Cell Recognition and the Immune Response

The ability of cells to recognise 'self' and 'non-self' is fundamental to the immune system and to several important medical applications, including blood transfusions, organ transplants, and autoimmune diseases. This lesson covers the molecular basis of cell recognition, the role of antigens and MHC markers, blood group systems, and the context of transplant rejection. This material supports AQA specification section 3.2.4 and connects to the broader topic of immunity.

Key Definition: An antigen is any molecule (usually a protein or glycoprotein) that is recognised by the immune system and can trigger an immune response. Self-antigens are molecules on the surface of an organism's own cells that are recognised as 'self'; non-self antigens (foreign antigens) are those from other organisms or substances.

---

Self vs Non-Self Recognition

Every nucleated cell in the body displays self-antigens on its surface. The immune system must distinguish between self-antigens (which should not trigger an immune response) and foreign antigens (which should trigger an immune response).

Major Histocompatibility Complex (MHC) Markers

The key self-antigens are MHC molecules (in humans, these are called HLA — human leucocyte antigens):

• MHC class I molecules are found on the surface of virtually all nucleated cells in the body. They display fragments of intracellular proteins (peptides) on the cell surface.

  • If a cell is healthy, MHC I displays normal self-peptides — and the immune system ignores it.
  • If a cell is infected by a virus or has become cancerous, MHC I displays abnormal peptides (e.g., viral proteins or mutant proteins) — and cytotoxic T lymphocytes (CD8⁺ T cells) recognise and destroy the cell.

• MHC class II molecules are found only on antigen-presenting cells (APCs) — including macrophages, dendritic cells, and B lymphocytes. They display fragments of ingested foreign antigens.

  • After phagocytosis, the pathogen is digested, and its peptide fragments are loaded onto MHC II molecules and presented on the cell surface.
  • Helper T lymphocytes (CD4⁺ T cells) recognise the antigen–MHC II complex and become activated, triggering the adaptive immune response.

Immune Tolerance

During development, the immune system undergoes a process of self-tolerance:

• In the thymus, developing T cells are tested against self-antigens. T cells that react strongly to self-antigens are eliminated (clonal deletion) or rendered non-functional (central tolerance).
• B cells undergo a similar selection process in the bone marrow.
• This ensures that, under normal circumstances, the immune system does not attack the body's own tissues.

Key Definition: Autoimmune disease occurs when the immune system fails to distinguish self from non-self and mounts an immune response against the body's own tissues. Examples include type 1 diabetes (immune destruction of pancreatic β-cells), rheumatoid arthritis (attack on joint tissues), and multiple sclerosis (attack on the myelin sheath of neurones).

---

Blood Group Antigens

Blood groups are determined by the presence of specific glycolipid antigens (also called agglutinogens) on the surface of red blood cells. The ABO blood group system is the most important for transfusion compatibility.

The ABO System

Blood Group	Antigens on Red Blood Cells	Antibodies in Plasma
A	A antigen	Anti-B antibodies
B	B antigen	Anti-A antibodies
AB	A and B antigens	Neither anti-A nor anti-B
O	Neither A nor B antigens	Anti-A and anti-B antibodies

• The antigens are glycoproteins/glycolipids on the red blood cell surface — they differ in the specific sugar residues attached to the lipid.
• The antibodies are present naturally in the plasma (they are not produced in response to exposure, unlike most antibodies — they are believed to arise from exposure to similar antigens on gut bacteria in early life).

Transfusion Compatibility

If a patient receives blood with antigens that their antibodies recognise, agglutination (clumping) occurs:

• The antibodies bind to the foreign antigens on the transfused red blood cells, causing them to clump together.
• Agglutinated red blood cells can block small blood vessels, and the clumped cells are destroyed (haemolysis), releasing haemoglobin that can damage the kidneys.
• This transfusion reaction can be fatal.

Compatibility rules:

• Group O is the universal donor — O red blood cells have no A or B antigens, so they will not be agglutinated by the recipient's anti-A or anti-B antibodies.
• Group AB is the universal recipient — AB plasma has no anti-A or anti-B antibodies, so it will not agglutinate any donor red blood cells.
• In practice, matching the exact blood group is always preferred.

The Rhesus System