Innate immunity, often referred to as natural or non-specific immunity, constitutes the body's first line of defence against pathogens and antigens. Antigens, substances capable of triggering immune responses, come in various forms, such as bacteria cell wall lipopolysaccharides and pollen, encompassing proteins, glycoproteins, lipoproteins, and more. . The immune system identifies these threats through pattern recognition receptors, initiating a cascade of responses to neutralize them. For a more broader overview of the immune mechanisms, see the article on components of immunity.
Cardinal Features of Innate Immunity
⦿Active since birth.
⦿Native.
⦿No immunogenic memory.
⦿Non-Adaptive.
⦿Non-specific.
⦿First line of defence.
Barriers: The Obstacle Course for Pathogens
Physical Barriers
The innate immune system strengthens the body with various barriers, creating strong defences against invading pathogens. The skin is arguably the most important barrier stopping the entry of pathogens into the body. It is a physical barrier, the keratinized squamous epithelium makes it watertight. In places where skin is not present, such as orifices, a mucous coat forms the barrier. The mucous catches and sweeps away the pathogens. In the eye, the tears, together with the blinking, washes away any germs like the windscreen wiper of a car wiping away the dust. Moreover, the hair at than airs (nostrils) will catch any foreign bodies entering the airway. Finally, the coughing and sneezing reflex will expel any foreign bodies that manage to bypass the hairs at the nostril.
Microbial Barriers
To the very few pathogens that bypass those intense physical barriers, comes the next challenge. If they manage to adhere to any of the mucosal surfaces or the skin, they would still have to compete for resources with millions of commensal bacterial flora that has made those surfaces their home. The invading pathogen will soon run out of nutrients to survive or succumb due to the pathogen inhibitory substances produced by the normal bacterial flora.
Chemical Barriers
Those fortunate or virulent enough to triumph thought the previous hurdles are in for another treat. The bodily secretions contain their fair share of antimicrobial substances to fight infections. For instance, on the skin, a substance called Dermcidin Peptide will destroy the microorganisms that attempt to colonize it. This is produced by the sweat gland. The sebum produced by the sebaceous glands also contain a slightly acidic pH (4.5 -6.0) which maybe hostile to many microorganisms. But the acid game is really stepped up in the stomach thanks to the HCL production by the parietal cells of the gastric glands. Before they enter the stomach, they would have to survive the hydrolytic enzymes of saliva, such as α-Amylase. If the HCL wasn't enough, there are more horrors awaiting the pathogens who enter through the mouth because they would now have to feel the wrath of the proteolytic enzymes of the small intestine. The vaginal orifice is also protected by a chemical barrier maintaining an acidic pH which is hostile to many pathogens. Lysozymes in tears also protect the eye against microorganisms.
| Enzyme | Mechanism of Action | Found In |
|---|---|---|
| Lysozyme | Hydrolyzes peptidoglycan in bacterial cell walls, leading to lysis. | Tears, saliva, sweat, mucus |
| Lactoperoxidase | Catalyzes the production of reactive oxygen species (oxidized intermediates) that kill bacteria. | Saliva, milk |
| Lactoferrin | Binds iron, making it unavailable for bacterial growth (essential nutrient deprivation). | Milk, saliva, tears |
| Dermcidin | Forms ion channels in bacterial membranes, disrupting ionic balance and killing microbes. | Sweat |
| Beta Lysine | Acts against Gram-positive bacteria by disrupting their membrane integrity. | Sweat |
| Phospholipase A2 | Hydrolyzes phospholipids in bacterial membranes, causing membrane damage. | Saliva, tears, mucus |
| Bodily Secretion | pH | Acidic/Basic | Compound Responsible |
|---|---|---|---|
| Stomach (Gastric Juice) | 1.5–3.5 | Acidic | Acidic |
| Sweat | 4.5–6.0 | Acidic | Lactic Acid, Uric Acid, Dermcidin |
| Sebum (Skin Oil) | 4.5–6.0 | Acidic | Fatty Acids, Lactic Acid |
| Vaginal Secretions | 3.8–4.5 | Acidic | Lactic Acid (produced by lactobacilli) |
Innate Cells
Natural Killers
The innate immunity cells form the second line of defence against pathogens, and Natural Killer (NK) cells at the front line of that. NK cells make up 10-15% of the lymphocytes in peripheral blood and 1-2% of lymphocytes in the spleen. These are cytotoxic lymphocytes with large granules. However, they don't have T cell receptors or immunoglobulin (B cell) receptors. NK cells have large granules. They play a significant role in destroying tumour cells and cells infected with virus.
