L12

Question 1

Inflammation is

Answer 1

A non-specific response to infection or injury that is characterized by enhanced accumulation of immune cells and plasma proteins.

Question 2

Hallmarks of Inflammation

Answer 2

Redness (Rubor)
Heat (Calor)
Swelling (Tumor)
Pain (Dolor)
Loss of Function (Functio laesa)

Question 3

What causes inflammation?

Answer 3

injury, infection, disease

Question 4

The inflammatory process is a

Answer 4

normal and necessary response to injury and infection.
Substances are produced which lead to vasodilation and increased permeability of blood vessels.
Pain receptors can also be stimulated due to protein and fluid leak from damaged cells

Question 5

What would happen to wound healing if the inflammatory response was blocked or delayed?

Answer 5

Wound healing would be delayed, leaving the wound open and vulnerable to infection.

Question 6

Causes of Chronic Inflammation

Answer 6

Persistent infection
Immune-mediated inflammatory disease
Toxic agents

Question 7

Acute

Answer 7

Neutrophils, Monocytes/Macrophages, Mast cells, sometimes Eosinophils and Basophils

Question 8

Chronic

Answer 8

Monocytes/macrophages, T cells, sometimes neutrophils

Question 9

Proinflammatory cytokines:

Answer 9

Tumor Necrosis Factor (TNF)-α
Interleukin (IL)-1β
IL-6

Inflammatory Mediators

Question 10

Histamine, bradykinin, leukotrienes

Answer 10

Involved in vasodilation

Question 11

Prostaglandins

Answer 11

Derived from cell membrane phospholipids

Question 12

Prostaglandins work in concert with

Answer 12

histamine and bradykinin to accomplish the following:
Causes constriction (PGE2) or dilation of blood vessels (PGF2a)
Involved in the production or inhibition of clots
Act on the thermoregulatory center of the hypothalamus (PGE1)
PGE2 is involved in redness, edema, and pain

Question 13

Complement proteins

Answer 13

C5a is involved in monocyte/neutrophil recruitment

C3a and C5a can trigger mast cell degranulation

Question 14

Resolution of inflammation

Answer 14

The original stimulant must be removed/healed.
As the inflammatory stimulus diminishes there are reductions of inflammatory mediators, immune cell recruitment, etc. and the tissue can return to homeostasis.
Cytokines involved in turning off inflammation:
IL-10, Transforming Growth Factor (TGF)-β

Question 15

Want to stop inflammation? Acute:

Answer 15

The best way is to allow the body to heal.

Ice and elevation for swelling, Abx for infection, NSAIDs can also help.

Question 16

Want to stop inflammation? Chronic:

Answer 16

Glucocorticoid steroids, immunosuppressants, anti-leukotrienes, biologics

Question 17

Migration/Recruitment

Answer 17

the general process of leukocyte movement from blood to tissue

Question 18

Selectins

Answer 18

Low-affinity adhesion molecules involved in the early stages of leukocyte capture

Question 19

Integrins –

Answer 19

Adhesion molecules involved in later stages of leukocyte migration, can be low- or high-affinity

Question 20

Chemokines –

Answer 20

Chemotactic cytokine. Named/classified based on the location of the N-terminal cysteine residues, C, C-C, CXC, CX3C

Question 21

First Step: Tethering/Rolling

Answer 21

Slows the leukocyte down within the post-capillary venule

Selectin-mediated

Question 22

Selectins

Answer 22

Plasma membrane adhesion molecules
Recognize sialylated carbohydrates
Low affinity
P-selectins are stored in cytoplasmic granules so they can be expressed almost immediately
E-selectins can take upwards of 2 hours to be expressed

Question 23

Second Step: Integrin Activation

Answer 23

Chemokines produced by tissue immune cells or nearby epithelial cells act on the rolling leukocyte
Chemokine interaction with its chemokine receptor changes integrin affinity from low to high

Question 24

Chemokines

Answer 24

Chemotactic cytokines
Can be produced by leukocytes, epithelial cells, fibroblasts
Upregulated by the recognition of microbes and proinflammatory cytokines
Different combinations of receptors are expressed on different types of leukocytes

Question 25

Integrins

Answer 25

Cell adhesion molecules
Examples:
LFA-1 (leukocyte function-assoc. antigen 1)
Ligand is ICAM-1 (intercellular adhesion molecule-1)
VLA-4 (very late antigen 4)
Ligand is VCAM-1 (vascular cell adhesion molecule-1)
High-affinity selectins often cluster together to make more contacts with the endothelial cell

Question 26

Step 3: Adherence

Answer 26

High-affinity integrins bind to their ligands on the endothelial cell
The leukocyte eventually makes so many contacts it stops and flattens out along the endothelium
Cytoskeleton rearrangements

Question 27

Step 4: Migration (Diapedesis)

Answer 27

The leukocyte can now move from the blood into the tissue
But first…
The leukocyte must rearrange its cytoskeleton to squeeze through the endothelium
The tight junctions that hold the endothelial cells together must loosen
The leukocyte follows chemokines to the final site of infection.