Immunology Sepsis

Question 1

What are antimicrobial peptides

Answer 1

AMP

Peptides that defend against pathogens as part of the innate immune system

3 main groups:
* digestive enzymes and peptides disrupting the microbial cell membrane
* peptides binding essential pathogen cell elements
* peptides acting as decoy for bacterial attachment

Question 2

What do bacteria lack in their cell wall compared to eukaryotic cells?

Answer 2

• cholesterol
• negatively charged phospholipids

Question 3

What are the main PRR for gram positive versus gram negative bacteria? Which PAMPs do they detect?

Answer 3

Toll-like receptor 2 => gram positive bacteria (also gram neg)
* lipoteichoic acid
* peptidoglycans - also in gram negative

Toll-like receptor 4 => gram negative bacteria
* lipopolysaccharide

Question 4

Which PRR detect viral PAMPs?

Answer 4

TLR 3, 7, 8, 9

Detect viral RNA and DNA

Question 5

Which PRR detect DAMPs?

Answer 5

TLR 2, 3, 4, 9

Question 6

List DAMPs

Answer 6

• high mobility group box protein (HMBG) 1
• necrotic cells
• fibrinogen
• heat shock protein
• immunoglobulins
• defensins
• endogenous mRNA

Question 7

After PRR activation, what are the main pathways leading to inflammatory cytokine and chemokine production

Answer 7

MyD88 (most TLR can activate this pathway)
* IRAK activation
* IKKbeta stops inhibiting NFKB
* ativates AP-1 (activator protein 1)
* NFKB and AP-1 move into the nucleus and initiate inflammatory cytokine production, etc.

TRAM/TRIF (TLR 4)
* leads ultimately to interferone production

Question 8

What is produced after NFKB and AP-1 move into the nucleus and alter transcription?

Answer 8

• TNF-alpha
• IL-1, 6, 8
• acute phase proteins
• iNOS
• coagulation factors

Question 9

What cells predominantly produce TNF-alpha?

Answer 9

• T cells
• macrophages

Question 10

List the effects of TNF-alpha

Answer 10

• increases iNOS production –> vasodilation
• increases COX-2 production
• upregulates endothelial adhesion molecules (ICAM-1, VCAM, E-selectin) –> tethering, diapedesis of leukocytes
• induces TF expression
• downregulates anti-coagulant factors (e.g., thrombomodulin)

Question 11

Which inflammatory cytokines are the main pyrogens?

Answer 11

IL 1 and 6

Question 12

What is the main anti-inflammatory cytokine?

Answer 12

IL-10

Question 13

Where are acute phase proteins produced?

Answer 13

liver/hepatocytes

Question 14

What are the characteristics of the acute phase response?

Answer 14

• fever
• neutrophilia
• coagulation activation
• complement cascade activation
• serum ion and zinc binding
• enhanced gluconeogenesis
• increased muscle catabolism
• altered lipid metabolism

Question 15

What are the two groups of APP and what induces them?

Answer 15

group 1 induced by TNF-alpha, IL-1
group 2 induced by IL-6

Question 16

List negative acute phase proteins

Answer 16

• albumin
• protein C
• protein S
• antithrombin

Question 17

List 3 acute phase proteins

Answer 17

CRP
procalcitonin
fibrinogen

Question 18

What is the main key to coagulation activation in sepsis?

Answer 18

TF expression on macrophages, monocytes, tissue cells

Question 19

What are the effects of bradykinin?

Answer 19

• enhances vasodilation
• increases vascular permeability
• reduces platelet function

Question 20

What are the effects of kallikrein in sepsis?

Answer 20

• enhances fibrinolysis
• additional factor XII activation (complement pathway)

Question 21

How does ADAMTS-13 help in sepsis?

Answer 21

cleaves the ultra-large vWF multimers that otherwise lead to excessive PLT activation and micothrombi formation

human sepsis patients: lower ADAMTS-13 levels associated with poor prognosis