pastpaperbd/ Biology/ Notes/ Cell Recognition and the Immune System
T2

Cell Recognition and the Immune System

AQA spec ref: 3.2.4 - Cell recognition and the immune system

The immune system is the body's defence against pathogens (bacteria, viruses, fungi, parasites) and against abnormal cells such as cancer cells. It relies on the ability of immune cells to distinguish between self (your own cells) and non-self (foreign material). This recognition is based on surface molecules - glycoproteins and glycolipids on the plasma membrane - that act as molecular identity cards.

Antigens

An antigen is any molecule (usually a glycoprotein or polysaccharide on a cell surface) that can be recognised by the immune system and, if foreign, trigger an immune response. Antigens are found on:

  • The surface of pathogens (bacterial cell wall proteins, viral coat proteins)
  • Transplanted cells
  • Cancer cells (abnormal surface proteins)
  • Pollen, food molecules (in allergic responses)

Self-antigens are the surface molecules on your own cells. During development, the immune system learns to recognise these as self and does not attack them. This is called self-tolerance and is established in the thymus (for T cells) and bone marrow (for B cells). Failure of self-tolerance leads to autoimmune disease, where the immune system attacks the body's own tissues.

Non-Specific Defence

Before the specific immune response kicks in, the body relies on non-specific defences that act against any pathogen:

  • Physical barriers: skin, mucus in the respiratory tract, ciliated epithelium (cilia sweep mucus and trapped pathogens away from lungs), stomach acid
  • Inflammation: damaged or infected cells release histamine and cytokines, causing vasodilation and increased capillary permeability. This brings more phagocytes to the infected area and raises local temperature (inhibits pathogen growth).
  • Phagocytosis - the first cellular response (see below)

Phagocytosis

Phagocytes (neutrophils and macrophages) are white blood cells that engulf and destroy pathogens. The process:

  1. Phagocytes are attracted to the site of infection by chemotaxis - they follow chemical gradients of cytokines and complement proteins released by damaged cells and pathogens.
  2. The phagocyte detects the pathogen's antigens via surface receptors and engulfs it by endocytosis, forming a phagosome (a membrane-bound vesicle containing the pathogen).
  3. Lysosomes fuse with the phagosome to form a phagolysosome, releasing hydrolytic enzymes (lysozymes, proteases) that digest the pathogen.
  4. The digested material is egested, and fragments of the pathogen (antigens) may be displayed on the phagocyte's surface on MHC class II proteins - this makes the phagocyte an antigen-presenting cell (APC).

Macrophages are particularly important APCs - they present pathogen antigens to T helper cells to activate the adaptive immune response.

Specific Immune Response: Overview

The specific immune response is slower but more targeted than non-specific defences. It has two branches, both involving lymphocytes (B cells and T cells):

  • Humoral immunity - B cells produce antibodies against free antigens (e.g. bacteria, toxins in the blood and tissue fluid)
  • Cell-mediated immunity - T cells respond to cells presenting foreign antigens (infected cells, cancer cells, transplanted cells)

Both branches require clonal selection - the specific lymphocyte with the right receptor for the antigen is selected and proliferates.

T Lymphocytes and Cell-Mediated Immunity

T lymphocytes are produced in bone marrow but mature in the thymus (the T stands for thymus). Each T cell has a unique T cell receptor on its surface that recognises one specific antigen-MHC complex.

Activation of T cells:

  1. An APC (e.g. macrophage) presents a fragment of a pathogen antigen on its MHC class II protein.
  2. The T cell whose receptor fits that specific antigen-MHC complex binds to the APC.
  3. T helper cells (TH cells / CD4⁺ cells) are activated. They:
  • Release cytokines that stimulate both the humoral and cell-mediated immune responses
  • Stimulate B cells to divide and differentiate
  • Stimulate cytotoxic T cells to proliferate
  1. Cytotoxic T cells (TC cells / CD8⁺ cells) are activated (also by APC presentation). They:
  • Divide by clonal expansion
  • Recognise and kill infected cells, cancer cells, and transplanted cells displaying foreign antigen on MHC class I proteins
  • Kill by releasing perforins (proteins that form pores in the target cell membrane) and granzymes (enzymes that induce apoptosis)
  1. Regulatory T cells suppress the immune response once the infection is cleared, preventing excessive immune activity.
  2. Memory T cells persist long-term and allow a faster response if the same antigen is encountered again.

B Lymphocytes and Humoral Immunity

B lymphocytes are produced and mature in bone marrow. Each B cell has unique B cell receptors (membrane-bound antibodies) that recognise one specific antigen.

Activation of B cells (clonal selection):

  1. An antigen binds to a B cell with the complementary receptor. This alone gives a weak signal.
  2. A T helper cell (already activated by APCs) releases cytokines that provide the co-stimulatory signal for full B cell activation.
  3. The activated B cell divides rapidly by mitosis - clonal expansion produces a large clone of identical B cells.
  4. The clone differentiates into:
  • Plasma cells - effector cells that secrete large quantities of antibodies (thousands per second per cell). Plasma cells are short-lived.
  • Memory B cells - long-lived cells that persist after the infection is cleared. They carry the same receptor as the original B cell.

Antibodies

Antibodies (immunoglobulins) are glycoproteins produced by plasma cells. All antibodies have the same basic Y-shaped structure:

  • Two heavy chains and two light chains, joined by disulfide bonds
  • Constant region - same in all antibodies of the same class; determines the antibody's effector function
  • Variable region - different in every antibody; forms the antigen-binding site at the tips of the Y. The shape is complementary to one specific antigen.

Each antibody has two identical antigen-binding sites, so it is bivalent - it can bind two antigen molecules simultaneously.

