Immunology: The Body's Defense System

Immunology: The Body's Defense System

• Immunology is the science of the body's defense mechanisms against disease.
• The term "immunity" comes from the latin word "immunis" meaning "free of burden."

Immune Defenses

• Innate immunity (nonspecific) is the first line of defense against infectious agents.
  • It is nonspecific, meaning it protects against any pathogen, regardless of its type.
  • It has no memory, meaning it can't recall previous encounters with foreign antigens.
• Adaptive immunity (specific) is the third line of defense.
  • It is acquired during life and is based on a specific response to a specific microbe.
  • It has long-term memory for specific antigens.
  • It relies on specialized immune lymphocytes (B and T cells) and specific proteins (antibodies).

Innate Immunity

• First line of defense:
  • Physical barriers: intact skin, mucous membranes, mucus, tears, saliva, hairs, cilia, urine, vomiting, and defecation.
  • Chemical barriers: sebum, perspiration, lysozyme, gastric juice.
• Second line of defense:
  • Phagocytes: neutrophils, eosinophils, dendritic cells, and macrophages.
  • Inflammation: a localized response to injury or infection triggered by chemical signals.
  • Fever: an increase in body temperature triggered by the release of the cytokine IL-1.
  • Antimicrobial substances: proteins including those of the complement system and interferons.

Physical Barriers of the First Line of Defense

• Skin: a strong physical barrier, with the outer layer composed of dead cells containing keratin.
• Mucous Membranes: line the gastrointestinal, respiratory, and genitourinary tracts, offering less protection than the skin.
• Mucus: a glycoprotein produced by goblet cells that traps microbes.
• Tears: produced by the lachrymal apparatus of the eye, dilute and wash away microorganisms.
• Normal microbiota: the bacteria that normally reside in the vagina and other body sites, alter pH conditions, preventing pathogen overgrowth.

Second Line of Defense: Phagocytosis

• Phagocytosis: the process of cellular engulfment of solid particles, a major mechanism of immune defense.
• Phases of phagocytosis: chemotaxis, adherence, ingestion, and digestion.
• Chemotaxis: the attraction of phagocytes to microbes, driven by chemical signals like microbial products, components of white blood cells, and complement fragments.
• Adherence: the attachment of the phagocyte's membrane to the surface of the microbe.
• Ingestion: the engulfment of the microbe by phagocytic cell extensions, creating a phagosome.
• Digestion: lysosomes containing digestive enzymes fuse with the phagosome, forming a phagolysosome that destroys the microbe.
  • Lysosomal bactericidal factors include: hydrolyzing enzymes like lysozyme, lipase, protease, and toxic oxygen products.

Microbial Evasion of Phagocytosis

• Some microbes have evolved strategies to evade phagocytosis:
  • Inhibiting adherence: M protein (Streptococcus pyogenes), capsule (Streptococcus pneumoniae, Haemophilus influenzae).
  • Killing the phagocyte: leukocidin (Staphylococcus aureus), streptolysin (Streptococcus pyogenes).
  • Lysis of phagocyte membrane: membrane attack complex by Trypanosoma cruzi.
  • Inhibition of phagosome-lysosome fusion: Mycobacterium tuberculosis, Leishmania, Chlamydia, and HIV.
  • Remaining dormant inside the phagocyte: Brucella.
  • Formation of biofilms: preventing phagocytes from detaching bacteria from the biofilm structure.

Inflammation

• Inflammation is a localized response to injury or infection characterized by redness, swelling, heat, pain, and loss of function.
• Key features: vasodilation (increased blood flow), increased permeability of blood vessels (allowing fluid and immune cells to enter the tissue), and migration of phagocytes to the site of injury.

Fever

• Fever: an abnormally high body temperature controlled by the hypothalamus.
• Causes: infection triggers release of IL-1, which causes the hypothalamus to release prostaglandins, resetting the thermostat at a higher temperature.
• Effects on body: constriction of blood vessels, increased metabolic rate, shivering, and vasodilation and sweating (as fever subsides).
• Potential benefits: enhanced T lymphocyte production, intensified interferon action, slower growth of some microbes, and accelerated tissue repair.
• Dangers: death if body temperature surpasses 44-46°C.

Antimicrobial Substances

• Complement System: a group of proteins that circulate in the blood, involved in the lysis of microbes, inflammation, and phagocytosis.
• Interferons (IFNs): antiviral proteins that interfere with viral replication.

Adaptive Immunity

• Adaptive immunity: acquired during life, provides a more specific, targeted defense against specific pathogens.
• Components: specialized lymphocytes, B cells and T cells, and antibodies.
• B cells: responsible for antibody production.
• T cells: responsible for cell-mediated immunity.
• Antibodies: proteins that bind to specific antigens on pathogens, marking them for destruction.

Key Figures

• Bruce Beutler: American immunologist and geneticist, received the 2011 Nobel Prize in Physiology or Medicine for discovering Toll-like receptors (TLRs).
• Jules Hoffmann: French biologist, shared the 2011 Nobel Prize with Beutler for their discoveries concerning the activation of innate immunity.
• Ralf Steinman: Canadian immunologist, also received the 2011 Nobel Prize for his discovery of dendritic cells and their role in adaptive immunity.