Inflammation 2 Flashcards
vascular changes associated with acute inflammation
vasodilation - increased blood flow
increased vascular permeability - interstital fluid and proteins
steps of leukocyte recruitment
- margination
- rolling
- adhesion
- transmigration
leukocyte activation
- phagocytosis
- dectruction of phagocytosed material
end result of leukocyte recruitment & activation
resolution/scarring/chronic inflammation
leukocyte rolling
Sialyl-Lewis X oligosaccharide
E-selectin (CD62E) on endothelial cells are induced by what
TNF and IL-1
P-selecting (CD62P) are on what type of cell
endothelial cells and platelets
P-selectin (CD62P) release is mediated by
histamine
integrin adhesion transmembrane glycoproteins are induced by
LTB4 and C5a
name the cellular adhesion molecules on endothelial cells
ICAM
VCAM
increased integrin affinity and increased expression of integrin ligands (CAMS) lead to what type of adhesion
stable adhesion
function of diapedeis
squeeze between cells at intracellular junctions
what is chemotaxis
movement toward chemical gradient (LTB4, C5a, IL-8 and bacterial products)
leukocytes secrete
collagenases
CD31 (PECAM-1) are found on what cell types
- endothelial cells
- leukocytes
function of CD31
mediates binding
what are the 3 steps of phagocytosis
- recognition and attachment of particle to ingesting leukocyte
- engulfment, with subsequent formation of phagocytic vacuole
- killing and degradation of ingested material
what are the opsonins of phagocytosis
IgG
C3b
what are the leukocyte receptors of phagocytosis
Fc receptor
complement receptors CR1 and CR3
how does engulfment occur during phagocytosis
pseudopods extend around object forming phagocytic vacuole
how does phagocytosis kill, degrade and injest material
- fusion of phagocytic vacuole with lysosome (phagolysosome)
- lysosomal enzymes
- production of reactive oxygen species
what is the goal of reactive oxygen species
kill microbe with HOCl
what is the resolution of acute inflammation
- injurious stimulus cleared
- mediators and acute inflammatory cells clear
- neutrophils undergo apoptosis
- replacement of injured cells
what are the negative outcomes of acute inflammation
- scarring
- chronic inflammation
scarring (fibrosis) of acute inflammation caused by
- extensive tissue was damaged
- injured tissue filled in with connective tissue
chronic inflammation results from acute inflammation when
injured stimulus NOT cleared
what are the 3 defects in Leukocyte Function
- leukocyte adhesion deficiency
- chronic granulomatous disease (CGD)
- Chediak-Higashi syndrome
leukocyte adhesion deficieny is defective in what
LAD1 - defective CD18 beta subunit of integrin
LAD2 - absence of sialyl-Lewis X due to defect in fucose metabolism
result of leukocyte adhesion deficiency
- impaired adhesion of neutrophils to endothelium and thus impaired acute inflammatory response
- recurrent bacterial infections which lack neutrophls in tissue
- increased circulating neutrophils
- when baby is born, umbilical cord will take longer to separate
what is chronic granulomatous disease (CGD)
a defect in the oxidative burst due to a mutation in NADPH oxidase complex
patients with chronic granulomatous disease are suscpetible to what
catalase positive organisms, which eliminate the HOCl
what test is performed to confirm chronic granulomatous disease
nitroblue tetrazolium test - no dye in CGD
what is Chediak-Higashi syndrome
- disorder in the trafficking of organelles
- impaired funsion of phagosome with lysosomes
what is observed with Chediak-Higashi Syndrome
- giant granules in leukocytes (granules from Golfi do not distribute properly in cytoplasm)
- increased death of neutrophils in bone marrow (neutropenia)
- secretion of lytic secretory granules in T-cells is affected
serous inflammation is triggered by
- agents causing mild dmage to blood vessel walls
- cytokines assocaited with increased vascular permeability
serous inflammation produces
exudate composed of watery fluid containing very little protein
in serous inflammation where does the exudate accumulate serum
- tissues (skin blister caused by a mild burn)
- natural cavities like the pericardial sac
- pleural or peritoneal cavities (plural effusion ascitis)
in serous inflammation what causes the exudate to accumulate serum
the secretion of reactive mesothelial cells
fibrinous exudate may be degraded by
-fibrinolysis
fibrinous exudate is removed by
macrophages resotring the normal tissue structure (resolution)
if macrophages fail to completely remove the fibrin, what happens
the fibrin will organize into granulation tissue with newly formed blood vessels resulting in scar formation (organization)
what happens if the fibrinous exudate is present in the pleural cavity
the process may end with the formation of dense scar tissue that bridges and obliterates the pleural cavity (fibrnous adhesion)
purulent or suppurative inflammation is a result of
severe inflammatory insult
in purulent or suppurative inflammation the exudate is composed mainly of
a large # of neutrophils (purulent exudate)
why does necrosis occur in purulent or suppurative inflammation
many neutrophils die or degenerate in the inflammed area releasing their lysosomal granules causing necrosis
what is pus
gelatinous mixture of a large number of neutrophils, many of them degenerated, necrotic tissue debris, and fibrinous material
ulcer results from
necrosis caused by an acute inflammator episode involving the mucosal lining or surface of an organ
ulcer formation is followed by sloughing of
the nectoric tissue and formation of a crater
causes of ulcer
bacterial or fungal infection, tissue injury by chemical or physical agents and ischemia
appearace of ulcers
May be deep or shallow, depending on the nature of the injurious agent and the length of the inflammatory process
healing process of ulcers
May heal either by resolution with no sequelae or by leaving behind a crater lined by fibrous tissue.
