Docstoc

Immunity

Document Sample
Immunity Powered By Docstoc
					Immunity
Innate (or natural) immunity: Non
specific defenses or barriers to infection
which are (in healthy people) always
present.

Adaptive (or acquired) immunity: A
response that is directed toward a specific
pathogen and develops over time and has
“memory” (reactivity changes with repeated
exposure).
Innate Immunity Components
  Physical
     o Barriers to infection e.g. skin
     o Flushing mechanisms e.g. coughing,
       urine flow
  Chemical responses e.g. lysozyme in
   tears, complement
  Cellular e.g. phagocytic cells (able to
   engulf and ingest material)
Specific Immunity
Components
  Chemical – the humoral immune
   response using antibodies

  Cell mediated  cells that are directed
   by the immune response to attack an
   invader.
The “Players”
Innate Immunity
  Complement:
    o A series of molecules present in
      serum, which interact with the
      bacterial cell membranes and with
      each other so that at completion they
      punch a hole in the bacterial
      membrane.
    o It is composed of a series of
      reactions, which act as a cascade
      with the product of one active on the
      next in the chain.
    o The products amplify the reaction,
      increase permeability of blood
      vessels and also act to attract cells to
      the site of the reaction. The products
      make the target more attractive to
      phagocytosis by immune cells
      (“opsonization”).
o It can be activated by interaction of
  one of the initial components with
  bacterial cell surface substances
  (“Lectin pathway”), bacterial
  products (the “Alternative
  pathway”), or by antibodies that have
  bound to antigens (the “Classical
  pathway”).
o There is a “recognition unit”, made
  up of some of the initial components.
o The final product is the “membrane
  attack complex”.
 Acute Phase Reactants
 Substances that rapidly increase in
 quantity in the body at the onset of
 infection. An example is C reactive
 protein. These may have antibacterial
 properties or be involved in
 sequestration of essential nutrients.

 Interferon (IFN)
 These are substances (IFN-,-,-) that
 are produced by virally infected cells
 which bind to receptors on other cells
 and prompt them to produce antiviral
 proteins.
 Phagocytic cells:
  PMN, monocytes, macrophages, are part
  of the innate system but have a role in
  activating the specific system and when
  activated become part of the specific
  system.

