Inflammatory reactions

Inflammation is a reaction of the body that occurs after tissue damage. People experience this reaction as very unpleasant, with symptoms such as swelling, pain, warmth and redness. Yet these symptoms have a clear function, they stimulate tissue recovery.

Origin of an inflammatory response:

Inflammation occurs after tissue damage. This tissue damage can be caused, for example, by an infection with a bacteria, fungus or virus. Tissue damage can also be caused by burning (heat) or an irritating substance (strong acids, bases, poisons). Damage to the tissue can also be caused by an allergy or autoimmune disease.

Function of an inflammatory response:

  • Preventing further spread of the harmful substances to nearby tissues
  • Getting rid of cell breakdown products and pathogens
  • Initiating recovery processes

If a barrier is damaged, pathogens can enter the body. SALT (skin associated lymphoid tissue) is activated. This keeps the invaders limited to the surface just under the skin and the pathogens cannot enter the bloodstream. Pathogens enter and bind to macrophages and dendritic cells. This produces TNF and IL-1. This leads to vasodilation and increased vascular permeability. The increased permeability ensures the exit of plasma. This causes swelling. This plasma contains all mediators of the 4 cascades (complement system, quinine system, coagulation system, fibrinolytic system). The increased permeability also causes white blood cells to escape.
The first to arrive locally are neutrophil granuloocytes. Next come the monocytes. These eat the pathogens (phagocytosis ). Local activation of the complement system enhances the process.

Complement system:

3 pathways initiate the cascade:

  • Classic pathway
  • Lectin pathway
  • Alternative pathway

The classical pathway is initiated when there is an antigen-antibody complex. This releases factors (C1, C2, C4).
In the lectin pathway, lectin binds to a pathogenic surface when MBP binds to MBP-associated serine esterase (ASP). This activates C2 and C4. The function of this pathway is to activate the classical pathway without an antibody.
In the alternative pathway, molecules with repetitive chemical structures (e.g. endotoxins, lipopolysaccharide, IgA or IgE) activate proteins B and P. This leads to activation of C3 and the further cascade follows . C3 is the first active molecule and is cleaved by C3 convertase into C3a and C3b. C3a results in the attraction of inflammatory cells. C3b ensures opsonization (preparing to be eaten) of pathogens. C3b also activates the further cascade. C5 is split into C5a and C5b. C5a does the same as C3a. C5b, together with C6, C7, C8 and C9, forms a pore in the pathogen membrane which leads to the death of the pathogen.

Quinine system:

Inflammatory mediators cause a decrease in the pH in the extracellular fluid. This creates kallikrein and ensures the formation of bradykinin from the bradykinin precursor. Bradykinin binds to receptors on the capillary wall. This opens the junctions between the cells and allows the leukocytes and fluid to leave the capillary and travel to the site of the infection. Bradykinin also binds to mast cells in the connective tissue of small blood vessels. Activation of the mast cells takes place due to a calcium influx. The activated mast cells release mediators:

  • Histamine: causes vasodilation and increased capillary permeability
  • Heparin: anticoagulant
  • Enzymes that cause proteolysis
  • Substances that attract neutrophils, basophils, eosinophils and monocytes
    • Cyclooxygenase (COX): ensures the formation of thromboxane, PGE2 and F2. These in turn cause vasodilation, platelet aggregation and stimulation of the pain receptors.
    • Lipooxygenase: ensures the formation of leukotrienes. Leukotrienes are vasoactive substances and they also cause edema.

 

Blood clotting system:

The main function here is to keep the microorganisms in place

Fibrinolytic system:

Breaking down the clotting.

Concepts

  • Chemotaxis : neutrophils and others are guided to the site of inflammation
  • Interferons (cytokine) are proteins produced by various host cells in response to an infection. They have antiviral activity by activating protein PKR. This blocks the ribosomes, so that the viruses can no longer replicate properly.
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