Innate Immune System Notes

Innate Immune System

Noncellular Nonspecific Defenses

• Skin (Integument):
  • Provides a physical barrier against bacteria, viruses, fungi, and parasites.
  • Contains antibacterial enzymes called defensins.
  • Sweat has antimicrobial properties.
  • Compromised skin (cuts, abrasions) allows pathogen entry.
• Respiratory System:
  • Mucous membranes lined with cilia trap particulate matter and push it to the oropharynx.
  • Mucus prevents bacteria and viruses from accessing lung tissue.
• Other Mucous Membranes:
  • Around the eye and in the oral cavity.
  • Produce lysozyme, a nonspecific antibacterial enzyme, secreted in tears and saliva.
• Gastrointestinal Tract:
  • Stomach secretes acid, eliminating most pathogens.
  • Gut is colonized by bacteria that compete with potential invaders.
  • Antibiotics can reduce gut flora, allowing for pathogen growth.
• Complement System:
  • Proteins in the blood act as a nonspecific defense against bacteria.
  • Activated via:
    • Classical pathway: requires antibody binding to a pathogen.
    • Alternative pathway: does not require antibodies.
  • Complement proteins create holes in bacterial cell walls, causing osmotic instability.
  • Considered nonspecific because it cannot be modified to target specific organisms over others.
• Interferons:
  • Produced by virus-infected cells.
  • Prevent viral replication and dispersion.
  • Cause nearby cells to:
    • Decrease production of viral and cellular proteins.
    • Decrease permeability, hindering viral infection.
    • Upregulate MHC class one and class two molecules, increasing antigen presentation.
  • Responsible for flu-like symptoms (malaise, tiredness, muscle soreness, fever) during viral infection.

Cells of the Innate Immune System

• Cells are always poised and ready to attack when noncellular defenses are breached.
• Macrophages:
  • Type of agranulocyte residing within tissues.
  • Derived from blood-borne monocytes, becoming resident populations.
  • Examples: microglia (central nervous system), Langerhans cells (skin), osteoclasts (bone).
  • Activated macrophages:
    • Phagocytize invaders via endocytosis.
    • Digest invaders using enzymes.
    • Present peptides to other cells using MHC (major histocompatibility complex).
    • Release cytokines to stimulate inflammation and recruit immune cells.
• MHC Molecules:
  • MHC Class I:
    • Displayed by all nucleated cells.
    • Presents any protein produced within the cell.
    • Allows monitoring of cell health and detection of intracellular pathogens.
    • MHC I pathway is often called the endogenous pathway since antigens come from inside the cell.
    • Infected cells can be killed by cytotoxic T lymphocytes.
  • MHC Class II:
    • Displayed mainly by professional antigen-presenting cells (macrophages, dendritic cells, some B cells, certain activated epithelial cells).
    • Presents antigens originated outside the cell.
    • MHC II pathway is often called the exogenous pathway.
• Antigens:
  • Substances, usually pathogenic proteins, targeted by antibodies.
  • Cells of the innate immune system also present antigens, leading to activation of both innate and adaptive immune systems.
• Pattern Recognition Receptors (PRR):
  • Special receptors on macrophages and dendritic cells (e.g., Toll-like receptors - TLR).
  • Recognize categories of invaders (bacterium, virus, fungus, parasite).
  • Allow for appropriate cytokine production to recruit the right type of immune cells.
• Natural Killer (NK) Cells:
  • Nonspecific lymphocytes that detect downregulation of MHC molecules.
  • Induce apoptosis in virally infected cells and cancer cells.
• Granulocytes:
  • Include neutrophils, eosinophils, basophils, and mast cells involved in nonspecific defense.
  • Neutrophils:
    • Most populous leukocyte in blood; short-lived (around five days).
    • Phagocytic cells targeting bacteria.
    • Follow bacteria using chemotaxis (movement according to chemical stimuli).
    • Detect opsonized bacteria (marked with antibodies).
    • Dead neutrophil collections form pus during infections.
  • Eosinophils:
    • Contain bright red-orange granules.
    • Involved in allergic reactions and parasitic infections.
    • Release histamine, leading to vasodilation and increased leakiness of blood vessels.
    • Inflammation is useful against extracellular pathogens.
  • Basophils:
    • Contain large purple granules.
    • Involved in allergic responses.
    • Least populous leukocyte in the bloodstream under normal conditions.
  • Mast Cells:
    • Similar to basophils but with smaller granules.
    • Exist in tissues, mucosa, and epithelium.
    • Release histamine in response to allergens, leading to inflammatory responses.