 Mast Cells
 Cells found in the tissues that contain
 granules that are rich in histamine and
 inflammatory mediators. These are
 released on stimulation by complement
 products and IgE, promoting local
 inflammation.
Humoral
  Antigens: molecules which stimulate an
   immune response.
      Some antigens can only be
       recognized after having been
       processed by T cells.
      “haptens” are substances which are
       too small by themselves to elicit an
       immune response but maydo so
       when bound to a larger molecule.
  Epitope: the molecular structure on an
   antigen that the antibody interacts with.
   An antigen may have many epitopes.
 Antibodies: (=immunoglobulins)
  proteins produced by the body that bind
  to antigens.
     each molecule is “Y” shaped and has
      two variable regions that bind to
      antigens, and a “constant” (“Fc”) end
      that binds to the host‟s receptors
     Antigens may be on the surface of
      organisms , they may be substances
      in the serum, including toxins, or
      viruses. An antibody may or may
      not be able to neutralize the toxin or
      virus.
     Normally a mixture of antibodies of
      a class is produced to different
      epitopes of the antigen. This is a
      “polyclonal response”.
     A preparation of pure antibodies of a
      single type, all directed at the same
      epitope can be made; these are
      “monoclonal antibodies”.
 The strength of the binding between
  an antibody and an antigen is called
  the affinity. It often increases with
  second or more exposures to an
  antigen.
 different types (“classes”) are
  produced that have different
  properties. These are IgM, IgG, IgA,
  and the less plentiful IgE and IgD.
IgM:
o This is the first antibody produced in
  response to a first infection
o It occurs as 5 units that are attached,
  and so is a big molecule that does not
  get into tissue from blood or cross
  the placenta.
o Complement binds to it very well
IgG:
o IgG is the most plentiful
  immunoglobulin
o It is produced after IgM in infection,
  a process called class switching,
  where the IgG antibody produced by
  a cell has the same specificity for an
  antigen as the IgM it replaces.
o It is produced predominately when
  exposure to the agent occurs in a
  second infection (boosting response).
o Its production is controlled by T
  cells.
o It binds to complement (“fixes
  complement”), attracts phagocytes,
  and opsonizes well. It penetrates
  tissue and crosses the placenta.
IgA
o Occurs as single or paired molecules
o Secretory IgA is found in secretions
  (e.g. tears, saliva, respiratory
  secretions, colostrum)
o Its production is controlled by T
  cells.
IgE
o Activities are anti parasitic and
  involved in hypersensitivity
  reactions
IgD
o Found as a receptor on B cells cell
  surface.
Cells
  Polymorphonuclear leukocytes
   (neutrophils, PMN) white blood cells
   able to phagocytose invaders. They are
   the most common WBC, and are short
   lived. They circulate in blood and enter
   the tissues, gathering at the site of
   infection. Pus is largely made up of
   PMN.
  Eosinophils are white blood cells
   (WBC) that are anti-parasitic. They
   contain granules that stain red with the
   dye eosin. They may also be increased
   in hypersensitivity states (e.g.asthma).
  Basophils are cells that are involved in
   hypersensitivity reactions.
 Mononuclear phagocytic system
  o Monocytes are WBC that circulate
    until stimulated to differentiate into
    macrophages or one of a family of
    phagocytic cells (dendritic cells)
    found in various organs throughout
    the body.
  o Macrophages are larger and longe
    lived than PMN and are found in the
    tissues. They are able to:
       Phagocytose invaders
       Present the antigens to T
        lymphocytes for development of
        specific immunity
       “Call for help” by secreting
        cytokines.
 Dendritic cells are phagocytic cells
  descended from monocytes or the
  lymphocyte cell lines, which are like
  little octopuses.
      They are widely distributed in tissues
       in an immature form
      They are very good at presenting
       antigen to T lymphocytes.
      The immature form phagocytoses
       antigen and then becomes mature,
       stops its phagocytosis and goes to the
       lymph node to deliver the antigen to
       the T cells.
Lymphocytes
   B Cells        Differentiate in Bone
    marrow in mammals.
      Give rise to plasma cells, which are
       antibody “factories” or to memory
       cells, which circulate and are primed
       to produce a specific antibody if they
