Activation Of Innate Immunity - Bowden

Question 1

What does the IL-1/IL-6/TNF-α cocktail do? 7

Answer 1

Bone marrow –> neutrophil mobilization

Liver –> acute phase proteins (APP) produce Ex. Mannose binding lectin, C-reactive

Hypothalamus –> increased body temperature

Fat & Muscle –> energy mobilization for heat

Question 2

What causes fever? 8

Answer 2

IL-1/IL-6/TNF-α cocktails effect on the hypothalamus

Question 3

What are the physiological effects of fever? 8

Answer 3

Bacterial and viral replication slows

Human cells become more resistant to negative effects of TNF-α

Makes the adaptive immune system more potent

Question 4

What causes the liver to produce APP? 9

Answer 4

Macrophages secrete IL-6 (also IL-1) causing the liver to produce acute phase proteins

Question 5

What is the most widely used indicator of acute inflammation? 10

Answer 5

C-Reactive protein (can increase 100-1000x)

Question 6

What is TNF-α effect (alone) on endothelial cells? 11

Answer 6

Increased membrane permeability

Question 7

What is the coupled action of TNF and IL-1? 11

Answer 7

Expression of adhesion molecules on endothelial cell surfaces

Causes leukocytes to secrete IL-1 & IL-6

Question 8

When could you say that complement was acting as part of the humoral immunity? 13

Answer 8

When the classical pathway of complement is active

Question 9

What’s happening in the Alternative pathway of complement pathways? 14

Answer 9

aka the lectin pathway

C3 –> C3b + C3a (constantly happening)

C3b cleaves C5

C5 –> C5b + C5a

C5b helps to form the MAC

Question 10

What is an incredibly good opsonizer? 14

Answer 10

C3b

Question 11

What is the most potent Anaphylatoxin? 15

Answer 11

C5a

Question 12

What do anaphylatoxins do? 15

Answer 12

Induce smooth muscle contraction

Induce degranulation of mast cells/basophils

Induce vasodilation

Induce membrane permeability

Question 13

What are the anaphylatoxins? 15

Answer 13

C3a, C4a, C5a

Question 14

What is the coupled role of IL-1 and TNF-α? 17

Answer 14

To increase expression of P & E selectins on endothelium (the inside of blood vessels)

Question 15

What slows down approaching neutrophils? 17

Answer 15

Expression of P & E selectins (bind, release, bind, release)

Question 16

What is the purpose of causing a rolling effect in neutrophils by the endothelial selectins? 18

Answer 16

To allow the neutrophils to slow and be able to receive local chemokines

Question 17

What is the effect of the release of IL-8 during cellular adhesion to endothelial cells by neutrophils? 18

Answer 17

To cause expression of integrins so that neutrophils can pass through the endothelium

Question 18

What are the integrin binding components between a neutrophil and the endothelium? 18

Answer 18

Neutrophils - LFA1

Endothelial - ICAM1

Question 19

What are the integrin binding components between a macrophage and endothelium cells? 18

Answer 19

Macrophage - VLA4

Endothelium - VCAM1

Question 20

What are the three key processes of the acute inflammatory response? 20

Answer 20

Vasodilation

Increased vascular permeability

Emigration of leukocytes from blood into damaged area

Question 21

What is omphalitis? What causes it?22

Answer 21

Lack of healing of the umbilical stump leads to infection

Caused by CGD chronic granulomatus disease

Question 22

You get a cut on your hand. What do you Effect to be in there area within four hours, what about within 36 hours?

Answer 22

4 hours - neutrophils

36 hours - macrophages

Question 23

What is LAD 1? 24

Answer 23

Leukocyte Adhesion Deficiency 1

Lack of CD11a expression integral to LFA-1 function (found on neutrophils)

Question 24

What adhesion molecules do T cells use to bind endothelium? 26

Answer 24

Mac-1 (integrin)

Question 25

What is the difference between LAD 1, 2, 3? 26

Answer 25

LAD I and III --> adhesion defect LAD II --> rolling defect

Question 26

What kind of relationship do CD11 and CD18 share? 26

Answer 26

They are coexpressed. A mutation in one will disable the other

Question 27

With someone suffering from a Leukocyte Adhesion Deficiency what would you expect not to find? 27

Answer 27

Absence of pus formation due to a lack of neutrophils

Question 28

How does Stpahylococci evade the innate immune system? 28

Answer 28

They're resistant to reactive oxygen species through the production of catalase which breaks down reactive oxygen species

Question 29

What are 3 acute phase proteins? 9

Answer 29

C-reactive proteins Fibrinogen Mannose-binding lectin

Question 30

What is the function of C-reactive protein? 9

Answer 30

Acts as an opsonin by binding phosphorylcholine on bacterial surfaces

Question 31

What is the function of mannose-binding lectin? 9

Answer 31

Acts as an opsonin by binding residues on bacterial surfaces

Question 32

What is the lone effect of TNF-α on the heart, Endothelial cells, and muscle? 11

Answer 32

Heart --> lowers CO Endothelial cells --> thrombus production and increased permeability Muscle --> insulin resistance

Question 33

What is the effect of pyrogens (IL-1, IL-6, TNF-α) on the bone marrow? 11

Answer 33

Leukocyte production

Question 34

What is unique about TGF-β? 6

Answer 34

Allows for wound repair without regulatory immune cells in the vicinity

Question 35

What secretes IL-10 and what is its function? 6

Answer 35

Macrophages, DC, and Tregs Contraction of cells after threat elimination