extensive catabolism of fat and muscle. Which cytokine listed plays the largest role?
a. IL-8
b. IFN-y
c. TNF
d. IL-2
c. Tumor Necrosis Factor (TNF)
which mechanism is predominately response for pain during infection?
a. humoral immune response
b. cell-mediated immune response
c. local production of inflammatory mediators
c. local production of inflammatory mediators —> increases responsiveness of sensory nerve endings
what process causes the experience of flu symptoms such as muscle/joint pain, fever, sleepiness, loss of appetite, malaise
secretion of cytokines by monocytes and T cells (most notably IFN)
in a histological section of a biopsy from an infected portion of a lung, what immune cells would be most abundant?
lymphocytes and macrophages —> granulomatous inflammation
