3. Inflammation

What is the inflammation response? Where does it happen?

An immediate, local, non specific event that occurs in vascularised tissue against a variety of injury causing stimuli.

Where do prostaglandins come from?

Arachidonic acid from the plasma membrane of mast cells is converted into prostaglandin.

Where do histamines come from?

Injured cells, mast cells, basophils, platelets

It is the major effector response in...

Innate immunity.

How does swelling help with healing?

It helps with healing because exudate contains nutrients such as oxygen, inflammatory mediators and leukocytes.

Where do bradykinins come from?

It is a plasma protein that is produced by the liver and is activated by tissue injury.

What does the inflammatory response do?

It is successful in eliminating most infectious agents and other unwanted substances from the body.

Where are leukocytes recruited from and to during inflammation? And why?

Leukocytes are recruited from the blood to the infected tissue, which is a systemic response. This prevents entry of potentially harmful substances and the nonspecific response to a wide range of potentially harmful substances following their entry into the wound.

What are the specific leukocytes that are recruited?

Mast cells Basophils Monocytes (which turn into macrophages) Neutrophils Natural killer cells

Where do neutrophils and macrophages come from?

Neutrophils circulate in the blood and they are first at the scene of tissue injury. Macrophages are derived from monocytes that are found resting in the tissues.

What is the role of neutrophils and macrophages?

Engulf unwanted substances such as infectious agents (bacteria) and cellular debris (dying neutrophils and damaged host cells) through phagocytosis.

What do mast cells and basophils release?

Granules that contain substances such as histamine (stimulates vasodilation and increases capillary permeability), heparin (anticoagulant) and eicosanoids (increases inflammation due to release from the plasma membrane).

What are the 5 cardinal signs of inflammation?

Redness, heat, pain, swelling, loss of function. This is the local response.

What causes heat?

There is an increased metabolism rate due to recrution of leukocytes to the area and the variety of responses in local blood vessels (vasodilation, increased permeability) due to released chemicals.

What do these pyrogens target?

They target the hypothalamus

What does this stimulation do?

When the hypothalamus is targeted, this causes the release of prostaglandin E2 which raises the temperature set point of the hypothalamus to above normal (>37degrees).

What specific released chemicals? What do they do?

-Histamines that bind to H1 receptors on the vascular smooth muscle cause these cells to relax, causing vasodilation. Histamines also increase the permeability of capillaries -Prostaglandin: cause vasodilation -Bradykinin: cause vasodilation and increased permeability of capillaries =This causes an increased blood flow to the area (resulting in redness).

What does fever do?

-Inhibits the reproduction of bacteria and viruses -Promotes interferon release (which inhibits viral replication) -Increases activity of the adaptive immunity -Accelerates tissue repair -Increases cell adhesion molecules on the endothelium of capillaries in the lymph nodes, resulting in more immune cells migrating out of the blood and into the lymphatic tissue. -The liver and spleen bind zinc and iron (minerals needed by microbes) to slow microbial reproduction.

What causes loss of function?

Caused by swelling and pain. It helps to protect the area further, helping with healing.

What do NKC's release?

Cytotoxic chemicals (perforin and granzymes).

What causes swelling?

Due to increased blood flow (vasodilation caused by histamines, prostaglandins and bradykinins) and increased capillary permeability (caused by bradykinin and histamines) there is an increased amount of fluid loss (exudate) from the capillaries into the interstitial space.

How does pyrexia come about?

Fever comes about as a result of the release of pyrogens (e.g. interleukin-1, interferons, toxins produced by infectious agents) or in response to trauma, drug interactions or brain tumours.

Where do natural killer cells accumulate?

In the secondary lymphatic structures such as the lymph nodes, tonsils and spleen.

What is the role of mast cells and basophils?

Increase fluid movement from the blood to the injury site due to these released substances. They also serve as chemotactic chemicals and this attracts the immune cells as a part of the inflammatory response.

What causes pain?

The first step of inflammation involves damaged cells of injured tissue, basophils and mast cells to release chemicals (histamines, prostaglandins and chemotactic factors) all stimulate nociceptors which causes pain. Also, the compression of exudate on the endings of nociceptors contributes to the feeling of pain.

What causes redness?

The released chemicals bring more oxygen and nutrient to the injury site. (such as histamines that bind to H1 receptors on the vascular smooth muscle and causes these cells to relax and prostaglandin) cause vasodilation. This causes an increased blood flow to the area (resulting in redness)

What is the role of NKC?

Their role is to go through a process called "immune survaillance" (patrols the body to detect unhealthy cells) and to destroy a wide variety of unwanted cells (virus infected/bacterial/tumour cells).