Blood and Immunity
Nucleus-Free Red Discs, Gene-Shuffling Antibodies, and Self-Destructing Neutrophils
Adult human red blood cells physically eject their nucleus, mitochondria, and ribosomes before leaving the bone marrow. Throwing away their genetic blueprints and oxidative power plants turns them into flexible, non-dividing bags of 270 million hemoglobin molecules that never consume a single molecule of the oxygen they carry to tissues.
Why mammalian red blood cells are shaped like biconcave doughnuts rather than spheres: a sphere holds the maximum volume for its surface area and bursts if stretched. The biconcave disc provides 40 percent extra slack membrane area so an 8-micrometer cell can fold like a crepe and squeeze through a 3-micrometer brain capillary intact.
Because red blood cells lack ribosomes to repair their stiffening membranes, they wear out after 120 days of traversing 500 kilometers of turbulent vessels and are recycled in the spleen. To keep your blood count steady, bone marrow stem cells manufacture and release 2.5 million fresh erythrocytes every single second.
Fetal hemoglobin (HbF, composed of two alpha and two gamma chains) binds inhibitory 2,3-BPG less tightly than adult hemoglobin (HbA, two alpha and two beta chains). That shift gives fetal blood higher oxygen affinity so the fetus can strip oxygen across the placental membrane from its mother's venous blood.
Immunologist Susumu Tonegawa solved in 1976 how a human genome with only 20,000 genes can build 100 billion different antibodies capable of binding novel synthetic chemicals. Maturing B-cells use RAG recombinase enzymes to physically cut, shuffle, and paste Variable (V), Diversity (D), and Joining (J) gene segments together like a slot machine.
Because random V(D)J gene shuffling inevitably creates T-cells that attack the body's own healthy organs, the thymus runs a lethal two-step boot camp. Thymic medullary cells express the AIRE gene to display sample proteins from every organ in the body, executing 98 percent of developing T-cells by apoptosis before they ever reach the blood.
Every nucleated cell in your body continuously chops up a random sample of its own internal proteins using proteasome barrels and displays the 9-amino-acid peptides on its surface inside MHC Class I cradles. Passing cytotoxic CD8+ T-cells inspect every cradle and destroy the host cell if they detect a viral or cancer peptide.
When certain herpesviruses and tumors evade T-cells by forcing the infected cell to pull down its MHC Class I cradles, Natural Killer (NK) cells catch the trick via Klas Kärre's "missing-self" rule. NK cells carry inhibitory receptors armed to kill any cell that fails to show a valid MHC Class I identity card.
Neutrophils—making up 60 percent of circulating white blood cells—have a final kamikaze weapon discovered by Arturo Zychlinsky in 2004. When overwhelmed, they decondense their own nuclear DNA, lace it with bactericidal histones and myeloperoxidase, and spew it out as sticky Neutrophil Extracellular Traps (NETs) to ensnare bacteria.
Platelets (thrombocytes) are not whole cells at all, but 2-micrometer cytoplasm shards pinched off from giant bone-marrow megakaryocytes. When a blood vessel tears under high shear stress, coiled von Willebrand factor (vWF) unrolls like flypaper to snag passing platelets in milliseconds and plug the breach before fibrin clotting begins.
Once an infection is cleared, 95 percent of expanded effector lymphocytes commit programmed cell suicide while 5 percent become long-lived memory cells in the bone marrow. In 2008, ninety-year-old survivors of the 1918 influenza pandemic still carried memory B-cells producing neutralizing antibodies against the 1918 H1N1 virus ninety years after exposure.
Fever is not a chaotic thermostat malfunction caused by pathogen heat. When macrophages detect bacterial lipopolysaccharide, they release prostaglandin $\text{E}_2$ (PGE2) into the preoptic hypothalamus to deliberately raise the core set-point to $39^\circ\text{C}$—accelerating T-cell proliferation while ordering the liver to lock free serum iron away from bacteria.