Immunology week 3 Flashcards

Question

Inflammatory Mediators ● TNFa, IL1, IL6, IL8 ● IL-6 specifically stimulatates production of what?

Answer 1

● IL-6 ○ Stimulates production of acute phase proteins (CRP)

Answer 2

● C3a & C5a ○ Most relevant complement component for inflammation ○ C3a & C5a increase vascular permeability which stims chemotaxis of neutrophils, eosinophils, & monocytes

Answer 3

Prostaglandins ○ Contribute to vasodilation, cap. Permeability, pain, & fever ○ PGE1 &2 increase the effects of histamine ○ Thromboxane-(oddball) ■ Platelet aggregation & vasoconstriction

Answer 4

○ Smooth muscle contraction ○ LTB4= chemoattractant of neutrophils ○ slow reacting substances of anaphylaxis

Answer 5

● Vasoactive amines ○ **Histamine** & serotonin ■ Found in mast cells ■ Result in dilation & increased permeability

Answer 6

○ Activates neutrophils and is a potent eosinophil chemoattractant ○ Inc. plasma proteins and results in edema

Answer 7

● Kinins- bradykinin (physio1 flashback) ○ Increase capillary permeability & pain

Answer 8

○ Blocks the BV from losing blood and blocks pathogens from entering

Answer 9

PRO-INFLAMMATORY CYTOKINES: TNF-a, IL-1, IL-6,IL-8

Answer 10

● Vascular stage ● Cellular stage

Answer 11

● Vascular stage **○ Phase 1**- vasoconstriction ■ Short lived ■ Allows for clothing to occur **○ Phase 2**- active vasodilation ■ Dilation ■ Increase in BF & cellular metabolism ■ Causes **redness and heat** **○ Phase 3**- passive vasodilation ■ BV stop reacting to nervous and humoral stimuli ■ Results in s**welling, pain, and impaired function**

Answer 12

○ Movement of leukocytes into the area of injury

Answer 13

● **Chemotaxis**- migrate in response to a chemical rxn

Answer 14

●** Rolling**- leukocytes slow down increase expression of adhesion molecules

Answer 15

● **Migration**- to the tissue spaces

Answer 16

**● Phagocytosis-** neutrophils and macs engulf/ degrade the bact, etc

Answer 17

● **Neutrophils, macs, NK** are the first cells to move out of the vasculature.

Answer 18

Neutrophils, macs, NK are the first cells to move out of the vasculature. ● They do this by using CAM to migrate to tissues where inflammation is occurring.

Answer 19

● Both the endothelium and leukocytes express CAM’s.

Answer 20

● CAM ○ Constitutively expressed-> ■ Expressed 24/7 ○ Expressed on local conditions ■ Ex. inflammation

Answer 21

● The types of CAMS ○ Selectins ○ Mucins **○ Integrins ○ Ig- superfamily CAM**

Answer 22

● Selectins ● Bind to carbohydrate moieties ●** Responsible for leukocyte interaction with the endothelium during the initial vascular phase of inflammation** ● Selectin L (CD62L) ● **Selectin E (CD62E) ● **Selectin P (CD62P)

Answer 23

● Selectin L (CD62L) ○ Expressed on leukocytes

Answer 24

● **Selectin E (CD62E) ○ Synthesized following stimulation

Answer 25

● **Selectin P (CD62P) ○ Contained in granules in endo. Cells ○ Released granules fuse w/ the cell membrane

Answer 26

CD34 aka GlyCAM-1 PSGL-1

Answer 27

● CD34 aka GlyCAM-1 binds to CD62L

Answer 28

● PSGL-1 on neutrophils binds to selectins E and P on endothelial cells

Answer 29

● Heterodimeric proteins that contain an A & B chains which forms a binding site that the ig- superfamily can bind to

Answer 30

● Divided into subgroups based on beta chain (B1-B7)

Answer 31

B2=expressed by leukocytes ○ Deficiency in B2-> LAD ○ Leukocyte adhesion deficiency-

Answer 32

**Leukocyte adhesion deficiency- autosomal recessive disease (recurrening bacT infections)b/c neutrophils cannot extravasate.**

Answer 33

IG superfamily ○ Immunoglobulin like domains ○ Binds to integrins ○ Expressed on endothelial cells ○ ICAM-1 (CD154) ○ ICAM-2 (CD102) ○ ICAM-3 (CD50) ○ VCAM (CD106)

Answer 34

**○ MadCAM-1 contain IG-like domains and mucin domains ■ Able to bind to both selectins and integrins**

Answer 35

1. Rolling 2. Activation ● Adhesion ● Diapedesis (migration)

Answer 36

Rolling ○ Leukocytes mucin CAMS bind to selectin E & P on endothelial cells. ■ They slow down and they roll on the endothelium

Answer 37

Activation ○ Increase in chemokine secretion by endothelial cells and increased chemokine receptor expression on leukocytes results in the activation of leukocytes ○ Integrins on leukocytes change to high- affinity state

Answer 38

Adhesion ○ Integrins bind firmly to the endothelium ○ Immobilization (handcuffed) -> this is where migration will occur!

