The Immune System

The immune system is the body's defence against infectious disease caused by pathogens — organisms or agents that cause disease, including bacteria, viruses, fungi, and protoctists. Understanding how the body recognises and destroys pathogens, the distinction between non-specific and specific immunity, and the principles of vaccination and immunological therapies is essential for A-Level Biology.

Key Definition: A pathogen is an organism or agent that causes disease. Pathogens include bacteria, viruses, fungi, and protoctists. They cause disease by damaging host cells and tissues, and/or by producing toxins.

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Non-Specific Defences (Innate Immunity)

Non-specific defences are the body's first and second lines of defence. They act against all pathogens, regardless of type, and do not require prior exposure. They respond rapidly but do not confer lasting immunity.

First Line of Defence — Physical and Chemical Barriers

Barrier	How It Prevents Infection
Skin	A continuous physical barrier; the outer layer (epidermis) consists of dead, keratinised cells that pathogens cannot penetrate easily. Sebaceous glands secrete sebum, which contains fatty acids that inhibit bacterial growth. The skin also has a slightly acidic pH (~5.5), which discourages colonisation by many microorganisms.
Mucous membranes	Line the respiratory, digestive, and urogenital tracts. Goblet cells secrete sticky mucus that traps pathogens and particles. Ciliated epithelium in the airways sweeps the mucus (and trapped pathogens) upwards towards the throat, where it is swallowed and destroyed by stomach acid (the mucociliary escalator).
Stomach acid (HCl)	The highly acidic environment of the stomach (pH ~2) denatures the proteins and enzymes of most ingested pathogens, killing them.
Lysozyme	An enzyme found in tears, nasal secretions, and saliva that breaks down peptidoglycan in bacterial cell walls, causing bacterial lysis.
Commensal (normal) flora	Beneficial bacteria that colonise the skin and gut outcompete potential pathogens for nutrients and space, and some produce antimicrobial substances.

Second Line of Defence — Non-Specific Internal Responses

If pathogens breach the first line of defence, non-specific internal mechanisms are activated.

Phagocytosis

Key Definition: Phagocytosis is the process by which specialised white blood cells (phagocytes) engulf and destroy pathogens and cellular debris.

The main phagocytes are neutrophils (the most abundant white blood cells, short-lived, first to arrive at an infection site) and macrophages (larger, longer-lived, derived from monocytes, also function as antigen-presenting cells).

A described diagram of phagocytosis would show the following steps:

1. The phagocyte is attracted to the pathogen by chemicals released from damaged cells and by pathogen surface molecules — this is chemotaxis.
2. The phagocyte recognises the pathogen. This recognition can be direct (phagocyte receptors bind to pathogen-associated molecular patterns, PAMPs, on the pathogen surface) or indirect (the pathogen is coated with opsonins such as antibodies or complement proteins, which enhance phagocytosis — a process called opsonisation).
3. The phagocyte extends pseudopodia (extensions of the cell membrane and cytoplasm) around the pathogen, engulfing it into a membrane-bound vesicle called a phagosome.
4. Lysosomes within the phagocyte fuse with the phagosome, forming a phagolysosome. The lysosomes release hydrolytic enzymes (lysozyme, proteases) and reactive oxygen species that digest and destroy the pathogen.
5. The products of digestion are absorbed by the phagocyte. Indigestible material is expelled by exocytosis.
6. In the case of macrophages, antigens (fragments of the pathogen's proteins) are displayed on the surface of the macrophage, bound to MHC class II proteins (major histocompatibility complex). The macrophage now functions as an antigen-presenting cell (APC), which is essential for activating the specific (adaptive) immune response.

flowchart TD
    A["Pathogen enters body"] --> B["Chemotaxis:
Phagocyte attracted to pathogen"]
    B --> C["Recognition:
Receptors bind to PAMPs
or opsonins on pathogen"]
    C --> D["Engulfment:
Pseudopodia surround pathogen
→ Phagosome formed"]
    D --> E["Lysosome fuses with phagosome
→ Phagolysosome"]
    E --> F["Hydrolytic enzymes +
reactive O₂ species
digest pathogen"]
    F --> G["Macrophage displays antigens
on MHC II → becomes APC"]
    G --> H["Activates adaptive
immune response"]

Exam Tip: When describing phagocytosis, always include the following key terms: chemotaxis, engulfment, phagosome, lysosome fusion (phagolysosome), digestion, and (for macrophages) antigen presentation. Many students forget antigen presentation, which is crucial for linking innate to adaptive immunity.

The Inflammatory Response

When tissue is damaged or infected, an inflammatory response is triggered:

1. Damaged cells and mast cells release histamine, which causes local vasodilation (arterioles widen, increasing blood flow to the area — causing redness and heat) and increased capillary permeability (gaps between endothelial cells widen, allowing plasma proteins and phagocytes to move from the blood into the tissues).
2. Neutrophils and macrophages are attracted to the site by chemotaxis and begin phagocytosis.
3. Swelling (oedema) occurs as fluid accumulates in the tissue. Pain results from the pressure on nerve endings and from chemical mediators.

