Lecture 11- Overview of classification of immunological disease Flashcards
why are the immunological disease a result of?
Immune system may fail to control the infection:
Pathogen factors-Evasion mechanism
Host factors- immunodeficiency
How can the immune system may cause disease directly?
- Failure of tolerance- allergy and auto-immunity
- immune system inappropriately activated for unknown reason- IBD
what are the type 1 hypersensitivity according to gel and coombes?
- IgE mediated allergy
- B cells class switch to IgE antibody. Secreted IgE is picked up by tissue mast cells and circulating basophils
- Cross-linking of allergen-specific IgE antibodies by allergen activates the mast cell
- Mast cell rapidly ‘degranulates’ releasing histamine, tryptase and other pre-formed mediators
- Pharmacological effects of histamine lead to symptoms in the affected organ(s)
-In health, believed to assist with parasite immunity
Explain type II hypersensitivity?
- Refers to pathology directly mediated by antibodies
- mismatch blood transfusion reactions are an example of type II hypersensitivity
- IgM antibodies against AB antigens develop during first year of life
- The antibodies are an example of isoantibodies – develop against similar antigens on surface of gut bacteria and cross-react with red cell antigens
Describe Type 2 hypersensitivity: haemolytic disease of newborn?
- Major blood group system is ABO
- D antigen (rhesus) is a secondary classification
- Majority of the population are D+
- Mother may be sensitised by exposure to the fetal red cells during pregnancy
- Parturition
- Trauma
- Antibodies may cause disease
Describe type 2 hypersensitivity auto-immune haemolysis?
- Red blood cells plus anti-RBC autoantibodies EITHER
- FcR cells in fixed mononuclear phagocytic system
- Phagocytosis and RBC destruction
- Complement activation and intravascular haemolysis
- Lysis and RBC destruction
Haemolytic disease of the newborn and complications?
- Autoimmune haemolysis highly deleterious to fetus
- growth retardation, cardiovascular failure, neurotoxicity from high bilrubin
Haemolytic disease of the newborn and management?
- 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; fetal red cells then destroyed, preventing sensitisation
describe Type III hypersensitivity?
- Describes the disease caused by the complex of antibody and antigen complex
- normally these are soluble and are removed by the spleen
- in some situation they become insoluble
What are the possible situation when the antibody and antigen complexes become insoluble?
1) Large quantity of antigen
2) Large quantity of antibody
3) interaction between these two are very strong
- complexes are of the correct size
describe the features of the local immune complex disease?
- painful lesions of the fingertip pulps due to deposition of the circulating immune complexes
- May be seen in infective endocarditis
- may be seen in other diseases with immune complex deposition SLE
Explain :Type III hypersensitivity: Serum sickness causes?
A generalised transient immune complex mediated syndrome
-Mainly results from injection of certain immunogenic drugs or anti-sera produced in animals- e.g. snake evenomation
What are the symptoms of the Type III hypersensitivity: serum sickness?
- Rash
- Fever
- Arthritis
- Glomerulonephritis
Describe the Type III hypersensitivity: Hypersensitivity pneumonitis?
AKA- extrinsic allergic alveolitis
- Patient becomes sensitised to an environmental antigen by repeated exposure, producing large quantities of IgG antibodies
- Immune complexes form in the lung upon re-exposure causing shortness of breath and cough
Describe the Type III hypersensitivity: Hypersensitivity pneumonitis causes?
mould spores in hay (farmers)
Pigeon feathers and stool (pigeon fanciers lung)
-Initially transient- repeated exposure causes lung scarring
Describe Type IV hypersensitivity: Delayed-type hypersensitivity?
Reactions are mediated by the antigen specific effector T cells
- takes at least 24 hours to process and present antigen
- Reactions do not develop for at least 24 hours post exposure
- in Skin known as contact dermatitis
Explain the mechanism of contact dermatitis?
- Sensitising agents are typically highly reactive small molecules which can penetrate the skin
- these react with self proteins to create protein hapten complex that are picked up by langerhan cells
- Langerhans cells leave the skin and enter the lymphatic system
What are the example material that can cause contact dermatitis?
nickel
molecules in perfumes
cosmetics
Contact dermatitis: sensitisation process?
- The Langerhan cells process and present the antigen together with MHC class II
- in some individuals, the complexes are recognised as foreign
- the activated T cells then migrate to the dermis
Contact dermatitis mechanism ?
- Contact sensitising agent penetrates the skin and binds to self proteins, which are taken up by Langerhan cells
- Langerhan cells present self peptides haptenated with contact sensitizing agent to Th1 cells which secrete interferon Y and other cytokines
- Activated keratinocytes secrete cytokines such as IL-1 and TNF alpha and chemokines CXCL8, CXCL11 and CXCL9
- The products are keratinocytes and Th1 cells activate macrohages to secrete the mediators of inflammation
How do you test for contact dermatitis?
Patch testing:
- antigen impregnated patch placed on the back
- Nickel, cobalt, chrome, epoxy resin lanolin etc
- Results after 2 days
What is another example of a type IV hypersensitivity reaction and its function?
Tuberculin skin test (TST):
Used to determine previous exposure to TB
-
How is TST administered and what does the result show?
Tuberculin injected intradermally (tuberculin=complex mixture of antigens derived from MTB)
Local inflammatory response evolves over 24-72 hours if previously exposed
-Mediated by Th1 cells
Describe the mechanism of TST?
- Antigen is injected into the subcut tissue
- Processed by local antigen processing cells
- A Th1 effector cell recognises antigen and releases cytokines which act on the endothelium
- Recruitment of phagocytes and plasma of site of antigen injection causing visible lesion
How are the TB specific Th1 cells detected?
- Interferon gamma release assay
Explain the mechanism for the detection of Th1 cells specific to TB?
Previous TB exposure:
Memory Th1 cells recognise the antigen
-they are primed and release cytokine within short timeframe
-No previous TB exposure:
-No primed memory T cells specific for MTB
-No Interferon gamma produced in short amount of time
describe the issues with gel and coombes classification?
- oversimplifies the immunology: even in apparently simple situation such as auto-immune haemolysis- many components of the immune system are involved
- Many disease are much more complex particularly chronic inflammatory diseases
