Memory tricks for fluid balance and the body's defenses

Fluid balance: capillary filtration produces ~3 L/day excess interstitial fluid — lymphatic capillaries absorb this and return it to blood via thoracic duct (left side) and right lymphatic duct (right side). Without lymphatics → edema. Immunity: lymph passes through lymph nodes where pathogens, cancer cells, and debris are filtered and destroyed by macrophages and lymphocytes. Lymphoid organs (thymus, spleen, lymph nodes, MALT) are sites of immune cell development and activation. Fat absorption: lacteals (lymphatic capillaries in intestinal villi) absorb dietary fats (chylomicrons) → chyle → thoracic duct → blood. Bypasses portal system.

Thymus: primary lymphoid organ — where T cells mature and learn self-tolerance. Located in mediastinum. Most active in childhood — involutes after puberty. Cortex (immature T cells) → medulla (mature T cells). Thymic selection: positive (T cells that recognize self-MHC survive) + negative (T cells that attack self-antigens eliminated). Spleen: largest lymphoid organ — filters BLOOD (not lymph). White pulp (immune responses to blood-borne antigens) and red pulp (destroys old RBCs). Lymph nodes: filter LYMPH — stationed along lymphatic vessels. Site of adaptive immune responses to antigens. Cortex (B cells) + paracortex (T cells) + medulla. MALT (Mucosa-Associated Lymphoid Tissue): tonsils, Peyer's patches (ileum), appendix — defend mucosal surfaces.

Innate immunity: fast (minutes to hours), non-specific, no memory. First line: physical barriers (skin, mucus, cilia, stomach acid). Second line: inflammation, fever, phagocytes (neutrophils, macrophages), NK cells, complement, interferons. Pattern recognition: Toll-like receptors (TLRs) detect PAMPs (pathogen-associated molecular patterns) — conserved foreign molecules. Adaptive immunity: slow (days first exposure, hours on re-exposure), antigen-specific, has memory. T lymphocytes (cell-mediated) and B lymphocytes (humoral/antibody). Both cooperate: innate activates adaptive (dendritic cells present antigen to T cells), adaptive enhances innate (antibodies opsonize bacteria for phagocytosis).

MHC class I: on ALL nucleated cells — presents intracellular peptides (virus, tumor) to CD8+ cytotoxic T cells → cell killed. MHC class II: on professional APCs only (dendritic cells, macrophages, B cells) — presents extracellular peptides to CD4+ helper T cells → activates response. Memory trick: MHC I × CD8 = 8. MHC II × CD4 = 8. Both products equal 8. T cell activation requires TWO signals: Signal 1 = TCR binds MHC-peptide. Signal 2 (costimulation) = CD28 on T cell binds B7 on APC. Signal 1 alone → anergy (unresponsiveness). This two-signal requirement prevents autoimmune reactions to self-antigens. CTLA-4 competes with CD28 — immune checkpoint exploited in cancer immunotherapy.

Th1 (induced by IL-12): secretes IFN-γ → activates macrophages → kills intracellular bacteria (TB, Listeria) and viruses. Th2 (induced by IL-4): secretes IL-4, IL-5, IL-13 → activates eosinophils and mast cells, drives IgE production → fights parasites and helminths. Also responsible for allergic responses. Th17 (induced by IL-6 + TGF-β): secretes IL-17 → recruits neutrophils → fights extracellular bacteria and fungi. Implicated in autoimmune diseases (psoriasis, IBD, RA). Treg (regulatory, FoxP3+): secretes IL-10 and TGF-β → suppresses immune responses → prevents autoimmunity and limits collateral damage.

B cells are activated by antigen + T cell help → proliferate in germinal centers → affinity maturation (somatic hypermutation) → class switching → plasma cells (antibody factories) or memory B cells. IgM: first antibody produced — pentamer, excellent at complement activation, cannot cross placenta. Primary response marker. IgG: most abundant (80%) — crosses placenta (maternal immunity), secondary response, opsonization, complement. IgA: secretory — in tears, saliva, breast milk, GI/respiratory mucus — first line at mucosal surfaces. IgE: lowest concentration but highest potency for allergy — binds mast cells and basophils → degranulation → anaphylaxis. IgD: mainly on naive B cell surface as BCR. Allergic response: IgE on mast cells + allergen → histamine → urticaria, anaphylaxis.

Classical pathway: activated by antibody-antigen complexes (IgG or IgM) → C1 → C4 → C2 → C3. Links adaptive to innate. Lectin pathway: mannose-binding lectin (MBL) detects mannose on bacterial surface → C4 → C2 → C3. Innate, no antibody needed. Alternative pathway: spontaneous low-level C3 hydrolysis → amplified on foreign surfaces (no antibody). All converge at C3 → four outcomes: Opsonization (C3b coats bacteria → phagocytes eat them), Chemotaxis (C5a attracts neutrophils), Mast cell degranulation (C3a, C5a — anaphylatoxins), Lysis (C5b-9 = MAC punches holes in membrane). Deficiency: C3 deficiency → severe bacterial infections. C5-C9 deficiency → Neisseria infections.

Type I (Anaphylactic): IgE pre-bound to mast cells + allergen → immediate degranulation → histamine → urticaria, bronchoconstriction, anaphylaxis. Minutes. Treat with epinephrine. Examples: peanut allergy, bee sting, latex allergy. Type II (Cytotoxic): IgG or IgM binds cell surface → complement or ADCC destroys cell. Hours. Examples: hemolytic disease of newborn (Rh), Goodpasture's, myasthenia gravis, Graves' disease. Type III (Immune complex): antigen-antibody complexes deposit in tissues → complement → inflammation. Days. Examples: serum sickness, SLE, post-streptococcal GN, rheumatoid arthritis. Type IV (Delayed, T cell-mediated): no antibody — sensitized T cells → 48-72 hours. Examples: contact dermatitis, TB skin test (PPD), transplant rejection, MS, T1DM.

Active immunity: body makes its own antibodies and memory cells → long-lasting. Natural active: infection → recovery → lifelong immunity (chickenpox). Artificial active: vaccination → immunological memory without disease. Passive immunity: pre-made antibodies transferred → immediate protection but no memory → temporary (weeks to months). Natural passive: IgG crosses placenta + IgA in breast milk → newborn protection for 3-6 months. Artificial passive: injection of immune serum (immunoglobulins) → used for rabies exposure, snakebite, tetanus post-exposure. Herd immunity: when enough of population is immune (natural or vaccine) → pathogen cannot spread → even unvaccinated are protected. Threshold varies (measles ~95%, polio ~85%).