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NONSPECIFIC DEFENSE

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NONSPECIFIC DEFENSE Powered By Docstoc
					THE IMMUNE SYSTEM


 Prof. Khaled H. Abu-Elteen
    Terminology
   Types of Symbiosis ( Living togathers)
    - Amensalism
   A symbiotic relationship in which one species is
    harmed, but it isdifficult to see how the other species
    benefit.
    –   Mutualism
          A symbiotic relationship in which both species benefit
    –   Commensalism
          A symbiotic relationship in which one species benefits,
           and the other species is neither helped nor harmed
   Types of Symbiosis (cont.)
    –   Parasitism
         •   A symbiotic relationship in which one
             species benefits, and the other species is
             harmed
         •   Generally, the species that benefits (the
             parasite) is much smaller than the species
             that is harmed (the host)
   Disease and Infectious Disease
    –   Disease
          Any deviation from a condition of good
           health and well-being
    –   Infectious Disease
          A disease condition caused by the presence
           or growth of infectious microorganisms or
           parasites
Immunology lingo
   Antigen
    –   Any molecule that binds to immunoglobulin or T cell receptor
   Pathogen
    –   Microorganism that can cause disease
   Antibody (Ab)
    –   Secreted immunoglobulin
   Immunoglobulin (Ig)
    –   A glycoprotein produced in response to the introduction of an antigen
   Vaccination
    –   Deliberate induction of protective immunity to a pathogen
   Immunization
    –   The ability to resist infection
TYPES OF IMMUNITY.
 Nonspecific: Skin and mucous membranes,
  Phagocytosis, Inflammation, and The
  Complement System.
 Specific: Humoral(Antibody-Mediated) and
  Cell-Mediated.
Nonspecific Immune Response
   Physical and Mechanical Barrier’s
   Chemical Factor’s
   Biological Factor’s
   Phagocytosis and Associated with Blood and
    lymph

   Defenses that protect from ANY pathogen
    regardless of type and species( Bacteria, Fungi,
    Protozoa, etc).
    Physical and Mechanical Barrier’s
 THE SKIN: First Line Of Defense.
 Repels many organisms: difficult to get
  through.
 Epithelium lines all body systems exposed to
  external environments including the respiratory,
  digestive and urinary systems.
 Secretes liquid which are mildly acidic which
  hinder bacterial growth.
 Lack of nutrition for microbial growth.
DEFENSES
–   Dry
      usual   infection sites are wet areas, skin folds, armpit,
      groin
–   Acidic (pH 3.0- 5.0)
–   Temperature less than 37oC
      Some    pathogens grow best <37oC
–   Lysozyme and toxic lipids
      pore,   hair follicles, sweat gland
–   Resident microflora
      mainly   G+
–   Skin-associated lymphoid tissue (SALT)
 Tears and saliva contain lysozymes which
  dissolve the wall of bacteria.
 Cilia of respiratory tract trap bacteria in
  mucus.
SKIN AND MUCOUS
MEMBRANES:1st line of defense
   Mechanical Factors:
   Skin.
   The Epidermis.
   Keratin.
   Mucous Membranes.
   Lacrimal Apparatus ------>
   Cilliary Escalator [ mucocilliary Escalator
    Action).
LACRIMAL APPARATUS.
CILIARY ESCALATOR.
Flushing Mechanisms
 Epiglottis.
 Urine and Vaginal secretions.
 Sneezing, coughing, swallowing reflex
 Movement of Fluids across their surfaces
  (Saliva)
 Washing action of tears
CHEMICAL FACTORS.
 Sebum and fatty acids in skin ( e.g.
  unsaturated fatty acids as Olic acid).
 Gastric Juice (Low pH stomach ).
 Lyzozyme: degrade the bacterial cell wall
 Antimicrobial peptides (β Lysine) with high
  quantity of Lysine or Arginine. Act by
  disruption of plasma membrane of
  microorganisms.
Complement:complex        of 17 proteins
(Glycoproteins) present in normal serum) C1,
C2, C3 …..etc. Function: Lysis of microbes,
Neutralization of viruses, Enhancement of
phagocytosis, Damage of plasma membrane,
Recruitment of Phagocytes,
Interferons   : Family of Glycoproteins that
block Viral Replication by rendering host cells,
NORMAL MICRIBIOTA AND
NONSPECIFIC RESISTANCE.
 Microbial Antagonism.
 Commensalism.
 Competitive Exclusion: Opportunistic
  pathogens.
 Natural Resistance: Microorganisms has a
  host range
Cells of the Immune system:
FORMED ELEMENTS IN BLOOD.
 Many cells of
  the immune
  system derived
  from the bone
  marrow
 Hematopoetic
  stem cell
  differentiation
Components of blood
Serum vs. Plasma
 Serum: cell-free liquid, minus the
  clotting factors
 Plasma: cell-free liquid with clotting
  factors in solution (must use an
  anticoagulant)
 Contain protein: Albumin, Globulin
  and Fibrinogen.
Components of blood
LEUKOCYTES.
 Divided into two main categories based on
  their appearance under the light microscope:
 Granulocytes Versus Agranulocytes.
 Granulocytes: Neutrophils(stain lilac),
  Basophils (stain blue-purple), and
  Eosinophils (stain red or orange).
NEUTROPHILS ( 60% of WBC)
   Commonly called
    polymorphonuclear
    leukocytes (PMNs).
   Multinucleated.
   Highly phagocytic and
    motile.
   Active in the initial stages
    of infection.
   Short life span (hours)
   Very important at
    “clearing” bacterial
    infections
   Innate Immunity
BASOPHILS (1% of WBC)
   Role is not clear.
   Release substances,
    such as histamine, that
    are important in
    inflammation.
   Might be “blood Mast
    cells’
   Important in allergic
    reactions
Eosinophils ( 3% of WBC)
   Somewhat phagocytic.
   Have the ability to leave
    the blood.
   Major function is to
    produce toxic proteins
    against certain parasites
    such as worms.
   Involved in allergic
    inflammation
   Double Lobed nucleus
   Orange granules contain
    toxic compounds
AGRANULOCYTES.
 Monocytes ( 5% of all WBC).
 Macrophages.
 Lymphocytes ( 30% of all WBC) .
MONOCYTES.
   Phagocytosis and killing
    of microorganisms
    –   Activation of T cells and
        initation of immune
        response
   Monocyte is a young
    macrophage in blood
   There are tissue-specific
    macrophages
   Antigen Presentation
MACROPHAGES.
   Maturation and
    proliferation of is one
    factor that is
    responsible for the
    swelling of lymph
    nodes during an
    infection.
Lymphocytes
 Many types:
 B-cells produce
  antibodies( Humoral
  immunity)
 T- cells (Cellular
    immunity)
     – Cytotoxic T cells
     – Helper T cells
   Memory cells
Lymphocytes
   Plasma Cell (in tissue)
    –   Fully differentiaited B
        cells, secretes Ab
   Natural Killer cells
    –   Kills cells infected with
        certain viruses
    –   Both innate and adaptive
    –   Antigen presentation
TH cells play a central role in the immune system


