2.4 Immunity

Pathogens, Infection, and Plant Defences

A pathogen is any biological organism or infectious agent capable of causing disease in a host organism. Pathogens span six distinct groups:

• Prions: Infectious, abnormally folded proteins that contain no genetic material (neither DNA nor RNA). A prion acts as a template, forcing normal proteins in brain tissue to misfold into diseased forms. This triggers fatal neurodegenerative conditions such as Bovine Spongiform Encephalopathy (BSE) in cattle, scrapie in sheep, and Creutzfeldt-Jakob Disease (CJD) in humans.
• Viruses: Non-cellular obligate intracellular parasites composed of a nucleic acid core (DNA or RNA) enclosed in a protein capsid coat (for example, influenza, human immunodeficiency virus, and tobacco mosaic virus). They can only reproduce inside a living host cell.
• Bacteria: Microscopic, single-celled prokaryotic organisms that cause disease through cellular damage or toxin secretion (such as Streptococcus, Salmonella, and Mycobacterium tuberculosis).
• Fungi: Heterotrophic eukaryotic organisms that absorb nutrients from their surroundings (including Candida causing thrush, tinea causing athlete's foot, and Hymenoscyphus fraxineus causing ash dieback in ash trees).
• Protists: Single-celled eukaryotic organisms that are distinct from plants, animals, and fungi (such as Plasmodium, transmitted by mosquitoes to cause malaria).
• Parasitic animals: Multicellular invertebrates that live in or on a host at the host's expense. These include endoparasites like tapeworms and roundworms, and ectoparasites like ticks, fleas, and mites.

Plants Defend Themselves Too

Unlike animals, plants lack circulating white blood cells and antibodies. Their immune response relies entirely on non-specific anatomical and chemical adaptations:

• Anatomical adaptations: A waxy cuticle and thick bark act as mechanical barriers; thorns, spines, and stinging hairs deter grazing herbivores; and wounds can be sealed off with resin or callose.
• Chemical adaptations: Plants produce toxic or distasteful compounds such as tannins, alkaloids (for example, caffeine and nicotine), and antimicrobial proteins that kill or inhibit attacking fungi and bacteria.

Innate Immunity: Surface Barriers and Internal Defences

Innate immunity is the non-specific defence system present from birth. It responds immediately and identically to every foreign invader without requiring prior exposure, and it leaves no immunological memory.

The First Line of Defence: External Physical and Chemical Barriers

• Skin forms a continuous, tough mechanical barrier of keratinised cells. Breaches are rapidly sealed by blood clotting to prevent microbial entry.
• Sebaceous glands secrete sebum, an oily substance that lubricates the skin and contains antibacterial chemicals that inhibit microbial growth.
• Mucous membranes produce sticky mucus across the respiratory, digestive, and urogenital tracts to trap microbes. In the airways, microscopic cilia beat rhythmically to sweep mucus upwards to the throat to be swallowed or coughed out.
• Lysozyme is an antimicrobial enzyme present in tears, saliva, and perspiration that hydrolyses the peptidoglycan cell walls of bacteria, causing them to burst by osmotic lysis.
• Stomach acid (hydrochloric acid) maintains a pH of 1 to 2, denaturing microbial enzymes and destroying swallowed pathogens.
• Beneficial microflora are harmless bacteria that normally live in the gut and vagina; they produce lactic acid and outcompete incoming pathogens for nutrients and space.

The Second Line of Defence: Internal Non-Specific Defences

• Phagocytosis: When pathogens breach physical barriers, circulating monocytes and tissue macrophages engulf foreign particles into vacuoles and digest them enzymatically using lysosomes.
• Natural killer cells: Cytotoxic innate lymphocytes that patrol blood and tissues. NK cells detect and destroy abnormal host cells—such as virus-infected cells or emerging tumour cells—spontaneously, without requiring specific antigen recognition.
• Defensive proteins: Interferons are signalling proteins released by virus-infected cells that stimulate neighbouring cells to produce antiviral enzymes. Complement is a group of blood proteins activated in a cascade that burst pathogen membranes and coat pathogens so phagocytes engulf them more easily.
• Inflammation: Damaged tissues release histamine, which dilates local blood vessels and increases capillary permeability. This brings extra blood flow, warmth, and swelling while drawing phagocytic white blood cells directly into the infected area.

