28 - Natural Resistance - Humoral Factors of Natural Resistance, drawing on the provided sources:
Humoral factors are soluble components found in the blood and extracellular fluids that contribute to the body's natural resistance (innate immunity). These are part of the non-specific defense mechanisms.
Key humoral factors involved in natural include:
- Complement System:
- It is a biochemical cascade composed of plasma proteins synthesized in the liver.
- The complement system circulates in the blood and plays a crucial role in defense against infections.
- It helps get rid of pathogens and is a potent tool for fighting off viral infections.
- It is a non-specific defense mechanism. Direct complement activation plays a significant role in all infections.
- Complement can be activated through three main pathways:
- Classical Pathway: Activated by the binding of antibodies (IgG or IgM) to a pathogen's surface.
- Alternative Pathway: Activated directly by microbial surfaces, independent of antibodies. This involves spontaneous activation of C3 and an amplification loop involving factors B, D, and properdin.
- Lectin Pathway: Initiated by the binding of mannose-binding lectin (MBL) to specific carbohydrates (mannose) on the surface of pathogens.
- Activation leads to the formation of C3 convertase and C5 convertase, which can result in the formation of the Membrane Attack Complex (MAC).
- Important biological effects of complement components include:
- C3b, which results in the opsonization of microorganisms, making them easier for phagocytes to engulf.
- C3a and C5a, which are anaphylatoxins that contribute to the degranulation of mast cells and basophils and increase vascular permeability. C5a initiates the chemotactic recruitment of granulocytes and monocytes.
- Activation of complement induces phagocyte migration to the infection site.
- Gram-negative bacteria can have serum resistance by modifying their lipopolysaccharide to prevent alternative pathway activation.
- Interferons (IFNs):
- These are cytokines that are crucial in the immune response to viral infections.
- They are produced very quickly and are first responders.
- Type I interferons (including IFN-α and IFN-β) are primarily involved in the antiviral immune response. Type II interferon (interferon γ) is important for activating immune cells like macrophages and NK cells.
- Interferons bind to cell receptors and induce an antiviral state by prompting the synthesis of other proteins that inhibit viral replication.
- They act as signalling molecules to trigger increased MHC I presentation on neighbouring cells, helping T-cells identify infected cells.
- Interferons α and β promote NK activation.
- Interferons can build up temporary resistance to viral infection. They are considered potent tools for fighting viral infections.
- Lysozyme: