Hypersensitivty reactions Flashcards
What’s the main cause of immunodeficiency in the UK?
Malnutrition
esp >65yrs
Define hypersensitivity
The antigen- specific immune responses that are either inappropriate or excessive and result in harm to host
- tissue destruction or change in function
What are the two types of hypersensitivity triggers (antigens)?
Exogenous antigens - non infectious substances (innocuous)
Infectious microbes
Drugs (penicillin)
Intrinsic antigens - infectious microbes with similar structure to internal antigen e.g. Rheumatic fever (mimicry), self antigens (auto-immunity)
Types of hypersensitivity reactions
Type 1/ immediate (allergy) (IgE mediated)
- environmental non infectious antigens
Type 2/ antibody mediated (against membrane bound antigen, organ specific - IgG, sometimes IgM
Type 3/ immune complexes mediated - soluble antigen so immune complex circulates (mostly systemic) - IgG mediated, sometimes IgM
Type 4/ cell mediated (delayed) (environmental infectious agents and self antigens)
Two phases of hypersensitivity reactions
Sensitisation phase - first encounter with antigen, activation of APCs & memory effector cells (once exposed = sensitized)
Effector phase - pathologic reaction upon re-exposure to same antigen & activation of memory cells of the adaptive immunity
Describe type 2 hypersensitivity reactions
Usually develops within 5-12hrs
Involves IgG or IgM antibodies
Targets cell bound antigens
Exogenous: blood group antigens, Rhesus D antigens
Endogenous: self antigens
Induces different outcomes: tissue/ cell damage, physiological change
Type 2 hypersensitivity mechanisms
Tissue/ cell damage ~
Complement activation (to a new foreign tissue) : cell lysis (MAC), neutrophil recruitment/ activation (C3a/ C5a)/ opsonisation (C3b)
OR
Antibody- dependent cell cytotoxicity (to you own self tissue) : NK cells
Physiological change ~
Receptor stimulation or receptor blockade
Give examples of type 2 hypersensitivity diseases involving tissue/ cell damage
Complement activation:
- haemolytic disease of the newborn, antigen = Rhesus D e.g. Rh+ father & Rh- mum have Rh+ bby, 1st pregnancy Rh+ antigens enter mum during delivery -> mother produces anti-Rh antibodies. 2nd Rh+ pregnancy - antibodies cross placenta & damage fetal RBCs 3rd trimester
Haemolytic Transfusion reactions, antigen = ABO system/ RhesusD - life threatening, shock, kidney failure, circulatory collapse
Antibody- dependent cell cytotoxicity:
Autoimmune haemolytic anaemia (warm & cold), immune thrombocytopenia purpura, Goodpasture’s syndrome (glomerulonephritis)
Which blood type is best to give if unsure? Which blood type can receive any type?
If unsure give: O-
Can receive anything: AB+
(Although transfused blood may have antibodies, won’t be a cascade increasing supply so will have no effect)
Which antibodies does each blood type contain?
Rhesus negative has antibodies against positive
Type A - antibodies against B
Type B - antibodies against A
Type AB - no antibodies
Type O - antibodies against A and B
How can you prevent haemolytic disease of the newborn?
Give Rho(D) immune globulin (human)/ RhoGAM to mum before delivery
Binds fetal RBCs & clears Rh+
Give 2 examples of type 2 hypersensitivity reactions involving physiological change
Receptor stimulation: Grave’s disease - increased thyroid activity, antigen = TSH receptor (antibodies bind receptor & stimulate)
Receptor blockade: myasthenia gravis, impaired neuromuscular signalling, antigen = acetylcholine receptor (numbness, paralysis, weakness)
Therapeutic approaches for type 2 hypersensitivity reactions caused by tissue/ cell damage
- anti-inflammatory drugs (complement activation targeted)
- plasmapheresis (separate plasma, clear it from antibodies/ inflammatory mediators then return)
- splenectomy (reduces opsonisation/ phagocytosis, risk encapsulated organisms)
- intravenous immunoglobulin (IVIG) IgG degradation
Therapeutic approaches for type 2 hypersensitivity reactions caused by physiological change
Correct metabolism - anti thyroid drugs in Grave’s disease
Replacement therapy - pyridostigmine in Myasthenia Gravis (increases Ach)
What can plasmapheresis therapy be used to treat?
Myasthenia gravies
Goodpasture’s syndrome
Grave’s disease
Short term relief & allows healing of damaged tissue
Describe type 3 hypersensitivity reactions
Usually develops within 3-8hrs
Involves soluble immune complexes between IgG or IgM and antigens
Targets soluble antigens - foregoing (infection) or endogenous (self antigens)
Tissue damage caused by deposition of immune complexes in host tissues
Key factors affecting immunocomplexes pathogenesis for type 3 hypersensitivity
Complex size (small & large size ICS cleared easier than intermediate size)
Host response (low affinity antibody or complement deficient)
Local tissue factors (haemodynamic factors, physiochemical factors)
All of these affect the persistence of immunocomplexes deposition in: joints, kidney, small vessels, skin etc.
Give three examples of diseases caused by type 3 hypersensitivity reactions
- Rheumatoid arthritis (self-antigen) - antigen = Fc portion of IgG (75%), articular & extra-articular features, episodes of inflammation/ remission
- glomerulonephritis (infectious) - bacterial endocarditis, hepatitis B infection (immune complexes deposit)
- systemic lupus erythematosus, antigen = Ds- DNA, most prevalent immune complexes disease, female X9 (mouth, muscles, joints,psychological, face, pleura, pericardium, respiratory, renal, miscarriages)
Describe type 4 hypersensitivity
Usually within 24-72hrs
Involves lymphocytes and macrophages (antibodies come later)
Different subtypes (clinical outcomes)
- contact hypersensitivity
- tuberculin hypersensitivity
- granulomatous hypersensitivity
2 steps in type 4 hypersensitivity tissue destruction
- Sensitisation phase: APCs: macrophages -> delayed typed hypersensitivity cells -> TH1 response (CD8)
- Effector phase: TH1 products (IFN gamma, TNF beta, IL-2/3/8) -> macrophage activation (TNF receptor, O2 radicals, NO) -> granuloma
3 diseases caused by type 4 hypersensitivity to exogenous antigens
- contact hypersensitivity (48-72hrs post exposure), epidermal reaction, needs endogenous proteins e.g. nickel, poison ivy, organic chemicals
- granulomatous hypersensitivity (21-48hrs post exposure), tissue damage e.g. TB, leprosy, schistosomiasis, sarcoidosis (when host can’t remove microbe)
- tuberculin hypersensitivity (48-72hrs) dermal reaction
3 diseases caused by type 4 hypersensitivity to endogenous antigens
Pancreatic islet cells: insulin dependent diabetes mellitus
Thyroid gland: Hashimoto’s thyroiditis
Fc portion of IgG: Rheumatoid arthritis
Type 3 & 4 hypersensitivity therapy
Anti-inflammatory drugs: non-steroidals, corticosteroids (oral prednisolone), second drugs as steroid sparing agents (<10mg oral steroids) e.g. azathioprine
Monoclonal antibodies: B cells and T cells, cytokines network, APCs