Acquired Immunity: Distinctions, Principles, and Graphs

Acquired (adaptive) immunity is a targeted defence system that develops throughout an organism's lifetime. It relies on lymphocytes, recognises specific molecular shapes, and establishes long-term immunological memory.

Distinguishing Innate from Acquired Immunity

If asked to distinguish them in an examination: innate immunity is present from birth, acts immediately against any pathogen and leaves no memory, whereas acquired immunity develops after exposure, targets one specific antigen and produces memory cells.

Antigens and Antibodies

• An antigen is any substance—usually a protein or polysaccharide, often on the surface of a pathogen—that the immune system recognises and that stimulates an immune response, including the production of specific antibodies. Molecules on the body's own cells are called self-antigens; the immune system normally learns to ignore these, a state known as self-tolerance.
• An antibody is a specialised Y-shaped immunoglobulin protein produced by plasma B lymphocytes that binds with complementary precision to one specific matching antigen.

Reading an Antibody-Titre Graph

When measuring blood antibody concentration (titre) over time following two separate exposures to the same antigen:

1. Primary lag phase: After the first exposure, there is a delay of roughly 7 to 14 days before antibodies appear in blood, as the matching lymphocyte is selected and divides.
2. Primary peak: Antibody levels rise slowly, reach a relatively low peak, and then decline as the infection clears.
3. Secondary response: Following a second exposure, the lag is virtually absent (1 to 3 days).
4. Secondary peak: Antibody levels rise faster, reach a much higher concentration, and remain high for longer.
5. Biological cause: Memory B cells already exist in large numbers and divide immediately into antibody-secreting plasma cells, clearing the pathogen before symptoms can develop.

Specialised White Blood Cells (Higher Level)

White blood cells (leucocytes) originate from stem cells in the bone marrow. Higher Level candidates must compare their origin, maturation site, and precise physiological role.

Memory Hook for T Lymphocytes

• Helper: calls the others in (activates B cells and killer T cells).
• Killer: destroys infected body cells with perforin.
• Suppressor: switches the response off when the threat has gone.
• Memory: remembers the specific antigen for next time.

Clinical illustration: The Human Immunodeficiency Virus (HIV) specifically targets and destroys helper T cells. Without helper T cells releasing activating cytokines, neither antibody production by B cells nor cytotoxic action by killer T cells can be coordinated, leaving the body vulnerable to secondary opportunistic infections.

Active and Passive Immunity, Vaccines, and Antibiotic Resistance

Acquired immunity is categorised by whether the host manufactures their own antibodies (active) or receives pre-formed antibodies from another source (passive).

Active immunity requires the recipient's own B lymphocytes to respond to an antigen, forming antibody-producing plasma cells and durable memory cells. Passive immunity provides immediate but temporary protection because the recipient receives ready-made antibodies. The recipient's own lymphocytes are never activated, so no memory cells are produced; once the transferred antibodies break down, immunity disappears.

Passive immunity can be delivered medically by injecting ready-made antibodies from a donor—sometimes referred to as an antibody booster injection, antiserum, or antitoxin (for example, tetanus antitoxin after a puncture wound or snake antivenom). Do not confuse an antibody booster injection with a vaccine booster: a vaccine booster delivers antigens to stimulate the patient's own active response and memory cells, whereas an antibody booster injection delivers pre-formed antibodies for immediate, passive defence.

A vaccine introduces a non-pathogenic preparation containing killed microbes, weakened (attenuated) pathogens, isolated surface antigens, or mRNA that directs host cells to make a viral antigen. This stimulates a primary immune response without triggering severe disease, producing memory cells that protect against future infection.

Treating Microbial Diseases and Antibiotic Resistance

Strategies to treat microbial diseases:

• Antibiotics: for bacterial infections (targeting cell wall or ribosome targets).
• Antiviral drugs: for some viral infections.
• Antifungal drugs: for fungal infections such as thrush or athlete's foot.

Strategies to prevent microbial diseases:

• Vaccination.
• Personal hygiene such as handwashing and correct use of PPE.
• Safe handling, cooking and storage of food, and access to clean water and sanitation.
• Controlling vectors such as mosquitoes and ticks, isolating infectious people, and avoiding misuse of antibiotics.

Antibiotics are chemical substances that kill or inhibit bacteria by disrupting bacterial cell wall synthesis or bacterial ribosomes. Antibiotics are completely ineffective against viruses because viruses do not possess bacterial cell walls, ribosomes, or their own metabolic machinery.

