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.

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.

Worked example

A patient receives a cut on the hand. Within an hour, the area is red, warm, swollen and painful.

Explanation. Damaged cells and mast cells released histamine, causing vasodilation (redness, heat) and increased capillary permeability (swelling). Pain came from stretched tissue and prostaglandin sensitisation of pain receptors. Neutrophils migrated to the wound by chemotaxis and phagocytosed any bacteria entering through the cut. The inflammatory response is non-specific, meaning the response is the same regardless of pathogen type.

Common traps

Confusing innate with adaptive. Innate is fast (minutes to hours), non-specific, and lacks memory. Adaptive is slow (days), specific to one antigen, and produces memory cells.

Forgetting the inflammatory mediators. Markers expect histamine (the main vasodilator), prostaglandins (pain), and cytokines (signalling).

Mixing up NK cells and cytotoxic T cells. NK cells are innate, recognising reduced MHC. Cytotoxic T cells are adaptive, recognising specific antigens on MHC class I.

Saying inflammation is bad. It is protective when controlled. Chronic or systemic inflammation (sepsis) is harmful, but acute inflammation is the immune system working correctly.

In one sentence

The innate immune response uses physical, chemical and biological barriers as the first line of defence, then deploys phagocytes, natural killer cells, complement proteins and the inflammatory response as the second line, producing a fast non-specific reaction that buys time for the adaptive response to develop.