Defence against disease

A pathogen is anything living or virus-like that causes disease in a host. Because pathogens can pass between hosts, the illnesses they cause are called infectious or communicable. That separates them from conditions such as cancer, malnutrition or inherited disorders, which you cannot catch.

The word is mainly used for four groups, and each has features you can use to identify it:

• Bacteria: prokaryotes with a peptidoglycan wall. Most species are harmless; those that are not include the causes of cholera and tuberculosis.
• Viruses: not cells. A virus is nucleic acid in a protein coat and can reproduce only inside a host cell, so every virus is a parasite.
• Fungi: eukaryotes with chitin walls, responsible for infections such as athlete's foot.
• Protists: single-celled eukaryotes, including the parasite that causes malaria.

Some parasitic worms also cause human disease. No archaeon is known to be a human pathogen, and scientists still debate why.

The first job is to stop pathogens entering at all.

Skin defends in two ways. As a physical barrier, its outer layer of dead, keratin-filled cells is tough and sealed with lipid, and shedding removes microbes that settle on it. As a chemical barrier, its secretions lower the surface pH and sweat contains lysozyme, an enzyme that damages bacterial walls.

Mucous membranes line the airways, gut and other openings. They are thin and living, so they need more protection. Mucus traps particles, and in the airways, cilia sweep it up to the throat to be swallowed. Stomach acid then kills many of the microbes that arrive.

Exam note: you do not need to draw or label skin.

A cut breaks the barrier, so it must be sealed quickly. Doing this limits blood loss and keeps pathogens out.

1. Platelets collect at the wound and stick together, which is enough to plug a tiny break.
2. Platelets and damaged tissue release clotting factors, starting a cascade.
3. The cascade converts prothrombin into the enzyme thrombin.
4. Thrombin rapidly converts soluble fibrinogen into insoluble fibrin fibres.
5. The fibres form a mesh that traps erythrocytes, and this is the clot.

Watch out: fibrinogen is the soluble starting material and fibrin is the insoluble product. Write that a clot "prevents the entry of pathogens", not that it "stops diseases getting in".

Both start when a pathogen gets past the surface barriers. The only innate component you must know is the phagocyte.

Phagocytes are white blood cells that leave the blood by amoeboid movement, squeezing through capillary walls and crawling to the infected tissue. They recognise a pathogen, engulf it by endocytosis so it sits inside a vesicle, then fuse a lysosome with that vesicle. Lysosomal enzymes digest the pathogen.

Lymphocytes circulate in the blood and are also held in lymph nodes. Two kinds matter here: B-cells, which go on to make antibodies, and helper T-cells, which activate B-cells.

You carry a huge number of different B-cell types. Each type can make one specific antibody. That variety lets the body respond to almost any antigen, but it also means only a few cells match any one antigen when it first appears.

A B-cell stays inactive until it receives two signals:

1. Direct contact with its specific antigen.
2. Contact with a helper T-cell that has been activated by the same antigen.

A phagocyte that has engulfed a pathogen displays pieces of it on its surface. A helper T-cell with the matching receptor binds to these and becomes activated. It then finds and activates the B-cell that matches the same antigen.

Watch out: helper T-cells do not secrete antibodies. Their role is to activate the B-cell.

Too few B-cells match any one antigen to make enough antibody. So an activated B-cell first divides repeatedly by mitosis, forming a clone of identical cells. Most of them become plasma cells, whose rough ER makes large amounts of the same antibody for secretion. This process is known as clonal selection.

HIV passes from one person to another in body fluids, for example through sexual intercourse, shared hypodermic needles, breastfeeding and transfusions or transplants from unscreened donors. It does not pass through sharing a glass or towel, and mosquitoes do not transmit it.

The implications are practical. Condoms, clean needles and screening of donated blood all break the route of transmission, and knowing how HIV does not spread helps to reduce stigma.

Watch out: HIV is transmitted. AIDS is the condition that can follow, and it is not itself transmitted.

HIV is a retrovirus. Proteins on the virus bind to receptors called CD4 on helper T-cells, and its RNA core enters the cell. The enzyme reverse transcriptase copies the RNA into DNA, which is inserted into a host chromosome. The cell can then make new viruses, and over time infected lymphocytes are lost.

Only certain types of lymphocyte are infected, but losing them has wide effects. With fewer helper T-cells, fewer B-cells are activated and antibody production falls. The body then cannot fight opportunistic infections that a healthy person would normally overcome. This stage is AIDS, acquired immunodeficiency syndrome.

Antibiotics can treat a patient safely because bacteria and human cells differ. They target features found only in prokaryotes, such as cell wall synthesis or 70S ribosomes. Human cells have no cell wall and have different ribosomes in their cytoplasm, so they are not harmed.

Viruses have no cell wall, no ribosomes and no metabolism of their own. There is nothing for an antibiotic to act on, so it will not control a viral infection.

Watch out: it is wrong to say that antibiotics fail because viruses "hide inside cells". The reason is that viruses lack the structures antibiotics act on.

This is natural selection. A random mutation, or a gene gained from another bacterium on a plasmid, makes a cell resistant. When an antibiotic is used, the susceptible bacteria die and the resistant ones survive and reproduce with less competition. Repeating this with different antibiotics can produce multiresistant strains such as MRSA.

Careful use slows this down: prescribing antibiotics only when needed, finishing the course, keeping hospitals hygienic and limiting routine use in farming. It matters because new antibiotics are hard to develop.

A zoonosis is an infectious disease that can transfer from another species to humans. Many pathogens stick to one host, but others cross, especially when people and animals live closely together.

COVID-19 shows how serious a recent transfer can be, with worldwide effects on health and daily life.

A vaccine contains antigens, or DNA or RNA coding for antigens. It may be a weakened or inactivated pathogen, a purified part of one, or a nucleic acid such as the mRNA in some COVID-19 vaccines. It stimulates a primary immune response and the production of memory cells, without causing the disease. If the real pathogen arrives later, the fast secondary response deals with it.

When you evaluate data, think about what else could explain a pattern, such as the amount of testing, how cases are reported, or differences in public health rules. Try it with real figures on the WHO COVID-19 dashboard; slide 29 gives the steps.