Lecture 2: Inflammation

Inflammation is a protective response to…(3)

• eliminate the initial cause of cell injury (foreign invaders and necrotic tissue) with WBC

• clean infection and other noxious stimuli

• initiate repair of injured tissue

In which instances can inflammation be a harmful reaction if it is also a protective response?

• too strong

• prolonged

• inappropriate (autoimmune disease)

T/F: the goal of inflammation is to bring cells of host defense such as leukocytes and plasma proteins to the site of infection or injury

true

The inflammatory reaction develops in stages known as the 5 R’s, what are they?

• recognition of injurious agent

• recruitment of leukocytes

• removal of agent

• regulation of the response

• resolution/repair

Describe the onset, cellular infiltrate, tissue injury, fibrosis, and local and systemic signs of acute and chronic inflammation

Acute

• onset: fast - min to hours

• cellular infiltrate: neutrophils

• tissue injury: mild and self-limited

• fibrosis: non

• local and systemic signs: prominent (bug bite)

Chronic

• onset: slow - days

• cellular infiltrate: monocytes/macrophages and lymphocytes

• tissue injury: significant

• fibrosis: in severe and progressive instances

• local and systemic signs: variable, usually modest

When does fibrosis occur?

In response to long standing damage.

In times the body is unable to regenerate tissue leading to scarring

What are the cardinal signs of inflammation?

• heat (calor)

• redness (rubor)

• swelling (tumor)

• pain (dolar)

• loss of function (functio laesa)

Which cell types arrive to the injury site in acute inflammation?

leukocytes and plasma proteins

What are the two components of acute inflammation

Vascular changes

• vasodilation and increased vascular permeability allow plasma proteins to leave circulation

• the endothelial cells are activated and that increases migration of leukocytes

Cellular events

• leukocytes (mostly neutrophils) are recruited allowing for elimination of agent

What are the stimuli of acute inflammation?

• infection

• trauma

• tissue necrosis

• foreign body

• immune reactions (hypersensitivity)

How does acute inflammation recognition occur?

• Microbes, necrotic cells, and foreign substances are recognized by receptors (toll-like receptors TLR) on phagocytes, dendretic cells and epithelial cells on the PM

• Inflammasome recognize dead cell products

  • activate cytokine interleukin 1B which recruits leukocytes

Compare the intracellular and extracellular pathway for recognizing acute inflammation

Extracellular

• receptors on the cell surface or in the extracellular environment to detect microbes and tissue injury

• TLR receptors detect bacterial cell wall components

• release extracellular mediators (histamine, prostaglandins) producing vasodilation, vascular permeability, neutrophil, and chemotaxis

Intracellular

• sense infection or damage inside the cell with macrophages, dendritic cells, and neutrophils

• Inflammasomes detect

  • can trigger inflammatory cell death

In acute inflammation, what occurs during vascular changes?

• vasodilation causes increased permeability bringing cells and proteins to injury site

• arteriolar vasodilation increases blood flow causes erythema and warmth

• Microvasculture increases blood viscosity = slowing circulation to prevent movement of bacteria

• Neutrophils accumulate at vascular surface

• protein rich fluid (exudate) moves into the extravascular tissues causing an increase in osmotic pressure causing more water in the tissues = causing edema

Exudate vs Transudate

Exudate - protein rich fluid (opaque) and a response to inflammation

Transudate - intersitiual fluid accumulation caused by increased hydrostatic pressure

• low protein concentration

• non-inflammatory response

What is included in leukocyte recruitment in an acute inflammation?

1. leukocyte rolls along the vessel wall by selectins (proteins)

2. Adhesion to the endothelium with integrins (proteins)

3. migrates between endothelial cells

4. migrates in the interstitial tissue toward a chemotactic stimulus (following a chemical signal) to the macrophage (possibly to interstitial tissue where edema is ocurring due to inflammation)

During an acute inflammation, leukocyte activation includes phagocytosis. What are the 3 steps?

1. Recognition and attachment of particle to the ingesting leukocyte

2. Engulf the phagocytic vacuole (phagosome)

3. kill and degrade ingested material

______ are extracellular fibrillary networks produced by neutrophils in response to pathogens and inflammatory mediators. They trap microbes to prevent their spread and cause cell death

Neutrophil extracellular traps (NETs)

• acute inflammation - leukocyte activation

How can leukocytes induce tissue injury/ in which circumstances?

