Hypersensitivity Flashcards
What is hypersensitivity?
Immune response which is damaging rather than helpful to the host, instead of protective immune reaction, it is exaggerated inappropriate and damaging to the host.
What is Type 1 responses mediated by?
By IgE which induces mast cell activation
What is Type 2 responses mediated by?
By IgG which can engage FC-receptors and complement-mediated effector mechanisms directed against cell surface matrix antigens
What is Type 3 responses mediated by?
By IgG directed soluble antigens, and the tissue damage involved is caused by responses triggered by immune complexes
What is Type 4 responses mediated by?
Responses are T-cell mediated
What are the 3 types of Type 4 hypersensitivity?
- Tissue damage is caused by the activation of macrophages by TH1 cells, which results in an inflammatory response
- Damage is caused by activation by TH2 cells of inflam responses in which EOSINOPHILS predominate
- Damage is caused directly by cytotoxic T-cells
What happens in a type 1 response? Give an example of a type 1 allergy/response?
Immediate response, IgE, Hayfever,
Immediate response is due to the cytokine storm
Why is type 1 response so rapid?
The host has pre-existing IgE Ab to the antigen (pollen)
IgE has very high affinity to Fc-receptor
Activation of mast cells and eosinphils Fc-receptor via antigen binding to the bound IgE molecules
Immunological memory
Classical inflammatory response but EXAGGERATED
Describe the Eosinophil response in type 1 hypersensitivity?
Macrophages engulf antigen, present it to t-cells, TH2 cells, b-cells, cytokines, IL-5 etc., activated eosinophils, cytokine storm—> airway inflammation—> mucus production, remodelling from scarring, eotaxin is associated with eosinophils. Eotaxin is used as a therapeutic strategy. Enzyme that is dangerous and looked at the most that is produced by eosinophils is MMP9 which causes matrix protein degradation
What is type 2 hypersensitivity caused by?
By sepcific Ab binding to cells or tissue antigens.
Antibodies are of the IgM or IgG classes and cause cell destruction by Fc dependent mechanisms either directly or by recruiting complement via the classical pathway
What is Immune mediated/Autoimmune Haemolytic anemia and describe what happens?
Loss of RBC due to their destruction
Destruction due to Ab binding to RBC leading to ADCC/MAC
Toxin/drug/antibioticx/virus/parasites bind to the surface o RBC and anti-drug Ab attack cells—> Epitopes binding to RBC makes them be recognised as NON-SELF
It can occur in the blood stream or outside the blood stream
In most cases in dogs, haemolysis occurs outside the blood stream in the spleen. Liver and bone marrow
Type 2: What is Rhesus disease?
If mother RH negative and baby positive, there may be a problem if the Fetal Rh positive blood mixes with the mothers Rh- negative blood.
Left untreated the mothers blood will make Ab that attack the Rh positive blood of the fetus
these Ab can cause health problems for the fetus, these include blood problems or even death through sepsis.
If mother positive, and baby negative nothing happens to the
How is Rhesus disease prevented?
The disease is prevented by vaccinating the Rh-negative mother with Rh immune globulin during the mothers pregnancy with an Rh-positive foetus. This prohibits the development of Rh-positive Ab, or destroy any such Ab present in the mothers blood thereby protecting any future Rh+ foetuses.
What Goodpastures disease and how is it treated?
Uncommon condition which typically causes rapid destruction of the kidneys and bleeding into the lungs, due to the dev of anti-GBM Ab that bond to the glomeruli causing tissue damage
Treatment is normally immunosuppressive drugs, steroids
What is Myasthenia Gravis and what is done to improve the condition?
AUTOIMMUNE DISORDER OF PERIPHERAL NERVESIN WHICH Ab form against Ach, results in progressive reduction in muscle strength
Removal of thymus improves the condition, thymus is suspected to be the site of autoantibody formation. However the stimulus that initiates the autoimmune process has not been identified
What is the Arthus reaction?
Local Type 3 hypersensitivity reaction (e.g. after a vaccine shot)
Why is Type 3 reaction slower than Type 1?
FcgammaRIII is a low affinity receptor and because the threshold for activation via this receptor is considerably higher than for the IgE receptor the reaction is slow compared with type 1 reactions
Type 4: Also known as delayed type hypersensitivity or DTH, cause inflammation and a swelling, how?
Contact sensitizing agent penetrates the skin and binds to self proteins which are taken yp by langerhan cells
Langerhans present self peptides hapteneated with the contact sens agent to TH1 cells which secrete IFN gamma and other cytokines
Activated keratinocytes secrete cytokine such as IL1 and TNF alpha and chemokines such as CXCL8 etc.
The products of keratinocytes and TH1 cells activate macrophages to secrete mediators of inflammation
What are granulomas and how are thy maintained?
Inert foreign body materials and intracellular microorganisms, that are capable of inducing a cell mediated immune response.
Macrophages present it on T-cells
Activated T-cells produce Il-2 , ifn-GAMMA WHICH CAUSES ACTIVATED MACRPHAEGS TO AGGREGATE INTO NODULES
Continued release of cytokines result in sustained recruitment and activation of lymphocytes and macrophages —> maintenece of theese immune mediated granulomas
What is the Hygiene Theory?
CLEAN ENVIRONMENT, CAUSES IMMUNE SYSTEM TO BE DORMANT, WHEN AN ANTIGEN COMES OVER WHICH SHOULDN’T CAUSE A RESPONSE CAUSES THE IMMUNE SYSTEM TO GO CRAZY
What are the treatments for TH2 activation?
Induce regulatory T-cells: administration of cytokines or injection of specific antigen or peptides
What are the treatments for activation of B cell to produce IgE?
Block co-stimulation or inhibit TH2 cytokines: INHIBIT CD40L, IL4, IL13
What are the treatments for mast cell activation?
Inhibit effects of IgE binding tothe mast cell: Blockade of IgE receptor
What are the treatments for Mediator action?
Inhibit synthesis of specific mediators: Antihistamine drugs, lipooxygenase inhibitors
What are the treatments for Eosinophil-dependent inflammation?
Block cytokine and chemokine receptors that mediate eosinophil recruitment and activation: Inhibit IL5, Block CCR3
Why changing the pathway from TH2 to TH1 pathway are source of treatment or prevention for allergic reaction?
While Th2 cells promote airway inflammation in asthma, it has been proposed that Th1 cells, which secrete interferon (IFN)-γ, protect against allergic disease by dampening the activity of Th2 effector cells