       come into contact with the
       appropriate antigen.
      During development B cells are
       produced that each recognizes a
       specific antigen. There are so many
       B cells, that a wide range of antigens
       can be recognized.
          When an antigen binds to
           antibody on the surface of the
           B cell, it stimulates the cell to
           divide and to increase in
           number (“clonal expansion”).
 With clonal expansion,
  mutations occur in the genes
  controlling the antibody
  region that binds to the
  antigen.
 The antibodies produced vary
  in their ability to bind and
  those B cells that produce the
  antibody that binds best are
  stimulated to increase.
 This causes the B cells that
  best recognize an antigen to
  increase in response to it, and
  to improve the specificity of
  the antibody produced.
 T cells         Develop in the
  thymus
     They control the immune
      response by producing cytokines
     They are able to directly kill
      foreign tissue cells, virally
      infected cells, or tumour cells.
     They activate phagocytic cells to
      destoy the organisms they have
      ingested.
     Some develop into memory cells
      (as do some B lymphocytes).
     Generally T cells express CD-4
      or CD-8 but some which are
      specialized for killing cells, NK
      (Natural Killer) cells do not
      express either.
There are different populations of T cells
that perform each of these functions.
           CD 4 T cells, or “T helper
            cells”, activate and control the
            immune response.
                o They respond to the signals
                  of the cell presenting the
                  antigen and differentiate
                  either into TH1 cells that
                  promote a local response
                  with inflammation and is
                  good at handling
                  intracellular pathogens, e.g.
                  viruses, mycobacteria,
                  fungi;
                o or TH2 cells that promote
                  antibody production and
                  memory cells. This is a
                  systemic response that
                  happens later in the
                  infection than the TH1.
  CD 8 cells or “suppressor T
   cells” patrol looking for virally
   infected cells, or tumours. When
   they detect them they start to
   divide and differentiate into
   Cytotoxic T Lymphocytes and
   are able to destroy the target
   cells. CD 8 cells also can
   suppress Helper T cell function
   using inhibitory cytokines.
- Large granular lymphocytes
  (Natural Killer cells) contain
  granules of cytotoxic material,
  which they use to kill virally
  infected cells and tumor cells.
  (These are similar but distinct from
  CD-8 T cells).
  o They have Fc receptors to allow
    them to detect cells coated with
    antibody, which they then
    destroy.
Communication between cells
   Cytokines (most common types are
interleukins, also tumor necrosis factors etc.)
           Substances produced by cells that
               Bring about differentiation of
                cells
               Cause activation of
                phagocytic cells and
                lymphocytes
               Influence inflammation
               Influence cell mediated
                responses and antibody
                responses.
           They are usually produced in
            combinations
           They may act on different cells
            differently
           T lymphocytes are an important
            source.
Antigen presentation
 o Antigens must be presented to T cells for
   them to act upon them.
 o An important role is played by the Major
   Histocompatibility Complex Class1 and
   Class II molecules (MHC I, MHC II).
 o MHC I is found on all cells and is
   essential for recognition of “self”. They
   are used in tissue typing to determine if
   transplants will be compatible (HLA
   typing).
 o MHC II is found on monocytes,
   macrophages, B cells, dendritic cells and
   phagocytic cells related to macrophages
   that are found in the tissues.
o Antigen is broken down into peptides by
  the initial cell prior to presentation.
o The resulting short peptides are
  presented associated with the MHC
  molecules.
o Antigen is presented with MHC I to CD
  8 T cells
o Antigen is presented with MHC II to CD
  4 T cells
o T cells recognise the peptides to be viral,
  or bacterial debris and become activated,
  producing ctokines to begin activity in
  other cells.
Anatomical Organization of the
Immune System

