Acute and Chronic Inflammation

Question 1

What five categories cause acute inflammation?

Answer 1

1. Infection
2. Trauma (mechanical/thermal/chemical/radiation)
3. Tissue necrosis for any reason (ischemic/trauma)
4. Foreign Material
5. Immune Reaction

Question 2

Where are Toll-like receptors found?

Answer 2

Found on most cells, but cleverly both on the surface of host cells AND within the cells

Question 3

What are the two important families of receptors for inflammatory processes?

Answer 3

1. Toll-Like Receptor Family

2. Inflammasome

Question 4

What occurs after a toll-like receptor is bound by an antigen?

Answer 4

It activates transcription factors that prompt the production of proteins that mediate inflammation, interfere with action of infectious agents (interferons) and promote lymphocyte activation.

Question 5

What is an inflammasome?

Answer 5

It is a complex of several different types of receptor

Question 6

What happens after an inflammasome is bound to an antigen?

Answer 6

It stimulates inflammation via activation of caspase-1

Question 7

What do inflammasomes recognize as their antigens?

Answer 7

They recognize some microbial components, as well as pieces of dead cells

Question 8

What activates caspase-1?

What does caspase-1 activate?

Answer 8

Inflammasome

Interleukin-1 beta (IL-1 beta)

Question 9

What is one function of IL-1 beta in inflammation?

Answer 9

Recruits leukocytes

Question 10

What are the two main changes in vessels that lead to an exudate?

Answer 10

1. Dilation of vessels

2. Increased permeability

Question 11

What is the difference between exudate and transudate?

Answer 11

Exudate- Edema with a lot of proteins and inflammatory cells. (seen in acute inflammation)

Transudate- Edema fluid with low protein content

Question 12

Dilation of arterioles produces what clinical symptoms?

Answer 12

Rubor and Calor

Question 13

What are three mechanism by which permeability may occur?

Answer 13

1. Endothelial cell contraction
2. Injury of the endothelial cells
3. Transcytosis

Question 14

What causes the endothelium to quickly and fleetingly contract?

Answer 14

Histamine (produced by mast cells, basophiils, and platelets)

Question 15

What causes the endothelium to contract long-term but takes longer to develop (hours)?

Answer 15

Il-1 and TNF (produced by macrophages, mast cells, and endothelial cells)

Question 16

What cell is responsible for releasing toxic compounds that can directly injure endothelial cells?

Answer 16

Activated leukocytes.

Question 17

Describe transcytosis.

Answer 17

Vesicles take material from the endothelial cell membrane facing the vessel interior and move it to the extravascular side

Question 18

What system acts to drain fluid and debris from the area of injury?

Answer 18

Lymphatic system

Question 19

What are the four phases of leukocytes recruitment?

Answer 19

1. Margination/rolling
2. Adhesion
3. Transmigration
4. Chemotaxis

Question 20

Activated endothelial cells produce a protein that binds leukocytes.

What is the protein?

What activates it?

What part of the endothelial protein binds the leukocyte?

Answer 20

1. Selectins (E- and P- selectin)
2. E-selectin is stimulated by IL-1
   P-selectin is stimulated by histamine
3. Selectins bind sugars that are present on the surface of leukocytes

Question 21

Are selectins present on inactivated endothelium?

Answer 21

No. Selectins are only produced in activated endothelial cells

Question 22

What happens when leukocytes are activated by local chemokines inside the vessel?

Answer 22

The integrins on the surface of the leukocyte change shape and cluster together.

Question 23

What are integrins?

Answer 23

Proteins found on leukocytes that change shape when the leukocyte is activated by chemokines. They bind to ligands on the endothelial surface and stop the leukocyte from rolling.

Question 24

What is diapedesis?

Answer 24

The process in which leukocytes push between endothelial cells

Question 25

Through which vessel does transmigration occur?

Answer 25

The venules

Question 26

What enzymes do leukocytes produce to brake up the basement membranes of venules?

Answer 26

Collagenases

Question 27

Describe the process of chemotaxis.

Answer 27

Leukocytes contractile elements are linked to receptors for these chemicals; thus the direction of greatest chemotactic chemical density determines the direction of movement

Question 28

What chemicals cause chemotaxis?

Answer 28

Cytokines secreted by cells involved in the injury or infection Proteins unique to bacteria Proteins from the complement system (esp. C5)

Question 29

List functions promoted by leukocyte activation.

Answer 29

1. Phagocytosis 2. Killing/degradation of the phagocytized microbe 3. Extracellular secretion of microbicidal compounds 4. Production of mediators

Question 30

How does phagocytosis occur?

Answer 30

1. Specific affinity for the microbial components | 2. Recognition of opsonins

Question 31

What are three types of opsonins?

Answer 31

1. IgG antibodies 2. Compliment system molecules 3. Colectins

Question 32

What happens after a bacteria is phagocytized?

Answer 32

The lysosome binds with the phagosome and the contents are destroyed

Question 33

What is contained inside the lysosome?

Answer 33

ROS. Formed by: 1. Oxidation of NADPH by phagocyte oxidase which converts oxygen to superoxide. Superoxide spontaneously converts to H2O2 2. Myeloperoxidase + chloride ions converts H202 to hypochlorous radical (strong oxidizer) 3. Elastase 4. Lysozyme

Question 34

What are NETs?

Answer 34

Extracellular traps produced by neutrophils. Neutrophils use their nuclear chromatin that provides a scaffolding in which antimicrobial compounds are embedded

Question 35

What are three general outcomes of acute inflammation?

Answer 35

1. It resolves- Injured tissue can regenerate 2. Chronic Inflammation- Offending agent is not removed. Can either resolve or form scarring 3. Scarring- connective tissue fills the void (celled fibrosis). This can lead to significant function impairment

Question 36

Is acute inflammation part of the innate or adaptive immune system?

