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Immunodeficiency

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					 Immunodeficiency
   The appearance of HIV/AIDS revealed
    the profound impact of
    immunodeficiency
    – Infections like TB, for example, might
      otherwise be kept in check, but in an
      immunodeficient host, the disease is allowed
      to progress
   There is a wide array of factors that
    cause immunodeficiency; primary
    immunodeficiency is caused by genetic
    factors, and secondary immunodeficiency
    is caused by external factors
   Immunodeficiency can result from
    defects in our external defences, our
    innate immune system, and/or our
    adaptive immune system
   In some cases, drugs can induce an
    immunodeficient state; this can result as
    a ‘side effect’ of drugs, or it may be the
    specific reason for use of the drug
 Genetic        Factors
   Primary immune defects are typically caused by
    recessive mutations that inhibit the normative
    development of some component of the immune
    system (e.g., an important protein or enzyme)
    – Recessive traits are problematic when an individual
      has two copies of the defective gene
    – X-linked defects are found on X chromosomes; as
      a result, women are less likely to suffer their
      effects, but they can still pass heritable defects on
      to about one half of their children
    – Men with the X-linked mutation will suffer its
      effects, but their children will not be
      immunodeficient because their mother will provide
      a normal X chromosome (unless she is a carrier)
    – Such inherited traits can only involve defects in the
      germ line, that is, in reproductive cells; other
      mutations may affect the individuals carrying them,
      but they are not passed on to succeeding
      generations
    – Autosomal traits occur outside of the X and Y
      chromosomes, so they can affect both sexes,
      although the trait must be dominant, or carried by
      both parents
 Defects      in External Defences
   Immunodeficiency resulting from
    variations in external defences are likely
    due primarily to individual-level variations
    in the production of antimicrobial
    substances (e.g. on the skin or mucosa)
   Variations may also occur in the
    manufacture of antiviral molecules,
    although this may be due to secondary
    factors such as diet, lifestyle, stress, etc.
   Cystic Fibrosis is a defect in external
    defences that inhibits one’s ability to
    clear the air passages of the lungs
    – It is due to a common mutation of a single
      gene; however, since it must be passed on by
      both parents (it is a recessive trait), it is
      relatively uncommon
    – It is well-placed to be subject to genetic
      testing and gene therapy
 Defects      of Innate Immunity
   Defects of Complement
    – Hereditary Angioedema – a condition
      involving the overactivity of complement (due
      to a deficiency in inhibitory molecules);
      results in repeated inflammatory responses
      and swelling of mucosa; may cause swelling
      of the larynx, difficulty breathing, and/or
      intestinal obstruction
    – Immune Complex Disease – low or absent
      complement levels required in the clearing of
      antibody-antigen complexes; can cause
      damage to healthy tissues
    – Low or absent levels of complement
      necessary for cell lysis; problematic in
      meningitis and gonorrhoea
    – The absence of C3, which is important in
      fighting the most common pathogens
 Defects  of Myeloid
    (Marrow-Derived) Cells
   Reticular Dysgenesis – absence or low
    levels of bone marrow-derived immune
    cells; fatal
   Neutropenia – low or absent neutrophil
    (PMN) numbers; causes recurrent skin
    and throat infections
   Lazy Leukocyte Syndrome – inability to
    respond to inflammation, cross over from
    circulation into affected tissues, or
    generate oxidative killing molecules;
    causes high blood leukocyte levels, and
    an increased risk for mycotic and/or
    staph infections, which may lead to the
    development of abscesses
    – High levels of T Cells in response can cause
      granuloma formation (chronic granulomatous
      disease)
   Absent or inactive NK Cells
 Defects       of Adaptive Immunity
 Reticular Dysgenesis – see above
 Severe Combined Immune Deficiency – a
    reduction or absence of T Lymphocytes, due to
    defects causing diminished maturation of immune
    cells, or an increased mortality of lymphocytes
    due to build-up of a toxins
   Di George Syndrome -- Absence of thymus,
    therefore absence of T Lymphocytes; commonly
    leads to death from otherwise well-controlled
    diseases or as a result of vaccination
   Agammaglobulinaemia (Bruton’s Disease) –
    absence of B Cells and the antibodies that they
    produce; an X-linked disease that results in
    recurrent extracellular infections such as
    pneumonia
   Hypogammaglobulinaemia – the temporary lack
    of one class of antibody, typically IgA; may be
    coupled with increased levels of IgM or IgE
 Secondary            Immunodeficiency
   Malnutrition – reduced calorie consumption or protein
    deficiencies diminish the availability of the ‘building
    blocks’ of immune cells; Antibody production can be
    severely limited, with reductions in other immune cells
    to follow
   Iron – deficiency or excesses can impair immune
    function; used by the immune system in its microbe-
    killing pathways, but also consumed by pathogens
   Zinc, Selenium, Vitamins A,B,C, and E – thought to be
    vital to immune system function, but the specific
    mechanisms by which this is so are not clear
   Infection – immunosuppression that often accompanies
    the action of pathogens; HIV/AIDS is notable for its
    immunosuppressive action
   Trauma – Burns, loss of blood, septic shock, surgery,
    etc., are often accompanied by immunosuppression;
    may result from negative feedback as a reaction to the
    initial hyper-response of the immune system
   Drugs – can reduce immune function as an effect or as
    a side-effect
   Tumours – can displace healthy, functioning tissues
    (such as bone marrow) that are critical in the
    production of immune cells
   Stress – pathways are not well understood, but may be
    due to hormones produced in response to stimulation
    of the sympathetic nervous system, notably cortisol

				
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posted:12/8/2011
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