inflammation

Question 1

what is inflammation? what is the goal?

Answer 1

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

Question 2

what is acute inflammation?

Answer 2

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”

Question 3

what is chronic inflammation?

Answer 3

associated with lymphocytes, plasma cells, and macrophages
insidious onset
long duration
fibrosis, vascular proliferation, and tissue destruction
immunospecific

Question 4

what are the three major events occuring in acute inflammation?

Answer 4

1: hemodynamic changes
2: increased vascular permeability
3: extravasion of leukocytes

Question 5

what do eosinophils look like histologically?

Answer 5

bilobe nucleus

bright red dots in cytoplasm

Question 6

what do neutrophils look like histologically?

Answer 6

very pale granules

irregular, sometimes trilobe, nuclei

Question 7

what do macrophages look like histologically?

Answer 7

pale cytoplasm

kidney shaped nucleus

Question 8

what do plasma cells look like histologically?

Answer 8

clockwork nucleus

Question 9

what would you see in the first steps of inflammation (histologically)?

Answer 9

mast cells release granules
margination of leukocytes - will be attached to surface of blood vessel inside lumen
edema around vessel

Question 10

what are some stimuli that can initiate inflammation?

Answer 10

bacteria
foreign bodies
trauma
dead tissue
antibody-complement

Question 11

what does acute inflammation look like histologically?

Answer 11

lots of neutrophils
some macrophages
few plasma cells and eosinophils
tissue damage

Question 12

what is the sequence of events in acute inflammation?

Answer 12

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

Question 13

what are the hemodynamic changes seen with acute inflammation?

Answer 13

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

Question 14

what are the mechanisms of vascular leakage?

Answer 14

endothelial gaps open in venules
direct damage to vessels
leukocyte-induced endothelial damage
increased transcytosis (VVOs)
new vessel formation

Question 15

what are the mechanisms of edema formation? (5)

Answer 15

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

Question 16

what is extravasation?

Answer 16

change in normal flow
when you expand the vessel, laminar flow is disrupted and leukocytes start to roll along the vessels =>=> adhesion, diapedesis, transmigration

Question 17

what are the four families of adhesion molecules?

Answer 17

selectins
immunoglobulin superfamily
integrins
glycoproteins

Question 18

what do selectins do/bind to?

Answer 18

molecules on the surface of cells that bind to glycoproteins

Question 19

what do members of the immunoglobulin superfamily do/bind to? what are some examples?

Answer 19

have dicysteine bridge in protein chain
bind to integrins
ICAM and VCAM

Question 20

what do integrins bind to?

Answer 20

heterodimers
bind to immunoglobulin superfamily proteins
play large role in imflammation, wound healing, etc.

Question 21

what are some glycoproteins that selectins bind to?

Answer 21

PSGL-1
ESL-1
CD34
glycam-1

Question 22

what does ICAM bind to? what is its function?

Answer 22

LFA-1
MAC-1
integrins on leukocytes

adhesion/arrest, diapedesis

Question 23

what does VCAM bind to? what is its function?

Answer 23

alpha4beta1
alpha4beta7
integrins on leukocytes

adhesion

Question 24

what does P-selectin bind to? what is its function?

Answer 24

PSGL-1

rolling of monocytes, leukocytes

Question 25

what does E-selectin bind to? what is its function?

Answer 25

ESL-1

rolling/adhesion

Question 26

what do glycam-1 and CD24 bind to? what are their function

Answer 26

L-selectin
Leukocyte-homing to HEV
poly/mono - rolling

Question 27

what does PECAM-1 bind to? what does it do?

Answer 27

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

Question 28

how is a site of inflammation “mopped up”?

Answer 28

steps = 
1: recognition
2: engulfment
3: killing/degradation
done via phagocytosis by neutrophils

Question 29

how do neutrophils recognize things that need to be phagocytosed (opsonin and leukocyte receptor pairs)?

Answer 29

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

Question 30

what can cause chronic inflammation?

Answer 30

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

Question 31

where do giant cells come from? in what situations would you expect to see them? what do they look like?

Answer 31

derived from highly active macrophages
in chronic inflammation
have many nuclei because tried to divide or multiple macrophages have fused

Question 32

what are the two types of giant cells? how will they appear different?

Answer 32

foreign body - lots of cytoplasm, nuceli scattered all over the place
langhans type - lots of cytoplasm, but nuclei line up as ring around cytoplasm

Question 33

what is a granuloma? what types of cells are involved? what is the result?

Answer 33

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