Hypersensitivity Flashcards
Type 1 Hypersensitivity Reaction
Allergic response within 5-10 mins of exposure to a specific allergen
IgE causing mast cell degranulation
T1HR Mechanism
- Antigen (exogenous substance -pollen) stimulates B cell to produce specific IgE w help of t helper cells.
- IgE binds and coats mast and basophils via Fc receptors and sensitises them
- Later exposure to the same antigen cross links the bound IgE on sensitised mast cells
- Triggers degranulation
Leads to
- Increased vasc perm
- broncho constriction
- chemotaxis of eosinophils, neuts and lymphocutes
- Hypotension
- oedema
- rashes
- anaphylaxis
Examples of T1HR
Asthma, Hayfever - antigen enters via resp mucus membrane
Urticaria
Anaphylaxis - antigen parentally administered
T2HR
Antibody mediated cytotoxic reaction involving IgG or IgM antibodies binding to cell surface antigen
Resulting in:
- Complement activation through classical pathway
- leads to lysis, mast cell activation and nut recruitment
- Mobilisation and activation of nuts, eosins, monos and NKs
T2HR example
Transfusion reactions
Autoimmune Haemolysis
Haemolytic disease of the newborn
T3HR example
Autoimmune eg SLE, RA
T4HR example
Pulmonary TB
Contact dermatitis
GVH disease
Pathophysiology of Anaphylaxis
T1 HR
Triggers: Drugs, food, environment
Phase 1: Initial exposure
- APC + Antigen -> T-Cell -> B cell
- B Cell produces specific IgE
- IgE binds to and coats basophils and mast cells, via the Fc receptors.
- Mast cells and basophils (Blood and tissue) are sensitised
Phase 2: Second exposure
- Antigen binds IgE on surface of mast and basophils.
- Causes mast cell degranulation systemically.
Early Phase Anaphylaxis
Early Phase:
- first 15-30 mins
- mast and baso degranulation
- early mediators: histamine, serotonin and triptase
- effects: bronchocons, VD, cap leakage, decreased pre load etc, nausea.
Late Phase Anaphylaxis
Late Phase
- 4-6 hours later
- Chemotaxis of eosinophils, neutrophils, lymphocytes
- leading to inflammation
- Mediators: PGs, LKs, BKs, platelet activating factor.
- Effects: Same as early phase.
Clinical Features of Anaphylaxis
Mucocutaneous
- VD + CL = Angioedema, urticaria
CV
- VD + CL = <BV = <Preload = <CO = < MAP = Collapse
Resp
- BC
GIT
- Nausea/vomiting, Diarrhoea
Histamine Role in Allergy
Basic amine derived from histidine
- H1 and H2.
MOA:
- H1: GqPCR
- H2: GsPCR
CVS:
- H1 = >AV delay, coronary VC. VD + CL due to >NO production.
- H2 = > ionotropy, coronary VD
RESP:
- H1: BC
- H2: BD
GIT: H2 = > Gastric acid secretion
Tryptase
Sereine protease located in mast cells.
Major component of mast cell degranulation.
Activates complement cascade, coagulation cascade and chemotaxis CVS: VD, CL
Resp: BC
Levels are measured to confirm anaphylaxis, however a negative level doesn’t exclude anaphylaxis
When is tryptase measured
Immediately, I hr, 4 hrs and >24hrs post onset of symptoms
Type 2 HR
Antibody mediated cytotoxic reaction
- Antigen is cell surface or tissue bound.
- IgG or IgM antibodies bind surface antigen
- Results in complement activation via classical pathway.
- Mobilisation and activations of immune response resulted cytotoxicity.
Results in antibody mediated damage to target cells
Clinical Picture of T2HR
Depends on target tissue.
- Organ specific diseases
- Myasthenia Gravis
- Glomerulonephritis - Autoimmune Blood cell destruction
- Haemolytic anaemia
- thrombocytopenia - Transfusion reactions
- ABO incompatibility - Haemolytic disease of the new born
- Rh Isoimmunisation - Hyperacute allograft rejection
T3HR
Immune Complex Deposition
Immune complex mediated reaction
results in deposition of AG-AB complexes in host tissues.
This leads to complement activation - nut infiltration and tissue damage.
AG AB complexes are usually cleared by phagocytes
- In T3HR, three is either too many or the complexes are too small to be cleared effectively.
- AGAB excess leads to formation of immune complexes (complement activation)
- These immune complexes are deposited in the tissue, causing a reaction from the activated complements.
- The tissue depends on the reaction: Localised: complexes formed in the tissues resulting in localised effects
Systemic: Complexes formed in the circulation and then deposited in the tissues causing systemic effects.
Localised: Arthus Reaction
Systemic: serum sickness - vasculitis
T4HR
Delayed Cell mediated HR
1) Antigen presentation to T cell = release of cytokines (IL2, IL4, IFNy)
2) Cytokines activate Macs = cell damage.
3) T cells become sensitised for future exposure
Inflammatory response and activation of macrophages is localised
Mantoux test
Example of T4HR
1) Infection w m.tuberculosis
- Infection - T helper cells recognise antigen.
- T-Cells proliferate, forming a population of helper T cells that are sensitised.
2) Mantoux test
- T cells presented w antigen by APC.
- Recognised antigen
- Release cytokines + activate MACS
- localised reaction.C
contact dermatitis
Haptens deposited in skin
Too small to to be antigenic
Combine w intradermal protein carriers to become antigenic
Transplant Immunology
Allograft
Graft from a genetically different donor of the same species
- Most organ transplants
Autograft
Graft from a genetically identical donor
- Self self
Xenograft
From different species
- Porcine valve
Graft Vs Host
Transplant rejection
Transplant rejection
- Host vs Graft
- Blood transfusion is a blood transplant
- Your immune system recognises foreign tissue and destroys the graft
- Hyperacute, Acute and delayed.
- Hyperacute: Mins - Hours. Antibody mediated. Immediate reaction to foreign antigen. Leads to destruction, immune response, graft wont take. EG ABO incompatability
- Acute: Days to weeks
Cell mediated or antibody mediated - Chronic Rejection: Weeks to years
Common in cardiac transplant. Thrombosis and macrosclerosis, proliferation of SM cells due to repeated inflammation. - Due to poor HLA matching
GVH:
- Must involve cells that are able to form an immune response
eg BM transplant, stem cells
- these cells recognise the self cells as foreign and form an immune response to that.
