Hyper sensitivty, autoimmunity? Flashcards
What are types of hypersensitivity?
Type 1 immediate = allergy.
Type 2 = autoantibodies.
Type 3 = deposition of immune complexes.
Type 4 = T cell mediated tissue injury.
= Type II-IV are autoimmune reactions.
What is type 1?
Mast cell degranulation caused by antigen cross-linked IGE/FCR complex.
(IgE antibodies cross-link as a result of binding different epitopes on the same antigen)…
Mast cell mediate increase vascular permeability, vasodilation, bronchial SM contraction + local inflammation.
Degranulation in connective tissue in skin causes massive histamine release, less histamine content in the lung mast cells.
After generation of sensititivty, the reaction is immediate after exposure to antigen and has strong genetic predisposition.
Repeated exposure strengthens responses.
What is special about allergens?
Allergens don’t trigger an innate response - so do not activated Th1 cells or macrophages.
Allergens are small, glycosylated molecules with high body fluid solubility and have multiple epitopes for IgE cross-linking.
Il-4 promotes Th2 development and antibody classswitching to IgE
What is Type II hypersensitivity?
Three mechanisms:
Complement activation stimulates phagocytosis in case of haemolytic anaemia
= antibodies to RBCs activate complement and leads to opsonisation of RBCs = macrophages = phagocytosis…
(Mother produces antibodies of foetal blood, cross placenta and attack RBCs)
Glomerular nephritis - recruitment of neutropils causing tissue damage.
= antibody Fc recruits neutrophils with FcR = degranulation causes inflamed kidney tubules..
Bind receptor and inhibit function - Myasthenia Gravis = antagonist autoantibodies block nACh receptors at NMJ, lead to reduction in nACh at NMJ and muscular weakness.
= Neostigmine and hysoscine.
= Antibodies act only extracellularly, so target cell surface/circulatory things.
What is type III hyper sensitivity?
Circulating immune complexes can deposit and cause complement activation and FCR mediated recruitment of neutrophils.
- release of RONS and granule enzymes.
Circulating antibodies could cross-link by binding to multiple epitopes of same antigen…
Often deposit in small vascular beds, joints + renal glomeruli…
= Only treated by steroids…
SLE is an example of systemic disease.
What is Type IV?
Delayed type hypersensitivity = Type IV.
Cell mediated tissue injury by Th1 and CD8 (Tc) cells.
Release of IFN-y activates macrophages, with TNFa to induce inflammation.
Macrophages, Th1 and CD8 Tc cells release hydrolytic enzymes, RONs and cytokines.
= TYPE 1 DIABETES!!!
What is autoimmunity?
T cells are screened in the thymus for self-reaction.
Autoimmunity arises from a breakdown in mechanisms normally responsible for maintaining self tolerance!
Genetic susceptibility, environmental triggers, organ/system specific = Type 1 diabetes (type IV HS) or SLE (Type III HS).
Exposure to tissue can expose more epitopes.
May initiate from a single epitope, but as more WBCs are recruited and more tissue exposed - more epitopes…
= can result in chronic disease from epitope spreading…
= Treated with anti-inflammatory + disease modifying drugs…
Examples of autoimmune conditions I could discuss?
Rheumatoid arthritis - inflammation, destruction of joints, can invole antibodies.
(Th1 driven aswell as autoantibodies target collagen in cartilage, requiring B cells and therefore Th2 activation!)…. Th1 cells relesae Il-1, IFN-y = activate macrophages + recruitment..
HLA-DR4 risk factor.
=Naproxen/steroids _ disease modifiying drug = methotrexate.
Type IV - delayed Type Hypersensitivity.
Cell mediatec tissue injury from Th1 and CD8 Tc cells.
- Antigen presentation to Th1 cells - secrete IFN-y.
= IFN-y recruits macrophages and TNF induces inflammation and recruitment.
Tc cells + neutrophils release RONS and proteases…
Attack pancreatic beta cells which are source of insulin….
= NEED EXOGENOUS INSULIN.
Risk factors for autoimmunity?
Autoimmune reactions more common in females - role of oestrogen.
Risk factors:
HLA-DR4 in RA.
Occur after chronic infection like tuberculosis.
- Pathogen not fully exterminated - primed cells search for pathogen become self-ssensitiised.
Molecular mimicry - self-protein resembles pathogen and activates primed cells…
What steps are taken for transplantation?
Immune response of recipient to donor tissue.
Donor MHC/HLA recognised as foreign by Th1/Th2 - activation of antibody response also direct mediated cytotoxicity.
Blood and tissue typing.
Preformed antibody checked.
MHC compatibility.
Graft vs Host disease - donor organ attacks recipient due to present of donor immune cells in graft…
What is blood typing?
ABO antigens expressed on RBCs.
All have basic glyolipid antigen O.
Some can have attached carbohydrates A or B.
Body produces antibodies against antigens we don’t have.
Recipient of blood transfusion/transplant MUST NOT have antibodies for donors antigen/blood typ.e
E.G Group A have circulated anti-B antibodies.
- Group O are universal donors - can donate to everyone as no one produces antibodies for group O!!!
What is immunodeifiency?
Can be congenital or acquired:
Congenital - mutations in genes for antibodies or cytokine receptors - fails to fully activate immune system.
SCID…
Acquired - HIV/AIDS destroys CD4 cells and Th cells…
HIV infects dendritic cells, so carried to lymph nodes.
HIV infects T cells from CD4/chemokine receptors - gradually cause lymphopenia + patient dies from opportunistic infections…