How antibiotic resistance develops through natural selection:

1. A random mutation occurs in bacterial DNA that gives resistance (for example, a gene coding for an enzyme that destroys the antibiotic).
2. When the antibiotic is administered, non-resistant bacteria are killed, but the resistant bacterium survives.
3. The resistant bacterium reproduces rapidly by binary fission, passing the resistance gene to all offspring.
4. Over time, resistant strains become dominant, rendering the antibiotic ineffective.

Strategies to slow antibiotic resistance:

• Prescribe antibiotics strictly for bacterial infections, never for viral illnesses like colds or flu.
• Patients must complete the full prescribed course so that partially resistant bacteria are not left behind.
• Ban routine, prophylactic use of antibiotics in farm animal feed.
• Maintain strict hospital hygiene and isolate patients infected with resistant strains such as MRSA.

Modelling Viral Replication: DNA vs. RNA Viruses (Higher Level)

Viruses lack metabolic machinery, organelles, and ribosomes. They are obligate intracellular parasites that replicate solely by taking over a host cell's resources.

The Five Stages of Viral Cellular Replication

1. Attachment: Viral surface glycoproteins bind with complementary lock-and-key specificity to receptor molecules on the host cell membrane.
2. Entry: The viral nucleic acid enters the host cell. The capsid may remain outside, the viral envelope may fuse with the host membrane, or the virus may enter whole via endocytosis, after which host enzymes digest the protein coat to release the genome.
3. Synthesis: The viral genome hijacks host cell machinery. Host transcription and translation are suppressed, while host ribosomes, amino acids, tRNA, ATP, and enzymes are forced to synthesise viral nucleic acids and viral capsid proteins.
4. Assembly: Newly synthesised viral genomes and protein capsomeres assemble spontaneously inside the host cell to construct thousands of intact new virions.
5. Release: Progeny viruses exit the host cell. Non-enveloped viruses typically cause osmotic lysis, bursting and destroying the host cell. Enveloped viruses bud off through the host membrane, taking a layer of phospholipid membrane with them.

When a Virus Does Not Destroy the Cell Straight Away: Viral Latency

Not all viral infections lead immediately to cell lysis. Some viruses integrate their genetic material into host chromosomes and enter a dormant or latent state. The viral genome is replicated silently alongside host DNA each time the cell divides, producing no symptoms. Under conditions of physical or emotional stress, illness, or immunosuppression, the virus reactivates and enters the lytic cycle. A classic example is the varicella-zoster virus: initial infection causes chickenpox, after which the virus lies latent inside sensory nerve ganglia for decades, occasionally reactivating later in life as shingles.

Comparison of DNA and RNA Viruses

The high mutation rate of RNA viruses causes frequent alterations in their surface antigen shapes. Existing antibodies and memory cells fail to recognise the new shapes, enabling updated strains to bypass existing population immunity.

Disease Emergence, Population Immunity, and Society (Higher Level)

An emerging infectious disease is one that has newly appeared in a population, or has existed previously but is rapidly increasing in incidence or geographical range, affecting plants or animals.

Interrelated Factors Driving Disease Emergence

• Persistence of the pathogen in a host: Pathogens that establish long-term latency or asymptomatic carrier states stay in hosts longer, multiplying opportunities for transmission.
• Mutations: Rapid mutation rates generate novel antigen shapes that evade existing host immunity.
• Antibiotic or chemical resistance: Heavy agricultural and clinical drug use selects for resistant pathogens, defeating standard treatments.
• Immunity level in the population: Low vaccination rates leave large pools of susceptible hosts.
• Mobility in affected populations: Global air travel and commercial transport move infected people, animals, and agricultural goods across continents in hours. For example, ash dieback (Hymenoscyphus fraxineus), a destructive fungal tree disease, was introduced into Ireland in 2012 via imported infected ash saplings.
• Reproduction number (R₀): Determines the intrinsic spread of the disease.

The Basic Reproduction Number (R₀) and Population Immunity

The basic reproduction number (R₀) is the average number of secondary infections generated by a single infected individual in an entirely susceptible population where nobody is immune and no control interventions have been introduced.