Cells important in the immune system
originate in the bone marrow and some
develop in the thymus. These are the
primary lymphoid organs.
   The lymphoid cell line gives rise to
    lymphocytes.
   The myeloid cell line give rise to white
    blood cells (including PMN and
    macrophages) as well as red blood cells
    and platelets.
   These cells can be identified based on
    the receptors they express on their
    surface. Each receptor is referred to by a
    “CD” number, e.g. CD-4 is expressed
    by T helper cells, CD-8 by T suppressor
    cells. There are more than 200 CD
    markers, and they are used to allow us to
    determine the types of cells and their
    function.
Lymphocytes are based in the
secondary lymphoid organs
   Lymph nodes (“glands”)
    o These become swollen when
      responding to infection because of
      lymphocyte proliferation within
      them.
    o They are strategically placed to
      screen lymph draining from the
      limbs (in the groin and axillae),
      mouth and pharynx (groups
      distributed in the neck), the gut
      (groups distributed in the
      retroperitoneum), and respiratory
      pasages (hilum of the lungs and
      around the trachea).
 Spleen
   o Acts as a “super” lymph node
   o Screen out old or infected blood
     cells, encapsulated bacteria , and
     viruses
 Mucosa associated lymphoid tissue
  (MALT) e.g. gut associated = GALT;
  bronchial associated = BALT. This
  includes the peyer‟s patches in the gut,
  tonsils, and appendix.
    o These are rich in memory cells and
      plasma cells and sample the flora and
      watch for pathogens.
Hypersensitivity
  An Immune Response that occurs as an
   exagerated or inappropriate form.
  There are four mechanism which may
   proceed simultaneously but which have
   different time courses and effects.
Type 1 or Immediate
Hypersensitivity
 The cause of allergic asthma, hayfever,
  eczema, peanut allergy, anaphylaxis
 Person develops IgE antibodies to a
  substance (Sensitization), e.g. pollen, a bee
  sting or an antibiotic (mucous membrane
  exposure may favour IgE production)
 Subsequently, on re-exposure, antigen reacts
  with IgE bound to mast cells, causing
  degranulation of the mast cells and release
  of vasoactive substances.
 Anaphylaxis occurs when the release is
  more general, and results in an increase in
  smooth muscle contraction, increased
  vascular permeability, and a fall in blood
  pressure, and may lead to respiratory or
  circulatory collapse and are life threatening.
 The initial reaction occurs within an hour
  but a late reaction takes place after 4-12
  hours.
Type 2 or Antibody Mediated
Hypersensitivity
o The cause of transfusion reactions,
  haemolytic disease of the newborn, and
  some automimmune disease.
o Antibodies are produced to a target which
  can be foreign or from host tissue.
o Binding of the antibody causes activation
  of cell mediated or complement mediated
  causing destruction or damage to the
  target..
o The reaction onset is 8 hours, or chronic in
  autoimmune disease.
 Type 3 or Immune Complex
 Mediated Hypersensitivity
 The cause of serum sickness,
  glomerulonephritis in endocarditis,
  autoimmune disease like rheumatoid
  arthritis, SLE.
 A large quantity of soluble antigen in
  plasma reacts with antibody and forms large
  antigen-antibody complexes, overwhelming
  the normal ability of red cells to take them
  up for transport and removal in the liver.
 These are trapped in capillaries (esp in the
  kidney) and activate the complement
  cascade
 Basophils and platelets which all increase
  vascular permeability. PMN are attracted
  and are unable to phagocytose the immune
  complexes and release granules of damaging
  enzymes, causing local tissue damage.
 The reaction may begin with 6 hours of
  exposure.
Type 4 or Delayed Type
Hypersensitivity
 o Seen in tuberculin skin tests, contact
   dermatitis, granuloma formation
 o Sensitization to an antigen occurs when
   the antiogen is processed by a tissue
   phagocytic cell and the antigen is
   presented to T lymphocytes in the local
   lymph nodes.
 o On re-exposure, the T cells initiate a cell
   mediated response using monocytes,
   macrophages and lymphocytes, which
   invade the area with the antigen..
 o Antibodies are not involved in this
   reaction
 o The reaction occurs in 24-48 hours, but if
   the reaction is chronic and the antigen
   cannot be cleared, the area becomes
   surrounded by macrophages with
   lymphocytes and fibrosis occurs to form a
   granuloma.
Immunodeficiency States
Causes:
     Primary
          o Genetic

