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Innate Immune Response


									Innate Immune Response
        Chapter 15
• First line of defense are barriers that shield interior of body from the
  external surroundings

• Anatomical barriers include skin and mucous membranes
    – Provide physical separation
    – Membranes bathed in antimicrobial secretions
Physical barriers
  – Skin
  – Mucous membranes
  – Provides the most difficult barrier for microorganisms to

  – Composed of two main layers

       • Dermis

       • Epidermis
          – Composed of many layers of epithelial cells
          – Outermost sheets of cells embedded with keratin
          – Outer layers slough off taking microbes with them
Mucous membranes
 – Constantly bathed with mucus

 – Some mucous membranes have mechanisms to
   propel microorganisms and viruses to areas where
   they can be eliminated:

    • Peristalsis
    • Urine flow
    • Ciliated cells that line the trachea
Antimicrobial substances present on the skin and the and
mucous membranes

          – Enzyme that degrades peptioglycan

          – Breaks down hydrogen peroxide to produce destructive oxidizing

          – Sequesters iron from microorganisms

          – Antimicrobial peptides that form pores microbial membranes
         Cells of the Immune System

Always found in normal blood
   – Numbers increase during infection

Some cells play dual roles in both innate and
adaptive immunity
Blood cell formation called hematopoiesis
   – Blood cells including immune cells originate from hematopoietic
     stem cells in bone marrow

   – Blood cells stimulated to differentiate by a group of cytokines
     called colony-stimulating factors (CSFs)
General categories of blood cells

  Red blood cells (RBC)
     • a.k.a erythrocytes
     • Carry oxygen in blood

     • Fragments of megakaryocytes
     • Important component in blood clotting

  White blood cells (WBC)
     • a.k.a leukocytes
     • Important in host defenses
     • Divided into four categories
         – Granulocytes        - Mononuclear phagocytes
         – Dendritic cells     - Lymphocytes
   – Contain cytoplasmic graduals

   – Divided into three types
       • Neutrophils
       • Basophils
       • Eosinophils
   – Most abundant and important
     in innate response
   – Sometimes called
     polymorphonuclear cells

   – Involved in allergic reactions
   – Induce inflammation

   – Important in expelling
     parasitic worms
   – Active in allergic reactions
Mononulcear phagocytes
  – Collection of phagocytic
    cells called mononuclear
    phagocyte system

  – Include monocytes
     • Circulate in blood
     • Macrophages differentiate
       from monocytes

         – Abundant in liver,
           spleen, lymph nodes,
           lungs and peritoneal
   Cells of the Immune System
• Dendritic cells
   – Branched cells
     involved in adaptive
   – Function as scout in
      • Engulf material in tissue
        and bring it to cells of
        adaptive immunity
  Cells of the Immune System
• Lymphocytes
  – Involved in adaptive
  – Two major groups
     • B lymphocytes
         – B cells
     • T lymphocytes
         – T cells
  – Another type
     • Natural killer
         – Lacks specificity of B
           and T cells
             Cell Communication
• In order for immune system to respond, cells
  must communicate with the environment and
  with each other

• Cell surface receptors are the “eyes” and “ears”
  of the cell

• Cytokines are the “voice”

• Adhesion molecules act as the “hands”
  – Cytokines bind to surface receptors and regulate cell
     • Chemokines
         – Enhance ability of cells to migrate to appropriate site in body

     • Colony stimulating factors
         – During immune response, directs immature leukocytes to correct
           maturation pathway

     • Interferons
         – Also associated with inflammatory response

     • Interleukins
         – Important in innate and adaptive immunity

     • Tumor necrosis factor
         – Instrumental in initiation of inflammation and apoptosis
               Sensor Systems

Systems within the blood that detect signs of
tissue damage or microbial invasion

Recognize to “patterns” associated with microbes
Toll-like receptors (TLR) and NOD proteins
  – TLR allow cells to detect molecules associated with

  – TLR found in variety of cell types

  – NOD proteins recognize microbial-specific substances
    within the host cell cytoplasm
  – Series of inactive proteins circulating in blood and fluids

  – Enhances the adaptive immune response

  – Stimulation of inactive proteins initiates a cascade of
    reactions that activate other complement proteins
  – Complement system composed of nine major proteins
       C1 – C9

  – Activation of complement results in:
       Lysis of foreign cells
  – Complement system composed of nine major proteins
       C1 – C9
       Certain proteins split into “a” and “b” fragments after

  – Activation of complement leads to major protective
       Lysis of foreign cells

  Three pathways of activation
     • Alternative pathway
     • Lectin pathway
     • Classical pathway
Alternate pathway
  – Binding of complement protein C3b to microbial cell
    surface initiates the activation of other compliment proteins

  – C3b always circulates at low levels
    in blood
Lectin pathway
  Activation requires mannan-binding lectins (MBL)

  Binding of MBL to microbial surface
  activates other complement proteins
Classical pathway
  Antibody binding to microbial surface
  activates other complement proteins
  – Complement components C3a and C5a induce
    changes in endothelial cells
     • Increases vascular permeability

  – C3b binds foreign material (e.g. microbial cells)
     • Allows phagocytes to more easily engulf foreign cells/material
Membrane Attack Complex

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