17.1 Immunology: When the immune system gets it wrong Flashcards
What kind of hypersensitivity occurs in Type II and Type III reactions?
What do they have in common?
Type II: Antibody mediated
Type III: Immune complex
Both IgM, IgG
What is the classical complement pathway activated by?
Activated by Fc portion of immunoglobulin in antigen-antibody complex (C1)
What are the steps in the classical pathway complement activation?
C1 complex: cleaves C4
C4b cleaves C2 (C2b)
C3 convertase (C4b2b) splits many C3 into C3b and C3a
C3b binds to C4b23b=C5 convertase
C3b also binds to R’ on phagocytes, opsonisation, removal of immune complexes
C5 convertase splits C5 into C5a and C5b
C5a: Mediator of inflammation, phagocyte recruitment
C5b-C6-C7-C8-C9= Membrane Attack Complex (transmembrane pore and lysis of microbes)
When is type II hypersensitivity triggered?
What are the 2 outcomes?
- Binding of Abs to host antigens
1. Injury due to activation of effector mechanisms (C’, inflammation)
2. Abnormal physiological response
What are 2 examples of Type II hypersensitivity autoimmune conditions?
Graves disease (stimulating Ab)
Myasthenia Gravis (inhibitory Ab)
What are some Type II hypersensitivity responses that target erythrocytes? (3)
Transfusion reactions (carbohydrate antigens)
Drug allergies (splenic MP phagocytose, haemolytic anaemia/thrombocytopeni
Haemolytic disease of newborn (IgG reacting to child’s Rh antigens)
How do we prevent haemolytic disease of the newborn?
Ensure mother gets Anti-Rh antibodies within 24hrs of delivery (1st and each after that) to remove fetal RBCs from circulation
What is a Type II hypersensitivity response that targets tissues?
What is the presentation?
Goodpasture’s syndrome, Abs against Collagen IV
Presentation is nephritis
What is the mechanism for Graves Disease?
Thyroid specific, B cell mediated
Autoantibodes bind to TSH R’ (on thyroid cells)
Stimulation leads to hyperthyroidism
What is the mechanism for Myasthenia Gravis?
What does this result in?
Auto-antibodies target ACh R’, stops ACh access.
R’s also get degraded and dwindle in number.
Muscle wasting and death results
When do Type III hypersensitivity reactions occur?
When immune complexes (of self or foreign Ag) are excessively produced and insufficiently cleared.
Pathology depends on where these deposit.
How does the body usually get rid of immune complexes?
What is needed?
Removed in the spleen by resident macrophages (after complement fixation)/Fc mediated opsonisation.
High affinity IgG (to fix C’)
How does the size of immune complexes affect their clearance from circulation?
Large complexes e.g trimers, activate C’ better and are better at binding FcR = removal by RBCs
Why would an immune complex not be cleared from circulation? (3)
Ag excess
Low affinity Ab
Insufficient C’ activation
What is the mechanism for Type III hypersensitivity? (3)
Deposition on vessel walls=C’ activation
CKs, platelets, basophils and mast cells activated
Increased vascular permeability (vasoactive amines)
