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.

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.

Examples in context

Example 1. Ross River virus immunity in Brisbane. A Brisbane resident bitten by an Aedes vigilax mosquito and infected with Ross River virus mounts a layered response. First line: intact skin and mucous membranes (failed at the bite). Second line: macrophages phagocytose virus particles at the bite site, complement opsonises virions, and inflammation (redness, swelling, heat) recruits more cells. Third line: dendritic cells present viral peptides on MHC class II to helper T cells (clonal selection); helper T cells activate B cells that proliferate and secrete IgM, then IgG specific to Ross River envelope protein. Cytotoxic T cells kill infected joint cells. Within ten days, antibodies clear viraemia; memory B and T cells provide lifelong immunity, so reinfection is rare.

Example 2. Lone Pine Koala Sanctuary chlamydia screening. Koalas at Lone Pine carry Chlamydia pecorum, an intracellular bacterium that infects conjunctival and urogenital epithelium. Innate responses (neutrophils, complement) are insufficient because the bacterium hides inside host cells. The adaptive response relies on cell-mediated immunity: cytotoxic T cells (CD8+) recognise infected cells via MHC class I peptides. A koala chlamydia vaccine developed at the University of the Sunshine Coast uses the major outer-membrane protein (MOMP) to prime T helper and B cell responses; vaccinated koalas show measurable IgG titres above 1:1000 and reduced disease severity at twelve-month follow-up.

Try this

Q1. Distinguish between humoral and cell-mediated adaptive immunity, naming the principal cell type and the targets of each. [3 marks]

• Cue. Humoral: B cells, antibodies, extracellular pathogens. Cell-mediated: cytotoxic T cells, infected cells.

Q2. A blood test on a patient three weeks after infection with SARS-CoV-2 shows IgM declining, IgG rising and memory B cell count elevated. Identify the phase of immune response and justify the IgG dominance. [3 marks]

• Cue. Class switching during late primary response; IgG has higher affinity and is longer-lasting.

Q3. Refer to the inflammatory response. (a) Identify three cardinal signs and name the chemical mediators responsible. (b) Explain how phagocytosis bridges innate and adaptive immunity. (c) Justify whether chronic inflammation is beneficial or harmful. [2+2+2 marks]

• Cue. (a) Redness, heat, swelling; histamine, prostaglandins. (b) Dendritic cells present antigens to T cells. (c) Harmful; causes tissue damage in conditions like rheumatoid arthritis.