Animal Immune System

• The immune system defends animals against pathogens, enabling them to limit or avoid infections.
• Adaptations have arisen over evolution to protect animals against many pathogens.

Innate Immunity

• It is a set of immune defenses common to all animals.
• Protects from pathogens that include bacteria, fungus, and viruses.
• Foreign molecules or cells do not have to be pathogenic to elicit an immune response.
• Defenses prevent pathogens from entering the body, like the outer covering, and secretions.
• Openings are required for gas exchange, nutrition, and reproduction.
• Linings of the digestive tract, airway, and other exchange surfaces act as additional barriers to infection.
• Immune cells produce receptor molecules that bind to molecules from foreign cells/viruses to activate defenses.
• Recognition proteins trigger an innate immune response when bound to a pathogen.

Innate Immunity of Invertebrates

• Insects in terrestrial and freshwater habitats teeming with diverse pathogens highlight the effectiveness of invertebrate innate immunity.
• The insect exoskeleton provides a physical barrier against most pathogens via chitin.
• Chitin also lines the intestine, blocking infection by many pathogens.
• Lysozyme, in the digestive system, breaks down bacterial cell walls, acting as a chemical barrier.
• Insect immune cells produce recognition proteins that bind to broad classes of pathogens .
• Because such molecules are nonexistent in animal cells, they function as "identity tags" for pathogen recognition.
• Hemocytes, the major immune cells in insects, are phagocytic, ingesting and breaking down microorganisms by phagocytosis.
• Some hemocytes produce defense molecules to entrap larger pathogens, such as Plasmodium.
• Many other hemocytes release antimicrobial peptides, circulating throughout the insect body and inactivating or killing bacteria/fungi by disrupting their plasma membranes.
• The innate immune response of insects is specific for particular classes of pathogens; the recognition proteins bind and activate a transmembrane receptor.
• Toll activates production and secretion of antimicrobial peptides that kill fungal cells.
• Mammalian cells use receptor proteins very similar to the Toll receptor to recognize viral, fungal, and bacterial components.
• A discovery was recognized with the Nobel Prize in Physiology or Medicine in 2011.
• Insects have specific defenses to protects against viral infections of viruses.
• Many viruses that infect insects consist of a single strand of RNA.
• The RNA strand becomes the template for synthesizing double-stranded RNA.
• Animals do not produce double-stranded RNA, so its presence triggers a specific defense:
• The viral genome is cut which turns it against itself.

Innate Immunity of Vertebrates

• Innate immune defenses coexist with the adaptive immunity system.
• Mammals have similar defenses to invertebrates via barrier defenses, phagocytosis, and antimicrobial peptides.
• Mammals also have unique defenses like natural killer cells, interferons, and the inflammatory response.

Barrier Defenses

• Barrier defenses block pathogens including mucous membranes and the skin.
• Mucous membranes line the digestive, respiratory, urinary, and reproductive tracts and produce mucus to trap pathogens/particles.
• Ciliated epithelial cells sweep mucus and entrapped material upward to prevent lung infection.
• Saliva, tears, and mucous secretions that bathe exposed epithelia provide a washing action and inhibits colonization.
• Body secretions create an environment that is hostile to pathogens.
• Lysozyme destroys the cell walls of susceptible bacteria as they enter the openings around the eyes / upper respiratory tract.
• The acidic environment of the stomach (pH 2) kills most pathogens in food/water and those in swallowed mucus.
• Secretions from oil and sweat glands give human skin pH 3-5, acidic enough to prevent bacterial growth.

