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Foundations in Microbiology - PowerPoint

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					NONSPECIFIC HOST DEFENSE
      MECHANISMS
                           1
HOST DEFENSE MECHANISMS




                          2
• 1st LINE OF DEFENSE -
  – intact skin
  – mucous membranes & their secretions
• 2nd LINE OF DEFENSE -
  – phagocytic white blood cells
  – inflammation        -complementnonspecific
  – fever               -interferon
• 3rd LINE OF DEFENSE-
  – B & T lymphocytes                specific
  – antibodies

                                            3
1st LINE OF DEFENSE
         PHYSICAL BARRIERS
• First line of defense are
  barriers that shield interior of
  body from external
  surroundings
• Anatomical barriers include
  skin and mucous membranes
   – Provide physical separation
   – Membranes bathed in
     antimicrobial secretions


                                     5
         PHYSICAL BARRIERS
• Physical barriers
   – Skin is most visible barrier
   – Covers majority of surfaces
     in obvious contact with
     environment
   – Mucous membranes barrier
     that lines digestive tract,
     respiratory tract and
     genitourinary tract
      • Mucous protect these
        surfaces from infections


                                    6
         PHYSICAL BARRIERS
• Skin
  – Provides the most difficult barrier to penetrate
  – Composed of two main layers
     • Dermis
         – Contains tightly woven fibrous connective tissues
            » Makes extremely tough
     • Epidermis
         – Composed of many layers of epithelial cells
            » As cells reach surface, they become increasingly flat
         – Outermost sheets of cells embedded with keratin
            » Makes skin water-repellent
         – Outer layers slough off taking microbes with it
                                                                      7
     PHYSICAL BARRIERS

• Mucous membranes
  – Constantly bathed with mucus
    • Helps wash surfaces
  – Some mucous membranes have mechanisms to
    propel microorganisms and viruses to areas
    where they can be eliminated



                                                 8
      PHYSICAL BARRIERS
• Mucous membranes
  – Constantly bathed with
    mucus
     • Helps wash surfaces
  – Some mucous
    membranes have
    mechanisms to propel
    microorganisms and
    viruses to areas where
    they can be eliminated

                             9
      CHEMICAL BARRIERS
• Sebaceous secretions
• Lysozyme, an enzyme
  that hydrolyzes the
  cell wall of bacteria, in
  tears
• High lactic acid &
  electrolyte
  concentration in sweat

                              10
      CHEMICAL BARRIERS
• Skin’s acidic pH
• Hydrochloric acid in
  stomach
• Digestive juices and
  bile of intestines
• Semen contains
  antimicrobial chemical
• Vagina has acidic pH

                           11
       SPECIALIZED CHEMICAL
             BARRIERS
• Antimicrobial substances
   – Both skin and mucous membranes are protected by variety
     of antimicrobial substances including
      • Lysozyme
          – Enzymes that degrade peptioglycan
          – Found in tears, saliva, blood and phagocytes
      • Peroxidase
          – Found in saliva, body tissues and phagocytes
          – Breaks down hydrogen peroxide to produce reactive oxygen
      • Lactoferrin
          – Sequesters iron from microorganisms
              » Iron essential for microbial growth
          – Found in saliva, some phagocytes, blood and tissue fluids
      • Defensins
          – Antimicrobial peptides inserted into microbial membrane
                                                                        12
          – Found on mucous membranes and in phagocytes
          NORMAL FLORA
• Normal flora
  – Defined as microorganisms found growing on
    body surfaces of healthy individuals
  – Not technically part of immune system
     • However, provides significant protection
  – Protects through competitive exclusion
     • Covers binding sites
        – Pathogens can’t bind
     • Competes for nutrients
        – Nutrients unavailable for pathogens
                                                  13
       GENETIC IMMUNITY

• Some hosts are genetically immune to the
  diseases of other hosts.
• Some pathogens have great specificity
• Some genetic differences exist in
  susceptibility



                                             14
2nd LINE OF DEFENSE
A HEALTHY IMMUNE SYSTEM
   IS RESPONSIBLE FOR:
1. Recognition of
   foreign material
2. Surveillance of the
   body
3. Destruction of
   entities deemed to be
   foreign