     Secondary
          o Resulting from Therapy
                  cancer chemotherapy
                  steroids
                  post transplant
                  splenectomy

          o Cancer (especially hematological
            malignancies)

          o Infection e.g. HIV, an infection of
            T cells and macrophages
            especially.
          o Starvation

          o Pregnancy – mild, but sufficient to
            increase the susceptibility to
            malaria and TB for example.

          o Neonates are relatively
            immunodeficient because of
            immaturity of the immune system

Genetic
  Deficiencies of components of the
   immune system result in “gaps” in the
   defenses.
  Complement deficiencies
     o May occur as a result of lack of any
       of the complement components.
     o Causes failure of the cascade
     o Loss of early components result in
       increased Staphylococcal, and
       Streptococcal infections
   o Loss of late components results in
     increased Neisseria infections
 Defects in Phagocytic Cell Function
   o These predispose to bacterial
     infections.
   o Inability to kill organisms that have
     been ingested is typical of Chronic
     Granulomatous Disease.
     Staphylococci and other catalase-
     producing organisms tend to cause
     infections.
 Lymphocte Function
   o There are a variety of syndromes
     where there is deficiency in the
     lymphocyte including Subacute
     Combined Immune Deficiency
     (SCID) agroup of diseases in which
     there are low antibody levels, and
     lack of lymphoid tissue because of
     failure of their development.
   o These patients will present with
     infections as the maternal immunity
     transfered at birth wears off.
 T cell deficiencies
   o Tend to get infection with viruses,
     especially herpes family,
     intracellular bacteria, and fungi.
 B Cell deficiencies
   o Tend to get bacterial infections
Iatrogenic (Caused by treatment)
   Chemotherapy
     o Many of these agents affect
       lymphocytes particularly. They act
       by interfering with cell division and
       therefore inhibit regeneration of cells
       that have a rapid turn over e.g. PMN.
       After treatment with these agents
       often the numbers of PMN (and
       other blood cells) will drop and may
       remain depressed for 1-4 weeks
       depending on the therapy, during
       which time there is a greatly
       increased risk of infection.
  Corticosteroids (e.g.prednisone,
   dexamethasone)
     o Damp down inflammation by many
       mechanisms including anti
       macrophage and anti T lymphocyte
       effects, and interruption in the
       presentation of antigens and decrease
       antibody responses.
Post Transplant
  Commonly used agents include
   cyclosporinA, tacrolimus and serolimus
   which inhibit lymphocyte function. The
   result is immunosuppression with a
   predisposition to infections of T cell
   deficiency.

Splenectomy
  Removal of the spleen may be required
   because of trauma or as part of treatment for
   malignancies, or other conditions. Rarely it
   may be congenitally absent.
  The spleen is the main site of production of
   opsonizing antibody.
  It removes circulating microorganisms,
   immune complexes, and old blood cells.
  Removal increases the risk of life
   threatening infection with encapsulated
   organisms including Streptococcus
   pneumoniae, Haemophilus influenzae, and
  Neisseria meningitidis, and also Salmonella
  and other less common bacteria.
 These infections can progress very rapidly
  from health to death in <24 hours
 Immunization is recommended to patients
  who are going to undergo splenectomy to
  S.pneumoniae, H. influenzae and N.
  meningitidis
Sequence of Events in the
Immune Response
First Exposure - Initial Response
  Microorganisms gain entry through a
  breach in skin (the innate defense barrier).
  Tissue based macrophages and dendritic
  cells phagocytose some bacteria and process
  the antigens to present to T cells in the local
  lymph nodes.
  Complement is activated by the antigens
  on the suface of the organisms and a
  membrane attack complex is formed which
  punches holes in the bacterial cell
  membrane, killing some of the organisms.
  Inflammatory mediators, e.g. histamine,
  tumor necrosis factor  (TNF-), are
  released from cells that increase vascular
  permeability, and blood flow. The site will
  begin to appear red, swollen, warm to touch,
   and painful. These are the classic signs of
   inflammation.

