IMMUNOLOGY

• Immune system


  A complex collection of tissues and soluble mediators positioned throughout the body
• Immune system


  • Provide a coordinated response to protect the host from infection
  • Preventing invasion
  • Eradicating pathogens
• Immune system


  • Ability to recognize a pathogen and mount an exact appropriate response
• Anatomical and physiologic barriers of the body

  • Physicochemical barriers
  • Skin and mucosal epithelia
  • Secreted products (sweat, mucus, and acid)
• Natural or constitutive defenses

  Present and active even before any pathogen is encountered
• Innate immunity


  Immediate response to infection
• Innate immunity


  • Immune system's ability to distinguish self from non-self
  • Non-specific
• Some components of the physicochemical barriers are also part of the innate immune system
• Saliva contains lysozyme (damage bacterial cell walls)
• Adaptive immune response


  • Highly specific targeted defenses
  • Takes time to develop
  • Once active, it is a powerful and highly effective
• Adaptive immune response


  • Specific to an individual pathogen and variable
  • Different pathogens elicit different adaptive immune responses
  • Has exclusive ability to remember any previous encounters with the same pathogen
• Innate immune response


  • Body's immediate response to an infection
  • Non-specific response
  • When activated, can present as an inflammatory response
• Inflammation


  • Body's response to injury or tissue damage
  • Purpose: To limit, and then repair, the damage brought about by any injurious agent
• Inflammation involves: Interaction of the microvasculature, circulating blood cells, other immune cells in the tissues, and their secreted effector molecules
• Neutrophils


  • Most abundant leukocytes in the blood stream (4,000 – 10,000/mm3)
  • The first cells to respond to infection
  • Short – lived (few hours to days)
  • Die rapidly by apoptosis after reaching the tissue and exerting their effect
• Monocytes


  • Much lower numbers within the blood (500 – 1000/mm3)
  • They are longer lived
  • Can also migrate into tissue and differentiate into Macrophage
• Macrophage


  • Phagocytosis of infecting microbes
  • Antigen presentation
  • General removal of dying or damaged host cells
  • Trash can of immune system
  • Release cytokines and chemokines
• Pattern recognition receptors (PRR)

  • Receptors involved in microbial recognition
  • Identify structures that are shared by various microbes and are generally NOT present on host cells
  • Recognized pathogen-associated molecular patterns (PAMP)
• Mannose-binding lectin (MBL)


  • A free circulating plasma protein
  • Activate the complement cascade via the lectin pathway
  • Belong to a larger family "C-type lectin receptors"
  • Detect carbohydrate moieties on pathogens
• Toll-like receptor (TLR)


  • A membrane bound signaling PRR receptor
  • Can be expressed either on the external cell membrane or on intracellular vesicles
  • Recognize extracellular pathogens
• Toll-like receptor (TLR)


  • Increased production of inflammatory mediators (cytokines and chemokines)
  • Enhanced phagocytosis
  • Upregulation of costimulatory molecules on the cell surface, cell migration
  • Increased processing and presentation of pathogen antigens
• NOD-like receptor (NLR)


  • Located in the cytoplasm
  • Act as intracellular sensors triggering the NFkB pathway
• NOD-like receptor (NLR)


  • Increased phagocytosis
  • Increased production of cytokines and chemokines
  • Activate inflammasome
  • Caspase-1 activation processing and release of IL-1 and IL-18
• RIG-1-like receptors


  • Detect viral RNAs
  • Stimulate antiviral responses through the production of type I interferons
• Cytokines


  • Small (less than 20kDa) peptides or glycoproteins active at concentrations between 10-9 and 10-15 mole/L
  • Exert their effects by interacting with specific receptors on the surfaces of their target cells
• Cytokines


  • Paracrine action
  • Autocrine action
  • Endocrine action
• Cytokines (innate)


  • Macrophages activated by direct interaction with pathogens are major producers of a number of cytokines that amplify inflammation
  • TNF-a – increases vasodilation
  • IL-1, IL-6, and IL-8 – recruit additional neutrophils and monocytes into the infected tissue
• Cytokines


  • Colony-stimulating factors
  • Interferons (IFN)
  • Interleukins
  • Tumor Necrosis factor (TNF) FAMILY
• Chemokines


  Bring about chemokines-cell movement in response to chemical stimuli
• Complement system


  • Plays an important role in antimicrobial host defense
  • A series of proteins, present in the blood, whose activation leads to destruction of bacterial cell walls and consequent death of the pathogen
• Complement system pathways


  • Alternative pathway
  • Lectin pathway
  • Classic pathway
• Alternative and lectin pathways

  • Activate complement during the innate response and in the absence of antibody
  • Early complement proteins are activated by directly binding to structural components of the invading pathogen
• Lipopolysaccharide found on Gram negative bacterial cell wall triggers the ALTERNATIVE PATHWAY
• Mannose and other carbohydrates found in the cell walls of fungi, bacteria, and viruses trigger the LECTIN PATHWAY
• Classic pathway


  Activated later in the immune response when antibody produced during the adaptive response binding to microbial antigens
• Classic pathway


  • Comprises complement components C1q, C1r, C1s, C4, and C2
  • Activation of these components leads to the activation of C3 (absolute requirement)
  • Terminal membrane attack complex (C5, C6, C7, and C9) is then activated
  • Cell lysis triggered by C1q binding an IgG or IgM bound to its specific antigen
• Membrane attack complex (MAC)


  Assembles on the surface of infecting organisms and breaches the integrity of the pathogen by insertion into their membranes
• Complement system


  • Opsonization enhances phagocytosis
  • Recruitment of the inflammatory cells through chemotaxis and stimulating the degradation of immune cells (anaphylatoxin activity)
• Adhesion molecules


  • Molecules and ligands that mediate adhesion between cells or between cells and the extracellular matrix
  • They are transmembrane glycoproteins
  • They deliver intracellular signals
  • They are primarily involved in promoting cell-cell interactions and cell migration during an immune response
• Adhesion molecule types


  • Integrins
  • Immunoglobulin supergene family adhesion molecules
  • Selectins
  • Mucin-like vascular addressins