Normally, when an NK cell binds to a cell, the MHC I ligand in the healthy cell binds to the NK inhibitory receptor in the NK cell, inhibiting the NK cell. In contrast, tumour cells and viral infected cells lack MHC I expression. Therefore, the NK inhibitory receptor in not bound with anything. Lack of inhibition causes the release of the granules in the cell, which contain Perforin. The Perforin essentially punches holes in the defective cell's membrane, which destroys it. The dead bodies are dealt by the clean-up crew -phagocytes.
Phagocytes
These are cells that scavenge, and remove dead cells and microorganism by engulfing them. The most active phagocytes are Macrophages, A.K.A. Monocytes, in blood and Histiocytes in connective tissue. However, the most numerous phagocyte in blood is the Neutrophil. Fixed reticuloendothelial cells in liver, spleen lymph nodes and bone marrow are examples of specialized phagocytic macrophages. After the macrophage engulfs a pathogen, it secretes interleukin 12 (IL 12) which act on the NK cell. NK cell secretes Interferon γ which will signal the macrophage to digest the engulfed pathogen.
Antigen Presenting Cells (APCs)
APCs capture antigens and present them to T cells to activate the T cell response, which is a part of the adaptive immunity. APCs are the communicating bridge between the innate and adaptive immune responses. Dendritic cells are the most important APCs. They move to lymphoid organs and activate T cells. Other than dendritic cells, Macrophages and B cells can also act as APCs. The role of an APC is to engulf the antigen, process it, and then present it on the surface along with an MHC II molecule.
Soluble factors
This is also a part of the second line of defence in the innate immunity. Interferons, complement proteins, acute phase proteins, and enzymes like lysozyme and lactoferrin constitute soluble factors that bolster innate defences against pathogens.
| Immune Factor | Function | Source |
|---|---|---|
| Interferons | Proteins against viral infections | Various cells in the body |
| Complement | Proteins in serum and body fluids | Liver |
| Acute Phase Proteins | Including C-reactive protein, fibrin, etc. | Liver |
| Properdin | Facilitates complement activation | T cells, monocytes, and mast cells |
| Beta Lysine | Antibacterial protein from platelets | Platelets |
| Lactoferrin | Iron-binding protein | Milk, saliva, tears, |
| Transferrin | Iron-binding protein | Liver, immune cells |
| Lactoperoxidase | Produces oxidized intermediates, found in saliva, milk | Saliva, milk |
| Lysozyme | Hydrolyses cell walls of bacteria | submucosal glands, neutrophils, and macrophages |
Inflammation
Inflammation acts as a secondary line of defence within innate immunity, characterized by the release of chemical mediators that trigger a series of localized responses. These mediators include histamines, prostaglandins, and cytokines, which induce vasodilation, increase vascular permeability, and recruit immune cells to the site of infection or injury.
Inflammatory barriers unleash chemical mediators that trigger inflammation, a process characterized by redness, swelling, heat, pain, and loss of function. This orchestrated response aims to contain and eliminate threats, mobilizing various immune cells to the site of infection or injury. Furthermore, innate immune cells, including natural killer (NK) cells, macrophages, eosinophils, and neutrophils (collectively known as NK MEN), engage in antibody-dependent cell-mediated cytotoxicity (ADCC). Through this mechanism, these cells release perforins to execute extracellular killing, neutralizing pathogens and bolstering the body's innate defence mechanisms.
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