Vertebrate Innate Immunity

In animals, there are two types of immunity: innate immunity is common among all animals, and adaptive immunity is found only in vertebrates. Innate immunity offers a primary defense in all animals and sets the stage for adaptive immunity in vertebrates.

Innate immunity includes barrier defenses and molecular recognition that relies on a small set of receptor proteins that bind to molecules or structures that are absent from animal bodies but common to a group of viruses, bacteria, or other pathogens.

Barrier Defense

Mammals have mucous membranes and skin as their barrier defenses. The mucous membranes line the respiratory, digestive, urinary, and reproductive tracts, producing mucus, a viscous fluid that traps pathogens and other particles. In airways, ciliated epithelial cells sweep mucus and entrapped material upward, preventing infection in the lungs. Saliva, tears, and mucous secretions which contain lysozyme bathe various exposed epithelia, wash away intruding bacteria and fungi, and destroys the cell walls of susceptible bacteria. The gastric juice (pH 2) as well as skin secretions such as oil and sweat (pH 3-5) also help prevents the growth of many bacteria.

Cellular Innate Defense

Mammals rely on recognition protein called Toll-like receptor (TLR) to detect, devour, and destroy invading pathogens. Each TLR protein binds to fragments of molecules characteristic of a set of pathogens. Upon recognizing the pathogen, TLR proteins produce signals that initiate responses tuned to the invading microorganism.

The two main types of phagocytic cells in the mammalian body are neutrophils and macrophages.

Neutrophils: circulate in the blood, get attracted by signals from infected tissues and then engulf and destroy the infecting pathogen.

Macrophages: larger phagocytic cells; migrate throughout the body or reside permanently in organs and tissues where they are likely to encounter pathogens, engulf, then destroy or present antigens.

Some other notable cells that are involved in innate defense include dendritic cells, eosinophils, and natural killer cells.

Dendritic cells: mainly populate tissues that contact the environment, such as skin; like macrophages, they are antigen-presenting cells (APC), engulfing pathogens and presenting the antigens.

Eosinophils: often found in tissues underlying an epithelium; defend against multicellular invaders such as parasitic worms by discharging destructive enzymes.

Natural killer cells: circulate throughout the body, detect the abnormal array of surface proteins characteristic of some virus-infected and cancerous cells, and release chemicals that lead to cell death.

Peptide and Protein Production

Pathogen recognition triggers the production and release of a variety of peptides and proteins that attack pathogens or impede their reproduction.

Antimicrobial peptides: damages broad groups of pathogens by disrupting membrane integrity.

Interferons: proteins that provide innate defense by interfering with viral infections; can be secreted by virus-infected cells to limit cell-to-cell infection, or secreted by some white blood cells to help activate macrophages.

Complement system: consists of roughly 30 proteins in blood plasma; circulate in an inactive state and are activated by substances on the surface of many pathogens, leads to lysis of invading cells.

Inflammatory Response

Characterized by 1. rubor (redness), 2. calor (heat), 3. tumor (swelling), 4. dolor (pain), and 5. function laesa (loss of function).

It is a set of events triggered by signaling molecules released upon injury or infection.

Step1: Activated macrophages discharge cytokines, signaling molecules that recruit neutrophils to the site of injury or infection. At the same time, mast cells, immune cells found in connective tissues, release the signaling molecule histamine at sites of damage.

Step2: Local blood supply increases, capillaries widen and become more permeable, allowing the delivery of antimicrobial peptides to the site. Activated complement proteins promote further release of histamine, attracting more phagocytic cells. Pus, a fluid rich in white blood cells, dead pathogens, and debris from damaged tissue, accumulates.

Step3: Phagocytic cells such as neutrophils digest pathogens and cell debris at the site and the tissue heals.

The three basic inflammations:

Local Inflammation

Systemic Inflammation (throughout the body)

Chronic Inflammation (ongoing)

Toll-like Receptor (TLR)

Antigen-Presenting Cells (APC)

Reference:

Campbell, et al. Biology: A Global Approach. 11th ed., Pearson, 2017.