• If R₀ < 1: Each case infects fewer than one other person on average; transmission declines and the outbreak dies out.
• If R₀ = 1: Each case infects exactly one other person; the disease remains stable and endemic.
• If R₀ > 1: Each case infects more than one person; transmission increases exponentially, with epidemic or pandemic potential.

Population immunity (herd immunity) is the collective protection given to an entire population—including unimmunised individuals—when a high enough proportion is immune (via vaccination or past recovery) that transmission chains break. In an ongoing outbreak, the actual transmission rate is the effective reproduction number (R), which falls as the proportion of immune individuals rises. Diseases with very high R₀ values, like measles (R₀ ≈ 12–18), require significantly higher vaccination coverage (about 95%) to achieve population protection than diseases with lower R₀ values.

Why Knowledge of Emerging Diseases Matters to Society

• Surveillance and containment: Early detection via hospital monitoring and wastewater testing allows isolation, contact tracing, and vector control to prevent healthcare services being overwhelmed.
• Biotechnology: Rapid gene sequencing of new pathogens enables researchers to engineer diagnostic tests and targeted vaccines (such as mRNA vaccines) in record time.
• Agriculture and economy: Monitoring plant and animal diseases protects livestock and crop yields. Ash dieback has killed vast numbers of native Irish ash trees, requiring costly felling and replanting schemes.
• Balancing costs: Society must weigh containment measures (travel curbs, school closures, livestock culling) against economic and social costs, while addressing vaccine inequality and misinformation.

Autoimmune Disorders

An autoimmune disease occurs when the immune system loses self-tolerance, failing to distinguish self-antigens from foreign antigens and attacking the body's own tissues:

• Type 1 diabetes: Cytotoxic T cells attack and destroy the insulin-secreting beta cells in the islets of Langerhans of the pancreas.
• Rheumatoid arthritis: Chronic immune inflammation destroys the synovial membranes of joints.
• Multiple sclerosis: The immune system attacks and destroys the myelin sheath of neurons in the brain and spinal cord, slowing or blocking nerve impulse conduction.

Key terms

Pathogen

Any biological organism or infectious agent capable of causing disease in a host organism.

Antigen

Any substance—usually a protein or polysaccharide, often on the surface of a pathogen—that the immune system recognises and that stimulates an immune response, including antibody production.

Antibody

A specialised Y-shaped immunoglobulin protein produced by plasma B lymphocytes that binds with complementary specificity to a matching antigen.

Innate Immunity

Non-specific physiological defence mechanisms present from birth that resist all foreign agents equally without providing immunological memory.

Acquired Immunity

Specific defence developed over an organism's lifetime mediated by lymphocytes and antibodies, characterised by immunological memory.

Active Immunity

Resistance developed when an organism's own lymphocytes synthesise antibodies and memory cells following direct exposure to an antigen.

Passive Immunity

Short-term resistance conferred by receiving pre-formed antibodies from another organism without generating memory cells.

Phagocytosis

The cellular process by which specialised white blood cells surround, engulf, and enzymatically digest foreign microorganisms and debris using lysosomes.

Natural Killer (NK) Cell

A cytotoxic lymphocyte of the innate immune system that destroys virus-infected and cancerous body cells without requiring prior antigen exposure.

Monocyte

A phagocytic white blood cell that circulates in the blood before migrating into tissues to mature into an antigen-presenting macrophage.

Helper T Cell

A T lymphocyte that coordinates the immune response by recognising presented antigens and releasing cytokines to activate B cells and killer T cells.

Killer T Cell

A cytotoxic T lymphocyte that binds to abnormal or infected host body cells and releases perforin to destroy them via lysis.

Suppressor T Cell

A regulatory T lymphocyte that stops and downregulates the immune response once an infection has been cleared.

Memory T Cell

A long-lived T lymphocyte formed during an infection that remains in lymphoid tissue to rapidly trigger killer and helper T cell responses upon reinfection.

Memory B Cell

A long-lived B lymphocyte formed during an infection that remains in lymphoid tissue to rapidly divide into antibody-secreting plasma cells upon reinfection.

Prion

An infectious, misfolded protein lacking nucleic acids that converts normal proteins into diseased forms, causing fatal neurodegenerative illness.

Basic Reproduction Number (R₀)

The average number of secondary infectious cases produced by a single primary case in a completely susceptible population with no interventions.

Autoimmune Disease

A disorder in which the adaptive immune system fails to recognise self-antigens and attacks the organism's own healthy tissues.