        Antigen
        Presenting
        Cell
Dendritic Cells
 Activation of T cells and
  initiate adaptive immunity
 Found mainly in
  lymphoid tissue
 Function as Antigen
  Presenting Cells (APC)
 Most potent stimulator of
  T-cell response
    Mast Cells
 Expulsion of parasites through release
  of granules
 Histamine, leukotrienes, chemokines,
  cytokines
 Also involved in allergic responses
Other Blood Cells
   Megakaryocyte
    –   Platelet formation
    –   Wound repair
   Erythrocyte
    –   Oxygen transport
Cells, tissues and organs of
the immune system
   Immune cells are bone marrow-derived, & distributed through out
    the body

   Primary lymphoid organs:
     – Thymus: T cell maturation
     – Bone marrow (bursa of Fabricius in birds): B cell maturation


   Secondary lymphoid organs:
     – Lymph nodes
     – Spleen
     – Mucosal lymphoid tissues (lung, gut)
      2º
           2º


                     1º
                          Major Tissues
2º
                 2º
                             Primary Lymph
2º                            tissues
                2º
                              –   Cells originate
                                  or mature
     2º
                1º
                             Secondary
                              Lymph Tissues
COMPONENTS OF THE
LYMPHATIC SYSTEM.
Dendritic cell
   (sentinel)
The bursa of Fabricius in birds
ACTION OF PHAGOCYTIC
CELLS.
 Wandering macrophages.
 Fixed macrophages.
 Mononuclear phagocytic
  (reticuloendothelial) system.
 During the initial infection, granulocytes,
  especially neutrophils are many and they
  dominate.
Opsonization.
   Opsonization - coating micro-organisms with
    plasma proteins – aids phagocytosis.
   Complement binds to antibody-antigen targets.
   Promotes adhesion between opsonized cell &
    macrophages.
   Opsonin binds to receptors on phagocyte
    membrane.
PHAGOCYTOSIS: 2ND LINE
OF DEFENSE.
 Cell Eating.
 Phagocytes: Cells that perform
  phagocytosis.
 Are mostly types of white blood cells or
  derivatives of white blood cells.
THE MECHANISM OF
PHAGOCYTOSIS.
 Chemotaxis.
 Adherence.
 Ingestion.
 Digestion.
3. Phagocytosis & oxidative
burst.
    Certain WBCs - phagocytosis.