The Arrival of PMN
  Complement components diffuse out
  from the site of infection and attract PMN
  that are patrolling in the blood.
  The PMN will migrate to the site of
  infection (“Chemotaxis”).
  The PMN begin to “roll” along the
  endothelial lining of the blood vessels and
  bind more closely to it as they are attracted
  and activated by the inflammatory signals.
  They penetrate the endothelium and enter
  the tissues (“Diapedesis”).
  The PMN phagocytose the organisms
  which, once inside the cell, are killed in a
  “phagocytic vacuole” by an “oxidative
  burst” resulting from fusion with granules
  that contain reactive oxygen radicals
  (hydrogen peroxide) generated within the
  PMN.
  The accumulating PMN form pus.
Activation of the Specific Response
  The activation of T cells in the lymph
  nodes causes proliferation of lymphocytes
  and the lymph node becomes enlarged and
  often tender. T cells are activated and
  defend against intracellular organisms, B
  cells are activated and develop into plasma
  cells producing antibody after 5-7 days.
  Initially IgM is produced and then with class
  switching the antibody changes to IgG.
  In the lymph node the T cells activate
  macrophages so they become more effective
  at killing the organisms, by producing more
  reactive sustances to fuse to the phagocytic
  vacuoles, and these arrive at the site of
  infection after 1-3 days.
  Antibody binding to the organism
  promotes phagocytosis (opsonization) and
  activates complement. Initially this occurs
  in the blood with IgM, later in the tissues
  with IgG.
 If organisms have spilled into the
 blood, macrophages in the spleen clear
 them.
 A more severe infection will result in
 the production of cytokines that cause
 fever, and the production of acute phase
 reactants. The bone marrow produces
 more PMN and the WBC becomes
 raised.
 Memory cells are generated that are
 long lived and are able to respond to
 reexposure by generating antibody
 (especially IgG) rapidly.
 As the infection subsides T cells
 suppress the immune response and
 conditions return to normal, but there
 may be residual tissue damage
 manifested by fibrosis and scarring.
 If the infection is chronic the site
 may be infiltrated with macrophages and
 lymphocytes, forming a granuloma,
 which is walled off by fibroblasts.
Viral Infection
  If the infection is caused by a virus,
  interferon is produced locally at the site of
  infection. Interferon results in inhibition of
  viral replication, it “warns” adjoining cells
  and renders them resistant to infection,
  activates the immune system, and the host
  experiences a feeling of malaise with muscle
  aches and fever.
  Fever inhibits many viruses that are
  unable to multiply at raised temperatures.
  Macrophages phagocytose virus and
  debris of cells killed by virus and present the
  antigens to the T cells to activate the specific
  immune response.
  NK cells may be activated by interferon
  to eliminate infected cells.
Re-exposure
  The presence of memory cells
  enables a more rapid and vigorous
  response when antigens are presented by
  macrophages or dendritic cells.
  Antibody, predominately IgG is
  more rapidly produced.
  Infection maybe extinguished before
  the host becomes aware of any
  symptoms of it.
Evasion of the Immune Response

Bacteria may evade the immune response
by:
  Destroying complement components
    e.g. Gp A Streptococci
  Destroying immunoglobulin e.g.
    Neisseria may produce an IgA protease.
  Preventing phagocytosis e.g.
    encapsulated organisms
  Preventing intracellular killing after
    being phagocytosed:
  Bacteria may prevent the phagocytic cell
    from killing them e.g. M. tuberculosis
  Bacteria can be transported inside cells
    throughout the body. Activation of
    macrophages results in the cell
    becoming able to kill the organisms
    inside it.
  Some bacteria are not killed by the usual
    mechanism inside the cell phagocytic
    vacuole e.g. Salmonella
 Bacteria growing inside the cytoplasm of
  cells are protected from antibody or
  detection by the immune system.e.g.
  Listeria
 Bacteria (or other organisms) may
  change their surface antigens rapidly
 The immune system generates a specific
  response but it does not recognise the
  changed organism.
Immunization

This is the use of a specific immune response to
prevent or lessen the severity of disease
resulting from infection or the products of an
infection (e.g. toxins)
Passive Immunization
 o The host receives antibody produced by
   another host.
 o Naturally occurring: the neonate receives
   antibody transplacentally from the mother,
   or in colostrum.
 o Therapeutic: Antibody (immunoglobulin or
   Ig) is given :
     o To provide rapid protection after a
       potential exposure to an agent e.g. after a
       needle stick.
     o To lessen the severity of ongoing disease
       e.g. antibody given in necrotizing
       fasciitis
     o For individuals unable to produce
       antibody
 o This protection is short lived (2-3 months)
   and has no long term protection is generated.
 o Examples: Hepatitis B Ig, Varicella Zoster
   Ig (VZIG), Rabies Ig, RSV can be either
   hyperimmune Ig or monoclonal Ig
Active Immunization (= vaccination)
 o The generation of immunity by
   administering an antigen to elicit an immune
   response in the host.
 o Among the first types was Jenner‟s
   administration of cowpox virus (vaccinia) to
   prevent smallpox.

