Epithelial Surfaces and Antimicrobial Defense

Epithelial Surfaces

• Epithelial surfaces are the first line of defense against pathogens
• Tight junctions hold epithelial cells together
• Mucosal epithelia secrete glycoproteins like mucin, which coat bacteria and wash them away
• Peristalsis and mechanical movements prevent pathogen attachment
• Commensal bacteria are beneficial and inhibit pathogen colonization
• Epithelial cells produce antimicrobial proteins and chemicals like digestive enzymes, bile salts, and fatty acids

Epithelial Surfaces - Antimicrobial Components

• Lysozyme is an antimicrobial enzyme found in tears, saliva, and phagocytes that breaks down peptidoglycan in bacterial cell walls
• Antimicrobial peptides like defensins, cathelicidins, and histatins disrupt cell membranes of bacteria and fungi, as well as the cell envelope of some viruses
• These peptides are thought to create pores in cell membranes, potentially contributing to pathogen invasion

Epithelial Surfaces - Carbohydrate-binding Proteins

• Carbohydrate-binding proteins, known as lectins, bind to peptidoglycan on bacteria and elicit bactericidal effects
• C-type lectins require calcium (Ca) for carbohydrate recognition

Complement System

• The complement system is a major defense mechanism after epithelial barriers are breached
• It consists of over 30 proteins primarily produced in the liver
• These proteins circulate in an inactive form
• Complement activation occurs through three pathways:
  • Classical pathway: Antibody-triggered activation
  • Alternative pathway: Activated by pathogens alone
  • Lectin pathway: Activated by lectin-type proteins

Complement System - Activation and Function

• Complement system activation involves proteolysis, whereby proteins are digested to their active form
• Complement proteins successively cleave and activate one another, known as a cascade reaction
• Complement proteases are synthesized as inactive pro-enzymes (zymogens) which are activated by proteolytic cleavage
• The complement system addresses pathogens by
  • Triggering inflammation
  • Facilitating phagocytosis
  • Initiating the membrane attack complex (MAC)

Induced Responses of Innate Immunity

• The immune system deploys effector mechanisms tailored to individual pathogens
• These mechanisms include
  • Cell-mediated mechanisms
  • Humoral mechanisms

Antibodies

• Antibodies protect against pathogens and their toxic products
• They are found in plasma and extracellular fluids (formerly called humors)
• Antibodies are also known as humoral immunity

Antibodies - Classes and Functions

• Antibodies have five classes (or isotypes) based on differences in their constant regions:
  • IgM
  • IgG
  • IgA
  • IgE
  • IgD
• Each class has specific functional properties

Antibodies - Neutralization, Opsonization, and Complement Activation

• Antibodies can neutralize pathogens by blocking their access to cells
• Antibodies can also opsonize pathogens, coating them and facilitating phagocytosis by phagocytes with Fc receptors
• Antibodies further lead to the activation of the complement system, which can lyse pathogens

T Cells

• T cells are crucial for eliminating intracellular pathogens and contribute to cell-mediated immunity within the adaptive immune response
• T cells develop in the thymus
• T cells are classified based on their type of T cell receptor, primarily
  • CD8+ T cells
  • CD4+ T cells
• CD4 and CD8 act as coreceptors, recognizing different regions of MHC molecules and coordinating T cell responses

T Cells - MHC Class I and MHC Class II

• MHC class I and MHC class II molecules present peptides from intracellular and extracellular sources, respectively
• These peptides are trapped within a groove, forming peptide-MHC complexes which are transported to the cell membrane
• T cells recognize and interact with these peptide-MHC complexes to initiate immune responses.