the innate immune response, including physical, chemical and microbiological barriers and the inflammatory response; and the adaptive immune response, including the roles of B cells, T cells (helper and cytotoxic), antibodies, antigens, and immunological memory

What this dot point is asking

VCAA wants the innate immune response (barriers, inflammation, phagocytes) and the adaptive immune response (B cells, T cells, antibodies, memory), including the humoral and cell-mediated branches, and the key difference: specificity and memory.

The answer

The immune system has two branches that work together: the innate response (fast, non-specific, no memory) and the adaptive response (slower, specific, with memory).

The innate immune response

The innate system is the first line of defence. It is present from birth, acts within minutes to hours, and treats every pathogen the same way.

Physical barriers.

• Skin. Tough, dry outer layer (keratinised dead cells) that few pathogens can penetrate.
• Mucous membranes. Line the respiratory, digestive, urogenital and reproductive tracts. Mucus traps pathogens.
• Cilia. In the respiratory tract, cilia sweep trapped pathogens up to be coughed, sneezed or swallowed.
• Tears, urine flow and peristalsis. Physically wash pathogens away.

Chemical barriers.

• Stomach acid (pH about 2) kills most bacteria in food.
• Lysozyme in tears, saliva and mucus digests bacterial cell walls.
• Antimicrobial peptides (defensins) on the skin and in mucus.
• Sebum on the skin lowers pH and inhibits bacterial growth.

Microbiological barriers.

• The normal microbiota (commensal bacteria on the skin, in the gut and elsewhere) compete with pathogens for space and nutrients and produce antimicrobial substances.

Cells of innate immunity.

• Neutrophils. Most common white blood cell; first to arrive at infection; phagocytose bacteria.
• Macrophages. Larger phagocytes that engulf pathogens and present antigens to T cells, linking innate to adaptive immunity.
• Dendritic cells. Specialised antigen-presenting cells; capture pathogens and carry them to lymph nodes.
• Natural killer (NK) cells. Destroy virus-infected and cancerous cells by triggering apoptosis.
• Mast cells. Release histamine, triggering inflammation.

The inflammatory response. When tissue is damaged or infected, mast cells release histamine and cytokines, causing:

1. Vasodilation. Blood vessels widen, increasing blood flow (redness, heat).
2. Increased permeability. Plasma leaks into tissue (swelling).
3. Chemotaxis. Phagocytes are attracted to the site.
4. Phagocytosis. Pathogens are engulfed and digested.
5. Pain. Pressure on nerves and chemicals like prostaglandins.

Systemic responses include fever (cytokines reset the hypothalamic thermostat) and leukocytosis (increased white blood cell count).

The adaptive immune response

The adaptive system is specific (targets one pathogen), takes days to mount on first exposure, and produces memory so the second exposure is much faster and stronger.

Antigen presentation

Dendritic cells, macrophages and B cells engulf pathogens, break them down and display fragments (antigens) on MHC class II molecules on their surface. Infected body cells display fragments of internal pathogens on MHC class I molecules.

Clonal selection

Each B cell and T cell carries one specific receptor. When the receptor matches a presented antigen, the cell is selected, activated and proliferates (clonal expansion).

Helper T cells (CD4+)

Bind antigen on MHC class II. Once activated, they secrete cytokines that coordinate the rest of the adaptive response: activating cytotoxic T cells, stimulating B cell proliferation, and amplifying macrophage activity.

Cytotoxic T cells (CD8+)

Bind antigen on MHC class I (on infected body cells). They release perforin (which makes pores in the target cell membrane) and granzymes (which trigger apoptosis), killing the infected cell. This is cell-mediated immunity.

B cells

Bind free antigen using their B cell receptor (a membrane-bound antibody). With help from helper T cells, they differentiate into:

• Plasma cells. Antibody factories. Secrete huge numbers of soluble antibodies into the blood and lymph.
• Memory B cells. Long-lived cells that respond rapidly to future infections.

This is humoral immunity.

Antibodies (immunoglobulins). Y-shaped proteins with two antigen-binding sites specific to one antigen. They work by:

• Neutralisation. Block pathogens from binding to host cells.
• Agglutination. Clump pathogens together so they can be phagocytosed.
• Opsonisation. Coat pathogens, making them easier for phagocytes to engulf.
• Activating the complement cascade. Triggers lysis of pathogens.

The main classes are IgG (most abundant in blood), IgM (first to appear, large pentamer), IgA (in mucus and milk), IgE (allergies and parasites) and IgD (B cell receptor).

Memory and the secondary response. After the infection is cleared, most effector cells die. Memory B and T cells persist for years. If the same pathogen is encountered again, the secondary response is:

• Faster (days instead of weeks).
• Larger (more antibodies and effector cells).
• More targeted (higher-affinity antibodies due to affinity maturation).

This is the basis of immunity after natural infection or vaccination.

Comparing innate and adaptive

The two branches communicate constantly. Antigen-presenting cells of the innate system trigger the adaptive response, and cytokines from adaptive cells amplify innate functions.

Examples in context

Example 1. SARS-CoV-2 immunity at the Doherty Institute. Doherty Institute immunologists distinguished innate from adaptive responses to SARS-CoV-2. Within hours of infection, innate barriers (mucus, ciliated epithelium) and inflammatory cells (neutrophils, macrophages) respond non-specifically. Interferon signalling alerts neighbouring cells. Within days, adaptive immunity activates: B cells produce antibodies specific to spike protein; cytotoxic T cells (CD8+) recognise and kill virus-infected cells; helper T cells (CD4+) coordinate the response. Immunological memory persists, so a second exposure produces faster and stronger response - the basis of mRNA vaccine efficacy. Antibody titres can be measured in serum at the Royal Melbourne Hospital pathology lab to assess immunity.

Example 2. Childhood vaccination at Victorian Department of Health. Victoria's National Immunisation Program delivers vaccines that exploit adaptive immunity. The MMR vaccine, given at 12 and 18 months, contains live attenuated measles, mumps and rubella viruses. The child's immune system mounts a primary response: B cells producing antibodies and forming memory B cells; T cells doing the same. Years later, if the child encounters wild measles, memory B cells reactivate within hours, producing high-affinity IgG antibodies and clearing the virus before symptoms develop. Herd immunity threshold for measles is around 95 percent because R0 is roughly 15. Falling vaccination coverage in some Victorian suburbs has caused localised outbreaks.

Try this

Q1. Distinguish innate from adaptive immunity with respect to speed of response, specificity and memory. [3 marks]

• Cue. Innate: fast (hours), non-specific, no memory. Adaptive: slower (days), specific, immunological memory.

Q2. A child receives the first dose of an HPV vaccine. (a) Predict the antibody titre profile over 6 weeks. (b) After a second dose 6 months later, predict and explain the new profile. [3 marks]

• Cue. (a) Primary response: slow rise from 0 to peak around 3 weeks, then decline. (b) Secondary response: much faster rise, higher peak, longer-lasting; due to memory B cells.

Q3. Refer to herd immunity. (a) Define herd immunity. (b) Calculate the herd-immunity threshold if R0 = 4. (c) Explain why falling MMR vaccination in certain Victorian suburbs has caused outbreaks. [2+2+2 marks]

• Cue. (a) Indirect protection of unvaccinated when most of population is immune. (b) Threshold = 1 - 1/R0 = 1 - 0.25 = 75 percent. (c) Below threshold, chains of transmission can sustain; clustering of unvaccinated children amplifies local spread.