Investigate the innate and adaptive immune systems in mammals, including the response of animal innate immunity to infection (first and second lines of defence, including the inflammatory response)

What this dot point is asking

NESA wants you to describe the two innate (non-specific) lines of defence in mammals, name the cells and chemicals involved, and explain the inflammatory response in detail. Innate immunity is examined every year in either multiple choice or short response.

The answer

The mammalian immune system has three layers. The first and second lines of defence are innate (non-specific), responding identically to any pathogen. The third line is adaptive (specific) and is covered in the next dot point. The diagram below traces what happens when a pathogen breaches each layer.

First line of defence: barriers

The first line prevents pathogens from entering the body. It is always active and requires no recognition.

Physical barriers.

• Skin. A multilayered keratinised epidermis is the largest barrier. Continuous shedding of skin cells removes attached pathogens.
• Mucous membranes line the respiratory, digestive, urogenital and conjunctival tracts. Mucus traps pathogens; ciliated epithelium sweeps them out.
• Hair, nasal turbinates and eyelashes filter incoming air and debris.

Chemical barriers.

• Stomach acid (pH around 2) kills most ingested pathogens.
• Lysozyme in tears, saliva and sweat digests bacterial cell walls.
• Sebum on skin lowers pH and contains antimicrobial fatty acids.
• Antimicrobial peptides (defensins) puncture pathogen membranes.

Biological barriers.

• The normal microbiota on skin and in the gut outcompetes invading pathogens for nutrients and attachment sites.

Second line of defence: innate cellular response

If a pathogen breaches the first line, the second line activates within minutes to hours. It is still non-specific but now involves cells and signalling molecules.

Phagocytic cells.

• Neutrophils are the first responders. They migrate to the site within minutes and engulf pathogens.
• Macrophages arrive later and have higher capacity. They also present pathogen fragments to T cells, bridging to the adaptive response.
• Dendritic cells in tissue engulf pathogens and travel to lymph nodes to activate T cells.

Natural killer (NK) cells. Lymphocytes that recognise virus-infected and cancerous cells by their reduced MHC class I expression. They release perforin (forms pores in membranes) and granzymes (induce apoptosis).

Complement system. A cascade of around 30 plasma proteins that:

• Mark pathogens for phagocytosis (opsonisation).
• Recruit phagocytes (chemotaxis).
• Form a membrane attack complex (MAC) that lyses pathogen membranes.

Interferons. Cytokines released by virus-infected cells that signal neighbouring cells to enter an antiviral state, slowing viral spread.

The inflammatory response

Inflammation is the most visible part of the innate response. It has four cardinal signs: heat, redness, swelling and pain.

Steps.

1. Tissue damage. Pathogens or wounding trigger damaged cells and mast cells to release histamine, prostaglandins and bradykinin.
2. Vasodilation. Local blood vessels widen, increasing blood flow (heat, redness).
3. Increased capillary permeability. Plasma proteins and fluid leak into tissue, causing swelling (oedema).
4. Chemotaxis. Cytokines attract neutrophils, then macrophages, to the site of damage.
5. Phagocytosis. Pathogens are engulfed and destroyed.
6. Resolution. Macrophages clear debris. Tissue repair begins.

If infection becomes systemic, cytokines (especially IL-1) act on the hypothalamus to raise the body's setpoint, producing fever. Mild fever enhances immune cell activity and slows pathogen growth.

Examples in context

Example 1. Splinter wound and the inflammatory response. A child running barefoot on a Coogee beach gets a splinter in the heel. Within minutes, mast cells in the surrounding dermis release histamine, dilating local blood vessels (vasodilation) and increasing capillary permeability. Blood plasma leaks into the tissue, producing the four classical signs of inflammation: heat (calor), redness (rubor), swelling (tumor) and pain (dolor). Neutrophils squeeze out of capillaries by diapedesis within 1 to 2 hours, attracted by chemokines released from damaged cells. They phagocytose bacteria from the splinter, with the resulting pus being a mixture of dead neutrophils, bacteria and tissue debris. The whole response is innate and operates identically every time, regardless of which bacterium is present.

Example 2. Mucociliary escalator in a Sydney commuter with a viral cold. Each breath drawn on a crowded Town Hall train platform carries roughly 10000 microbes into the airways. The respiratory epithelium's first line of defence is the mucociliary escalator: goblet cells secrete sticky mucus that traps inhaled particles, and ciliated epithelial cells beat in coordinated waves to sweep the mucus upward at roughly 1 cm per minute toward the pharynx, where it is swallowed and destroyed by stomach acid. Lysozyme in mucus also chemically degrades bacterial cell walls. Smoking paralyses cilia, which is why smokers cough more (manually clearing what cilia normally clear) and are more prone to respiratory infections like bronchitis.

Try this

Q1. Identify three components of the first line of defence in humans and state the function of each. [3 marks]

• Cue. Skin (physical barrier), mucous membranes (trap pathogens), stomach acid (chemical kill), lysozyme in tears/saliva (enzymatic kill), commensal microbiota (competitive exclusion).

Q2. A graph shows neutrophil count at a wound site rising from 100 cells per mm cubed at time 0 to 2500 at 6 hours, then declining to 800 by 24 hours. Describe the response over time and explain why neutrophil numbers decline after the peak. [3 marks]

• Cue. Rapid recruitment during inflammation, then apoptosis after phagocytosis and clearance by macrophages.

Q3. Compare innate and adaptive immunity. (a) State two features that distinguish them. (b) Describe one example of how innate immunity initiates an adaptive response. (c) Justify why a person with a defective innate response is more susceptible to a wider range of infections than one with a defective adaptive response. [2+2+2 marks]

• Cue. (a) Speed (minutes vs days), specificity, memory. (b) Dendritic cells phagocytose pathogen and present antigen to T cells. (c) Innate is the first barrier against all pathogens; without it nothing gets stopped early.