Human Immune System

Immune System

• The immune system is composed of two divisions: Innate Immunity and Adaptive Immunity.
• Innate Immunity is also known as nonspecific immunity, where immune cells attack anything they view as foreign to the host.
• Adaptive Immunity, also known as specific immunity, involves immune cells targeting specific microorganisms.

Innate Immunity

• Innate Immunity is composed of three main lines of defense:
  • The first two lines are part of Innate Immunity (nonspecific immunity).
  • The third line of defense involves methods of immunity for specific pathogens following exposure and is part of Adaptive Immunity (specific immunity).

First Line of Defense

• The body's natural barriers and secretions:
  • Prevent pathogens from entering the body in the first place.
• Mechanical and Chemical Barriers:
  • Skin:
    • The largest organ of the body, composed of two main layers: Epidermis and Dermis.
    • Provides physical barrier protection:
      • Epidermis made up of many layers of cells that are tightly packed together, preventing pathogens from penetrating unless injured.
      • Dermis contains tough fibers called collagen, giving strength and elasticity to skin, allowing it to withstand damage and puncture.
  • Chemical Barrier Protection:
    • Dendritic cells in the epidermis perform phagocytosis against colonization and infection by pathogens.
    • Defensins, antimicrobial peptides, are produced by sweat glands to kill microbes on the skin.
    • Lysozymes destroy cell walls of bacteria by breaking bonds between sugar molecules.
    • Sebum, an oily substance secreted by sebaceous glands in the dermis, has two methods of antimicrobial function:
      • Keeps skin pliable, making it more resistant to injury.
      • Lowers skin pH to around 5, inhibiting bacterial growth.
• Mucous Membranes:
  • Mucous secreting membranes cover all body cavities open to the environment.
  • Examples:
    • Respiratory tract: Goblet cells secrete mucous that traps microbes, and ciliated cells propel microbe-containing mucus out of the respiratory tract.
    • GI tract: High acidity (low pH) of the stomach kills most microbes, and saliva contains lysozymes and other antimicrobial molecules.
    • GU/Reproductive tract: Mucous membrane provides a physical barrier to infection, and urine flushes microbes out of the urethra.
    • Eyes: Lacrimal glands produce lysozymes in tears.

Normal Microbial Flora

• Microbial flora refers to the normal microbial life that exists on and within a body at any given time.
• Most microbial life is harmless and beneficial to humans.
• Examples:
  • E. coli in the human gut produces Vitamin K as a byproduct of its metabolic reactions, which human cells can then utilize.
  • Normal microbial life consumes available nutrients and makes life inhospitable to other microbes.
  • It also changes pH, creating an environment hospitable to existing microbial life.

Innate Genetic Immunity

• Some individuals are born with genes that offer them protection from certain pathogens.
• Examples:
  • HIV Immunity: About 1% of the population has a mutation in the CCR5 receptor, preventing HIV from entering T cells.
  • Malaria Immunity: Patients with Sickle Cell Disease are immune from malarial infection due to the shape of their red blood cells.

Second Line of Defense

• This occurs when the first line of defense is breached and is carried out by different cells and chemical mediators.
• Leukocytes (White Blood Cells):
  • Granulocytes:
    • Basophils: Release histamine in inflammatory response.
    • Eosinophils: Target parasites and play a role in asthma and some allergic reactions.
    • Neutrophils: Perform phagocytosis.
  • Agranulocyte:
    • Lymphocyte:
      • B cell: Involved in adaptive immunity.
      • T cell: Involved in adaptive immunity.
      • NK (natural killer) cell: Targets virally infected cells and cancer cells.
    • Monocyte:
      • Macrophage: Performs phagocytosis.

Phagocytosis

• The consumption of a pathogen.
• Primarily performed by neutrophils and macrophages.
• Occurs in five steps:
  • Chemotaxis: Attraction of neutrophils and macrophages to the pathogen.
  • Adherence: Attachment of macrophages and neutrophils to the pathogen.
  • Ingestion: Formation of a phagosome by coating the pathogen in a membrane.
  • Death of Pathogen: Fusion of the phagosome with a lysosome containing hydrolytic enzymes and digestive chemicals.
  • Elimination: Removal of remnants of the pathogen via exocytosis.

Opsonization

• Process by which a pathogen is covered by antibodies or complement proteins to make it easier to be recognized by phagocytic cells.

Eosinophils

• Attach to surface of parasitic helminths (worms) and secrete toxins that weaken/kill the parasite.

NK Cells

• Create toxic proteins, called porforins, which destroy the cell membrane of virally infected cells, certain tumor cells, and some varieties of parasites.

Interferon (INF)

• Protein molecules released by host cells in the presence of several pathogens, particularly viruses.
• Virally infected cells produce a small protein that spreads to neighboring cells and induces them to produce antiviral proteins that prevent viral replication from occurring.

Complement System

• A system of about 30 proteins, produced by the liver, which circulate through the bloodstream in an inactivated state.
• Can induce killing via opsinization (leads to phagocytosis) or cell lysis.

Inflammation

• Inflammation serves to localize the effects of injury (infection, toxin), minimize these effects, and destroy the pathogen when possible. It also sets the stage for tissue repair.
• Cardinal signs of inflammation: Rubror (redness), Calor (heat), Tumor (swelling), Dolor (pain), and Functio laesa (impaired function).
• Stages of Inflammation:
  • Injury releases chemical mediators, causing vasodilation, increased blood flow, and increased vascular permeability.
  • Increased permeability leads to fluid leaking from vessels into tissues, causing edema.
  • Pain may be caused by release of chemical mediators, nerve irritation by toxins, or pressure on nerves from edema fluid.
  • Vasodilation and hyperemia deliver clotting factors to the site of injury, or phagocytic cells to destroy invading pathogens.