HSC Exam Practice

Sample response. Innate immunity is a fast, non-specific immune defence that is present from birth. It detects broad molecular patterns shared by many pathogens (PAMPs) using pattern recognition receptors (PRRs) and responds within minutes to hours, without requiring prior exposure to the pathogen.

Marking notes. 1 mark for fast/non-specific/present from birth (any two of these); 1 mark for the detection mechanism (PRRs detecting PAMPs, or equivalent: "recognises broad patterns on pathogens").

Sample response. The five steps of phagocytosis are: 1. Chemotaxis — phagocyte moves along chemokine gradient toward the pathogen. 2. Adherence — PRRs on phagocyte bind PAMPs on pathogen surface. 3. Ingestion — pseudopods extend and engulf the pathogen, forming a phagosome. 4. Digestion — lysosome fuses with phagosome to form a phagolysosome; enzymes destroy the pathogen. 5. Antigen presentation — fragments displayed on MHC II to activate T cells.

Marking notes. 1 mark for correct identification of all five steps by name in order; 1 mark for the correct key event at steps 3 (phagosome) and 4 (lysosome/phagolysosome); 1 mark for step 5 correctly linking to MHC II and T cell activation.

Sample response. Neutrophils target pathogens directly — primarily bacteria and fungi that are present in the extracellular space or tissue. They identify pathogens by binding PAMPs on the pathogen surface using PRRs, then destroy them via phagocytosis. NK cells target infected or abnormal host cells — cells that have reduced or absent MHC class I molecules (the "missing self" signal), which occurs when cells are virus-infected or cancerous. NK cells do not engulf the pathogen; they kill the host cell that the pathogen is hiding inside, using perforin and granzymes.

Marking notes. 1 mark for neutrophil target (pathogens/bacteria/extracellular); 1 mark for NK cell target (infected/abnormal host cells with reduced MHC I); 1 mark for explicit comparison (neutrophils target the pathogen itself; NK cells target the infected cell that harbours the pathogen).

Sample response. Opsonisation is the process of coating a pathogen's surface with complement proteins or antibodies. Phagocytes possess specific receptors (opsonin receptors) that recognise and bind to these coating molecules with much greater affinity than they can bind to PAMPs on uncoated pathogens. This dramatically accelerates and strengthens the adherence step (step 2) of phagocytosis, reducing the time needed for a phagocyte to bind and engulf the pathogen, and increasing the probability of successful engulfment even when pathogen concentrations are low.

Marking notes. 1 mark for correct definition of opsonisation (coating with complement/antibodies); 1 mark for mechanism (phagocyte has receptors that bind to the coating molecules, not to the pathogen directly); 1 mark for functional consequence (faster/more effective adherence/engulfment).

Sample response. Dendritic cells are innate sentinel cells that patrol tissues. When they encounter and engulf a pathogen, they process it and display antigen fragments on MHC class II molecules on their cell surface. The dendritic cell then migrates from the tissue to the nearest lymph node, where it presents these MHC II-antigen complexes to naive T helper cells. This antigen presentation activates the T helper cells, initiating clonal expansion and the full adaptive immune response. Dendritic cells thus bridge the innate and adaptive systems — they sense the infection first (innate function) and then deliver the antigenic information required to launch a targeted adaptive response.

Marking notes. 1 mark for dendritic cells being innate and engulfing/processing antigen; 1 mark for migration to lymph nodes and MHC II presentation to T cells; 1 mark for the bridging function — explicitly stating that dendritic cells connect innate detection to adaptive activation.

Sample response. All healthy nucleated host cells display MHC class I molecules on their surface — a molecular signal that tells NK cells "I am a normal body cell." NK cells continuously patrol body tissues, constantly checking the MHC I status of surrounding cells. When a cell is infected by a virus, or becomes cancerous, viral proteins or tumour-suppressor loss often cause MHC class I expression to be reduced or eliminated from the cell surface. NK cells detect this "missing self" signal — the absence of normal MHC I — via inhibitory receptors that are usually engaged by MHC I on healthy cells. When no MHC I is present to engage these inhibitory receptors, the NK cell receives no inhibitory signal and activates. It then releases perforin (a pore-forming protein that punches holes in the target cell's plasma membrane) and granzymes (serine proteases that enter through the pores and trigger apoptosis inside the target cell), killing it and destroying the virus's intracellular replication site.

Marking notes. 1 mark for MHC class I as the normal "healthy self" signal on host cells; 1 mark for virus-infected or cancerous cells losing/reducing MHC I expression; 1 mark for NK cell detecting the absence of MHC I via inhibitory receptors (missing self strategy); 1 mark for the killing mechanism naming perforin AND granzymes with their respective functions (pore formation / apoptosis induction).

Sample response (a). There is a positive, dose-dependent relationship between IFN-α concentration and NK cell cytotoxic activity. At 0 U/mL (no interferon), NK cells kill approximately 12% of target cells — a low baseline. As IFN-α concentration increases logarithmically from 10 to 10 000 U/mL, NK cell killing rises in a sigmoidal pattern, from approximately 15% at 10 U/mL to approximately 89% at 10 000 U/mL. The largest increase occurs between 100 and 1000 U/mL, where activity rises from approximately 35% to 85%.

