Diseases of the immune system 💉

• hypersensitivity reaction is an overreaction to a harmless substance(s) which results in an immune response that causes inflammation and tissue damage
• how many groups can hypersensitivity by classified into?

  4 (I - VI)
• Thymus – discern between self and non-self
• Hypersensitivity reaction – cannot discern what is threatening or not (all autoimmunity can be categorized in the same way as hypersensitivity)
• Should someone else be considered a threat? Rather than intent, its whether we can educate the thymus, can’t show polymorphism so see others as threat, understanding us as an organism vs others
• outline the four types of hypersensitivity: they type, the Ig, what it is associaed with and common condintions?

  
• IgG and IgE need an adaptive response to produce that antibody
• the point you get symptoms is a cell causing damage not an antibody
• which immunoglobulin is produced in hypersensitivity:

  type 1 - IgE

  type 2 - IgG

  type 3 -IgG

  type 4 is the only one that is mediated by immune cells (adaptive T cells - Th1 and Th2 cells, CD8+ CTL)
• give examples of IgE promoted responses

  
• In type 1 see the same symptoms/ reaction but no parasite present, IgE binds to mast cells to kill parasites
• Allergen dose and route of exposure is related to the reaction

  intravenous - Release of histamine causes systemic increase in blood vessel permeability (ANAPHYLACTIC SHOCK)
• Allergen dose and route of exposure is related to the reaction

  • intravenous - Release of histamine causes systemic increase in blood vessel permeability (ANAPHYLACTIC SHOCK)
  • Subcutaneous - Local release of histamine causes oedema and reddening of the area (WHEAL AND FLARE REACTION, SKIN BLISTERS)
  • Inhalation - nasal irritation, increased mucus production, contraction of smooth muscles(RUNNY NOSE, BRONCHOCONSTRICTION)
  • Ingestion - Contraction of smooth muscle, increased fluid loss. Antigen may enter bloodstream (DIARRHEA, URTICARIA, ANAPHYLAXIS)
• Allergen dose and route of exposure is related to the reaction

  
• Why do we react this way to some antigens (type 1 hypersensitivity specifically)?

  • parasites infect through the skin and mucosal tissues
  • tissues predisposed to developing Th2 responses
  • parasitic worms use proteases to access body - body responds to proteases as allergens
  • parasites need to be expelled by muscle contraction and enzymatic breakdown
• how does the hygiene hypothesis tie in with hypersensitivity?

  
• atophy - tendency to develop allergic diseases

  Atopic individuals have higher levels of IgE and eosinophils in their blood.

  Strong genetic component to risk – polymorphisms of multiple genes including on chromosomes 5, 6 and 11.
• which polymorphisms affect structures and make atopic individuals susceptible to disease?

  •MHC II – Enhanced presentation of allergen peptides

  •IL-4R – Increased signaling from IL-4 

  •IL-4 – Variation in IL-4 expression

  •FcεRI – IgE binding
• Serum sickness – when animal serum containing antigens is given as a treatment (e.g to snake venom) but also occurs in response to some drugs

  
  

  Type III
• Arthus reaction is a type of serum sickness which manifests as cutaneous vasculitis, can be caused by vaccinations or insect bites (less common)

  
  

  Type III
• Syndromes in type IV hypersensitivity