inflammation Flashcards
what is inflammation? what is the goal?
host response comprising of movement of fluid and leukocytes from the blood to extravascular tissues
goal is to localize and eliminate material perceived as unwanted
what is acute inflammation?
associated predominantly with neutrophils and macrophages
characterized by pus
rapid onset, short duration
edema = exudation of fluid and plasma proteins
non-specific immune response - “natural immunity”
what is chronic inflammation?
associated with lymphocytes, plasma cells, and macrophages
insidious onset
long duration
fibrosis, vascular proliferation, and tissue destruction
immunospecific
what are the three major events occuring in acute inflammation?
1: hemodynamic changes
2: increased vascular permeability
3: extravasion of leukocytes
what do eosinophils look like histologically?
bilobe nucleus
bright red dots in cytoplasm
what do neutrophils look like histologically?
very pale granules
irregular, sometimes trilobe, nuclei
what do macrophages look like histologically?
pale cytoplasm
kidney shaped nucleus
what do plasma cells look like histologically?
clockwork nucleus
what would you see in the first steps of inflammation (histologically)?
mast cells release granules
margination of leukocytes - will be attached to surface of blood vessel inside lumen
edema around vessel
what are some stimuli that can initiate inflammation?
bacteria foreign bodies trauma dead tissue antibody-complement
what does acute inflammation look like histologically?
lots of neutrophils
some macrophages
few plasma cells and eosinophils
tissue damage
what is the sequence of events in acute inflammation?
1: stimulus
2: vessel changes = increased blood flow, vascular permeability - usually under influence of histamine
3: extravasation of leukocytes
4: “mopping up”
5: regeneration or repair
what are the hemodynamic changes seen with acute inflammation?
vasodilation => redness, warmth
microvascular leakage => swelling
hemoconcentration (because vessel is larger, and endothelial cells are stretched farther apart so liquid can leak out and blood concentrate) => slowed flow
all result in more leukocyte-endothelial interactions
what are the mechanisms of vascular leakage?
endothelial gaps open in venules direct damage to vessels leukocyte-induced endothelial damage increased transcytosis (VVOs) new vessel formation
what are the mechanisms of edema formation? (5)
1: increased hydrostatic P (due to elevated arterial blood flow and decreased venous blood flow out)
2: decreased blood oncotic pressure (low protein in serum)
3: endothelial/vascular damage
4: decreased lymphatic drainage (lymphatic blockage or destruction)
5: Na+ retention by kidneys
what is extravasation?
change in normal flow
when you expand the vessel, laminar flow is disrupted and leukocytes start to roll along the vessels =>=> adhesion, diapedesis, transmigration
what are the four families of adhesion molecules?
selectins
immunoglobulin superfamily
integrins
glycoproteins
what do selectins do/bind to?
molecules on the surface of cells that bind to glycoproteins
what do members of the immunoglobulin superfamily do/bind to? what are some examples?
have dicysteine bridge in protein chain
bind to integrins
ICAM and VCAM
what do integrins bind to?
heterodimers
bind to immunoglobulin superfamily proteins
play large role in imflammation, wound healing, etc.
what are some glycoproteins that selectins bind to?
PSGL-1
ESL-1
CD34
glycam-1
what does ICAM bind to? what is its function?
LFA-1
MAC-1
integrins on leukocytes
adhesion/arrest, diapedesis
what does VCAM bind to? what is its function?
alpha4beta1
alpha4beta7
integrins on leukocytes
adhesion
what does P-selectin bind to? what is its function?
PSGL-1
rolling of monocytes, leukocytes
what does E-selectin bind to? what is its function?
ESL-1
rolling/adhesion
what do glycam-1 and CD24 bind to? what are their function
L-selectin
Leukocyte-homing to HEV
poly/mono - rolling
what does PECAM-1 bind to? what does it do?
binds to itself - self-aggregating - expressed on both endothelial cells and leukocytes and binds to it’s counterpart on the other cell type as the leukocytes migrate out of the vasculature
expressed along margins of endothelial cell
how is a site of inflammation “mopped up”?
steps = 1: recognition 2: engulfment 3: killing/degradation done via phagocytosis by neutrophils
how do neutrophils recognize things that need to be phagocytosed (opsonin and leukocyte receptor pairs)?
Fc fragment of IgG; Ic(gamma)R
C3b; CR1, CR2, CR3 (Mac-1)
Collectins; C1q
opsonins are on the surface of material that needs to be phagocytosed
what can cause chronic inflammation?
autoimmune reactions
most viral infections (via CD8+ T cells)
intracellular bacterial pathogens (eg TB, leprosy)
acute inflammatory reactions that have persisted and become chronic - cells that are immunospecific will eventually show up
where do giant cells come from? in what situations would you expect to see them? what do they look like?
derived from highly active macrophages
in chronic inflammation
have many nuclei because tried to divide or multiple macrophages have fused
what are the two types of giant cells? how will they appear different?
foreign body - lots of cytoplasm, nuceli scattered all over the place
langhans type - lots of cytoplasm, but nuclei line up as ring around cytoplasm
what is a granuloma? what types of cells are involved? what is the result?
a nodular type of chronic inflammation
involves T cells, plasma cells, epitheliod histiocytes
collection of macrophages - look like epithelium, often surrounded by collar of lymphocytes and plasma cells
giant cells common
may be centrally necrotic (TB)
damages tissue structure and => scarring
caseous necrosis if necrosis