                           16
     SYSTEMS INVOLVED IN
       IMMUNE DEFENSE

• The reticuloendothelial system
• The spaces surrounding tissue cells that
  contains ECF
• The blood
• The lymphatic system

                                             17
SYSTEMS INVOLVED IN
  IMMUNE DEFENSE




                      18
     RETICULOENDOTHELIAL
            SYSTEM
• This system is formed of
  reticular fiber which form
  a support network
  enmeshing each cell.
• This mesh connects one
  cell to another within a
  tissue or organ
• Provides phagocytic WBC
  the ability to move within
  and between tissues

                               19
BLOOD




        20
     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
    colony-stimulating factor
                                                   21
         CELLS OF THE IMMUNE
               SYSTEM
• General categories of blood cells
   – Red blood cells (RBC)
      • a.k.a erythrocytes
      • Carry oxygen in blood
   – Platelets
      • 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
                                                           22
BLOOD CELLS




              23
        CELLS OF THE IMMUNE
              SYSTEM

• Granulocytes
  – Contain cytoplasmic graduals
  – Divided into three types
     • Neutrophils
     • Basophils
     • Eosinophils




                                   24
           CELLS OF THE IMMUNE
                 SYSTEM
• Neutrophils
   – Most abundant and important in
     innate response
   – Sometimes called
     polymorphonuclear neutrophilic
     leukocytes (PMNs)
• Basophils
   – Involved in allergic reaction
• Eosinophils
   – Important in expelling parasitic
     worms
   – Active in allergic reactions
                                        25
          CELLS OF THE IMMUNE
                SYSTEM

• Mononulcear phagocytes
   – Constitute collection of
     phagocytic cells called
     mononuclear phagocyte
     system
   – Include monocytes
       • Circulate in blood
       • Macrophages differentiate
         from monocytes
           – Present in most tissues
                » Abundant in liver,
                  spleen, lymph
                  nodes, lungs and
                  peritoneal cavity
                                       26
         CELLS OF THE IMMUNE
               SYSTEM

• Dendritic cells
   – Branched cells
     involved in adaptive
     immunity
   – Function as scout in
     tissues
      • Engulf material in tissue
        and bring it to cells of
        adaptive immunity



                                    27
     CELLS OF THE IMMUNE
           SYSTEM

• Lymphocytes
  – Involved in adaptive
    immunity
  – Two major groups
     • B lymphocytes
         – B cells
     • T lymphocytes
         – T cells
  – Another type
     • Natural killer
         – Lacks specificity of B
           and T cells
                                    28
LYMPHOCYTES




              29
               LEUKOCYTES
• Neutrophils- 55-90% - lobed nuclei with lavender
  granules; phagocytes
• Eosinophils – 1-3% - orange granules & bilobed
  nucleus; destroy eucaryotic pathogens
• Basophils, mast cells – 0.5% constricted nuclei, dark
  blue granules; release potent chemical mediators
• Lymphocytes – 20-35% - large nucleus B & T cells
  involved in the specific immune response
• Monocytes, macrophages – 3-7%- large nucleus;
  phagocytic
                                                     30
     CHARACTERISTICS OF
        LEUKOCYTES

• Diapedesis – migration of cells out of blood
  vessels into the tissues
• Chemotaxis – migration in response to
  specific chemicals which have passed
  through the 1st line of defense


                                             31
32
      CHARACTERISTICS OF
         LEUKOCYTES
• Group 1 - Toll-like
  receptors and NOD
  proteins
   – Found on variety of
     cells
   – Recognize families of
     compounds
   – Enable cells to sense
     invasion
      • Send signal to body to
        respond
                                 33
      LYMPHATIC SYSTEM

1. Provides an auxiliary route for return of
   extracellular fluid to the circulatory
   system
2. Acts as a drain-off system for the
   inflammatory response
3. Renders surveillance, recognition, and
   protection against foreign material

                                               34
35
        LYMPHATIC FLUID
• Lymph is a plasmalike liquid carried by
  lymphatic circulation
• Formed when blood components move out
  of blood vessels into extracellular spaces
• Made up of water, dissolved salts, 2-5%
  proteins
• Transports white blood cells, fats, cellular
  debris & infectious agents
                                                 36
           LYMPH NODES