1. Bystander tissue is injured during defense reaction

2. attempt to clear damaged and dead tissues (after MI)

3. inflammatory response directed at host tissues (autoimmune or allergic diseases)

What are 3 outcomes of acute inflammation

1. Complete resolution: regneration and repair

   1. inflammatory response is terminated

   2. necrotic debris, edema fluid, and inflammatory cells are cleared by phagocytes and lymphatic drainage + leukocytes secrete cytokines to initiate repair

2. Healing by CT replacement: scarring or fibrosis

3. Progression to chronic inflammation

Which morphologic pattern exemplifies:

• accumulation of serum-like protein-rich exudates

• skin blistering (burn/viral infection) - accumulation of serous fluid or beneath damaged epidermis

Serous inflammation

Which morphologic pattern exemplifies:

• characteristic of inflammation in the lining of body cavities including the meninges, percardium, and pleura

  • ex: fibrinous pericarditis

• occurs with severe injury increasing vascular permeability and fibrinogen passes through the endothelial barrier

Fibrinous inflammation

Which morphologic pattern exemplifies:

• collection of purulent exudate with presence of abscess

• ex: pyogenic (pus forming) organism - staphylococci

Suppurative (purulent) inflammation and abscess formation

focal collection of pus caused by seeding of pyogenic organisms into a tissue

Abscess

Which morphologic pattern exemplifies:

• local defect of the surface of an organ or tissue

• produced by necrosis of cells sloughing off necrotic and inflammatory tissue

• occurs in GI mucosa

• ex:diabetes

Ulcer

What are chemical mediators?

are substances (usually small molecules, peptides, or proteins) that are released by immune cells, damaged tissues, plasma proteins, or microbes.
They initiate, regulate, and resolve the inflammatory response.

They explain the cardinal signs of acute inflammation

Vasodilation is induced by _______ and is the cause of erythema and stasis of blood flow

chemical mediators

What is the role or function of histamine?

a chemical mediator that causes arteriolar dilation and increased vascular permeability

• can be released by vasodilation, mast cells, platelets

• stimulated by substances inducing inflammation, IL-1 and IL-8

What is the MAC complex and what is its role in the compliment system?

Stands for membrane attack complex and it creates holes in the target cell’s membrane leading to loss of osmotic balance (water rushes in) and cell lysis.

What is the function of the Coagulin and Kinin systems

Coagulation cascade will stop bleeding but also produces by-products that promote inflammation by recruiting leukocytes and increasing permeability.

Kinin system produces bradykinin a mediator of inflammation and pain.

• both are activated by factor 12 (Hageman factor)

Togther they function to seal an injury, recruit immune cells, increase vascular changes, and signal pain to the brain

When would we see chronic inflammation (give examples)

Persistent infections (TB, syphilis)

Immune-mediated inflammatory disease (RA, psoriasis)

Prolonged exposure to toxic agents (cholesterol crystals = atherosclerosis)

What is the role of macrophages?

Occur in an chronic inflammation response

• ingest and eliminate microbes and dead tissue

• initiate process of tissue repair

• secrete mediators of inflammation (cytokines)

• display antigens to T-lymphocytes

Chronic inflammation: What are eosinophils?

• found in inflammatory sites around parasitic infections and immune reactions mediated by IgE

• recruited by adhesion molecules and chemokines

Chronic inflammation: What are mast cells?

• participate in acute and chronic inflammation

• when antigen is encountered, mast cells release histamine causing vascular changes of acute inflammation (anaphylactic shock)

Chronic inflammation: What is granulomatous inflammation?

A form of chronic inflammation characterized by the formation of granulomas, which are aggregates of macrophages

Give examples of granulomatous inflammation

• TB

• leprosy

• syphilis

• Cat-stratch disease

• sarcodiosis

• Crohn disease

Systemic effects:

1. which leukocytes would we see dominate in a bacterial condition?

2. viral?

3. allergy such as hay fever, asthma or parasitic infection?

1. neutrophils

2. lymphocytosis

3. eosinophilia

Chemical mediators can be _____ and ______ derived

plasma, cell

Which chemical mediators are cell derived?

Histamine and serotonin