Inflammation

Question 1

What are the 3 roles of inflammation?

Answer 1

1. Deliver effector molecules to site
2. Induction of local blood clotting- keep infection in area
3. Promote repair of tissue

Question 2

How is inflammation initiated?

Answer 2

1. Platelets release blood-clotting proteins
2. A. Mast cells get injured and release histamine to initiate vasodilation, vascular permeability and activate endothelium
   B. MO recognizes pathogen via PAMPS and produces cytokines to recruit PMN
3. Neutrophils (via activated endothelium and diapedesis) kill pathogen by phagocytosis and secretion of factors
4. MO phagocytize and secrete cytokines to recruit more inflammatory cells
5. Inflammatory response continues until pathogen eliminated and wound is repaired

Question 3

What specific role do mast cells play?

Answer 3

Injury leads to endothelia cells express adhesion molecules E selectin, PMN chemotaxis, and release histamine to increase vascular permeability

Question 4

What are PAMPS?

Answer 4

Pathogen associated molecular patterns- molecules that are specific for microbes such as lipopolysaccharides, peptidoglycan, and bacterial lipoproteins
They can be in the membrane or secreted

Question 5

How do phagocytes recognize a pathogen?

Answer 5

Pattern Recognition Receptors.. Toll-like receptors and mannos receptors… leads to activation and release of mediators

Question 6

What effect do PRR recognizing PAMPs have on MO?

Answer 6

They release a range of cytokines that have systemic effects (fever, acute phase inflammation) and recruiting more cells to the site of infection.

Question 7

What are the differences between acute and chronic inflammation?

Answer 7

Acute- rapid, short onset.. PMN

Chronic- longer onset=tissue destruction… MO and lymphocytes

Question 8

What are the characteristics of the inflammatory response?

Answer 8

Rubor (redness), Calor (heat), tumor (swelling), dolor (pain), functio laesa (loss of function)

Question 9

What are the systemic signs of inflammation?

Answer 9

Increased temperature, tiredness, lack of appetite, nausea, dehydration, swollen lymph nodes, raised ESR

Question 10

What is ESR?

Answer 10

Erythrocyte Sedimentation Rate…inflammation increases fibrinogen in blood->formation of stacks–>settle faster

Question 10

What is fibrinous exudate?

Answer 10

Fibrinous- fibrin, fibrinogen, thick yellowish clear–> fibrinous inflammation

Question 10

What is serous exudate?

Answer 10

serous- serum (no cells or clotting factors) watery, clear–>mild acute inflammation

Question 10

What is purulent exudate?

Answer 10

purulent/suppurative- WBC, bacteria, fluid, proteins, fibrinogen and necrotic cell debris=thick white fluid–>severe infection or injury

Question 10

What is hemoragic exudate?

Answer 10

Whole blood–>capillary rupture

Question 10

What is the function of vasodilation?

Answer 10

Increases access for cells (neutrophils first)

Question 13

Describe adhesion and diapedesis

Answer 13

There is tight binding (adhesion) due to interaction with receptor molecules so cell “walks” between 2 endothelial cells via CD31 and is in the site of infection

Question 14

LAD 1 and LAD 2 deficiencies result in what?

Answer 14

LAD 1 failure to express integrin (CD18) so adhesion of leukocytes to endothelium is impaired
LAD 2 interaction of leukocytes with endothelial E and P selectins is impaired
=Recurrent bacterial and fungal infections, infected foci have few neutrophils/pus and heal poorly

Question 16

What are the signs of acute inflammation?

Answer 16

1. Vascular change- vasodilation via immediately histamine & NO and cytokines TNF alpha/IL1 later
2. Edema- vascular permeability increases due to histamines and leukotriene.
3. Exudate (fluid with high protein content and cell debris)
4. Neutrophilic infiltration

Question 19

What causes chronic inflammation result?

Answer 19

1. Persistent infections (chronic granulomatous)
2. Prolonged exposure to potentially toxic agents
3. Autoimmunity
4. Impaired immune function (LAD1/2

Question 20

What are possible outcomes of the inflammatory response?

Answer 20

Resolution, Fibrous scarring, Abcess formation (area walled off and forms cavity containing pus),
Chronic inflammation

Question 21

What are the major manifestations of chronic inflammation?

Answer 21

Longer onset
Infiltration w/ leukocytes
Tissue destruction
Proliferation of blood vessels and fibrosis as attempts to heal

Question 22

Which type of inflammatory molecules are pre-formed in secretory granules?

Answer 22

Histamine- released upon binding of IgE/D
Lysosomal enzymes
Serotonin- released upon platelet activation, vasodilation

Question 23

What types of histamine are there and what effects do they have?

Answer 23

H1R widely expressed= vasodilation, nasal congestion, pain and itching, bronchoconstriction, diarrhea (blockers=anti-histamines)
H2R stimulate gastric secretions (blockers= treat heartburn)
H3R and H4R not widely expressed

Question 24

Which inflammatory molecules have to be synthesized de novo?

Answer 24

AA metabolites (prostaglandins, leukotrienes)
Platelet activating factor
ROS, NO
cytokines

Question 25

What are the AA metabolites synthesized?

Answer 25

AA via COX I and II produce prostaglandins–>
I: GI protection, platelet function, kidneys,
pain and fever, vasodilation
II: Pain, fever, headache, inflammation
AA via 5-lipoxygenase produce leukotrienes
vascular permeability, bronchoconstriction,
chemoattractant

Question 26

How do NSAIDs work? What are the down sides to using them for an extended period of time?

Answer 26

Block COX I and II so blocking I can cause ulcers because usually I offers GI protection

Question 27

What does PAF do?

Answer 27

Inflammation, chemotaxis, oxidative burst, anapylaxis, AA metabolism, VASODILATION (1000x more potent than histamine)

Question 28

What is the danger of drugs that are synthetic interferons?

Answer 28

diverse side effects like anxiety, bone pain,diarrhea, hair loss, headache, nausea, etc

Question 29

What is the ‘master regulator’ of the immune response?

Answer 29

TNF principle defense to gram negative bacteria

Question 30

Which chemokines does IL1 induce?

Answer 30

IL6 and 8 which are involved in the acute phase response… act on liver to produce opsonins and coagulation factors