3 Immunology- Lec 3 Inflammation

Front 1

What are the 5 classic signs of inflammation? (RCTDF)

Back 1

- rubor: redness

- calor: heat

- tumor: swelling

- dolor: pain

- functio laesa: loss of function

Front 2

What is the sequence of events in acute inflammation?

Back 2

- transient vasoconstriction --> vasodilation (increased blood flow) --> increased vascular permeability --> hemoconcentration (slowing of flow/stasis) --> leukocyte trafficking

Front 3

After increased vascular permeability, during hemoconcentration (slowing of blood/stasis), this is time for the ________ to adhere and emigrate into the tissue

Back 3

- leukocytes

Front 4

Difference between arteries and veins: pressure, how is blood moved, way to maintain unidirectional flow?

Back 4

- arteries have high pressure, large smooth muscle wall, blood moved via smooth muscle contraction, BP & muscle contraction keep unidirectional flow

- veins have low pressure, very small smooth muscle wall, skeletal muscle contraction is how blood moves, valves maintain unidirectional flow

Front 5

_______ take the place of smooth muscle cells in capillaries

Back 5

- Pericytes

Front 6

What are the 3 types of capillaries?

Back 6

- continuous

- fenestrated

- intermediate

Front 7

Starling's Equilibrium: what keep fluid out of vessels? What brings fluid into vessels?

Back 7

- OUT: plasma hydrostatic pressure & tissue osmotic pressure

- INTO: tissue hydrostatic pressure & plasma osmotic pressure (albumin)

Front 8

Explain starling's equilibrum from ateriolar to venular, what is the only thing that changes? What happens to left over plasma?

Back 8

- high plasma hydrostatic pressure at start of arteriole --> fluid out, eventually gets pulled back in as plasma hydrostatic pressure drops

- only thing that changes is the plasma hydrostatic pressure

- left over plasma picked up by lymph

Front 9

Pathophysiology of edema: what happens to vascular permeability? lymphatic system? plasma hydrostatic pressure? plasma osmotic pressure?

Back 9

- increased vascular permeability (fluid & protein can leak out, less reabsorbed at venous end)

- lymphatic obstruction (excess tissue fluid accumulates)

- increased plasma hydrostatic pressure (usually venous obstruction - thrombus, heart failure)

- decreased plasma colloid osmotic pressure (renal loss or decreased liver synthesis)

Front 10

histamine released from mast cells does what?

Back 10

- promotes increased vascular permeability & vasodilation & adhesion molecule expression

- vasodilation: H1 receptors endothelium - produce NO, H2 receptors smooth muscle - relaxation

- vasoactive amine

Front 11

What does serotonin do (3 things)? What is it similar to?

Back 11

- promotes type I endothelial activation

- vasodilation via smooth muscle relaxation

- increased vascular permeability

- adhesion molecule expression

- very similar to histamine

Front 12

What does NO do (2 things)?

Back 12

- vasodilation (relaxation)

- reduced leukocyte adhesion to endothelium

Front 13

prostaglandin is useful for _______ & smooth muscle contraction, leukotrienes can cause ________

Back 13

- vasodilation

- bronchospasm & bronchoconstriction

Front 14

______ causes pain at the site of inflammation

Back 14

- bradykinin

Front 15

Arachidonic acid (AA) can be converted to ______ or ______. The first enzyme _______ cleaves AA from the plasma membrane. What is it inhibited by?

Back 15

- prostaglandins

- leukotrienes

- phospholipase A (PLA)

- inhibited by corticosteroids

Front 16

After PLA acts on AA, what are the two enzymes that can act on it to turn it into prostaglandin or leukotrienes?

Back 16

- cyclooxygenase: results in production of prostaglandins

- lipoxygenase: results in production of leukotrienes & lipoxins

Front 17

The cyclooxygenase pathway is mediated by two enzymes, _____ & _____ responsible for the production of _______. _____ is constitutively expressed by endothelium & smooth muscle & results in physiologic levels of prostaglandin. ______ is an inducible enzyme that produces excess prostaglandins.