Answer 39

Diapedesis (migration) ○ Leukocytes squeeze between endo. Cells and go to the site of inflammation ○ **Leukocytes bind to endo via PECAM-1 (CD131)!**

Answer 40

● Neutrophil extravasation ○ **First cell to arrive!!!** ○ Only bind to endo if there is inflammation ○ IL-8 & MIP-B activate neutrophils ○ Selectin L (binds to glycam) ○ PSGL-1 (binds selectins P & E) ○ Increase ICAM on endo and CD11a/ CD18 & CD11b/ CD18 (LFA-1 & MAC-1) on neutrophil allows for adhesion and migration

Answer 41

● Monocyte extravasation ○ Late to the party! ○ **VCAM** and ICAM-1 is only expressed after activation

Answer 42

Homeostatic migration ○ Small amount of monocytes can extravasate under normal conditions to replenish macs! ○ Regulated by CXCL14 ○ CD62L (selectin L)-> rolling ○ MCP-1 -> activation ○ PECAM-1-> migration

Answer 43

Complement receptors such as CR3 & CR4 bacT peptides participate in extravasation of monocytes into inflamed tissue

Answer 44

PRO-INFLAMMATORY CYTOKINES: TNF-a, IL-1, IL-6,IL-8

Answer 45

● Lymphocyte extravasation ○ Can recirculate and they live longer! ○ **They pass through capillary venules called endothelial venules (HEV)** ○ Selectins E and P, mucins, GlyCAM-1, ICAM-1, 2, 3, VCAM-1 and MadCAM-1= are involved

Answer 46

Typically we want the inflammatory response to stay in a localized area but this may not always happen.

Answer 47

Manifestations of systemic inflammation ■ Acute phase response ■ Alterations in WBC count ■ Pyrexia ■ Sepsis and septic shock

Answer 48

Systemic effects of inflammation ○ Loss of appetite ○ Altered sleep patterns ○ Lethargy ○ Muscular wasting ○ Metabolic acidosis

Answer 49

Inflamation Manifestations of inflamation -acute phase proteins leukocytosis and leutopenia high fever sepsis, septic shock anorexia altered sleep patterns lethargy muscular wasting metabolic acidosis

Answer 50

Acute phase proteins ○ Serum proteins that either increase or decrease in number during infection ■ Complement ■ C-reactive proteins ■ Haptoglobin ■ Serum amyloid ○ IL6 is the main proinflam cytokine that signals for APP

Answer 51

Positive APP- increase ○ Major- increase over 100-1000 fold & peaks at 24-48 hrs ○ Moderate increases 5-10 fold peaks at 48-72 hrs ○ Minor gradually increases 50-100%

Answer 52

● Negative APP- decrease

Answer 53

If not terminated chronic inflammation and cellular destruction will occur

Answer 54

TGF Beta from macs are released

Answer 55

IL-4 and IL-10 downregulate proinflammatory cytokines ● Downregulation of leukotrienes

Answer 56

**Upregulation of anti-inflammatory molecules like Interleukin 1 receptor antagonist or the double tumor necrosis factor receptor**

Answer 57

**Apoptosis of proinflammatory cells**

Answer 58

Also the pro-inflammatory cytokines have a short half life

Answer 59

Neutrophils undergo apoptosis

Answer 60

**Resolvins and protectins (from omega 3 polyunsaturated fatty acids) cause apoptosis of neutrophils***

Answer 61

**It ends with macs leaving through the lymphatics ○ Why does it make sense that macs would be the last to leave? (Think about M2)**

Answer 62

Resolution- complete restoration of the inflamed tissue ○ Occurs in short lived inflammation

Answer 63

Fibrosis- forms a scar & functional impairment can occur

Answer 64

Abscess formation

Answer 65

Chronic inflammation- prolonged inflammation ○ Tissue destruction

Answer 66

What are manifestations of inflammation? ● Manifestations of inflammation ○ Acute phase proteins ○ Leukocytosis and leukopenia ○ High fever ○ Sepsis, septic shock ○ Anorexia ○ Altered sleep patterns ○ Lethargy ○ Muscular wasting ○ Metabolic acidosis