Types of Active Immunization can be divided
into:
       Live attenuated
       Inactivated whole cell or subunit
       Toxoid
Live Attenuated
 o These use organisms which are limited in
   their ability to cause disease but share
   antigenicity with the virulent forms.
 o Attenuated organsim are those that have
   been repeatedly cultured in the lab until they
   have lost their virulence properties.
 o Administration need not be by injection, and
   may mimic the natural route of infection.
 o They have the advantage that they mimic a
   natural infection and give long term
   immunity, not needing booster doses.
The principle disadvantages are
  They may be virulent for immunosuppressed
   people or in pregnancy
  They may revert to the virulent form during
   the infection in the host
  They must be handled properly to maintain
   viability until they are used
Examples are
  Sabin polio vaccine this agent was used
   to eradicate polio in the Western
   hemisphere. It was cheap andd gave IgA
   immunity in the gut. Rarely, however, it
   reverted to the virulent form and so as
   wild type polio disappeared the vaccine
   became more dangerous than the risk of
   acquiring the disease and so it was
   replaced by the killed (Salk) polio
   vaccine.
  Measles/mumps/rubella vaccine (MMR)
   is used routinely in childhood and has
   been very successful in largely
   eradicating these diseases in the
   immunized.
Inactivated Vaccines
  These include whole cell, and subunit
   vaccines.
  They are often given with a substance that
   increases their immunogenicity (an
   “adjuvant” e.g. alum)
They usually are:
  Given by injection, and therefore they do not
   give a local IgA response (mucosal
   immunity).
  Require multiple doses
  Give immunity that wanes over time, so that
   reimmunization may be required.
  They give an antibody response but not cell
   mediated immunity.

Examples are:
Salk polio vaccine, hepatitis A vaccine,
Subunit vaccines
  These are made with purifed antigens
   derived from the pathogen and which are
   found to produce an effective immune
   response.
  These vaccines aer less prone to side
   efects than whole cell and are often very
   effective but are expensive.

Examples are Hepatitis B vaccine where the
outer coating (surface antigen) is used.
Haemophilus influenzae type B,
pneumococcal, and meningococcal vaccines
are prepared from bacterial polysaccharde
capsular material. As this material is not
very immunogenic, it is now often bound to
a protein (“conjugated”) to increase its
immunogenicity.
Toxoids
  These are inactivated toxins
  Immunization protects from the action of
   the toxin.
  Multiple doses are given, with an
   adjuvant to increase immunogenicity.
  These have been very effective vaccines.
  Examples are tetanus and diphtheria
   toxoid vaccines
Childhood Immunizations
 •   Federal recommendations from National
     Advisory Committee on Immunizations
     (NACI) with provincial implementation
     (varies between provinces).
 •   Have greatly reduced childhood
     morbidity and mortality
 •   Why do vaccine programs fail ?
 –   Many programs do not reach the target
     of 95%
 –   Missed opportunities by health-care
     workers and care-givers
 –   Improper vaccine storage
 –   Misconception of vaccine benefits, side-
     effects and contra-indications. The anti-
     vaccine „fringe‟.
Current Vaccine Targets
 •   Measles / Mumps / Rubella
 •   Diptheria / Polio / Tetanus / Pertussis
 •   Haemophilus influenza type B
 •   Hepatitis B
 •   Streptococcus pneumoniae
 •   Varicella
 •   Neisseria meningitidis
Diptheria / Tetanus / Pertussis
 •  Diptheria toxoid, tetanus toxoid, and
    acellular pertussis vaccine (DTaP)
 • primary immunization at 2,4,6 months
 with boosters at 18 months and 4-6 years.
 • often combined in a pentavalent form
 (contains 5 vaccines in one) with
 poliovirus and haemophilus b vaccines
 • acellular pertussis vaccine approved in
 1997 in Canada for primary vaccine has
 less adverse effects and better
 immunogenicity.