• Small, encapsulated, bean-shaped organs
  stationed along lymphatic channels & large
  blood vessels of the thoracic and abdominal
  cavities
• Contains both T and B lymphocytes



                                            37
38
RESULTS OF A MICROBE
PASSING THE 2ND LINE OF
       DEFENSE
   CELL COMMUNICATION
• In order for immune system to respond to
  trauma or invasion, cells must communicate
  with 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”

                                           40
   CELL COMMUNICATION
• Surface receptors
  – Membrane proteins to which signal molecules
    bind
  – Receptors specific to molecule to which it
    bonds
     • Binding molecules called ligands
  – When ligand binds, receptor becomes modified
    and sends signal to cell
     • Cell responds by initiating some action like
       chemotaxis
                                                      41
      CELL COMMUNICATION

• Cytokines are proteins made by certain cells as a
  mechanism to communicate with other cells.
  – Cytokines bind to surface receptors; and regulate cell
    function
  – Binding of a cytokine to its receptor induces a change
    in the cell such as growth, differentiation, movement,
    or cell death.
  – They can act locally, regionally, or systemically
                                                     42
                    CYTOKINES
Numerous cytokine classes
  • Chemokines – important in chemotaxis
      – Enhance ability of cells to migrate to appropriate site in body
  • Colony stimulating factors – Important in multiplication and
    differentiation of leukocytes
      – During immune response, directs immature leukocytes to correct
        maturation pathway
  • Interferons – important in control of viral infections
      – Also associated with inflammatory response
  • Interleukins – produced by leukocytes
      – Important in innate and adaptive immunity
  • Tumor necrosis factor – kill tumor cells
      – Instrumental in initiation of inflammation


                                                                          43
   CELL COMMUNICATION
• Adhesion molecules
  – Allow cells to adhere to each other
  – Responsible for the recruitment of phagocytes
    to area of injury
     • Epithelia cells lining blood vessels produce adhesion
       molecules that catch phagocytes as they pass by
        – Causes phagocytes to slow and leak out of vessels to area
          of injury



                                                                  44
        SENSOR SYSTEMS
• Systems within blood detect signs of tissue
  damage or microbial invasion
• Responds to patterns associated with danger
  by
  – Directly destroying invading microbe
  – Recruiting other host defenses



                                            45
                  SENSOR SYSTEMS
• Toll-like receptors (TLR) and
  NOD proteins
   – Pattern recognition receptors
   – TLR allow cells to “see” molecules
     signifying presence of microbes
     outside the cell
   – TLR found in variety of cell types
       • Recognize distinct “danger”
         compounds
            – Signal is transmitted
                 » Results in change of gene
                   expression of cell
   – NOD proteins are intracellular
     receptors that recognize bacterial
     cell wall components within
     cytoplasm
                                               46
          SENSOR SYSTEMS
• Complement system
  – Series of proteins circulating in blood and fluids
     • Circulate in inactive form
  – Augment activities of adaptive immune response
  – Stimulation of inactive proteins initiates cascade of
    reactions
     • Results in rapid activation of components
  – Three pathways of activation of the complement
    system
     • Alternative pathway
     • Lectin pathway
                                                         47
     • Classical pathway
                SENSOR SYSTEMS
• Alternative pathway
  – Quickly and easily initiated
  – Relies on binding of
    complement protein C3b to
    cell surface
     • Initiates activation of other
       compliment proteins
         – Allows formation of
           complement complex
  – C3b always circulating in
    blood so nearly any cell
    automatically triggers the
    pathway unless the body’s
    own cells stop the process
                                       48
                SENSOR SYSTEMS
• Lectin pathway
   – Activation requires mannan-
     binding lectins (MBL) on host
     cells
   – MBLs are pattern recognition
     molecules
       • Detect mannan
           – Polymer of mannose
               » Found in microbial cells
   – MBL attaches to surface of the
     microbe if mannan is present
       • Activates complement proteins



                                            49
         SENSOR SYSTEMS

• Classical pathway
  – Activation requires
    antibodies
     • Antibodies interact
       complement C1
         – Activates protein
             » Leads to
                activation of all
                complex
                proteins



