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B-lymphocyte development
Diagram
What are the heavy chain genes?
μ, sigma, gamma, episilon, alpha
Which are the iG classes?
M. D, G, E , A
Types 1,2,3+4 hypersensitivity
Type1: antigen specific igE - effector mast cell degranulation
Type2: antigen specific IgG - immune complex disease
Type3: antigen specific IgG - serum sickness
Type 4: delayed type hypersensitivity (lymphoid and myeloid cells)
Define hypersensitivity
- Adaptive immune responses elicited by non- infectious agent
- Associated with tissue damage/oedema mild to severe
What happens in IgE mediated anaphylactic shock?
Wide spread increase in vascular permeability and smooth muscle contraction resulting from a massive and systemic release of hisamine, leukotrines etc from mast cells and basophils
Catastrophic reduction in blood pressure leading to hypotensive shock (BP too low to perfume vital organs)
What is IgG mediated allergy?
- Also known as non-IgE antibody mediated allergic reaction
- IgE costs mast cells but cannot activate complement
- IgG stimulates complement and can activate mast cells
Two main types of kinases in Signal transduction
Tyrosine kinase
Serine/threonine kinase
Two types of GTP binding proteins
Trimeric G proteins
Monomeric GTPases
What are the 4 main types of receptors?
Give examples of each
- Ligand gated ion channels (ionotropic receptors)
Nicotinic ACh receptor - G-protein coupled receptors (metabotropic)
Muscarinic ACh receptor - kinase linked receptors
Cytokine receptors - Nuclear receptors
Oestrogen receptor
Which termini do the g-protein couples receptors have on their Extracellular and cytoplasmic faces?
Amino termini on Extracellular
Carboxy termini on cytoplasmic
Mechanism of action of G-protein receptor
Binding of the ligand to the receptor changes its conformation, causing it to bind to the Gα protein in such a way that GDP is displaced and GTP is bound.
This triggers Gbγ dissociation activating downstream pathways.
Activation is short-lived, as GTP bound to Gα hydrolyzes to GDP in seconds, leading to the re-association of Ga with Gbγ and inactivation of adenylate cyclase.
G-protein types:
Gaq (or Gq) - stimulates phospholipase C
Gs- stimulates adenylate Cyclades, increases cAMP
Gi- inhibits adenylate Cyclades, decreases cAMP
What is phospholipase C?
- proteins which possess distinct domain structures but catalyses the same reaction (PIP2 —> IP3 + DAG)
- some domains are common
- some domains are unique
Activated by different pathways
The process of active RAS protein
Active RAS protein –> MAP-kinase-kinase-kinase –> MAP-kinase-kinase –> MAP-kinase –> Protein X, Protein Y (these both cause cahnges in protein activity), gene-regulatory protein A and B (these both cause changes in gene expression.
at each kinase loss and at the end, ATP is converted to ADP.
How does patch testing work?
- tests for delayed hypersensitivity
- tests for contact allergy
- if a patient is allergic to the tested material, their CD8 lymphocytes are sensitised and contact with the offending allergen will cause them to secrete certain cytokines which will attract inflammatory cells to the site of contact and produce a positive reaction manifested my erythem, papules and vesicles
how do skin prick tests work?
- tests immediate type 1 hypersensitivity to allergens
- commonly used in patients with asthma, ectopic eczema
- detects IgE mediated allergic response to a specific inhalant or food allergy
- A positive result is usually regarded as being a wheal >/=3mm the negative control
What is in vitro measurement of igE antibodies and how does it work?
- diagnose type 1 allergy
• Multiple different assays
- RAST
- CAP-RAST
- ELISA
Actions of antibodies
• IgG1, IgG3 and IgM activate complement by classical pathway
• IgG1 and IgG3 cross the placenta
• IgE coats granulocytes (mast cell, eosinophils,
basophils
• IgA secreted across gut mucosal membranes to protect GI tract
Factors affecting social support
Migration
New technologies
What factors do social support help with?
suicide general morbidity general mortality mental and/or psychomsomatic illness reproductive health
Overarching situations where breach of confidentiality is acceptable
- Disclosures with consent
- disclosures required by law
- disclosures in the public interest
What are the pros and cons of skin prick test?
Pros:
• Relatively painless
• Low risk of side effects
• Cheap
• Reproducible
• Real time results demonstrable to patient
• False negatives uncommon if done properly
Cons:
• Full resus facilities should be available
• Antihistamines have to be stopped 48h before testing
• Itch can be uncomfortable
• Interpretation difficult in patients with active eczema
Pros and cons of IgE antibody measurement testing
Pros:
• Not influenced by current therapy (antihistamines)
• Can be performed when widespread skin disease
• Completely safe
• Evolving knowledge/technologies
Cons: • Painful (venepuncture) • Expensive • Results can take weeks • Difficult to interpret especially in context of high Total IgE (atopy) - titre important