 • Diptheria toxoid and tetanus toxoid (Td
   booster)
 • given at 14-16 yrs of age with boosters
 every 10 years
 • less diptheria toxoid (to decrease adverse
 reactions)
Polio Vaccine
 •   Available as inactivated (IPV, Salk) and
     live oral (OPV, Sabin)
 •   OPV induces a natural immunity with
     advantages of secretory-IgA production
     but shedding through GI tract offers
     opportunity for vaccine-associated
     infections
 •   Primary immunization at 2,4,6 mo. with
     boosters at 18 mo. and 4-6 yrs.
 •   May no longer be necessary in future
     decades if poliovirus infection is
     eradicated
 •   Oral polio vaccine no longer used in
     North America due to growing
     immunosuppressed population, and
     vaccine-asssociated paralytic polio.
Haemophilus type B vaccine
 •   Haemophilus influenza type B was the
     most common cause of bacterial
     meningitis and epiglottitis in Canada
     prior to 1995.
 •   The current vaccine consists of
     Polysaccharide conjugated to a protein
     (4 preparations exist).
 •   Conjugation to a protein activates T-cell
     dependant immunity (immunogenic in
     infants and improved memory)
 •   Hib vaccine can be given in conjunction
     with DTaP and polio
 •   Adverse reactions: fever, local redness,
     and swelling in < 5%
Measles-Mumps-Rubella
 •   Live-attenuated vaccine
 •   Primary immunization age 12-15 months
 •   2nd dose recommended at 18 mo. or 4-6
     yr s .
 •   Elimination of indigenous transmission:
     2005 goal
 •   Adverse reactions: rash and fever 5-
     10%
 •   Contraindications: severe acute illness
     or immunosuppression (Not egg allergy)
Influenza vaccine
 •   Inactivated whole or split-virus vaccine
 •   Vaccine changed annually depending on
     circulating strains
 •   Vaccine contains two influenza A strains
     (H2N3-like, H1N1-like) and an influenza B
     strain
 •   Recommended yearly to high-risk
     individuals and those capable of transmitting
     influenza to those at high risk (i.e. health
     care workers)

High Risk Groups who need to be
 vaccinated for influenza:
 •   Chronic cardiac or pulmonary disorders
 •   Residents of nursing homes and chronic care
     facilities
 •   Age > 65 yrs.
 •   Chronic conditions such as: Diabetes
     mellitus, cancer, immunosuppression, renal
     disease, anemia, hemoglobinopathy, HIV
 •   Children and adolescents requiring long-
     term aspirin
Hepatitis B
 •   Individuals infected at an earlier age
     have greater risk of liver failure,
     cirrhosis, and carcinoma
 •   Increasing cases in Canada throughout
     the 80‟s
 •   Purified HBsAg (recombinant or
     plasma-derived)
 •   3 doses at 0,1 and 6 months IM
 •   Schedule varies from province to
     province
 •   Booster not recommended
 •   Seroconversion rates: 90-95% in
     immunocompetent individuals.
Pneumococcal vaccines
Two vaccines:
  • Polysaccharide vaccine (23-valent) which
    will induce immunity against 90% of
    pneumonia strains of S. pneumoniae
 Efficacy ~ 80% in healthy adults
 Recommended to repeat vaccinations every 5
 years
 Recommended useage:
 • Age > 65yrs.
 • Asplenia, splenic dysfunction or sickle cell
 disease
 • Cerebrospinal fluid leaks
 • All „high-risk‟ persons who require
 influenza vaccine
Varicella Vaccine
 •   Live attenuated virus vaccine
 •   Given at age 12 months.
 •   If given >12 yrs of age requires 2 doses
 •   Extremely safe with < 5% of children
     developing several varicella lesions.
 •   Over 95% effective in preventing severe
     varicella infections
 •   Has the potential to make varicella an
     uncommon disease in North America
Summary
 •   Immunity can be conferred either through
     natural infection, passively via
     administration of antibody or through active
     immunization.
 •   Our current vaccine schedule has
     dramatically altered childhood morbidity
     and mortality.
 •   The immunogenicity of a vaccine depends
     on multiple factors and can be enhanced by
     adjuvants and hapten conjugates.

				
DOCUMENT INFO
Shared By:
Categories:
Tags:
Stats:
views:22
posted:8/7/2011
language:English
pages:65