Robbins: Chapter 3 Inflammation and Repair 

• %%What is Inflammation?%%

  • inflammation is a protective response to damage or infection of vascularized tissue
  • it triggers immune cells from the circulatory system to eliminate offending agents
  • phagocytic leukocytes, antibodies, complement proteins

• %%What are the four cardinal signs of inflammation?%%

  • redness
  • swelling
  • heat
  • pain
  • function ( later added)

• %%What are some causes for inflammation?%%

  • infections
  • tissue necrosis
  • foreign bodies
  • immune reaction (hypersensitivity)

• %%Steps in inflammation?%%

  • microbe enters body/ trauma

  • Recognition the skin barrier is broken and macrophage, dendritic cells, and Mast cells

  • cellular receptors for microbes → PAMPs(pathogen-associated molecular patterns)

  • senores of cell damage → DAMPs( damage-associated molecular patterns)

  • They recognize the microbe and trigger mediates amiens and cytokines) to recruit leukocytes

  • cytokines → what to do!

  • chemokines → where to go!

  • Removal of stimulus Monocytes → macrophages and Granulocytes eliminate microbes.

  • Repair of possible damaged tissue

    

  \

• %%3 major components of acute inflammation?%%

  • dilation of small vessels leading to an increase in blood flow
  • increased permeability of the microvasculature, enabling plasma proteins and leukocytes from the circulation
  • emigration of leukocytes from the microcirculation, their accumulation in the focus of injury, and their activation to eliminate the offending agent

• %%Difference between acute and chronic inflammation?%%

  • acute inflammation: is the initial rapid response (within minutes or hours) to eliminate offenders

  • characteristic:

    • vasodilation
    • edema (increased vascular permeability)
    • emigration of leucocytes( predominantly neutrophils)

  • Chronic inflammation: is triggered when the initial response fails to clear the stimulus

  • characteristics:

  • longer duration

  • more tissue destruction

  • dominated by lymphocytes and macrophages

  • more proliferation of blood vessels and fibrosis

    

• What is exudate and transudate? how is it related to acute inflammation?

  • %%exudate%%: extravascular fluid that has high protein concentration and contains cellular debris → implies existence of inflammatory process
  • in big amounts it is called pus
  • %%transudate%%: fluid with low protein content with little to no cellular material → produced due to hydrostatic imbalance but not due to inflammation
  • in big amounts called edema

• %%what are changes in vascular flow in response to inflammation?%%

  • increased blood flow → vasodilation → cause of heat and redness
  • increased permeability: exudate of fluid into extravascular tissue
  • loss of fluid → slower blood flow(stasis) + increased viscosity
  • as stasis develops neutrophils accumulate along the vascular endothelium( more this in a later question)

• %%What is the multistep journey of leukocytes?%%

  • (1) rolling → from center to endothelium walls with the help of selectins, which are the ligands found on leucocyte
  • (2) integrin activation by chemokines
  • (3) stable adhesion → integrins are the ligands found on leukocyte membrane that attach to the receptors on endothelial cells
  • (4) migration through endothelium (diaphyses/transmigration)

• %%What are chemoattractants? And give some examples.%%

  • Chemoatractes are produced by microbes and by host cells in response to n infections r tissue damage. They signal neutrophils and leukocytes towards which direction the inflammatory site is. First, neutrophils arrive to the site, but due to their short half-life, they are then replaced by Monocytes/Macrophages.
  • examples:
    • LTB4
    • C5a
    • IL-8

  

• %%What is key when terminating the inflammation and what are the associated steps?%%

  • Phagocytosis and clearance of the offending agent
  • (1) recognitions and attachment of the particle to be ingested by the leukocyte
  • (2) engulfment, with subsequent formation of a phagocytic vacuole
  • (3) killing or degradation of the ingested material with lysomome

• %%What is the function compliant system?%%

  • it only destroys bacteria by drilling holes into the cell walls of the bacteria
  • if this happens in normal healthy cell this causes major tissue damage

• %%What are the possible outcomes of acute inflammation ?%%

  • complete resolution
  • restoration of the site to normal tissue
  • removal of cellular debris
  • no edema
  • healing by connective tissue replacement
  • scarring or fibrosis
  • Progression of the response to chronic inflammation

• How can you recognize inflamed tissue under a microscope?

  • fluid-filled space → edema
  • fibrinous exudate
  • accumulation of granulocytes
  • purulent inflammation → pus( dead granulocytes)
  • ulcer → local tissue destruction

• Name different acute and chronic inflammatory diseases:

  • 

• What causes chronic inflammation?

  • Immune-mediated inflammatory( hypersensitivity)
  • autoimmune disease
  • allergies
  • Persistent or prolonged exposure to microbial infections by microorganisms that are difficult to eradicate
  • Due to a delayed response immune reaction
  • development if granulomatous inflammation
  • walling of epithelial cells due to dead granulocytes

• What are two types of macrophage activation?

• what are systemic effects of inflation

  • production of proteins: acute-pashe protein
  • C-reactive protein (CRP) and serum amyloid A protein( SAA)
  • Fever

• %%when does the repair of damage start?%%

  • the work simoultainsly and can´t be seen as separate processes

• inflammatory vs anti

  • autoimmune lymphocytes that recognize cells falsely
  • autoinflammatory aggressive cells that just fire but it is not targeted

• each phase of the inflammatory response are associated with disease with the off switch of proteins is faulty

• What happens when microbo flora crosses the one cell layer that protects

  • the first line of defense: innate immune → 99% of invasive microbes are depleted
  • epithelium
  • macrophages
    • neutrophils
  • adapt system is triggered by an innate system via chemokines( signaling molecules)
  • b and t cells

• Tuberculosis is a bacterium that causes a chronic inflammatory response

  • in crohns the histology looks similar because the body falsely reacts to microbes because the body confuses the two → genetic defects

• If you have impairment in innate response than their is a bigger/faster response of the auqired immune system to make up for the work

• lazy leukocyte syndrome

  • leuity work slower ad, therefore, cause chronic inflammation because they fulfill they job to slow

• post-infectious autoimmune disease!!

  • a microbe is recognized by t cell; however, after that the body confuses its own body causing chronic inflammation

• granuloma

  • to prevent spreading through the body
  • chronic granular disease
  • Hermans putlock disease

• neutrophils love shortly

• regulatory t cell -→ controls immune response (dampens it)

• T-cell diseases → organ specific

  • too many t cells or too little regulatory t cells

• repair and regeneration

  • repair → with scaring
  • regeneration → exact copy of what was damaged

• cholangiocytes: scar cells

• remodeling: differences in tissue in organs

• why repair and not regeneration

  • repair is faster

• Kupfer cells are macrophages in liver

• what happens after liver failure?

  • edema
  • turn yellow
  • very sensitive to toxins

• steps after cutting skin

  • \
  1. clotting
  • \
  1. epithelial cells
  • \
  1. granulation tissue

\