Cellular Immunity — MRCS Part B Surgical pathology

An immunology station arriving, by way of a burns patient with cellulitis, at cell-mediated and humoral immunity, complement and the causes of immune deficiency.

Innate defences

Skin and mucosa, mucus and cilia, stomach acid, lysozyme in tears and saliva, the normal flora, fever, the complement system, acute-phase proteins, and the cells: neutrophils, macrophages, natural killer cells, mast cells and eosinophils. It is fast, non-specific and has no memory.

Antigen and antibody

An antigen is any molecule the adaptive immune system can recognise and respond to; an epitope is the part of it a receptor binds. An antibody is an immunoglobulin made by plasma cells that binds a specific antigen: two heavy and two light chains, a variable region for binding and a constant region (Fc) that decides the class and its effect — IgG (the main serum antibody, crosses the placenta), IgM (first made, a pentamer, fixes complement well), IgA (secretions), IgE (allergy and worms), IgD.

Adaptive immunity

Specific for the antigen, slower to start, and remembered, so a second exposure gets a faster and larger response. It has two arms. Humoral immunity is B cells and antibody, effective against organisms and toxins outside cells: neutralisation, opsonisation and complement activation. Cell-mediated immunity is T cells: CD4 helper cells that direct the response through cytokines (Th1 activating macrophages, Th2 helping B cells, Th17 recruiting neutrophils, regulatory cells restraining it), and CD8 cytotoxic cells that kill cells presenting foreign peptide on MHC class I — virus-infected cells, tumour cells, transplanted tissue. It is the arm that handles intracellular organisms such as tuberculosis, and the one that rejects grafts.

Complement

About thirty plasma proteins activated in a cascade by antibody bound to antigen (classical pathway), by microbial surfaces (alternative pathway) or by mannose-binding lectin (lectin pathway), all converging on C3. Its products opsonise (C3b), attract and activate inflammatory cells (C3a, C5a), and lyse organisms through the membrane attack complex (C5–9). Deficiency of the late components causes recurrent Neisseria infection.

Lymphoid tissue

Primary lymphoid organs make and educate lymphocytes: the bone marrow (all lymphocytes, and B cell maturation) and the thymus (T cell selection). Secondary organs are where they meet antigen: lymph nodes, spleen, tonsils and the mucosal lymphoid tissue of the gut and airways.

Immune deficiency

Primary: defects of antibody (X-linked agammaglobulinaemia, common variable immunodeficiency, IgA deficiency), of T cells (DiGeorge), combined (SCID), of phagocytes (chronic granulomatous disease) and of complement. Secondary, far commoner: HIV, malignancy and its chemotherapy, steroids and immunosuppressants, malnutrition, diabetes, renal failure, splenectomy, extremes of age, and burns, which destroy the barrier, consume immunoglobulin and complement, and suppress cell-mediated responses.

Apoptosis and necrosis

Apoptosis is programmed, energy-dependent death of single cells: the cell shrinks, the chromatin condenses, the membrane stays intact and the fragments are eaten without inflammation. Necrosis is uncontrolled death of groups of cells from injury: swelling, membrane rupture, spilled contents and an inflammatory response.

The burns patient with cellulitis

Organisms: Streptococcus pyogenes and Staphylococcus aureus, with Pseudomonas, coliforms and MRSA in the hospitalised burn. Management: sepsis screen and cultures including the wound, intravenous antibiotics to local policy covering streptococci and staphylococci (flucloxacillin or co-amoxiclav, broadened for Pseudomonas or MRSA), fluid and nutrition, wound inspection with debridement of dead tissue, and early referral to a burns unit. Ludwig's angina is a spreading cellulitis of the submandibular and sublingual spaces, usually from a dental infection, which lifts the tongue and threatens the airway; the treatment is securing the airway, antibiotics and drainage.