Antimicrobial Proteins

Antimicrobial proteins are important components of the immune system. They aid the body in combating pathogens by either killing them directly or hindering their replication processes. Four main types of antimicrobial substances are interferons, the complement system, iron-binding proteins, and antimicrobial proteins.

Interferons

Interferons (IFNs) are proteins produced by lymphocytes, macrophages, and fibroblasts infected with viruses. While IFNs cannot prevent viruses from entering and attaching to host cells, they can prevent their replication. When virus-infected cells release these proteins, they diffuse to nearby uninfected cells. Here, they trigger the production of antiviral proteins that inhibit the replication of viruses. There are three types of interferons: alpha-, beta-, and gamma-IFN.

Alpha-IFN (IFN-α) enhances the activity of natural killer cells and increases the expression of MHC class-I molecules. While IFN-α is mainly produced by plasmacytoid dendritic cells and leukocytes, beta-IFN (IFN-β) is primarily produced by fibroblasts and epithelial cells. In addition to controlling viral infections, IFN-β helps reduce inflammation by inhibiting the production of pro-inflammatory cytokines. Gamma-IFN (IFN-γ), produced by T cells and natural killer cells, is critical for adaptive immunity and plays a key role in activating macrophages.

The Complement System

The complement system is a group of proteins in blood plasma and plasma membranes. When activated, these proteins enhance immune reactions. The complement system can be activated through three distinct pathways: the classical pathway, the alternative pathway, and the lectin pathway. Each pathway is triggered by different stimuli but converges on a common sequence of events leading to the immune response.

When activated, the complement system performs cytolysis by forming the membrane attack complex (MAC), which creates pores in pathogen membranes, causing them to burst. It also enhances phagocytosis through opsonization, where complement proteins coat pathogens, making them more easily engulfed by phagocytes. Additionally, complement proteins like C3a and C5a trigger inflammation by stimulating histamine release, increasing blood vessel permeability, and attracting immune cells to the infection site.

Iron-binding Proteins

Iron-binding proteins inhibit the growth of specific bacteria by reducing the availability of free iron. Many bacteria rely on iron for their growth and metabolism, so these proteins create an iron-limited environment that inhibits bacterial proliferation. Examples include:

• Transferrin in blood and tissue fluids.
• Lactoferrin in milk, saliva, and mucus.
• Ferritin in the liver, spleen, and red bone marrow.

Antimicrobial Proteins

Antimicrobial proteins (AMPs) are short peptides with a broad antimicrobial activity spectrum. These small proteins can directly kill pathogens by disrupting their cell membranes or viral envelopes, compromising their structural integrity. This disruption results in the death of the pathogen, making antimicrobial peptides a crucial first line of defense in the innate immune system. Examples of AMPs include dermcidin from sweat glands, thrombocidin by platelets, and defensins and cathelicidins by neutrophils, macrophages, and epithelia. In addition to killing a wide range of microbes, AMPs can attract dendritic cells and mast cells, which participate in immune responses. Interestingly, microbes exposed to AMPs do not appear to develop resistance, as often happens with antibiotics.