Marking notes (a). 1 mark for identifying the positive relationship (more IFN-α → more NK cell killing); 1 mark for describing the shape (sigmoidal/dose-dependent) and using at least one specific value from the graph.

Sample response (b). Interferons are soluble proteins released by virus-infected cells. They diffuse to neighbouring cells and NK cells, signalling that a viral infection is occurring in the tissue. NK cells have surface receptors for interferon, and binding of IFN-α activates signalling pathways that upregulate the expression of perforin and granzymes inside the NK cell — increasing its ability to kill target cells. This interaction is biologically significant because it allows the innate immune system to co-ordinate a rapid, area-wide antiviral response: the first few virus-infected cells produce interferons that activate large numbers of NK cells before the adaptive immune system is operational. This can limit viral replication and slow spread within the first hours to days of infection — before any T cells are activated or antibodies produced.

Marking notes (b). 1 mark for correctly identifying interferons as released by virus-infected cells and their role as signalling molecules; 1 mark for the mechanism (IFN binds NK cell receptors → upregulates killing machinery, e.g. perforin/granzymes); 1 mark for biological significance (rapid area-wide antiviral co-ordination before adaptive system activates; limits viral spread).

Sample response (c). Without interferon production, this patient's NK cell activity would remain at the low baseline level (~12% cytotoxic activity) regardless of viral infection, because interferons are required to activate NK cells to full killing capacity. Consequence 1: virus-infected cells throughout the body would not be killed at normal rates, allowing viral replication to continue unchecked inside host cells. Consequence 2: neighbouring uninfected cells would not receive the interferon "warning" signal and would not upregulate their own antiviral defences (e.g. producing antiviral proteins), leaving them more susceptible to infection. The patient would likely experience a more severe and prolonged infection, relying almost entirely on the eventual adaptive immune response for viral clearance.

Marking notes (c). 1 mark for correctly predicting reduced NK cell activity (remaining at baseline); 1 mark for consequence 1 (infected cells not killed / viral replication unchecked); 1 mark for consequence 2 (neighbouring cells not warned / antiviral defences not upregulated; or adaptive system overburdened; or more severe infection).

Sample response. The innate immune system performs two distinct but interdependent roles in immunity: it contains infections independently, and it activates and shapes the adaptive immune response. Both roles operate simultaneously from the moment of infection.

Independent containment begins within seconds of a pathogen entering tissue. Mast cells detect bacterial PAMPs via pattern recognition receptors (PRRs) and degranulate, releasing histamine that produces vasodilation and increases capillary permeability — delivering circulating immune molecules to the site. Complement proteins in the leaked plasma activate on contact with pathogen surfaces, coating the bacteria (opsonisation) and releasing chemokines. Neutrophils — the most abundant white blood cells and the innate system's primary first responders — detect the chemokine gradient and undergo diapedesis from capillaries, following it to the infection site. There, they engulf bacteria via phagocytosis: pseudopods extend and close around the bacterium (forming a phagosome), a lysosome fuses to form a phagolysosome, and digestive enzymes destroy the pathogen. For intracellular pathogens — viruses hiding inside host cells — natural killer (NK) cells patrol for the "missing self" signal: reduced MHC class I expression that virus-infected cells display. NK cells release perforin and granzymes to kill the infected host cell, destroying the viral replication site. Interferons released by infected cells further amplify NK cell killing and inhibit viral replication in neighbouring cells. Together, these mechanisms eliminate the majority of bacterial and viral infections before any adaptive response is required.

Simultaneously, the innate system initiates and shapes the adaptive response. Macrophages and dendritic cells engulf pathogens, process their proteins into antigen fragments, and display these fragments on MHC class II molecules. Dendritic cells specifically migrate from the tissue to lymph nodes, presenting MHC II–antigen complexes to naive T helper cells and initiating clonal expansion. The cytokine environment produced by innate cells (particularly IL-12, IL-6, TNF-alpha released by macrophages) determines the character of the adaptive response — whether it will be antibody-dominated, cytotoxic T-cell dominated, or both. Without this innate-mediated antigen presentation and cytokine signal, adaptive immunity cannot be activated effectively. The innate system is therefore not merely a stopgap but an essential architect of adaptive immunity.

Marking criteria.

1 mark — Identifies and names at least two innate cells involved in direct containment of infection (e.g. neutrophils, macrophages, NK cells, mast cells) with a specific function for each.

1 mark — Accurately describes the phagocytosis mechanism with at least three named steps (e.g. chemotaxis, adherence/PRR-PAMP binding, ingestion/phagosome formation, lysosome fusion/digestion).

1 mark — Accurately describes NK cell function, naming MHC class I as the signal checked, and perforin and/or granzymes as the killing mechanism.

1 mark — Names at least one soluble innate component (complement, interferons, or cytokines/chemokines) and correctly describes its role in containment or recruitment.

1 mark — Accurately describes the bridge between innate and adaptive systems — identifies dendritic cells (or macrophages) as antigen-presenting cells and describes MHC II presentation to T cells in lymph nodes.

1 mark — Explains how the innate cytokine environment shapes the character of the adaptive response (or how innate signals are required to activate adaptive immunity — without innate activation, adaptive immunity cannot function).

1 mark — Response reaches an integrative conclusion that the innate system performs both roles simultaneously and is not merely a stopgap — it is essential for both direct clearance and adaptive activation. Response uses precise lesson terminology throughout and maintains logical structure.