                                    50
            SENSOR SYSTEMS
• Complement
  – Complement system composed of nine proteins
     • C1 – C9
         – Numbered as discovered, not order of activation
     • Certain proteins split into “a” and “b” fragments after activation
         – C3 can spontaneously split to C3a and C3b
             » Insures enough C3b for activation of alternative pathway
  – Activation of complement leads to major protective
    outcomes
     • Inflammation
     • Opsonization
     • Lysis of foreign cells
                                                                            51
        SENSOR SYSTEMS

• Inflammation
  – Complement components C3a and C5a induce
    changes in endothelial cells
     • Effects vascular permeability associated with
       inflammation
• Opsonization
  – C3b binds foreign material
     • Allows phagocytes to easily “grab” particles

                                                       52
            SENSOR SYSTEMS
• Lysis of foreign cells
   – Complexes of C5b, C6, C7,
     C8 and multiple C9
     spontaneously assemble
      • Forms donut-shaped
        structure called membrane
        attack complex (MAC)
      • Creates pores in membrane
      • Most effective on Gram-
        negative cells
          – Little effect on Gram-
            positive cells

                                     53
ACTIVITIES OF PHAGOCYTES

1. To survey tissue compartments & discover
   microbes, particulate matter & dead or
   injured cells
2. To infest and eliminate these materials
3. To extract immunogenic information from
   foreign matter


                                          54
PHASES OF PHAGOCYTOSIS




                         55
              PHAGOCYTOSIS

• Process of phagocytosis
   – Chemotaxis
       • Cells recruited to infection
   – Recognition/attachment
       • Use receptors to bind
         invading microbes
   – Engulfment
       • Phagocyte engulfs invader      – Destruction and digestion
         forming phagosome                  • Organism killed due to
   – Phagosome lysosome fusion                lack of oxygen and
       • Phagosome binds                      decreased pH
         lysosome, forming              – Exocytosis
         phagolysosome
                                            • Phagocyte expels material
                                              to external environment
                                                                       56
 STAGES OF INFLAMMATION
1. Blood vessels dilate in response to chemical
   mediators and cytokines
2. Edema swells tissues, helping prevent spread of
   infection
3. WBC’s, microbes, debris and fluid collect to
   form pus
4. Pyrogens may induce fever
5. Macrophages and neutrophils engage
   phagocytosis

                                                     57
58
                  INFLAMMATION
• Inflammation occurs in
  response to tissue damage
• Four cardinal signs
   –   Heat
   –   Pain
   –   Redness
   –   Swelling
        • Loss of function
            – Fifth sign that can also be
              present


                                            59
          INFLAMMATION

• Factors that initiate inflammatory response
  – Microbial products trigger toll-like receptors of
    macrophages
     • Causes release of pro-inflammatory cytokines
  – Microbial cell surface can trigger complement
     • Leads to the production of C3a and C5a
  – Tissue damage results in enzymatic cascade
     • Cascades initiate inflammation

                                                      60
                     INFLAMMATION
• The inflammatory process
   – Initiation leads to a cascade of
     events
       • Results in dilation of blood vessels,
         leakage of fluid from vessels and
         migration of leukocytes and
         phagocytes
            – Leakage of phagocytes from blood
              vessels called diapedesis
   – Certain pro-inflammatory mediators
     cause the diameter of blood vessels
     to increase
       • Results in increased blood flow
            – Increased blood flow responsible
              for cardinal signs of inflammation

                                                   61
            INFLAMMATION
• Outcomes of inflammation
  – Intent is to limit damage and restore function
     • Inflammation itself can cause considerable damage
        – Release of toxic products and enzymes from phagocytic cells is
          responsible for tissue damage
  – If inflammation is limited to area of injury,
    damage is usually nominal
  – If inflammation results in delicate systems,
    consequences are more severe
     • Inflammation around brain and spinal cord can lead to
       meningitis
                                                                    62
                         FEVER
• One of the strongest indicators of infection
   – Especially of bacterial infection
• Important host defense mechanism
• Temperature regulation center of body responds to
  fever-inducing substances called pyrogens
   – Fever-inducing cytokines termed endogenous pyrogens
   – Microbial products termed exogenous pyrogens
• Resulting fever inhibits growth of pathogens by
   – Elevating temperature above maximum growth temperature
   – Activating and speeding up other body defenses

                                                           63

				
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