1. What are the three aspects of inflammation that Julius Cohnheim observed in the late 1800s that are still considered the main characteristics of inflammation?

vascular permeability increases, blood vessel dilation, adherence and immigration of the white blood cells

2. What are the two most important physical characteristics of mast cells?

1) contain granules, 2) have receptors that when stimulated will cause the exocytosis of inflammatory mediators

3. What are the four main “things” (name them and explain them) that stimulate the receptors on mast cells and therefore trigger exocytosis and the general activation of the mast cell?

1) the lippopolysaccarides 20 petoglycan on the cell wall of gram positive, 2) complement fragments C3A, C5a, also called anaphylotoxins can cause the blood pressure to drop to zero like some people have to bee stings and peanuts. 3)Allergens that will stimulate IgE antibodies on the mast cell.

4. Name and explain the function of the white blood cells that are recruited by chemotatic mediators released by the mast cells.

1)      First cell is monocyte that is recruited into the area of inflammation and differentiate into macrophages and phagocitize.

2)      2^nd: neutrophil will phagocitize and neutralize bacteria that are tagged with antibodies or anophylitoxins, C3b coated bacteria.  PMN’s are highà lots of inflammation. 

3)      Eosinophils: they also have granules filled with inflammatory mediators

5. What is (are) the main function(s) of the following inflammatory mediators released by the mast cells: tumor necrosis factor-alpha; chemokines; and histamines

1)      Tumor Necrosis Factor-alpha goes into the blood vessels, hits the receptors causing them to slow down and to move into the inflamed area.  It stimulates the cells to release their mediators. 

2)      Chemokines: Monocytes ,neutrophils, eosinophils,TH2,TH1 all have different receptors but they all have chemokine receptors. 

3)      Histamines: Stimulate receptors from endothelial cells causing a gap and fluid to be released into the area.

6. What is the derivative of leukotrienes?

Leukotrienes: primarily responsible for the bronchoconstriction during asthmatic attacks

Prostoglandins:  Actions are similar to histamines, but like bradykinin with stimulate pain receptors in the inflamed area to cause pain.  Unlike histamines, and bradykinin, they play a rold in coagulation.

Derivative of Thromboxanes

Thromboxanes: Stimulates aggregation of platelets and constriction of the blood vessels (Clotting)

-The release of the free arracidonic acids from the phospholipids on the surface of the mast cell.  It’s from this acid that these products will be formed.

1^st: the lipoxygenase pathway: produces a collection of leukotrienes (LT)

2^nd: the cyclooxygenase (COX) pathway: which produces prostaglandin H2 (PGH2).  PGH2 serves as the substrate for 2 enxymatic mathways: one leading to the production of several types of:

            -Prostoglandins (PG)

            -Thromboxanes (Tx)

- COX 1 is blocked by aspirin

8. Which pathway of the complement system is antibody dependent? Which one of the complement proteins initiates this pathway?

The classical pathway is antibody dependent.

Initiated by C1 Complex: Attaches to IgM or IgG

9. Which pathway of the complement system is antibody independcent? Which complement protein initiates this pathway?

The alternate Pathway is antibody-independent.

Initiated by c3-convertase

10. Both complement pathways result in the formation of what complex and what is the effect of this complex?

C3 Convertase

Slipts C3 into C3A and C3B, and C3B is going to hook onto C3 convertase and becaome C5 convertase and slpits into C5a and C5B.

11. What are the two anaphylatoxins of the complement system? Why are they called anaphylatoxins?

C3a and C5A because they activate mast cells

12. What is the end product of the complement cascade? What is it’s action on the target cell?

-the membrane attack complex

-Drills a hole in the membrane and you have osmotic lysis of the target cell.

13. What is the function of C59 or protectin?

Prevents the final assembly of the MAC attack and is found on all white blood cells.

14. What complement pathway is inhibited by C1-inhibitor? What condition is caused by a hereditary deficiency in C1-inhibitor?

-The classical complement

-Hereditary angioedema: an autosomal dominant disorder; can develop rapid sweeling of the hands, feets, limbs, face, intestinal tract, larynx or trachea.

15. What is the general outcome due to complement deficiencies?

Increased bacterial infections due to reduced opsonization and pagocutosis as well as preventing the formation of MAC

16. What are the three basic mechanisms the promote hemostasis?

1) Vasoconstriction: following damamge there is an immediate reflex that promotes vasoconstriction, thus diminishing blood loss.

2) Formation of a platelet plug: Exposed collagen promotes platelets to adhere; the undergo degranulation and release cytoplasmic granules, which contain serotonin, and ADP and Thromboxane A2.

3) Formation of a blood clot (Coagulation)

17. What causes platelets to degranulate? What are contained in these cytoplasmic granules? What is the function of each? How does “positive feedback” play a role in this?

The Thromboxane causes them to aggregate, degranulate, and adhere.

In cytoplasmic granules:

Seratonin: Vasoconstrictor

ADP: attracts more platelets to the area

Thromboxane A2: promotes platelet degranulation

-Positive feedback promotes the formation of a platelet plug.

18. Although both the intrinsic and extrinsic clotting pathways are initiated by distinct mechanisms, they both converge on what common pathway?

Activation factor X

19. When considering the extrinsic clotting pathway, what factor is released at the site of injury?

Tissue Factor

20. What factor is activated by the tissue factor?

Factor VII

21. What factor is activated by Factor VII

Factor X

22. Why is it that the intrinsic pathway is more involved than the extrinsic pathway?

Bc it’s a lot more clotting factors.

25. Hemophilia A results in the deficiency of what factor? Hemophilia B? Which one is the most prevalent? Which clotting pathway is affected by both?

-Hem. A: Deficiency in factor VIII.

-Hem. B:Deficiency in factor IX

-Hemophilia A is most prevalent.

26. What are the symptoms of Von Willebrand Disease (VWD)? What is the cause of VWD? What two roles does Von Willebrand factor play in coagulation?

Symptoms: Easy gum bleeding; frequent nosebleeds, easy bruising and heavy bleeding after small cuts or dental work. For women: heavy and long periods.

Not enough of Von Willebrand factor are produced.

1)      platelets cannot stick or adhere to the exposed collagen fibers to form the platelet plug in the second step without the collagen bibers being coated with Von Willebran factor.

2)      Von Willbrand factor is the carrier protein for clotting factor VIII.  It protects the factor VIII.

27. Define fibrinolysis? What is the main protease of this process? In what form (i.e., inactive) does this protease circulate? What two proteases convert the inactive form to the active form?

-Process whereby the fibrin clot is broken down.

-tisuue plasminogen activator and urokinase

-Inactive form of plasminogen

- tisuue plasminogen activator and urokinase

28. At the site of injury, what is the main source of tissue plasminogen activator (tPA)?

The damaged endothelium

29. What are the three thrombolytic agents and what do all three do? How are these agents used?

Tissue Plasmin activator

Urokinase:

Streptokinase:

Ll are used to activate plasminogen

Used in strokes to dissolve clots; periphery to dissolve clots in hands, treatments for venous thrombosis. Emergency treatment

30. What triggers the activation of the kinin system? What is the end product when the kinin system is activated? What are the actions of this product and what similarity does it have with protoglandins?

Triggered by Hageman Factor or factor XII.

End product is bradykinin.

They stimulate pain receptors in the tissue that it is released into, thus causing pain.