Week 6 - Intro To Inflammation

Front 1

What is inflammation? Can inflammation itself have deleterious effects?

Back 1

It is a physiologic process deisgned ro rid the body of damaged tissue or foreign invaders. It can certainly have deleterious effects

Front 2

What is the relationship between inflammation, innate immunity, and adaptive immunity.

Back 2

Generally, they are distinct, but there is some overlap between all three systems

Front 3

What are the signs of acute inflammation?

Back 3

Redness, heat, swelling, pain, pus production, and loss of function

Front 4

Why does redness occur?

Back 4

Capillaries dilate and RBCs leak into the tissues.

Front 5

Does the coagulation cascade play a role in innate immunity?

Back 5

It's increasingly believed yes

Front 6

Pus and neutrophils are associated with acute or chronic inflammation?

Back 6

Acute

Front 7

How does blood flow change during inflammation?

Back 7

The blood vessels dilate, slowing flow. Plasma leaks out, also flowing flow. This leads to margination of leukocytes

Front 8

How does vascular permeability increase?

Back 8

The endothelial cells retract due to mediator, and direct injury to the vessels also promotes leakage

Front 9

What changes in vasculature occur in inflammation?

Back 9

Decreased blood flow (vasodilaton, decease blood volume), edema, adhesion molecules for WBCs

Front 10

How do leukocytes extravate from blood vessels?

Back 10

They marginate due to decreased flow. They roll via temporary adhesions via selectins. They stick via integrin binding. They then pass through gaps in the endothelial cells via chemotaxis

Front 11

Differentiate selectins from integrins

Back 11

Selectins mediate weak attachment, integrins have strong attachment

Front 12

Do integrins also conduct signaing to and from leukocytes?

Back 12

Yes, they send signals to and from each other

Front 13

Differentiate P, L, and E selectins. What is the temporal difference associated with P and E selectins?

Back 13

P selectins are on platelets (and endothelia), L selectins are on leukocytes (expressed constitutively, but can also be more active when received signals), and E selectins are on endothelia, and are induced by inflammatory mediators. P selectins are the dominant selectin up to 1 hour after stimulus, and E selectins are dominant at later times

Front 14

How are leukocyte integrins related to immunoglobulin class receptors?

Back 14

Leukocyte integrins form firm adhesion with immunoglobulin class rceptors, and mediate movement across the epithelium into the matrix

Front 15

What two factors determine how well cells adhere?

Back 15

Affinity and avidity. Affinity is how well the receptor binds to the receptor, and avidity refers the total number of receptors binding

Front 16

What are LAD1? What portein is affected? What results from these?

Back 16

Leukocyte adhesion deficiency 1. The beta 2 integrin is affected. They result from defective leukocyte adhesion
They have gingivitis, skin infections, infections lacking pus, poor wound healing

Front 17

What causes leukocyte adhesion deficiency II?

Back 17

Inability of selectins to bind ligand (not an integrin problem)

Front 18

What is diapedesis?

Back 18

The movement of leukocytes from the lumen of BV to the ECM

Front 19

Describe the half life of neutrophils and eosinophils.
Compare this to macrophages

Back 19

They live 5-7 hours. Macrophages live about 14 days, they are relatively long lived

Front 20

What cells make up most of pus?

Back 20

Neutrophils

Front 21

Are neutrophils present in the tissues normally, or only when the tissue is inflamed. What are neutrophils function?

Back 21

Only when the tissue is inflamed. Phagocytosis and bacteria killing

Front 22

What are the two types of granules in neutrophils?

Back 22

Specific (secretory) and azuophil (phagocytic)

Front 23

What are granules called as they mature, as the neutrophil matures. Do neutrophils have all the armament they need to kill after two weeks in the bone marrow?

Back 23

They are called primary granules, then secondary granules. They have all the armament they need by two weeks

Front 24

How are neutrophils cleared?

Back 24

They are eaten by resident tissue macrophages in the liver and spleen

Front 25

Describe the neutrophil turnstyle.

Back 25

Neutrophils are made in bone marrow, released into the blood, and travel to tissue (usually liver or spleen). When macrophages phagocytose neutrophils, they do not release IL-23. When they don't eat neutrophils, they release IL-23. IL-23 sends a signal, via IL-17, to the bone marrow to produce and release more neutrophils

Front 26

How is the neutrophil turnstyle affected in LAD?

Back 26

It is affected because neutrophils can't enter the tissues. Therefore IL-23 release increases, which results in increased neutrophil production and release.

Front 27

What is chemotaxis? What protein do cells use to receive the chemotactic signal?

Back 27

Chemotaxis is movement toward or away from a stimuli, following chemicals. Cells use g protein coupled receptors.

Front 28

How many microbes be recognized?

Back 28

Through antibodies, complement, or directly through structure on the microbe (non-opsonic)

Front 29

How do phagocytes kill invaders?

Back 29

They engulf them, incorporate them into phagosomes. Here, they dump their granule contents on them or expose them to ROS

Front 30

What types of "weapons" does a neutrphil use?

Back 30

ROS, proteases, lysozyme, defensins

Front 31

What is the oxidative burst? What proteins mediates it?

Back 31

The oxidative bust is the release of ROS to engulfed invaders. NAPDH oxidase is needed to convert O2 to the superoxide anion. The superoxide anion is converted to H2O2 via superoxide dismutase, and then into HOCl (bleach) via myeloperoxidase

Front 32

What can microbicidal (anti microbial proteins) do?

Back 32

They can alter the permeability of the cell membrane, bind LPS, help phagocytosis, and put holes in the cell wall.

Front 33

What is the difference between activated and non activated macrophages?

Back 33

Activated macrophages have many granules, and non activated do not

Front 34

What are the tissue specific variants of macrophages?

Back 34

Kupffer cells (liver), microglia (brain), alveolar macrophages (lung)

Front 35

IMPORTANT: What is the difference between M1 and M2 macrophages?

Back 35

M1 is "classically activated." It does phagocytosing, killing, and is pro-inflammatory.
M2 is "alternatively" activated. It is anti-inflammatory.