when do monocytes peak
2-3 days
where are monocytes found
in the blood
mechanisms of monocytes
- migration
- roll
- adhese
- transmigrate
monocytes develop into
macrogphes in tissue
monocytes and macrophages participate in what type of immune systems
both innate and adpative or specific immune systems
monocytes represent what % of the circulating white cells
1 to 6%
monocytes can move into tissue and differentiate into
macrophages
monocytes can also differentiate into
dendritic cells (specialized antigen presenting cell)
life span of macrophages
can survive in tissue for several months
where can macrophages reside
fixed locations:
- alveolar macrophages in lung
- Kupfer cells in liver
- microglial cells in brain
macrophages can act as
antigen presenting cells
what are the 3 functions of macrophages that act as APC
- Digest and cleaved the original protein antigen into several small peptides. (13 to 18 amino acids)
- Load these short peptides into the groove of MHC class I or II proteins
- Display the antigen-MHC complex to an appropriate T cell in order to be activated
what are cytokines
poplypeptides functioning as mediators of inflammation and immune responses
cytokines are AKA
interleukins (communication btwn leukocytes)
cytokine of acute inflammation
TNF, IL-1, IL-6 recruit leukocytes and also cause systemic systems (fever)
function of IL-8
recruits neutrophils
function of IL-10 and TGF-B
anti-inflammatory
Th1 helper T-cells produce
IFN-Y
TH2 helper T cells produce
IL-4, IL-5 IL-10
when does chronic inflammation occur
- persistent infection
- infection with viruses, mycobacteria, fungi
- autoimmune disease
- foreign material
- malignancies
what are T lymphocytes
TCR and CD3 complex on cell surface recognize antigen on MHC molecules
function of CD4+ helper T cells
- recognize MHC class II on APC
- B7 molecule on APC binds CD28 on T cell
activated Th1 cells produce
IFNg (Classical pathway of macrophage activation), anti-virus
activated Th2 cells produce
IL-5 (eos activator) and IL4 & IL-13 (Alternative pathway, macrophage), anti-parasite
function of CD8+ cytotoxic T cells
recognize MHC 1 on all nucleated cells
CD8+ cytotoxic T cells are activated by
IL-2 from Th1 type T helper cell
CTLs kill by
performin/granzyme or activated CTLs
activated CTLs can express
Fas ligand and bine a target cell expressing Fas death receptor CD95
what are B lymphocytes
naive B cells made in bone marrow
function of B lymphocytes
recognize antigen with surface Ig molecules
stimulated B cells can differentiate into
plasma cells
what are granulomatous inflammation
- distinctive pattern of chronic inflammation
- lymphocytes and mutlinucleated giant cells
granulomatous inflammation characterized by
activated epithelioid hustiocytes
function of granulomatous inflammation
attempt to “wall-off” offending agents
granulomatous inflammation can be caused by
- Mycobacteria
- Fungi (Histoplasmosis, Blastomycosis)
- Sarcoidosis
- Reaction to foreign material
- Crohn’s disease
- Wegener Granulomatosis
E-selectin (CD62E) are found on what type of cell
endothelial cells