How antibodies work:

  • Agglutination - antibodies bind to multiple antigen-bearing pathogens, clumping them together. This prevents the pathogen from binding to host cells and makes it easier for phagocytes to engulf many at once.
  • Opsonisation - antibody coating marks pathogens for phagocytosis (phagocytes have receptors for antibody constant regions).
  • Neutralisation - antibodies block active sites on toxins or viral surface proteins, preventing them from binding to host cells.
  • Complement activation - antibody-antigen complexes activate the complement system, a cascade of proteins that punch holes in bacterial membranes and attract phagocytes.

The Primary and Secondary Immune Response

The primary response occurs on first exposure to a pathogen:

  • Takes 7 - 14 days to produce antibodies
  • Relatively low peak antibody concentration
  • The person usually becomes ill before immunity is established

The secondary response occurs on re-exposure to the same antigen:

  • Memory cells (B and T) divide rapidly - clonal expansion is much faster
  • Much faster (1 - 3 days) and produces a much higher peak antibody concentration
  • The response overwhelms the pathogen before symptoms develop - the person is immune

This immunological memory is the basis of vaccination.

Vaccination

A vaccine contains antigens (but not the live, virulent pathogen) in a form that stimulates an immune response without causing disease. The antigens trigger clonal selection and the formation of memory cells. On subsequent exposure to the real pathogen, the secondary response is rapid enough to prevent illness.

Vaccine forms: attenuated (weakened) live pathogen, killed pathogen, isolated antigens, toxoids, or mRNA vaccines (which cause cells to produce the antigen themselves).

Herd immunity: if a large proportion of a population is immune, transmission chains are broken and even unvaccinated individuals are protected. The proportion needed depends on the infectivity of the pathogen (R₀ value) - for measles (very infectious), ~95% coverage is needed.

Monoclonal Antibodies

Monoclonal antibodies are identical antibodies produced by a single clone of cells, all targeting the same antigen. They are produced by:

  1. Immunising a mouse with the target antigen→mouse produces specific B cells
  2. Fusing the specific B cells with myeloma cells (cancerous, immortal B cells)→hybridoma cells
  3. Hybridoma cells can both produce antibodies (like the B cell) and divide indefinitely (like the myeloma cell)
  4. Individual hybridoma cells are selected and grown in culture→monoclonal antibodies produced

Uses:

  • Diagnosis: pregnancy tests (detect hCG), ELISA assays for infectious disease diagnosis, flow cytometry
  • Cancer treatment: attached to drug molecules (immunotoxins), targeted to tumour-specific antigens - the antibody delivers the drug specifically to cancer cells
  • HIV testing and treatment
  • Research: used to locate and visualise specific proteins in cells

HIV and the Immune System

HIV (Human Immunodeficiency Virus) attacks T helper cells (CD4⁺ T cells) - the central coordinators of both humoral and cell-mediated immunity. HIV uses the CD4 protein on T helper cells as a receptor to enter the cell. Once inside, it uses reverse transcriptase to produce DNA from its RNA genome, which is then integrated into the host cell's DNA. Over time, T helper cell numbers decline. Without T helper cells, B cells and cytotoxic T cells cannot be properly activated. The immune system becomes severely compromised, leading to AIDS (acquired immune deficiency syndrome) - the patient becomes vulnerable to opportunistic infections that a healthy immune system would control easily.

HIV is a retrovirus because it uses reverse transcriptase to produce DNA from RNA.

Summary

  • Antigens - surface molecules recognised as self/non-self; foreign antigens trigger immune response
  • Phagocytosis - neutrophils/macrophages engulf and digest pathogens; macrophages present antigens via MHC II
  • T cells - mature in thymus; activated by APC-presented antigen. TH cells release cytokines; TC cells kill infected/abnormal cells via perforin/apoptosis; memory T cells persist
  • B cells - activated by antigen + TH cytokines; clone → plasma cells (antibodies) + memory B cells
  • Antibodies - Y-shaped, variable region = antigen-binding site (specific); mechanisms: agglutination, opsonisation, neutralisation
  • Primary response - slow, low; secondary response - fast, high (due to memory cells)
  • Vaccination - stimulates primary response and memory cell production
  • Monoclonal antibodies - from hybridoma cells; used in diagnosis and cancer therapy
  • HIV - destroys T helper cells→immunosuppression

AQA Exam Tips

  • Antigen definition: "a molecule (usually a protein/glycoprotein) on the surface of a cell that is recognised by the immune system." Do not say "foreign substance" - antigens include self-antigens.
  • Antibody structure: always state: two heavy + two light chains, constant region, variable region, antigen-binding site complementary to specific antigen.
  • T helper vs cytotoxic T cells: TH cells release cytokines to activate both B and TC cells. TC cells kill infected host cells (not pathogens directly). AQA distinguishes these carefully.
  • Clonal selection and expansion: the specific lymphocyte is selected by antigen binding → that cell divides (mitosis) to produce many identical clones. This is a two-step process AQA often tests.
  • Secondary response: faster and higher antibody concentration because memory cells are present at higher numbers, respond more quickly, and differentiate into plasma cells faster. State all three aspects.
  • Monoclonal antibody production: immunise mouse → isolate B cells → fuse with myeloma → hybridoma → select and clone. Know every step.
  • HIV: targets CD4⁺ T helper cells. Consequence: humoral and cell-mediated immunity both compromised (because TH cells are needed to activate both B and TC cells).
  • Vaccination vs artificial/natural immunity: natural active = having the disease; artificial active = vaccination; passive = receiving antibodies (e.g. mother to foetus via placenta, or injection). Active immunity involves memory cells; passive does not (so it doesn't last).