Blood Cells, Immune Defences and Blood Groups

Blood is about 55% plasma and 45% cells.

• All blood cells come from stem cells in the red bone marrow.
• Red cells have no nucleus and no mitochondria, which leaves more room for haemoglobin. They respire anaerobically and so do not use the oxygen they carry. They live about 120 days and are broken down in the liver and spleen.
• When blood $\mathrm{O_2}$ is low (for example at high altitude), the kidney releases erythropoietin (EPO), and the marrow makes more red cells.
• Clotting: damaged tissue and platelets set off a cascade that turns prothrombin into thrombin; thrombin turns soluble fibrinogen into insoluble fibrin threads that trap cells. $\mathrm{Ca^{2+}}$ and vitamin K are needed.
• A rise in white cells usually signals infection; a rise in red cells can follow a stay at altitude.

Non-specific (innate) defences act against any pathogen, quickly, in the same way every time.

• An antigen is a molecule, usually a protein or glycoprotein on a cell surface, that the immune system recognises as foreign.
• Phagocytosis: a neutrophil or macrophage engulfs a bacterium into a vesicle (phagosome); lysosomes fuse with it and their enzymes digest the bacterium.
• Opsonins (antibodies and some blood proteins) coat a pathogen so phagocytes take it up faster. Do not confuse them with opsin, the protein in the eye.
• Inflammation: damaged cells and mast cells release histamine, which widens arterioles and makes capillaries leaky. The area becomes red, hot and swollen, and white cells reach it faster.
• Fever: the hypothalamus raises the set point, which slows microbial growth.

Specific (adaptive) immunity recognises one antigen and remembers it.

• Clonal selection: the lymphocyte whose receptor fits the antigen is activated and divides by mitosis into many identical cells.
• B cells become plasma cells, which transcribe and translate antibody genes at a high rate (lots of rough ER), and memory B cells. B cells do not engulf and digest bacteria; phagocytes do that.
• Antibodies are Y-shaped proteins of four polypeptide chains (two heavy, two light) held by disulfide bonds. The tips (variable regions) bind one specific antigen. They clump pathogens together (agglutination), neutralise toxins and mark pathogens for phagocytes.
• Humoral response: B cells and antibodies in the body fluids. Cell-mediated response: T cells acting on infected cells.
• Primary response: slow (about a week) and small. Secondary response: faster and much larger, because memory cells are already present.

• Active immunity: the body makes its own antibodies and memory cells. Slow to start, long-lasting.
• Passive immunity: antibodies come from outside. Immediate, but no memory cells, so it lasts only weeks to months.
• A vaccine contains antigens without the disease: killed or weakened pathogens, inactivated toxins (toxoids), purified proteins, or mRNA that makes the body produce one viral protein. It causes a primary response and leaves memory cells.
• Booster doses produce a secondary response, raising antibody levels higher and for longer.
• Herd immunity: when most people are immune, a pathogen cannot spread, which protects those who cannot be vaccinated.
• Viruses whose antigens keep changing (influenza) need new vaccines often.

• ABO system: antigens A and B on red cells; the plasma has antibodies against whichever antigen is absent. The alleles for A and B are codominant; the allele for O is recessive.
• Agglutination (clumping) happens when donor red cell antigens meet matching antibodies in the recipient.
• Group O red cells have no A or B antigen, so they can be given to anyone (universal donor). Group AB plasma has no anti-A or anti-B, so AB people can receive any group (universal recipient).
• Rhesus: Rh positive cells carry the D antigen. An Rh negative person makes anti-D only after exposure. An Rh negative mother carrying an Rh positive baby can be sensitised at birth, so a later Rh positive baby may be harmed; an anti-D injection prevents this.
• Transplants: donor and recipient tissue types (MHC or HLA proteins) must be closely matched, and drugs suppress the immune system. The cornea has no blood vessels, so immune cells rarely reach it and it is usually transplanted without matching.