Describe the first, second and third lines of defence in vertebrates, including innate immune responses (barriers, inflammation, phagocytes) and adaptive immune responses (humoral immunity through B cells and antibodies, cell-mediated immunity through T cells)

What this dot point is asking

QCAA expects you to describe the three lines of defence and to distinguish innate (non-specific) from adaptive (specific) immunity. You should be able to explain phagocytosis and inflammation, and contrast the roles of B cells and T cells.

The answer

The vertebrate immune response is layered. Each line of defence catches pathogens that escape the previous one, with the deepest layer (the adaptive response) providing specificity and memory.

First line of defence: barriers

Physical and chemical barriers stop pathogens entering the body in the first place. Non-specific.

• Skin. Tough, dry, keratinised; very few pathogens can penetrate intact skin.
• Mucous membranes. Line the airways, digestive tract and urogenital tract. Mucus traps particles; cilia sweep mucus out of the lungs.
• Tears, saliva, sweat. Contain lysozyme, an enzyme that breaks down bacterial cell walls.
• Stomach acid. Low pH (around 2) kills most ingested bacteria.
• Vaginal acidity and beneficial microbiota. Prevent overgrowth of pathogens.
• Reflexes. Coughing, sneezing, vomiting and diarrhoea expel pathogens.

Second line of defence: innate immune response

Triggered when pathogens cross the first barrier. Non-specific (responds the same way to any pathogen) but rapid (minutes to hours).

The inflammatory response.

• Damaged cells and mast cells release histamine, prostaglandins and cytokines.
• Local blood vessels dilate (vasodilation) and become more permeable.
• Plasma leaks into the tissue, carrying clotting factors and complement proteins.
• Cardinal signs appear: redness, heat, swelling, pain.
• Cytokines and chemokines attract phagocytes from the blood to the site (chemotaxis).

Phagocytosis.

• Neutrophils arrive first (within hours); macrophages follow (within a day or two).
• The phagocyte engulfs the pathogen, enclosing it in a phagosome.
• The phagosome fuses with a lysosome to form a phagolysosome. Lysosomal enzymes and reactive oxygen species kill the pathogen.

Other innate components.

• Natural killer (NK) cells. Kill virally infected and cancerous host cells by releasing perforin and granzymes.
• Complement system. Plasma proteins that form pores in bacterial membranes (membrane attack complex), coat pathogens for phagocytosis (opsonisation) and amplify inflammation.
• Interferons. Released by virally infected cells; signal neighbouring cells to make antiviral proteins.
• Fever. Pyrogens (from pathogens and immune cells) reset the hypothalamic temperature set point upward. Higher temperature slows pathogen replication and speeds immune responses.

Third line of defence: adaptive immune response

Specific (recognises one antigen) and slow on first exposure (5 to 10 days), but produces memory cells for faster future responses.

Antigen presentation. Phagocytes and dendritic cells display fragments of digested pathogens on MHC class II molecules and travel to a lymph node. There they present the antigen to T cells.

Two branches.

Humoral immunity (B cells and antibodies).

• Each B cell carries a unique B cell receptor (membrane-bound antibody) specific for one antigen.
• A B cell that binds its matching antigen, with help from a helper T cell, is activated and undergoes clonal expansion.
• Most activated B cells differentiate into plasma cells that secrete large amounts of antibody. A few become memory B cells.
• Antibodies are Y-shaped proteins with two identical antigen-binding sites. They:
  • Neutralise pathogens and toxins by blocking binding sites.
  • Agglutinate (clump) pathogens, making them easier to phagocytose.
  • Opsonise pathogens by tagging them for phagocytosis.
  • Activate complement.
• Targets extracellular pathogens (most bacteria, free-floating viruses, toxins).

Cell-mediated immunity (T cells).

• T cells recognise antigen presented on MHC molecules.
• Helper T cells (CD4+). Recognise antigen on MHC II on antigen-presenting cells. Secrete cytokines that activate B cells, cytotoxic T cells and macrophages. Hub of the adaptive response.
• Cytotoxic T cells (CD8+). Recognise antigen on MHC I on infected host cells. Release perforin (makes pores in the target cell membrane) and granzymes (trigger apoptosis). Kill the infected cell along with the pathogen inside.
• Targets intracellular pathogens (viruses inside cells, intracellular bacteria like Mycobacterium tuberculosis) and abnormal cells (cancer).
• Memory T cells persist after the infection clears.

Primary and secondary response

Primary response. First exposure to an antigen. Slow (5 to 10 days to peak), produces lower antibody levels, generates memory cells. The host typically experiences symptoms.

Secondary response. Second (or later) exposure to the same antigen. Memory cells respond rapidly (within hours to a few days), produce higher antibody levels (mostly IgG) and often clear the pathogen before symptoms appear. This is the basis of long-term immunity and vaccination.

A typical primary response peaks around day 14 at relatively low antibody concentration, then declines; a secondary response peaks earlier (around day 4 to 7) at a much higher concentration and lasts longer.

Active vs passive immunity

• Active. The host's own immune system makes antibodies and memory cells. Acquired naturally through infection or artificially through vaccination. Long-lasting.
• Passive. Antibodies are received from another source (mother to fetus across the placenta, mother to infant in breast milk, antivenom injection). Immediate protection but short-lived; no memory cells are made.

Common traps

Calling innate immunity "weak". Innate immunity is rapid and powerful; many infections never reach the third line of defence.

Confusing antigen and antibody. Antigen is the foreign substance recognised; antibody is the protein the host makes in response.

Treating all T cells as identical. Helper T cells coordinate; cytotoxic T cells kill. They are different cell types with different surface markers (CD4 vs CD8) and different MHC recognition.

Forgetting memory cells. The primary response's most important output is often the memory cells, not the antibodies of that response.

Cross-link to Year 12 assessment

This dot point feeds directly into vaccines and antibiotic resistance (vaccines exploit the primary response to leave memory cells without causing disease). The MHC and antibody concepts reappear in Unit 4 IA3 contexts (monoclonal antibody therapy, immune-related biotechnology) and in EA Paper 1 short-response questions on the immune response.

In one sentence

The first line of defence (barriers) stops most pathogens entering; the second line (innate response: inflammation, phagocytes, complement, NK cells, interferons, fever) attacks any pathogens that breach barriers non-specifically and rapidly; the third line (adaptive response) uses B cells producing antibodies (humoral immunity, against extracellular pathogens) and T cells (cell-mediated immunity, against intracellular pathogens) to respond specifically, and leaves memory cells that produce a faster, larger secondary response on re-exposure.