IIT 5: Systemic Inflammatory Responses, Autoimmune Disease

Question 1

Define systemic inflammatory response syndrome (SARS)

Answer 1

Systemic consequences of localized or disseminated inflammation (systemic consequences of severe inflammation)

Question 2

Define Sepsis

Answer 2

SIRS caused by infection.

Question 3

Define bacteremia

Answer 3

The presence of bacteria in the bloodstream .

• low level often causes no clinical signs
• higher levels may causes sepsis or septicemia

Question 4

Define septicemia

Answer 4

Clinically apparent severe disease as a consequence of bacteria or bacterial toxins in the blood. Bacteria + clinical disease
-term to use is sepsis instead

Question 5

Define pathogenesis

Answer 5

• widespread distribution of the cause (eg systemic infection, anaphylaxis, etc)
• localized distribution of the cause (eg pneumonia) with systemic distribution of inflammatory mediators

Question 6

What do high levels of pro-inflammatory cytokines in the bloodstream affect?

Answer 6

Organs distant from the site of infection, leading to fever (hypothalamus), sickness behaviour (brain), leukocytosis (bone marrow) and changes in acute phase proteins (liver)
-SIRS represents the systemic responses to high levels of pro-inflammatory cytokines in the bloodstream

Question 7

What is involved in the localized inflammatory response?

Answer 7

• tissue damage leads to release of DAMPs (HMGB1, ATP, uric acid) OR infection leads to the presence of PAMPs (LPS, lipoteichoic acid, flagellin, viral nucleic acid) and these can activate pattern recognition receptors
• lead to inflammatory mediators like TNF, histamine, leukotrienes
• lead to leukocyte activation
• lead to endothelial activation

Question 8

What are the different pattern recognition receptors?

Answer 8

• cell surface receptors (toll like receptors, receptors for antibody and complement)
• cytoplasmic receptors (NOD like receptors, RIG 1 like receptors)
• soluble receptors (complement system, antibody, collectins)

Question 9

What does vasodilation from inflammatory mediators in localized inflammatory response lead to?

Answer 9

Hyperaemia and congestion -> cardinal signs of inflammation

Question 10

What does vascular permeability from inflammatory mediators in localized inflammatory response lead to?

Answer 10

Edema, fibrin, exudation -> eliminates the threat, initiates healing

Question 11

What does leukocyte activation from inflammatory mediators or pattern recognition receptors in localized inflammatory response lead to?

Answer 11

Diapedesis, chemotaxis, phagocytosis, killing (recruitment to tissue, adhere to vessel walls) -> eliminates the threat, initiates healing and may cause tissue damage (ischemia, free radical, protease)

Question 12

What does endothelial activation from pattern recognition receptors in localized inflammatory response lead to?

Answer 12

increased tissue factor, decreased protein c, decreased thrombomodulin -> hyper coagulability -> thrombosis -> tissue damage (ischemia, free radical, protease)

Question 13

What is involved in systemic inflammatory response syndrome and sepsis?

Answer 13

• tissue damage leads to release of DAMPs (HMGB1, ATP, uric acid) OR infection leads to the presence of PAMPs (LPS, lipoteichoic acid, flagellin, viral nucleic acid) and these can activate pattern recognition receptors
• lead to inflammatory mediators like TNF, histamine, leukotrienes
• lead to leukocyte activation
• lead to endothelial activation

Question 14

What is the effect of the acute phase response from inflammatory mediators in systemic inflammatory response?

Answer 14

• inflammatory mediators circulate through body and blood, effect on distant tissues
• fever, depression, inappetence, leukocytosis, acute phase proteins

Question 15

What is the effect of inflammatory mediators on vasodilation in systemic inflammatory response?

Answer 15

Vasodilation occurs throughout body and causes systemic hypotension (shock), which leads to increased heart rate and rest rate and tissue damage in kidney, liver, lung mostly

Question 16

What is the effect of inflammatory mediators on vascular permeability in systemic inflammatory response?

Answer 16

Increased vascular permeability leads to tissue edema, leads to tissue damage

Question 17

What is the effect of inflammatory mediators and pattern recognition receptors on leukocyte activation in systemic inflammatory response?

Answer 17

-oxygen and nitrogen radicles, proteases, tissue damage

Question 18

What is the effect of pattern recognition receptors on endothelial activation in systemic inflammatory response?

Answer 18

-endothelial activation (increased tissue factor, decreased protein C, decreased thrombomodulin) leads to increased coagulation can lead to disseminated intravascular coagulation, can cause tissue damage and consumptive coagulopathy

Question 19

What is an acute phase response?

Answer 19

Systemic adaptive responses to severe inflammation.

Question 20

What is the acute phase response largely driven by?

Answer 20

• the cytokines interleukin 6 (IL-6), IL-1
• TNF
• In mild inflammatory diseases, these cytokines are only active at the site of inflammation, and plasma cytokine binding proteins or cytokine inhibitors neutralize any cytokine that leaks into circulation

Question 21

What are the systemic changes in pathologic processes during disease (acute phase response)?

Answer 21

• fever
• anorexia, depression
• cachexia - catabolic state, lose weight/muscle mass
• leukocytosis
• cortisol secretion

Question 22

What are acute phase proteins?

Answer 22

Help identify animals in the acute stages of inflammatory disease. These are the proteins produced in the liver whose levels in plasma are changed by inflammation.

• eg haptoglobin, fibrinogen, C reactive protein
• a shift away from non-essential functions to deal with the imminent threat
• In acute phase, the liver decreases the production of negative acute phase proteins and increases the production of positive ones

Question 23

What does haptoglobin do?

Answer 23

• acute phase protein

- binds hemoglobin, making the iron in hemoglobin unavailable to most bacterial pathogens

Question 24

What does c reactive protein do?

Answer 24

• acute phase protein

- binds bacterial pathogens, reduces oxidative burst in neutrophils and binds to damaged tissues

Question 25

What are come functions of positive acute phase proteins?

Answer 25

These are helpful things.

• control of pathogens to deal with bacterial infections
• quell inflammation (reduce systemic inflammatory response)
• minimize tissue damage

Question 26

What happens in systemic inflammatory response syndrome?

Answer 26

The inflammatory stimulus acts on the macrophage, inflammatory mediators are produced like IL6, IL1, TNF alpha

• produce PGE2 which acts on hypothalamus to cause fever
• act on behaviour to cause malaise, anorexia
• act on marrow for leukocytosis (release NPs quickly, increase production)
• act on liver to make acute phase proteins
• these things have short half life, cytokine inhibitors in serum

Question 27

What are the different categories of SIRS?

Answer 27

• can either be infectious (sepsis) or non-infectious (like widespread tissue trauma)
• Infectious can be localized -> cytokinemia (eg bacteria only in lung tissue, cytokines throughout body for systemic inflammation) or disseminated: bacteremia (septicemia) where bacteria is throughout the body