Overview and classification of immunological disease Flashcards
Generally speaking, what happen in immunological disease
- Failure to control infection due to pathogen factors (evasion mechanism) or host factors (immunodeficiency)
- Direct causation due to 1.failure of tolerance 2. inappropriate activated
State the general mechanism for the 4 types of hypersensitivity
TYPE 1: IgE antibody directed against allergen triggers mast cell degranulation
TYPE 2: A pathogenic antibody directly causes disease
TYPE 3: Antibody-antigen complex mediated disease
TYPE 4: Inflammation directly mediated by T cells
Describe type 1 hypersensitivity
Give an example
- B cells class switch to IgE which is secreted and picked up by tissue mast cells and circulating basophils
- Cross linking of allergen-specific IgE antibodies by allergen activates mast cell
- Mast cell rapidly degranulates releasing histamine, tryptase and other mediators
- Results in pharmacological effects of histamine
- In health, it assists parasite immunity
Seasonal rhinitis, cat allergy
Describe type 2 hypersensitivity: AB Blood system and transfusion medicine
AB blood system and transfusion medicine
- e.g. mismatch blood transfusion reactions.
- IgM antibody against AB antigens develop in 1st year. They are isoantibodies which develop against similar antigens on surface of gut bacteria and cross react with red cell antigens
Describe type 2 hypersensitivity: haemolytic disease of the newborn
- D antigen (Rhesus) positive in majority of population
- Mother sensitised by exposure to fetal RBCs during pregnancy. If rhesus negative mother encounters rhesus positive fetal blood she will produce anti-D IgG
- Such antibodies may cause disease in subsequent pregnancies –> AI haemolysis –> growth retardation, CV failure, ‘hydrops fetalis’, neurotoxicity from high [bilirubin]
- Anti-D IgG bind to fetal RBC entering circulation, then destroyed preventing sensitisation (from16% to 0.1%)
Describe type 3 hypersensitivity
Example?
- Soluble complexes of antibody and antigen usually removed by spleen
- Can become insoluble and cause disease if:
large quantity of antigen or antibody
interaction between two is very strong
complex of correct size
Local immune complex disease
- painful lesions in fingers due to deposits of immune complex
- may be seen in infective endocarditis (Oslers nodes)
- may be seen in diseases with complex deposition e.g. SLE
Describe serum sickness
Type 3 hypersensitivity
- generalised transient immune complex mediated syndrome
- mainly results from injection of certain immunogenic drugs or anti sera produced in animals e.g. after snake bite
- rash, fever, arthritis, glomerulonephritis
Describe hypersensitive pneumonitis
aka extrinsic allergic alveolitis
Type 3 hypersensitivity
- sensitisation to environmental antigen by repeated exposure –> high IgG
- immune complexes form in lung upon re-exposure –> SOB and cough
- causes: mould spores in hay (farmers lung), pigeon feathers and stool (pigeon-fanciers lung)
- initially transient, lung scarring with high exposure
Describe type 4 hypersensitivity
What happens in contact dermatitis
DELAYED TYPE HYPERSENSITIVITY
- reactions mediated by antigen specific T cells (>24 hours after exposure as it takes times to process and present antigen)
- sensitising agents are typically highly reactive small molecules which can penetrate skin
- these react with self proteins to create protein hapten (small molecule which cannot produce immune response but can bind to protein to alter its immunogenicity) which are picked up by Langerhans cells which can migrate to regional lymph nodes
- e.g. nickel and molecule sin perfume/cosmetics
What is the role of langerhans cells in type 4 hypersensitivity
They process and present antigen together with MHC2
- in some susceptible people, complex is recognised as foreign –> activated T cells migrate to dermis
Consider a tuberculin skin test (TST)
- Indication:
- MOA:
- Determines previous exposure to TB
- Tuberculin injected intradermally –> local inflammatory response evolves over 24-72 hours if previously exposed; mediated by TH1 cells. Detection of TB-specific TH1 cells by interferon gamma release assay (IGRA) - add MTB peptides to blood –> APC present peptide MHC2 and secretes IL12
What is considered a positive result on a TST?
Before TB exposure: memory TH1 cells recognise antigen therefore this is a secondary immune response, they are ‘primed’ and release cytokines within this short timeframe
- same has lots of cells
If there was no prior TB exposure: no primed memory T cells specific for MTB. No interferon-y produced in short time frame.
- clear assay
What are the pros and cons of using the Gell and Coombes classification?
PROS
- classification by mechanism
- helps describe and understand disease
CONS
- not useful in clinical practice
- oversimplifies the immunology
- disease are more complex e.g. chronic inflammatory diseases –> mechanisms in this framework are not well described.
