Immune System: Innate & Adaptive Immunity

The immune system defends the body against pathogens — bacteria, viruses, fungi, and parasites — as well as abnormal host cells such as tumour cells. It operates through multiple overlapping layers of defence, broadly divided into innate (non-specific, rapid) and adaptive (specific, slower, with memory) immunity.

The first line of defence consists of physical and chemical barriers that prevent pathogen entry: intact skin (keratinised stratified squamous epithelium provides a tough, dry barrier), mucous membranes (trap particles; mucociliary escalator clears the respiratory tract), stomach acid (pH ~2 destroys most ingested organisms), normal flora (commensals occupy niches and compete with pathogens), and antimicrobial peptides (e.g., defensins in skin and gut epithelium).

The innate immune system is the second line of defence. It is activated within minutes to hours and does not distinguish between individual pathogens — it responds to conserved molecular patterns. Pattern recognition receptors (PRRs) — including Toll-like receptors (TLRs) on macrophages and dendritic cells — recognise pathogen-associated molecular patterns (PAMPs) such as bacterial lipopolysaccharide (LPS) and viral double-stranded RNA. Key innate effector cells include neutrophils (first to arrive at infection sites; engulf and destroy via phagocytosis, reactive oxygen species, and neutrophil extracellular traps), macrophages (tissue-resident phagocytes that also secrete cytokines and present antigens), natural killer (NK) cells (kill virus-infected and tumour cells by detecting loss of MHC class I), and mast cells (trigger inflammation via histamine release).

The complement system is a cascade of plasma proteins (C1–C9) activated by three pathways (classical, lectin, alternative) that converge on C3 cleavage. Complement functions include opsonisation (C3b coating pathogens for phagocytosis), chemotaxis (C5a attracting neutrophils), direct lysis (membrane attack complex C5b-9), and mast cell degranulation (C3a, C5a as anaphylatoxins).

Inflammation is the local vascular and cellular response to injury or infection, characterised by five cardinal signs: redness (rubor), heat (calor), swelling (tumor), pain (dolor), and loss of function (functio laesa). Vasodilation (mediated by histamine and prostaglandins) increases blood flow causing redness and heat. Increased vascular permeability allows plasma proteins to leak into tissue (swelling). Bradykinin and prostaglandins sensitise nociceptors (pain). Oedema and pain limit movement (loss of function).

The adaptive immune system develops over days to weeks and generates highly specific responses with immunological memory. It has two arms: Humoral immunity: B cells, on encountering antigen and receiving T helper cell signals, differentiate into plasma cells that secrete antibodies (immunoglobulins — IgG, IgM, IgA, IgE, IgD). Antibodies neutralise pathogens, opsonise them for phagocytosis, and activate complement. Cell-mediated immunity: T cells (CD4+ helper and CD8+ cytotoxic) are activated when their T cell receptor (TCR) binds antigen presented by MHC molecules. MHC class I (present on all nucleated cells) presents intracellular antigens (e.g., viral peptides) to CD8+ cytotoxic T cells, which kill infected cells by releasing perforin and granzymes. MHC class II (present on professional antigen-presenting cells: dendritic cells, macrophages, B cells) presents extracellular antigens to CD4+ helper T cells, which coordinate the immune response by secreting cytokines.

Clonal selection: each lymphocyte expresses a unique receptor. When antigen binds, that specific lymphocyte is selected and undergoes clonal expansion — producing effector cells and long-lived memory cells. Immunological memory allows faster, stronger responses upon re-exposure, which is the basis of vaccination.

Hypersensitivity reactions are exaggerated or inappropriate immune responses. Type I (immediate): IgE-mediated; mast cell degranulation within minutes (e.g., anaphylaxis, hay fever). Type II (cytotoxic): IgG/IgM against cell-surface antigens (e.g., autoimmune haemolytic anaemia, ABO incompatibility). Type III (immune complex): IgG/IgM antigen-antibody complexes deposited in tissues (e.g., serum sickness, SLE). Type IV (delayed-type/cell-mediated): T-cell mediated; 48–72 hours (e.g., tuberculin test, contact dermatitis, transplant rejection).