Overview and classification of immunological diseases Flashcards
How might the immune system fail to control infection?
Pathogen factors -> evasion mechanisms
Host factors -> immunodeficiency
How might the immune system cause disease directly?
Failure of tolerance e.g. allergy/autoimmunity
Immune system inappropriately activated for unknown reasons e.g. inflammatory bowel disease or for reasons that are known but poorly understood e.g. asbestos or cigarette smoke, or during infection.
What is type 1 hypersensitivity and give examples
IgE-mediated allergy.
B cells class switch to IgE antibody. secreted IgE is picked up by tissue mast cells + circulating basophils.
Cross-linking of allergen-specific IgE antibodies by allergen activates mast cell.
Mast cell rapidly degranulates releasing histamine, tryptase + other pre-formed mediators.
Pharmacological effects of histamine lead to symptoms in affected organ(s).
In health believed to assist with parasite immunity.
Seasonal rhinitis, cat allergy
What is type 2 hypersensitivity and give examples
AB blood system + transfusion medicine.
Pathology directly mediated by antibodies.
IgM antibodies against AB antigens develop during 1st year of life -> isoantibodies develop against similar antigens on surface of gut bacteria + cross-react with red cell antigens.
Autoimmune haemolysis, haemolytic disease of newborn, mismatch blood transfusion reactions.
What is haemolytic disease of the newborn?
Mother may be sensitised by exposure to fetal red cells during pregnancy -> parturition, trauma.
Antibodies may cause disease in subsequent pregnancies.
Autoimmune haemolysis can cause growth retardation, cardiovascular failure, hydrops fetalis, neurotoxicity from high bilirubin levels.
Rhesus-negative mothers with rhesus+ partner are given anti-D IgG during pregnancy at 28 weeks routinely +
after accidents, miscarriage or surgical delivery.
Binds to fetal red cells entering circulation + destroyed, preventing sensitisation.
How does autoimmune haemolysis occur?
Red blood cells + anti-RBC autoantibodies -> FcR+ cells in fixed mononuclear phagocytic system -> phagocytosis + RBC destruction. Or
Complement activation + intravascular haemolysis -> lysis + RBC destruction.
What is type 3 hypersensitivity?
Disease caused by complexes of antibody + antigen->
normal phenomenon.
Usually soluble, removed in spleen
Sometimes they become insoluble + cause disease.
Large quantity of antigen + antibody -> interaction is very strong.
Complexes are correct size.
Give examples of type 3 hypersensitivity
Local immune complex disease:
Deposition of circulating immune complexes -> painful lesions in fingertip pulp. in infective endocarditis (Osler’s nodes) + other diseases e.g SLE.
Serum sickness:
‘generalised’ transient immune complex-mediated syndrome -> injection of immunogenic drugs or anti-sera produced in animals e.g. after snake venomation -> rash, fever, arthritis, glomerulonephritis.
Hypersensitivity pneumonitis:
Sensitisation to environmental antigen by repeated exposure due to large quantities of IgG -> immune complexes form in lung causing SOB, cough -> mould spores in hay (farmers lung), pigeon feathers + stool (pigeon-fanciers lung). transient -> lung scarring.
What is type 4 hypersensitivity?
Delayed type hypersensitivity.
Mediated by antigen-specific effector T cells.
Takes time to process + present antigen -> reactions don’t develop for at least 24 hours following exposure.
In skin -> contact dermatitis.
How does contact dermatitis occur?
Sensitising agents -> highly reactive small molecules which can penetrate skin. react with self proteins to create protein-hapten complexes -> picked up by Langerhans cells which migrate to regional lymph nodes.
E.g. nickel + molecules in perfume / cosmetics.
Langerhans cells process + present antigen with MHCII.
In some susceptible individuals complexes are recognised as foreign. activated T cells migrate to dermis.
How does contact dermatitis: elicitation occur?
Contact-sensitising agent penetrates skin + binds to self proteins -> taken up by Langerhan’s cells.
Langerhans’ cells present self-peptides haptenated with contact-sensitising agent to Th1 cells which secrete IFN-gamma + other cytokines.
Activated keratinocytes secrete cytokines e.g. IL-1 + TNF-alpha + chemokines e.g. IL8, IP-9, Mig.
Products of keratinocytes + Th1 cells activate macrophages to secrete mediators of inflammation.
How can contact dermatitis be tested?
Patch testing: antigen-impregnated patch placed on back. nickel, chrome, cobalt, epoxy resin, lanolin etc.
results read after 2 days.
Give another example of a type IV hypersensitivity reaction
Tuberculin skin test (TST): determines previous exposure to TB. tuberculin injected intradermally (complex mixture of antigens derived from MTB). local inflammatory response evolves over 24-72 hours if previously exposed. mediated by Th1 cells.
What is the mechanism of TST?
Antigen injected into subcutaneous tissue + processed by local APCs.
Th1 effector cell recognises antigen + releases cytokines -> act on vascular endothelium.
Recruitment of phagocytes and plasma to site of antigen injection causes visible lesion.
Outline detection of TB-specific Th1 cells in vitro by interferon gamma release assay (IGRA)
MTB peptides ESAT-6 + CFP-10 added to blood in laboratory -> APC presents peptides with MHC2 + secretes IL-12.
Previous TB exposure -> memory Th1 cells recognise antigen. secondary immune response -> they’re primed + release cytokines within short timeframe.
No previous TB exposure -> no primed memory T cells specific for MTB. no interferon gamma produced in short timeframe.
