T1 L10 Overview & classification of immunological diseases Flashcards
What are the 2 ways an immunological disease can occur?
Immune system may fail to control infection
Immune system may cause disease directly
What are the 2 ways the immune system can fail to control the infection?
Pathogen factors
Host factors
What are the 2 ways the immune system can directly cause disease?
Failure of tolerance e.g. allergy / autoimmunity
Inappropriate activation of immune system
What is Gell and Coombes classification’?
System to classify immunologically mediated diseases in 1963
What does the Gell and Coombes classification refer to?
Mechanisms of disease when the immune system is inappropriately activated
What are the benefits of the Gell and Coombes classification?
Only successful attempt to classify disease by mechanism
Useful framework to describe and understand various diseases
What are the cons of the Gell and Coombes classification?
Not useful in clinical practice
Oversimplifies immunology
Many diseases are much more complex, particularly chronic inflammatory diseases which involve multiple immunological effector mechanisms
What is type I hypersensitivity?
IgE antibody directed against allergen triggers mast cell degranulation
What are some examples of type I hypersensitivity?
Seasonal rhinitis
Cat allergy
What is the mechanism of type II hypersensitivity?
Pathogenic antibody directly causes disease
Give examples of type II hypersensitivity conditions
Autoimmune haemolysis
What is the mechanism of type III hypersensitivity?
Antibody-antigen-complex mediated disease
Give examples of type III hypersensitivity
Serum sickness
Systemic lupus erythematosus
What is the mechanism of type IV hypersensitivity?
Inflammation directly mediated by T cells
Delayed-type hypersensitivity
Reactions don’t develop for at least 24h after exposure as it takes time to process and present antigen.
Give examples of type IV hypersensitivity
Contact dermatitis
Tuberculin reaction
What is the mechanism of type I hypersensitivity?
1) B cells class switch to IgE antibody
2) Secreted IgE picked up by tissue mast cells and circulating basophils
3) Cross-linking of allergen-specific IgE antibodies by allergen which activates mast cel
4) Mast cell degranulates releases histamine, tryptase and other pre-formed mediator
5) Pharmcaological effects of histamine cause symptoms in affected organ
What is haemolytic disease of the newborn?
Type 2 hypersensitivity
Mother is sensitised by exposure to foetal red cells during pregnancy
Antibodies can then cause disease in subsequent pregnancies
What are the consequences of autoimmune haemolysis to the foetus?
Growth retardation
Cardiovascular failure
Hydrops fetalis
Neurotoxicity
How is haemolytic disease of the newborn prevented?
Rhesus negative mothers with rhesus positive partners are given anti-D IgG during pregnancy
Binds to foetal red cells entering the circulation causing them to be destroyed to prevent sensitisation
When can antibody-antigen complexes cause disease?
If they become insoluble
- large quantity of antigen
- large quantity of antibody
- strong interaction between the 2
- complexes are of correct size
Describe local immune complex disease
Painful lesions in fingertip pulp caused by deposition of circulating immune complexes
Seen in infective endocarditis (Osler’s nodes)
Seen in other diseases with immune complex deposition (SLE)
Describe serum sickness
Generalised transient immune complex-mediated syndrome
Results from injection of certain immunogenic drugs or anti-sera produced in animals
- fever
- rash
- arthritis
- glomerulonephritis
Describe hypersensitivity pneumonitis
Extrinsic allergic alevolitis (EAA)
Patient becomes sensitised to environmental antigen by repeated exposure to produce large quantities of IgG antibodies
Upon re-exposure, immune complexes form in the lung leading to shortness of breath and cough
Describe sensitisation in contact dermatitis
Sensitising agents react with self-proteins to create protein-hapten complexes are picked up by Langerhans cells which migrate to regional lymph nodes
Langerhans cells process and present antigen with MHC II
Describe elicitation in contact dermatitis
Langerhans’ cells present self-peptides haptenated with contact-sensitising agent to Th1 cells which secrete IFN-y and other cytokines
Activated keratinocytes secrete cytokines such as IL-1, TNF-a as well as chemokines such as CXCL8, CDCL11, CXCL9
Products of keratinocytes and Th1 cells activate macrophages which secrete mediators of inflammation
What is the tuberculin skin test (TST)?
Use to determine previous exposure to TB
Tuberculin injected intradermally
Locally inflammatory response evolves over 24 to 72 hours
Mediated by Th1 cells
What is the mechanism of the TST?
Antigen injected into subcutaneous tissue which is presented by local antigen-presenting cells
Th1 effector cell recognises antigens to release cytokines to act on vascular endothelium
Recruitment of phagocytes and plasma to site of antigen injection leading to visible lesion
Describe the response of IGRA for previous TB exposure
Memory Th1 cells recognise antigen
Secondary immune response so cytokines are released within short timeframe
Describe the response of IGRA for no previous TB exposure
No primed memory T-cells specific for MTB
No interferon gamma produced in such a short timeframe