Cellular Innate Defenses

• Phagocytic cells in mammals and insects detect, devour, and destroy pathogens.
• Mammalian cells rely on the insect innate immune receptor Toll, binding to fragments of molecules.
• Toll-like receptor (TLR) binds to fragments of molecules.
• TLR3, on the inner surface of vesicles made by endocytosis, binds to double-stranded RNA, a certain viral nucleic acid .
• TLR4, located on immune cell membranes, recognizes lipopolysaccharide, a molecule on the surface of many bacteria.
• TLR5 recognizes flagellin, the main protein of bacterial flagella.
• The main two types of phagocytic cells in the mammalian body are neutrophils and macrophages.
• Neutrophils circulate in the blood, attracted to infected tissues, then engulf and destroy pathogens.
• Macrophages are larger phagocytic cells, migrating throughout the body; others reside in organs/tissues to encounter pathogens.
• Macrophages are located in the spleen, where pathogens in the blood are often trapped.
• Macrophages and neutrophils are components of the inflammatory response.
• Dendritic cells stimulate adaptive immunity against pathogens that they engulf. They mainly populate in tissues such as skin.
• Eosinophils defend against multicellular invaders, like parasitic worms, found beneath an epithelium, and discharge destructive enzymes.
• Natural killer cells circulate through the body and detect abnormal surface proteins found on virus-infected cells as well as cancerous cells.
• Natural killer cells do not engulf cells but release chemicals that lead to cell death, inhibiting spread of virus/cancer.
• Mast cells found in connective tissue are key contributors to the inflammatory response, and allergies.

Local Inflammatory Response

• The local inflammatory response is a set of events triggered by signaling molecules released upon injury/infection, reflecting changes like swelling/warmth.
• Activated macrophages release cytokines, signaling molecules that recruit neutrophils to site of injury/infection.
• Mast cells release the signaling molecule histamine.
• Histamine triggers nearby blood vessels to dilate and become more permeable.
• The resulting increase in local blood supply produces redness and increased skin temperature.
• Cycles of signaling and response continue inflammation; activated complement proteins promote further histamine release, attracting phagocytic cells.
• Enhanced blood flow delivers antimicrobial peptides for disrupturing membrane integrity to kill or inactivate pathogens.
• The result is an accumulation of pus, a fluid with white blood cells, dead pathogens, and debris.
• Pus and excess fluid are taken up as lymph, transported in the network of vessels known as the lymphatic system.
• Lymph nodes contain macrophages that engulf pathogens entering the lymph fluid.
• Dendritic cells reside outside the lymphatic system but migrate to the lymph nodes after interacting with pathogens, stimulating adaptive immunity.

Systemic and Chronic Inflammation

• A local inflammatory response due to minor injury/infection can expand to become systemic due to extensive tissue damage/infection.
• Cells in injured/infected tissues secrete molecules that stimulate neutrophil release from bone marrow.
• During severe infection, white blood cells in the bloodstream can increase severalfold within a few hours.
• A systemic inflammatory response has fever that substances released from activated macrophages reset the body's thermostat to a higher temperature.
• Elevated body temperature may enhance phagocytosis and accelerate tissue repair.
• Certain bacterial infections cause an overwhelming systemic inflammatory response, which can induce life-threatening septic shock.
• Septic shock is characterized by fever, low blood pressure, and poor blood flow, mostly fatal for the very old and very young, killing 200,000 yearly in the US.
• Chronic (ongoing) inflammation can threaten human health through disorders such as Crohn's disease and ulcerative colitis. Both debilitating disorders disrupt intestinal function due to an unregulated inflammatory response.

Antimicrobial Peptides and Proteins

• In mammals, pathogen recognition triggers release of peptides/proteins that attack pathogens or impede reproduction.
• Interferons and complement proteins are unique to vertebrate immune systems.
• Interferons provide innate defense by interfering with viral infections.
• Virus-infected body cells secrete interferon proteins to induce nearby uninfected cells to produce substances that inhibit viral replication to limit cell-to-cell spread.
• Interferons help control viral infections like colds/influenza; some white blood cells secrete a different interferon to help activate macrophages, enhancing phagocytic ability.
• Pharmaceutical companies mass-produce interferons with recombinant DNA technology to treat hepatitis C.
• The complement system has roughly 30 proteins in blood plasma.
• Proteins circulate in an inactive state, activated by pathogen surfaces, leading to biochemical reactions that lyse invading cells.
• The complement system also functions in the inflammatory response as well as in adaptive defenses.

Evasion of Innate Immunity by Pathogens

• Pathogens have developed adaptations to avoid destruction by phagocytic cells.
• The outer capsule that surrounds certain bacteria interferes with molecular recognition and phagocytosis.
• Streptococcus pneumoniae causes pneumonia and meningitis.
• Bacteria can resist breakdown after engulfment.
• Mycobacterium tuberculosis grows/reproduces within host cells, effectively hidden from the body's immune defenses.
• Tuberculosis (TB) attacks the lungs/tissues, killing +1 million people yearly around the world.