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

     Fig. 3.1 Sequence of events in an inflammatory reaction. Macrophagesand other cells in tissues recognize microbes and damaged cells and

  • %%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

       Table 3.1 Features of Acute and Chronic Inflammation

  • 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

 (C) The approximate kineticsof edema and cellular infiltration.

  • %%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:
    • Table 3.2 Disorders Caused by Inflammatory Reactions
  • 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