Defence against disease

📚The biology

Pathogens

An infectious disease is caused by a pathogen, a disease-causing organism that infects a host. A broad range of organisms infect humans, but the term is usually reserved for viruses, bacteria, fungi and protists (such as Plasmodium, which causes malaria). Archaea are not known to cause any human disease.

Careful observation drove some of the most important early progress. In Vienna in the 1840s, Ignaz Semmelweis noticed that women whose babies were delivered by doctors, who came straight from dissecting bodies, died of childbed fever far more often than those delivered by midwives, and that handwashing cut the death rate dramatically. In London in 1854, John Snow mapped cholera deaths and traced them to a single contaminated water pump. Both pointed to disease being carried by something transmissible, before germs were understood.

Skin and mucous membranes: the primary defence

The skin is both a physical and a chemical barrier. Its tough outer layer of dead, keratin-filled cells is difficult for pathogens to penetrate. Its surface is dry and slightly acidic, and sebaceous glands secrete oils with antimicrobial properties.

Mucous membranes line the airways, gut and reproductive tract, where the surface must be thin and moist. They secrete mucus, which traps pathogens; in the airways, cilia sweep the mucus up and away to be swallowed. Mucus, tears and saliva contain lysozyme, an enzyme that digests bacterial cell walls, and stomach acid kills many swallowed pathogens.

Blood clotting seals cuts

A cut breaks the skin barrier. Blood clotting seals it rapidly:

1. Damaged tissue and platelets release clotting factors.
2. These set off a cascade of reactions, each step activating the next and amplifying the response, leading to the production of the enzyme thrombin.
3. Thrombin rapidly converts the soluble plasma protein fibrinogen into insoluble fibrin.
4. Fibrin forms a mesh of fibres that traps erythrocytes (red blood cells), forming a clot that plugs the wound.

Innate and adaptive immunity

Phagocytes

Phagocytes are white blood cells that ingest and destroy pathogens:

1. They move from the blood into infected tissues by amoeboid movement, squeezing between the cells of capillary walls.
2. They recognize pathogens by molecules on their surfaces that are not found on the body’s own cells.
3. They engulf the pathogen by endocytosis, enclosing it in a vesicle (phagocytic vacuole).
4. Lysosomes fuse with the vacuole and release enzymes that digest the pathogen.

Lymphocytes

Lymphocytes are the white blood cells of the adaptive immune system. They circulate in the blood and are also found in large numbers in lymph nodes, where they are likely to encounter pathogens carried in lymph. An individual has an enormous number of different B-lymphocytes, each able to make one specific type of antibody. Between them they can recognize almost any antigen, but only a few B-cells respond to any one antigen.

Antigens

An antigen is a molecule that is recognized by the immune system and triggers antibody production. Most antigens are glycoproteins or other proteins, usually located on the outer surfaces of pathogens — viral capsids and envelopes, bacterial cell walls. Antigens on erythrocytes, such as the A and B antigens, can also stimulate antibody production if blood is transfused into a person with a different blood group.

Activation of B-lymphocytes

There are antigen-specific B-cells and antigen-specific helper T-cells. A B-cell only makes antibodies, and only becomes a memory cell, after it has been activated. Activation requires two things:

1. Direct interaction of the B-cell with the specific antigen it recognizes.
2. Contact with a helper T-cell that has also been activated by the same antigen (typically presented to it by a phagocyte that has digested the pathogen).

The requirement for two signals is a safeguard: it helps prevent B-cells from being activated against the body’s own molecules.

Clonal selection and plasma cells

Because only a small number of B-cells respond to any particular antigen, they could not make enough antibody on their own. Once activated, the B-cells divide repeatedly by mitosis, producing a large clone of genetically identical cells. Most differentiate into plasma cells, which have extensive rough ER and secrete large quantities of the same type of antibody. The antibodies bind to the antigen, helping to destroy the pathogen — for example by making pathogens clump together, neutralizing toxins or marking pathogens for phagocytes.

Memory cells and immunity

Some cells of the clone become memory cells, which survive in the body for many years. Immunity is the ability to eliminate an infectious disease from the body, and it is due to the long-term survival of these memory cells, which can make the specific antibodies needed.

