ALLERGY AND HYPERSENSITIVITY

Allergy and Hypersensitivity :


An  important  undesirable  side  effect  of  immunity  is the  development,  under  some  conditions,  of  allergy  or other  types  of  immune  hypersensitivity.  There  are  several  types  of  allergy  and  other  hypersensitivities,  some  of which  occur  only  in  people  who  have  a  specific  allergic tendency. 





Allergy Caused by  Activated  T Cells:   



Delayed-Reaction  Allergy Delayed-reaction  allergy  is  caused  by  activated  T  cells  and not  by  antibodies.  In  the  case  of  poison  ivy,  the  toxin  of poison  ivy  in  itself  does  not  cause  much  harm  to  the  tissues.  However,  on  repeated  exposure,  it  does  cause  the formation  of  activated  helper  and  cytotoxic  T  cells.  Then, after  subsequent  exposure  to  the  poison  ivy  toxin,  within a  day  or  so,  the  activated  T  cells  diffuse  from  the  circulating  blood  in  large  numbers  into  the  skin  to  respond  to  the poison  ivy  toxin.  And,  at  the  same  time,  these  T  cells  elicit a  cell-mediated  type  of  immune  reaction.  Remembering that  this  type  of  immunity  can  cause  release  of  many  toxic substances  from  the  activated  T  cells,  as  well  as  extensive  invasion  of  the  tissues  by  macrophages  along  with their  subsequent  effects,  one  can  well  understand  that  the eventual  result  of  some  delayed-reaction  allergies  can  be serious  tissue  damage.  The  damage  normally  occurs  in the  tissue  area  where  the  instigating  antigen  is  present, such  as  in  the  skin  in  the  case  of  poison  ivy,  or  in  the  lungs to  cause  lung  edema  or  asthmatic  attacks  in  the  case  of some airborne antigens.



 Allergies in the  “Allergic”  Person  Who Has Excess IgE  Antibodies :


Some  people  have  an  “allergic”  tendency.  Their  allergies are  called  atopic  allergies  because  they  are  caused  by  a nonordinary  response  of  the  immune  system.  The  allergic  tendency  is  genetically  passed  from  parent  to  child and  is  characterized  by  the  presence  of  large  quantities  of IgE  antibodies  in  the  blood.  These  antibodies  are  called reagins  or  sensitizing  antibodies  to  distinguish  them from  the  more  common  IgG  antibodies.  When  an  allergen  (defined  as  an  antigen  that  reacts  specifically  with a  specific  type  of  IgE  reagin  antibody)  enters  the  body, an  allergen-reagin  reaction  takes  place  and  a  subsequent allergic reaction occurs. 


A  special  characteristic  of  the  IgE  antibodies  (the  reagins)  is  a  strong  propensity  to  attach  to  mast  cells  and basophils.  Indeed,  a  single  mast  cell  or  basophil  can  bind as  many  as  half  a  million  molecules  of  IgE  antibodies. Then,  when  an  antigen  (an  allergen)  that  has  multiple binding  sites  binds  with  several  IgE  antibodies  that  are already  attached  to  a  mast  cell  or  basophil,  this  causes immediate  change  in  the  membrane  of  the  mast  cell  or basophil,  perhaps  resulting  from  a  physical  effect  of  the antibody  molecules  to  contort  the  cell  membrane.  At  any rate,  many  of  the  mast  cells  and  basophils  rupture;  others  release  special  agents  immediately  or  shortly  thereafter,  including  histamine,  protease,  slow-reacting  substance of  anaphylaxis  (which  is  a  mixture  of  toxic  leukotrienes), eosinophil  chemotactic  substance,  neutrophil  chemotactic substance,  heparin,  and  platelet  activating  factors.  These substances  cause  such  effects  as  dilation  of  the  local blood  vessels;  attraction  of  eosinophils  and  neutrophils to  the  reactive  site;  increased  permeability  of  the  capillaries  with  loss  of  fluid  into  the  tissues;  and  contraction  of local  smooth  muscle  cells.  Therefore,  several  different  tissue  responses  can  occur,  depending  on  the  type  of  tissue in  which  the  allergen-reagin  reaction  occurs.  Among  the different  types  of  allergic  reactions  caused  in  this  manner are the following. 



Anaphylaxis : When  a  specific  allergen  is  injected directly  into  the  circulation,  the  allergen  can  react  with basophils  of  the  blood  and  mast  cells  in  the  tissues  located immediately  outside  the  small  blood  vessels  if  the  basophils  and  mast  cells  have  been  sensitized  by  attachment of  IgE  reagins.  Therefore,  a  widespread  allergic  reaction occurs  throughout  the  vascular  system  and  closely  associated  tissues.  This  is  called  anaphylaxis.  Histamine  is released  into  the  circulation  and  causes  body-wide  vasodilation,  as  well  as  increased  permeability  of  the  capillaries with  resultant  marked  loss  of  plasma  from  the  circulation. Occasionally, a person who experiences this reaction dies of  circulatory  shock  within  a  few  minutes  unless  treated with epinephrine to oppose the effects of the histamine. Also  released  from  the  activated  basophils  and  mast cells  is  a  mixture  of  leukotrienes  called  slow-reacting substance  of  anaphylaxis.  These  leukotrienes  can  cause spasm  of  the  smooth  muscle  of  the  bronchioles,  eliciting  an  asthma-like  attack,  sometimes  causing  death  by suffocation. 



Urticaria  : Urticaria  results  from  antigen  entering  specific  skin  areas  and  causing  localized  anaphylactoid  reactions.  Histamine  released  locally  causes  (1)  vasodilation that  induces  an  immediate  red  flare  and  (2)  increased local  permeability  of  the  capillaries  that  leads  to  local  circumscribed  areas  of  swelling  of  the  skin  within  another few  minutes.  The  swellings  are  commonly  called  hives. Administration  of  antihistamine  drugs  to  a  person  before exposure will prevent the hives.



 Hay  Fever :  In  hay  fever,  the  allergen-reagin  reaction  occurs  in  the  nose.  Histamine  released  in  response to  the  reaction  causes  local  intranasal  vascular  dilation, with  resultant  increased  capillary  pressure  and  increased capillary  permeability.  Both  these  effects  cause  rapid  fluid leakage  into  the  nasal  cavities  and  into  associated  deeper tissues  of  the  nose;  and  the  nasal  linings  become  swollen  and  secretory.  Here  again,  use  of  antihistamine  drugs can  prevent  this  swelling  reaction.  But  other  products  of the  allergen-reagin  reaction  can  still  cause  irritation  of  the nose, eliciting the typical sneezing syndrome.

Asthma :  Asthma  often  occurs  in  the  “allergic”  type of  person.  In  such  a  person,  the  allergen-reagin  reaction occurs  in  the  bronchioles  of  the  lungs.  Here,  an  important product  released  from  the  mast  cells  is  believed  to  be  the slow-reacting substance of anaphylaxis, which causes spasm of  the  bronchiolar  smooth  muscle.  Consequently,  the  person  has  difficulty  breathing  until  the  reactive  products  of the  allergic  reaction  have  been  removed.  Administration of  antihistamine  medication  has  less  effect  on  the  course of  asthma  because  histamine  does  not  appear  to  be  the major factor eliciting the asthmatic reaction.

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