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Immunity — Guyton & Hall Textbook of Medical Physiology

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1. Innate vs. Acquired Immunity

• Innate (non-specific) immunity — pre-existing defenses (skin, phagocytes, complement, etc.) that act immediately against any foreign agent.
• Acquired (adaptive) immunity — developed after exposure to a specific invading agent; can achieve protection against doses up to 100,000 times the lethal level (e.g., botulinum and tetanus toxins).

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2. Acquired (Adaptive) Immunity

Types

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3. Antigens

• Any substance that triggers acquired immunity is an antigen (antibody generator).
• Usually proteins or large polysaccharides with MW ≥ 8,000 Da.
• Antigenicity depends on regularly recurring molecular groups called epitopes on the surface of the molecule.

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4. Lymphocytes — The Basis of Acquired Immunity

• Without lymphocytes (genetic lack or destruction), no acquired immunity is possible; a newborn would die of overwhelming bacterial infection within days.
• Located primarily in lymph nodes, but also in: spleen, thymus, bone marrow, GI submucosal areas, tonsils, and adenoids.
• Distribution is strategic: GI lymphoid tissue intercepts gut antigens; tonsillar tissue intercepts respiratory antigens; splenic/bone marrow lymphoid tissue intercepts bloodborne antigens.

Origin (Preprocessing)

• B lymphocytes — preprocessed in the bone marrow (in birds: bursa of Fabricius → "B").
• T lymphocytes — preprocessed in the thymus (→ "T").
• Both types are then seeded throughout peripheral lymphoid tissue.

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5. B-Lymphocyte System — Humoral Immunity & Antibodies

Antibody Formation by Plasma Cells

1. Antigen enters → phagocytized and presented by macrophages to adjacent B lymphocytes.
2. T-helper cells are simultaneously activated and provide additional B-cell stimulation.
3. Antigen-specific B lymphocytes enlarge → become lymphoblasts → plasmoblasts → plasma cells.
4. Plasma cells divide ~once every 10 hours for 4 days (~9 divisions) → ~500 cells per original plasmoblast.
5. Each mature plasma cell produces ~2,000 antibody molecules/second.
6. Plasma cells eventually exhaust and die after days to weeks.

Memory Cells & the Secondary Response

• Some lymphoblasts don't become plasma cells but instead form memory B cells, which populate all lymphoid tissue.
• Primary response: 1-week delay, weak, short-lived.
• Secondary response: rapid (within hours), far more potent, antibodies last for months.
• This is why immunization uses multiple doses spaced weeks to months apart.

Lifelong Immunity via Long-Lived Plasma Cells

• Short-lived plasma cells: rapid protection but undergo apoptosis within days.
• Long-lived plasma cells: reside in bone marrow and gut-associated lymphoid tissue (GALT); can produce antibodies for decades (e.g., smallpox antibodies detected 70 years post-vaccination; 1918 H1N1 survivors retained functional antibodies decades later).

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6. T-Lymphocyte System — Cell-Mediated Immunity

Activation of T Cells

• T lymphocytes respond only to antigens bound to MHC proteins on antigen-presenting cells (APCs).
• Three major APCs: macrophages, B lymphocytes, dendritic cells (most potent).
• Upon appropriate antigen exposure, T-lymphocyte clones proliferate and release activated T cells into the lymph → circulation → tissues → lymph again.
• Circulate throughout the body for months to years.
• Memory T cells also form, enabling faster, more powerful responses on re-exposure.

MHC Proteins

Types of T Cells

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7. Tolerance — Self vs. Non-Self

• During T-cell preprocessing in the thymus and B-cell preprocessing in the bone marrow, lymphocytes that react against the body's own tissues are clonally deleted or inactivated.
• Failure of this tolerance → autoimmune disease.
• Regulatory T cells further suppress autoreactive lymphocytes in the periphery.

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8. Passive Immunity

• Acquired passively by transfer of antibodies (or activated T cells) from another individual.
• Examples: maternal IgG transfer across placenta, antitoxin injections (tetanus antitoxin), immune serum.
• Protection is immediate but temporary — antibodies degrade over weeks to months; no memory is formed.

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9. Sex Differences in Immunity

• Women generally mount stronger innate and adaptive immune responses than men.
• This confers greater resistance to infection but also higher susceptibility to autoimmune diseases.
• Hormonal factors (estrogen, testosterone) and X-linked immune genes contribute to these differences.

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Summary Table

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