    Chemotactically attracted to disease / tissue
     damage foci.

Stages:
1.  Engulfment of particulate matter into phagosome.
    (e.g. bacteria, virions, cell debris, etc.).

2.   Phagosome fuses with lysosomes =
     phagolysosome.
3. Phagocytosis & oxadative
burst.
   Lysosomes contain enzymes = degrade
    biomolecules.

   E.g. acid hydrolases, lysozyme, neutral proteases,
    myeloperoxidase, lactoferrin, & phospholipase A.


 Human macrophage engulfing the fungus Candida
               albicans.
3. Phagocytosis & oxidative burst.


  
Yeast   Engulfed organisms killed in WBC by
        “respiratory (oxidative) burst".


       Many pathogens / parasites succeed because avoid
        phagocytosis.
      Neutrophil




        Human neutrophil kills yeast cell using
                 oxidative burst.
           Dye shows extent of reactions.
INFLAMMATION: Second line
of defense.
 Inflammatory response results in increased
  blood flow to infection; chemical attractants
  and flow of fluid to wound ( vasodilation).
 Together these cause swelling, heat, and
  pain.
 Fluids include histamine and serotonine
  (causes arterioles to dilate), and plasma
  (contains clotting factors to wall off area.
 Kinins: cause vasodilation and increased
  permeability of blood vessels.
 Prostaglandins: released by damaged cells,
  and intensifies the effects of histamin and
  kinins.
 Leukotrienes: produced by mast cells and
  basophils- Cause increased permeability,
  and attract phagocytes to pathogens.
 Vasodilation and increased permeability of
  blood vessels also help to deliver clotting
  elements to injured area.
 Blood clots prevent microbe from
  spreading, so a localized collection of pus
  results(abcess).
Inflammation.


    Inflammation - phagocytes & complement
     recruited to site tissue invasion.

    Non-specific reaction to tissue damage.

    Cell damage initiates inflammation.
Inflammation.
                • Vasodilation - swelling.
                • Adhesion of leukocytes to
                endothelial cells & migration
                phagocytes into tissues.
                • Redness (blood flow).
                • Pain (prostaglandins).
                • Heat (pyrogens).
                • Inflammation localised to area
                infection / injury and give pus.
                •Once organisms destroyed
                inflammation resolves.
Inflammation




               Figure 22.13
Types of Immunity




                    Figure 22.14
Types of immunity

   Innate (natural) immunity
    –   Phagocytes etc.
    –   Early, rapid responses, but limited & ‘non-specifc’


   Adaptive (acquired) immunity
    –   Lymphocytes (B & T cells)
    –   Take time but powerful - ‘specificity + memory’
Measles attacks & immunological memory
Vaccination protects us from infection by
inducing the adaptive immune response, but
bypassing the need for a primary infection
B Cells
work chiefly by secreting
soluble substances known
as antibodies (Ab)
Ab basic structure




                     domains
Ab V and C regions



 Fab
 region
 Antigen
 binding
 site

                     Fc region
                     Activate of
                     Complement
Figure 22.21 Antibody Structure




                             Figure 22.21a
Figure 22.21 Antibody Structure




                            Figure 22.21b-d
    Actions of antibodies include:
 Neutralization
 Agglutination and precipitation
 Activation of complement
 Attraction of phagocytes
 Opsinization
 Stimulation of inflammation
 Prevention of adhesion
Generation of immune response.

   Immunogen = any molecule that stimulates
    immune response. Proteins best immunogens >
    carbohydrates > nucleic acids. Lipids very poor.

   Antigen = molecule capable of generating
    antibody response.

   Antigen = antibody generating.

   Haptan= Ag incapable of stimulating immune
    response. Need carrier molecules for stimulating
    immune response
Generation of immune response.

~ 4-7 days to generate immune response.

   > 7 days get primary immune response.
   1st IgM produced then IgG.
   After ~3 weeks primary immune response turned
    off.
   Ab producing cells & memory B cells formed.
   Memory B cells secrete ab when same agent
    encountered again.
   This is secondary immune response.
   Memory lasts weeks / years.
Classes of Immunoglobulins

    Large globular glycoproteins released by B cells
     in the serum of blood tissue fluids and some
     secretions.
    Specifically interact with antigens.
5 classes Antibodies:
    1. IgM – largest & 1st Ab made. Neutralisation,
    fix complement, agglutinate & immobilise ags.
    2. IgG - main serum Ab. Able to crosses placenta.
    Synthesized during secondary immune response.
    All functions. Smallest ab.
3.   IgA - mucosal / secretory ab , present in mother
     milk.

4.   IgD - receptor ab found on surface
     immunocompetent cells.

5.   IgE - binds surface mast cells = degranulation &
     histamine release. Allergies.
   The End

				
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