The Innate Immune System

Innate immunity • • • • • • • Section of immune response that does not require antigen-specific clonal expansion to eliminate pathogen Responses are first-line, rapid and largely effective in preventing tissue invasion Essential to trigger the more specific adaptive immune response Physical barriers e.g. skin Mechanical barriers – tight cell junctions between skin cells, coughing, sneezing, flushing effect of urination Chemical barrier – acidic environment of stomach, effects of enzymes in saliva, alimentary tract Microbiological barrier – normal flora of respiratory and alimentary tracts Innate immunity mechanism • As soon as a pathogen breaches one of the epithelial barriers of the body, it will encounter cells with receptors that recognise its surface antigens. These cells are generally phagocytic macrophages. Once the macrophage engulfs the pathogen, it starts to release molecules (cytokines) that act as signals to other cells to change their behaviour. • Bacterial cell surfaces also have receptors that bind a set of plasma proteins known as complement. Once activated, these complement proteins attract phagocytic cells to attack the bacteria. Activated complement proteins therefore also act as chemo-attractants. Innate immunity results in an inflammatory reaction • The various cells involved in innate immunity, cytokines, and complement proteins initiate inflammation • Dilatation of blood vessels leads to heat and redness in tissue due to increased blood flow • Increased permeability of blood vessel walls results in leakage of fluid into the tissues → swelling • Swelling of tissue and the release of multiple different chemicals into area stimulates pain fibres → pain • Cardinal signs of inflammation: heat, redness, pain, swelling • Neutrophils are recruited to the site of inflammation by the chemokines o Predominant cell that phagocytose bacteria and fungi (assisted by macrophages) o Inflammatory cells = neutrophils and macrophages • Lymphocytes are later recruited to the site of inflammation after dendritic cells bearing the foreign antigen have migrated to the local lymph node and stimulated them o Acute v chronic inflammation can be partly distinguished by predominant cell type in tissue Antigen – substance that can induce an adaptive immune response (originally substance that induces antibody gen) Innate and adaptive immune responses (must coexist) • Leukocytes of innate immunity (mostly neutro + macro) are responsible for 1st line defence against invading pathogens, but also for presenting antigens to lymphocytes • Lymphocytes have some effector function but mainly call the neutrophils and macrophages back into action for their effector function • Dendritic cells: important surveillance cells in immune system o Migrate from blood to tissues o When they encounter an antigen, they ingest it and migrate to lymph nodes and present the antigen on their surface to lymphocytes for activation of adaptive immunity ▪ To activate lymphocytes in lymph node, dendritic cell must also secrete costimulatory molecules that signal the lymphocyte to begin process of adaptive immunity ▪ Can recognise some bacterial antigens through their receptors → engulfs pathogen ▪ Also engulf large amounts of extracellular material ▪ Micropinocytosis = can pick up pathogens without recognisable receptors/ virus-infected host cells → antigens are then liberated by intracellular digestion • Tissue injury: neutrophils+macrophages (innate) respond to tissue injury (even when noninfective) → repair