Back 17

- COX1

- COX2

- prostaglandins

- COX1

- COX2

Front 18

Platelets accumulating at inflammation express COX1 and their major product is ______ which does what? Endothelial & Smooth muscle cells express COX2 and it's major product is ______ which does what? The balance b/w these two will determine whether blood flow will be blocked or remain patent.

Back 18

- TXA2

- vasoconstriction, clotting & smooth muscle proliferation

- PGI2

- vasodilation, inhibits platelet aggregation, opposes action TXA2

Front 19

_______ block both COX1 & COX2, however the anti-inflammatory benefits are principally derived from blocking ______. What are some examples of drugs that block both? What are some drugs that block only COX2?

Back 19

- ns-NSAIDs (non-selective NSAIDs)

- COX2

- aspirin, indomethacin, ibuprofen

- s-NSAID (Vioxx, celebrex)

Front 20

______ causes hyperalgesia - pain at site of inflammations similar to bradykinin

Back 20

- PGE2

Front 21

______ turns AA into leukotrienes. _____ is a specific one which is chemotactic & activates neutrophils. Promotes aggregation, adhesion to endothelial & release of cytoplasmic vessels. What do leukotrienes do?

Back 21

- lipooxygenase

- LTB4

- vasoconstriction, increased vascular permeability (venules), bronchospasm

Front 22

______ are a mix of pro & anti inflammatory mediators

Back 22

- cytokines

Front 23

______ & ______ are two cytokines produced by dendritic cells & macrophages. They have both paracrine & autocrine effects. What are their paracrine effects? What do they do systemically?

Back 23

- TNF-alpha & IL-1

- activate endothelial cells

- fever, loss of appetite, ACTH & corticosteroid release, acute phase proteins released by liver

Front 24

________ Made by endothelial cells and stored preformed in Weibel Palade bodies. Promotes neutrophil recruitment & activation within acutely damaged tissues.

Back 24

- IL-8

Front 25

Capture & Rolling: _____ is constitutively expressed by leukocytes. ______ is contained within Weibel Palade bodies & rapidly moved to the surface of the endothelial cell upon activation. _____ is synthesized de novo by endothelial cells (4-6 hrs after activation). ______ is the ligand for all selectins expressed by both endothelial cells & leukocytes,

Back 25

- L-selectin

- P-selectin

- E-selectin

- PSGL1

Front 26

Slow Rolling: _____ is expressed on the leukocyte and binds to _____ on the endothelial cell. Binding to selectins in the first step triggers integrins to switch their _______

Back 26

- LFA-1

- ICAM-1

- affinity: low --> intermediate

Front 27

Arrest: What causes leukocytes to arrest on endothelial cell?

Back 27

- chemokines bind to receptor on cell surface to activate cell

- integrins change affinity from intermediate --> high affinity

Front 28

Most leukocyte migrate through the cell how? How do the others?

Back 28

- most do paracellular transmigration (following chemokine gradient)

- transcellular migration (common w/ tight junctions ie brain)

Front 29

______ activation is a rapid response which is independent of new gene expression and self-limiting. _______ is slower in onset, dependent on new gene expression, persist as long as inflammatory stimulus is not cleared.

Back 29

- Type I

- Type II

Front 30

Type I activation is mediated by _______. Does it desensitize? What does it do?

Back 30

- histamine

- receptor desensitizes or histamine removed & endothelial cell returns to normal state

- vasodilation, increased vascular permeability, P-selectin & IL-8 secreted from Weibel-Palade bodies

Front 31

Type II activation is mediate by _____ & ______. Does it desensitize? What does it do?

Back 31

- TNF-alpha & IL-1

- does not desensitize - lasts as long as stimuli there

- promotes endothelial activation, necrosis & increased vascular permeability, P-selectin, IL-8, E-selectin, ICAM