Topic 7+8 wound healing response&repair Flashcards

1
Q

Which inflammatory cells/leukocytes do we have?

A

Monocytes, lymphocytes (T+B) and granulocytes (eosinophils, neutrophils and basophils)

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2
Q

Whats the role of neutrophils?

A

They are involved in the acute phase of the inflammatory response and among the first ones to arrive. They migrate from the blood stream into the tissue and there they are capable of phagocytosis.

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3
Q

Whats the role of monocytes/macrophages?

A

Monocytes in the blood but they mature into macrophages when they migrate into the tissue and they also become granular and swell. They are involved in the chronic phase and they are capable of phagocytosis.

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4
Q

What does the number of neutophils vs. macrophages tell you?

A

At which stage the inflammation’s at. Acute or chronic phase.

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5
Q

What is diapedesis, or extravasation?

A

The process of cells squeezing through endothelial cells from the blood stream.

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6
Q

Why is chemotaxis important in the inflammatory process?

A

Cells senses (with receptors on the surface) a special molecule called chemoattractant and then start moving towards the concentration gradient. It changes its cytoskeleton. Help leukocytes to find site of injury or infection when they sense Kallikrein, prostaglandins, fibrin degradation products, tissue plasminogen or cytokines

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7
Q

Whats the basic principle of phagocytosis?

A

The microbe is recognized by antibodies and those will bind to the bacteria. C3b can then bind to the tail of the antibody and these 2 together are called opsonin. The receptor on the phagocyte membrane can then bind to the opsonin and the microbe is eaten and contained in a phagosome. This fuse with a lysosome which contains nasty molecules that break down the microbe. Cytokines are released to attract more immune cells.

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8
Q

What is frustrated phagocytosis?

A

When the object is to large or long for the macrophage to ingest it. Content from the lysosomes then spill out into the ECM which can kill the phagocytes and attracts even more macrophages and this goes on and on.

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9
Q

What does frustrated phagocytosis result in?

A

The fusion of many macrophages into a foreign body giant cell to be able to ingest the large object. These can secrete growth factors, cell signaling molecules and enzymes that attract fibroblasts and immune cells.

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10
Q

How does the blood coagulation and inflammatory response act at the biomaterial surface?

A

Activated platelets secrete granules that call on inflammatory cells. Neutrophils come first, then macrophages via membrane receptors that activates them to secrete granules and attract leukocytes. FBGCs are formed that bind via integrin receptors that try to eat the biomaterial, but they obviously cannot remove it.

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11
Q

What is the role of M1 activated macrophage?

A

The first macrophages will become M1. They promote continued inflammatory response as they secrete oxygen species, proteases and chemotactic substances to recruit more leukocytes.

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12
Q

What is the role of M2 activated macrophage?

A

Promotes next phases of wound healing steps. They secrete GFs, angiogenic factors, enzymes and chemotactic substances to recruit fibroblasts (to prod. ECM) & endothelial cells.

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13
Q

What is the main event during the repair phase?

A

The formation of granulation tissue (prod. of ECM and angiogenesis)

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14
Q

What is a granulation tissue?

A

A temporary tissue to fill the injury site and close the wound. The final stage of the repair phase.

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15
Q

What is the first stage of the formulation of granulation tissue?

A

Macrophages are the first to arrive. Enzymes (e.g. plasmin) are secreted to degrade the blood clot and fibrin fibers. M2 secrete GFs (FGF, PDGF, VEGF) to attract fibroblasts that get activated and as well secrete GFs - cause local cell proliferation.

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16
Q

What’s the second stage of the granulation tissue?

A

Fibroblasts produce ECM and secrete GFs like EGF (promotes fibronectin), TGF-beta (collagen, fibronectin, GAGs) and PDGF (fibronectin, hyaluronic acid)

17
Q

What’s the third stage of the granulation tissue?

A

Angiogenesis and wound contraction. New blood vessels are formed by sprouting from existing ones. Endothelial cells are recruited by GFs from inflammatory cells and they proliferate and mature into capillary tubes. Wound contraction due to fibroblasts differentiating into myofibroblasts that are muscle-like to contract the tissue.

18
Q

What’s characteristic about the granulation tissue?

A

Many newly formed blood vessels (create dots when looking at histological section - why called granular) and also many fibroblasts and much collagen that is aligned (causes tough tissue-scar).

19
Q

What happens in the granulation tissue during the remodeling phase?

A

ECM is remodeled - collagen changes from type III to I through degradation and it arranges into dense parallel bundles that is typical for scar tissue (not as strong or same structure as original tissue). When final the granulation tissue has been replaced by scar tissue.

20
Q

What is the foreign body reaction?

A

The presence of an implant which causes an immune response. Frustrated phagocytosis and formation of FBGCs at the material surface.

21
Q

What happens during fibrous capsule formation?

A

The building up of collagen and fibroblasts outside of the macrophage/FBGC layer at the implant surface. The granulation tissue does not become remodeled cuz of continous secretion of GFs from macrophages - inflammation never ends. The continuous recruitment of fibroblasts and prod. of collagen form a fibrous capsule that “walls off” the implant from the rest of the body.