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Specific Immune Response (Adaptive Immunity)

The specific immune response is the third line of defence. It is slower to develop (taking several days on first exposure) but is highly specific to a particular pathogen and confers immunological memory for faster responses upon re-exposure.

Key Definition: An antigen is a molecule (usually a protein or glycoprotein) that is recognised by the immune system and triggers an immune response. Antigens on the surface of pathogens are recognised as non-self (foreign), while the body's own molecules are recognised as self.

T Cells (Cell-Mediated Immunity)

T cells (T lymphocytes) mature in the thymus gland and are responsible for the cell-mediated immune response. T cells have specific T cell receptors (TCRs) on their surface that recognise antigens presented on MHC molecules by antigen-presenting cells (APCs).

Type of T Cell	Function
Helper T cells (Tₕ / CD4⁺)	Recognise antigens presented on MHC class II by APCs. They release cytokines (chemical signalling molecules) that: (1) stimulate B cells to divide and differentiate into plasma cells; (2) stimulate cytotoxic T cells to become active; (3) stimulate macrophages to increase phagocytosis; (4) promote the inflammatory response. Helper T cells are the central coordinators of the adaptive immune response.
Cytotoxic (killer) T cells (Tc / CD8⁺)	Recognise and destroy body cells that are infected with a pathogen (displaying foreign antigens on their MHC class I molecules), cancerous cells, and cells of transplanted tissue. They kill target cells by releasing perforin (which creates pores in the target cell membrane) and granzymes (which enter through the pores and trigger apoptosis — programmed cell death).
Memory T cells	Long-lived T cells that remain in the body after an infection has been cleared. If the same pathogen is encountered again, memory T cells enable a much faster and stronger secondary immune response.
Regulatory T cells (Treg)	Suppress the immune response after the pathogen has been eliminated, preventing excessive immune activity that could damage the body's own tissues. They help maintain self-tolerance (preventing autoimmune responses).

B Cells (Humoral Immunity)

B cells (B lymphocytes) mature in the bone marrow and are responsible for the humoral immune response (involving antibodies in body fluids — "humours").

1. Each B cell has unique antibody molecules (immunoglobulins) on its surface that act as receptors for a specific antigen.
2. When a B cell encounters its complementary antigen (and receives cytokine signals from a helper T cell), it is activated.
3. The activated B cell undergoes clonal expansion — rapid mitotic division to produce a large population of identical cells.
4. These cells differentiate into:
   • Plasma cells — short-lived cells (~2 weeks) that produce and secrete large quantities of antibodies (up to ~2,000 antibodies per second) into the blood and tissue fluid. These are the effector cells of the humoral response.
   • Memory B cells — long-lived cells that remain in the body for years (or a lifetime). They enable a rapid and enhanced secondary immune response upon re-exposure to the same antigen.

flowchart TD
    Ag["Antigen encountered"] --> BC["B cell with complementary
antibody receptor"]
    TH["Helper T cell
releases cytokines"] --> BC
    BC --> CE["Clonal expansion
(rapid mitotic division)"]
    CE --> PC["Plasma cells
(secrete antibodies
~2,000 per second)"]
    CE --> MC["Memory B cells
(long-lived, enable rapid
secondary response)"]
    PC --> Ab["Antibodies in blood
and tissue fluid"]
    Ab --> Agg["Agglutination"]
    Ab --> Neut["Neutralisation"]
    Ab --> Ops["Opsonisation"]

Antibody Structure

Key Definition: An antibody (immunoglobulin) is a Y-shaped glycoprotein produced by plasma cells. Each antibody is specific to one antigen and functions to neutralise pathogens, mark them for destruction (opsonisation), or activate complement.

A described diagram of an antibody would show a Y-shaped molecule composed of four polypeptide chains: two identical heavy chains (the long arms of the Y) and two identical light chains (shorter, forming the outer part of the upper arms). The chains are held together by disulphide bridges (covalent bonds between cysteine residues).

Each arm of the Y has a variable region at the tip — this is the antigen-binding site, and its shape is complementary to a specific antigen (like a lock and key). Because the antibody has two identical antigen-binding sites, it can bind to two antigen molecules simultaneously — this enables agglutination (clumping together of pathogens, making them easier for phagocytes to engulf).

The stem of the Y is the constant region (also called the Fc region), which is the same for all antibodies of the same class (e.g., IgG, IgM, IgA). The constant region determines the antibody's function — it can bind to phagocyte receptors (opsonisation), activate the complement system, or cross the placenta (IgG).

Functions of antibodies:

• Agglutination — antibodies bind to antigens on multiple pathogens, clumping them together and preventing them from entering host cells.
• Neutralisation — antibodies bind to toxins or viral surface proteins, preventing them from binding to host cell receptors.
• Opsonisation — antibodies coat the pathogen, making it easier for phagocytes to recognise and engulf it (the Fc region of the antibody binds to Fc receptors on phagocytes).
• Complement activation — the Fc region of antibodies activates the complement cascade, leading to the formation of a membrane attack complex (MAC) that creates pores in the pathogen's membrane, causing lysis.

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Primary vs Secondary Immune Response

A described graph comparing the primary and secondary immune responses would show antibody concentration (y-axis) plotted against time (x-axis). Two exposure events are marked.