Answer 36

Innate immune system

Question 37

What specific scenarios can lead to normal host tissue damage?

Answer 37

1. Tissue surrounding infectious agents may become damaged (tuberculosis) 2. Cleaning up necrotic tissue by the inflammatory process may cause additional damage 3. Inflammatory process is directed against host tissues

Question 38

Deficits in leukocyte function leads to what?

Answer 38

Increased susceptibility to infections

Question 39

Name one acquired deficiency of leukocytes.

Answer 39

Aplastic anemia due to chemotherapy Diabetes

Question 40

What is Chediak-Higashi Syndrome?

Answer 40

A genetic deficit from a mutation in the proteins responsible for trafficking of organelles; thus phagosomes and lysosomes cannot properly fuse.

Question 41

Patterns of acute inflammation can give a clue to the ___________.

Answer 41

etiology

Question 42

What are the main characteristics of chronic inflammation?

Answer 42

1. mononuclear cell infiltrate 2. Tissue destruction 3. Repair

Question 43

What are three characteristic settings of chronic inflammation?

Answer 43

1. Persistent infections 2. Immune-mediated disease 3. Prolonged exposure to toxins (endogenous substances)

Question 44

What are some examples of immune mediated diseases that cause chronic inflammation?

Answer 44

Lupus & Crohn's disease (auto-immune) Asthma (allergic disease)

Question 45

What is the structure of a granuloma?

Answer 45

Consists of enlarged macrophages that form a nodule, which is often surrounded by lymphocytes.

Question 46

Granulomas form around organisms to prevent their spread. Will this completely kill the organism?

Answer 46

Not always.

Question 47

What happens to a longstanding granulomatous infection?

Answer 47

A fibrosis forms around it

Question 48

What cell does a macrophage arise from?

Answer 48

Circulating blood monocytes

Question 49

What are four roles of macrophages?

Answer 49

1. Ingest microbes and necrotic cellular debris 2. Initiate tissue repair, which often results in fibrosis 3. Secrete inflammatory mediators that promote inflammation 4. Present antigens to the adaptive immune system

Question 50

What activates macrophages in the classical pathway?

Answer 50

Endotoxin INF-gamma Foreign material

Question 51

What activates macrophages in the alternative pathway?

Answer 51

IL-4 | IL-13 (from T cells, eosinophils, mast cells)

Question 52

What do macrophages of the classical pathway produce?

Answer 52

Reactive oxygen species Nitrous oxide Lysozymal enzymes Proinflammatory cytokines

Question 53

What do macrophages of the alternative pathway produce?

Answer 53

Growth factors: New vessel growth fibroblast activation

Question 54

What is the main functions of macrophages of the classical pathway?

Answer 54

Killing microbes | Chronic inflammation

Question 55

What is the main function of macrophages of the alternative pathway?

Answer 55

Tissue repair | Fibrosis

Question 56

Activation of lymphocytes is a function of adaptive or innate immune system?

Answer 56

Adaptive

Question 57

What does Th1 CD4+ T cells secrete?

Answer 57

IFN-gamma. This activates the classical pathway macrophages

Question 58

What do Th2 CD4+ T cells secrete?

Answer 58

IL-4 IL-5 IL-13 These activate the alternative pathway macrophages; also eosinophils

Question 59

What do Th17 CD4+ T cells secrete?

Answer 59

IL-17 which eventuates recruitment of neutrophils and monocytes.

Question 60

What two inflammatory reactions are characterized by conspicuous eosinophils?

Answer 60

1. Parasite infections- granules contain major basic protein which are toxic to parasites 2. Allergic reactions mediated by IgE

Question 61

Are mast cells part of acute or chronic inflammation?

Answer 61

Both

Question 62

Name two inflammatory mediators that are released by mast cells.

Answer 62

1. Histamine | 2. Arachidonic acid

Question 63

What antibody coats mast cells?

Answer 63

IgE

Question 64

Leukocytes produce three inflammatory proteins that have a systemic effect. What are they?

Answer 64

1. TNF 2. IL-1 3. IL-6

Question 65

What cell does IL-6 effect?

Answer 65

Liver hepatocytes

Question 66

What are three proteins that are produced in greater abundance in response to IL-6?

Answer 66

1. C-reactive protein (CRP) 2. Serum amyloid A (SAA) 3. Fibrinogen

Question 67

What is the role of C-reactive protein (CRP) and serum amyloid A (SAA)?

Answer 67

They adhere to cell walls and may act as opsonins

Question 68

In the presence of fibrinogen what clinical test is effect?

Answer 68

Erythrocyte sedimentation rate (ESR)

Question 69

What is the mechanism for leukocytosis early in an inflammatory process?

Answer 69

Under the influence of TF and IL-1 more leukocytes are released from the bone marrow. May also see an increased number of immature white blood cells.

Question 70

What is the mechanism for leukocytosis after a prolonged inflammatory response?

Answer 70

Continued inflammation leads to increased production of colony stimulating factors (CSFs) that increase bone marrow production of leukocytes

Question 71

What type of infection is associated with neutrophilia?

Answer 71

Bacterial infections

Question 72

What type of infection is associated with lymphocytosis?

Answer 72

viral infections

Question 73

What type of infection is associated with eosinophilia?

Answer 73

Asthma or parasitic infections

Question 74

What type of infection is associated with leukopenia?

Answer 74

Specific infections, e.g. Typhoid fever

Question 75

Name some other physiologic effects during acute-phase reaction.

Answer 75

Tachycardia, hypertension, hypohidrosis, rigors, chills, anorexia, somnolence, malaise