Immunological Diseases Flashcards
1
Q
What are the two main Immune system reasons for Immunological disease?
A
- Immune system may fail to control infection
- Pathogen factors (evasion mechanisms)
- Host factors (immunodeficiency)
- Immune system may cause disease directly
- Failure of tolerance (eg allergy/ autoimmunity)
- Immune system inappropriately activated for unknown reasons (eg inflammatory bowel disease) or
- for reasons that are known but poorly understood (eg asbestos or cigarette smoke) or during infection
2
Q
How are Immunological diseases classified?
A
- Gell and Coombes system
- Gell and Coombes hypersensitivity reactions types 1-4
3
Q
Explain what Type 1 Hypersensitivity is
- how is it clinically relevant
A
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
4
Q
Give examples Type 2 hypersensitivity diseases
A
- AB blood system and transfusion medicine
- Haemolytic disease of the newborn
- Autoimmune haemolysis
5
Q
AB blood system and transfusion medicine
A
a Type 2 hypersensitivity disease
- 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 is antibodies – develop against similar antigens on surface of gut bacteria and cross-react with red cell antigens
6
Q
What is Haemolytic Disease of the Newborn?
- Treatment
A
- a Type 2 hypersensitive immunological disease
- a Rhesus -ve mother may be sensitised to Rhesus D antigens due to exposure from fetal red cells during pregnancy
- parturition
- trauma
- they then develop antibodies that will cause this disease in subsequent pregnancies
- Growth retardation, cardiovascular failure, ‘hydrops fetalis’, neurotoxicity from high bilirubin levels
Rhesus-negative mothers with rhesus+ partner are given anti-D IgG during pregnancy
7
Q
How is Haemolytic disease of the newborn treated/ managed?
A
- 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
- Risk of maternal sensitisation reduced from 16% per pregnancy to 0.1%
8
Q
What is autoimmune haemolysis?
- clincical effect?
A
- spontansous formation of anti-RBC autoantibodies
- results in jaundice
9
Q
What is Type 3 hypersensitivity?
- when would this occur
A
- Describes disease caused by complexes of antibody and antigen
- Such complexes are a normal phenomenon
- Usually soluble, removed in spleen
- In some situations (below) they become insoluble and cause disease
- Large quantity of antigen
- Large quantity of antibody
- Interaction between the two is very strong
- Complexes are of the correct size
10
Q
What is a hand sign of type 3 sensitivity?
- which diseases would this sign be seen in?
A
- Painful lesions in the fingertip pulp due to deposition of circulating immune complexes
- May be seen in infective endocarditis (Osler’s nodes)
- May be seen in other diseases with immune complex deposition eg SLE
11
Q
What is Serum Sickness?
- presentation
A
- A ‘generalised’ transient immune complex-mediated syndrome
- type 3 sensitivity on gell coombs classification
- Mainly results from injection of certain immunogenic drugs or anti-sera produced in animals eg after snake envenomation
- after many doses of the antivenom, the body can become sensitized as it is derived from animal Ig
- Rash
- Fever
- Arthritis
- Glomerulonephritis
- due to immune complex deposition in the kidneys - once cleared it will clear
12
Q
What is Hypersensitivity pneumonitis?
- caused by?
- effect?
A
- 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
- Mould spores in hay (farmers lung)
- Pigeon feathers and stool (pigeon-fanciers lung)
- Initially transient, lung scarring with repeated exposure
13
Q
What is Type 4 Hypersensitivity?
A
- Delayed type hypersensitivity
- Reactions are mediated by antigen-specific effector T cells
- Because it takes time to process and present antigen, these reactions do not develop for at least 24 hours following exposure
- When it occurs in the skin it is known as contact dermatitis
14
Q
Explain how Contact dermatitis sensitisation occurs
- what can cause this sensitisation
A
- Sensitising agents are typically highly reactive small molecules that can penetrate the skin
- These react with self-proteins to create protein-hapten* complexes that are picked up by Langerhans cells, which migrate to regional lymph nodes
- Examples are nickel and molecules in perfume/ cosmetics
- The Langerhans cells process and present the antigen together with MHCII
- In some susceptible individuals, the complexes are recognised as foreign
- The activated T cells then migrate to the dermis
*small molecule which cannot produce an immune response by itself, but can bind to a protein to alter its immunogenicity
15
Q
How can an individual know if they are sensitized to something Type 4 sensitization?
A
- Get a patch test for contact dermatitis
- antigen-impregnated patch placed on the back
- nickel, chrome, cobalt, epoxy resin, lanolin
- results read after 2 days
16
Q
Explain what a Tuberculin skin test is (TST)
A
- a type 4 hypersensitivity reaction
- Used to determine previous EXPOSURE to TB
- 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