If the same pathogen infects again, memory cells recognize it and rapidly divide into plasma cells. The secondary response is faster, produces far more antibody, and usually destroys the pathogen before any symptoms develop.

HIV transmission

HIV (human immunodeficiency virus) is transmitted in body fluids — blood, semen, vaginal fluids and breast milk. Mechanisms include:

• unprotected sexual intercourse with an infected person;
• sharing needles among people who inject drugs;
• transfusion of infected blood or blood products (now rare where blood is screened);
• from mother to child during pregnancy, childbirth or breastfeeding.

HIV is not transmitted by everyday contact, sharing cups or insect bites.

HIV and AIDS

HIV infects and kills only certain lymphocytes: helper T-cells, which carry the receptor HIV binds to. Over years, their number falls. Because helper T-cells are needed to activate B-cells, the ability to produce antibodies against new infections declines. The person becomes vulnerable to opportunistic infections — such as tuberculosis, pneumonia caused by fungi, and certain cancers — that a healthy immune system would control. This condition is AIDS (acquired immune deficiency syndrome). Antiretroviral drugs can keep the virus suppressed and prevent AIDS developing.

Antibiotics

Antibiotics are chemicals that block processes that occur in bacteria but not in eukaryotic cells, so they kill or inhibit bacteria without harming human cells. For example, penicillin blocks the synthesis of bacterial cell walls, and streptomycin blocks protein synthesis on 70S ribosomes.

Antibiotics do not work against viruses. Viruses have no cell wall and no ribosomes or metabolism of their own; they reproduce using the host cell’s eukaryotic machinery, which antibiotics are designed not to affect. There is nothing in a virus for an antibiotic to block.

Antibiotic resistance

Strains of pathogenic bacteria have evolved resistance to several antibiotics, by natural selection:

1. In a large bacterial population, random mutation occasionally produces a bacterium with a gene that gives resistance to an antibiotic (for example an enzyme that breaks it down). Resistance genes can also be acquired from other bacteria on plasmids.
2. When the antibiotic is used, susceptible bacteria are killed and resistant ones survive.
3. The survivors reproduce rapidly, passing on the resistance gene, so the proportion of resistant bacteria increases.
4. Repeated exposure to several antibiotics can select for multiresistant strains, such as MRSA.

Careful use is needed to slow this: prescribing antibiotics only for bacterial infections, completing courses as directed, avoiding routine use in livestock, and preventing infection in hospitals. New techniques also open new avenues of research: automated screening of large libraries of chemicals, aided by computer models, is yielding new candidate antibiotics.

Zoonoses

A zoonosis is an infectious disease that can transfer from another species to humans. Zoonoses are very common — a majority of emerging infectious diseases in humans are thought to have animal origins — and they spread in varied ways:

Vaccines and immunization

A vaccine contains antigens of a pathogen — in weakened or killed pathogens, or as purified proteins — or nucleic acids (DNA or mRNA) with sequences coding for antigens, which the body’s cells then make. The vaccine stimulates the adaptive immune response: B-cells are activated, clones of plasma cells form, and memory cells are produced. This develops immunity to a specific pathogen without causing the disease. On later exposure to the real pathogen, the secondary response destroys it before it can cause illness.

Herd immunity

Members of a population are interdependent in their protection. If a sufficient percentage of a population is immune, an infected person is unlikely to meet a susceptible one, so transmission is greatly impeded and an epidemic cannot take hold. This also protects people who cannot be vaccinated, such as newborns or people with weakened immune systems. The more transmissible the disease, the higher the percentage that must be immune: a disease in which each case would infect 5 others in a fully susceptible population needs about 80% immune; for measles, which is far more contagious, the threshold is around 95%.

Scientists publish research so it can be evaluated by other scientists, but the media often report it while that evaluation is still under way. Vaccines are tested rigorously and the risk of side effects is minimal but not zero. Science deals in well-supported, pragmatic truths rather than absolute certainty, a distinction that is widely misunderstood and that anti-vaccine claims exploit.

Evaluating COVID-19 data

Two calculations are specifically required: