The immune system that protects the body from infections by harmful pathogens (virus, bacteria, fungus) comprises both innate and adaptive immune responses. The innate immune system is a non-specific immune response that provides the first line of defense from infection. It is also considered a natural immune response that is present since birth and is not induced due to previous exposure to an antigen or vaccination.
Immune System. Image Credit: Yurchanka Siarhei/Shutterstock.com
The innate immune response occurs because of genetic or physiological factors. Both innate and adaptive immune responses involve receptor-mediated signaling, specific protein secretion, and complex cell-to-cell communication. Generally, the innate immune system recognizes an infectious agent and triggers a sequence of events that can either independently remove the infection or deploy a highly specialized adaptive immune response.
Scientists have discovered that the innate immune system was developed as an essential response to infections roughly a billion years ago, an early stage in animal evolution. Primarily, the innate response can be categorized based on external and internal defenses.
While the external defense mechanisms such as skin and teardrops offer the first line of protection against harmful pathogens, the internal mechanism, i.e., stomach acid and cellular defenses, provide the second line of defense. The innate immune system can also be categorized in the following way:
- Physical barriers - This provides the first line of defense. These include skin, gut or the airways, eyelashes, etc.
- Cellular defenses - This provides a non-specific immune response. These include the key participants of natural immunity, namely, natural killer cells (neutrophils, macrophages), phagocytes, cytokines/chemokines, chitinases/chitinase-like proteins, acute-phase proteins, proteases, and the complement system. The cellular defenses recognize pathogens or harmful substances and activate mechanisms that neutralize or destroy them.
- Chemical barriers - This provides a defense mechanism that can destroy harmful agents. These include stomach acid, lysozyme in tears, antimicrobial peptides (AMPs), alarmins, and mucous.
How is the innate immune system activated?
The innate defense mechanisms get activated by genotoxic stress, tissue damage, and infection. It can recognize these situations through germline-encoded receptors, for example, pattern recognition receptors (PRRs).
Mechanism of the innate immune system
When a pathogen encounters a physical barrier of the host, at its contact interfaces, the microbial stimuli primarily activate the secretion of generic antimicrobial peptides. Some of the examples of generic antimicrobial peptides are defensins or cathelicidin/LL-37. Secretion of organ-specific mediators such as dermcidin for the skin also takes place.
The PRRs recognize the pathogenic microbial invasions through pathogen-associated molecular patterns (PAMPs) and nonpathogenic microbial invasion via microbe-associated molecular patterns (MAMPs), thereby, triggering downstream effector programs. Some of the innate PRRs include toll-like receptors (TLRs), complement receptors, nucleotide-binding oligomerization domain-like receptors (NOD), scavenger receptors, intracellular nucleic acid-sensing receptors, and C-type lectin receptors (CLRs).
When these receptors are exposed to microbes, they induce the secretion of chemoattractants (e.g., CXCL8) and cytokines. These molecules assist in the migration of innate immune cells into the infected target organ. Chemokines employ the innate immune cells via cognate G-protein-coupled chemokine receptors to sites of inflammation. Based on their functional role, i.e., basal homeostatic immune-cell trafficking or inflammation, chemokines can be categorized as homeostatic or inflammatory chemokines.
Innate immune cells
Innate immune cells comprise a wide array of myeloid and lymphoid cells. Myeloid-Derived Suppressor Cells (MDSCs) are cells that suppress T-cell responses. These cells include neutrophils and monocytes. In humans, both monocytes and neutrophiles express the myeloid markers CD11b and CD33.
However, these surface markers are also found on other immune cells. An important aspect of MDSCs is their precise cellular suppressive effector mode of action. Additionally, many mucosal tissues contain innate lymphoid cells (ILCs). Several types of cells involved in the innate immune response are discussed below.
- Neutrophils- Neutrophils are phagocytic cells that are immediately employed to the site of inflammation or infection through chemokine gradients. These are followed by monocytes and dendritic cells. Neutrophils are abundantly present and constitute around 50-60 percent of all leukocytes. These cells release toxins that may kill pathogenic bacteria and fungus, it may also recruit other immune cells to the site of infection. They can suppress adaptive T cell functionalities, such as T cell proliferation or cytokine production.
- Mast Cells- These cells are present in mucus membranes. They dilate blood vessels and induce inflammation through the release of heparins and histamines. They also deploy macrophages and neutrophils to the damaged targeted sites.
- Monocytes- These cells are stored in the spleen and migrate via blood vessels to infected tissues. These cells differentiate into macrophages and dendritic cells in response to inflammation.
- Macrophages-These are phagocytic cells that engulf the microbial pathogens and cancer cells. They also stimulate other immune cells. In humans, approximately 0.2 trillion macrophages are present in almost every tissue compartment. Besides phagocytes, these are also involved in the engulfment of apoptotic cells, and the production of inflammatory cytokines. Macrophages continuously scan the tissue and actively participate in maintaining homeostasis and integrity.
- Natural Killer Cells- These cells circulate in the blood and migrate into the tissue. They kill tumor cells and virus-infected cells.
- Dendritic Cells- These cells are present in the epithelial tissues of the skin, lung, and digestive tract.
- Basophils- These cells are predominantly responsible for the defense against parasites. They release histamines that cause inflammation.
- Eosinophils- These cells circulate in the blood and release a toxin that kills bacteria and parasites.
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