Hypersensitivity Reactions Flashcards
What are some diseases as a result of hypersensitivity reactions
Goodpastures, haemolytic, sle, myasthenia Gravos, RA, graves
What is hypersnsitivity
The term hypersensitivity describes “the antigen- specific immune responses that are either inappropriate or excessive and result in harm to host”
The mechanisms underlying these aberrant immune responses are those employed by the host to fight infections
What are types of triggers (antigens
• Hypersensitivity to exogenous antigens Non infectious substances (innocuous)
Infectious microbes
Drugs (Penicillin)
• Hypersensitivity to intrinsic antigens Infectious microbes (mimicry)
Self antigens (auto-immunity)
What are teh types of hypersensitivity reaction
• Type I or immediate (Allergy) - IgG
• Environmental non infectious antigens
• Type II or antiBody mediated -IgG, IgM - antigen on cell/tissue
• Type III or immune Complexes mediated- igG, IGM - soluble antigen
• Type IV or cell mediated (Delayed)
Environmental infectious agents and self antigens
- aleren, rest, self antigen
Whar are common features of hypersensitivity reaction
• Sensitization phase
First encounter with the antigen. Activation of APCs and memory effector cells. A previously exposed individual to the antigen is said to be “sensitized”
• Effector phase
Pathologic reaction upon re-exposure to the same antigen and activation of the memory cells of the adaptive immunity
First - o clinical manifestation. Second encounter - clinical manifestation.
Describe type 2 hypersensitivity
• Usually develops within 5-12 hr • 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
Describe type 2 hypersensitive machanisms
Cell expressing self antige - person expose to trigger - mounted immune resopns - secon eounter - antibody binds to self antigen - 2 things happen: (complement activation, antibody dependent cell cytotoxicity)
Immune mechanisms. Once compliment ctivated then (Complement activation
Cell lysis (MAC)
Neutrophil recruitment/
activation (C3a/C5a) Opsonisation (C3b)) compliment also releases neutrophil - damage cell/tissue. Opsonised - eutrophi then engulfs cel. FC receptors
Antibody-dependent cell cytotoxicity
(NK cells)
Receptor stimulation
Receptor blockade
What are examples of type 2 hypersensitivity
Haemolytic disease of the newborn (HDN) - Antigen = Rhesus D Transfusion reactions - Antigen=ABOsystem
Autoimmune haemolytic anaemia (warm and cold) Immune thrombocytopenia Purpura
Goodpasture’s syndrome
Graves’disease
− Increased thyroid activity − Antigen = TSH receptor
Myastheniagravis
− Impaired neuromuscular signalling − Antigen = Acetylcholine receptor
Describe the importance of complement pathways
S
Describe haemolytic transfusion an example of disease caused by type 2 hypersensitivity by IgM
An example of disease caused by type II hypersensitivity (IgM)
Haemolytic transfusion reaction
• Life-threatening condition
• Shock, kidney failure, circulatory collapse, and death
Immune mechanism
• Incompatibility in the ABO or rhesus D antigens
• Donor RBC destroyed by recipient’s immune system
• RBC lysis induced by type II hypersensitivity involving
by the naturally occurring antibodies (IgM)
Desribe haemolytic disease of the newborn as an example of disease caused by type 2 hypersensitivity
Rh pos father, rh negative mother, first child - rh+ antigens from first fetus go into mothers blood. The mother then produces anti rh antibodies. woman’s body mounts immune response against rh in fetus (second time) - damage fetus rbcs
Rhogam - immunoglobulin - IM - prevent the mother from mounting an immune response against the fetal cells - 72h after deliver
What are therapeutic approaches for tissue/cell amage in type 2 hypersensitivity reactions
• Anti-inflammatory drugs - Complement activation • Plasmapheresis Circulating antibodies and inflammatory mediators • Splenectomy - Opsonisation/Phagocytosis • Intravenous immunoglobulin (IVIG) - IgG degradation
What re the therapeutic approaches in physiological change as a result on the 2 reacto
- Correct metabolism
- Antithyroid drugs in Graves’s disease
- Replacement therapy
- Pyridostigmine in Myasthenia gravis - replace neurotransmitter
What is plasmapheresis thepay
Can get rd of palms, cytokines, replace with substitution fluid. Short term relief and allows healing of damaged tissue, used in Myasthenia gravis Goodpasture’s syndrome Graves’ disease
Gove an overview of type 3 hypersevitiity x
• Usually develops within 3-8 hr • Involves immune complexes between IgG or IgM and antigens • Targets soluble antigens - Foreign(Infection) - Endogenous (self antigens) • Tissue damage caused by the deposition of immune complexes in host tissues
What are key factors affecting IC pathogeneis
Complex size
Small and large size ICs cleared
Intermediate size ICs
Rbcs have a receptor for c3b - phagocytes can engulf this as it has been opsonised. I a patient has complement deficient - immune disease
• Host response
Low affinity antibody
Complementdeficiency
• Local tissue factors
Haemodynamic factors
Physicochemicalfactors
All of the above Persistence of ICs Deposition • Joint • Kidney • Small vessels • Skin Multisystem disease
Give an overview of type 3 mechanisms s
Ss Tend to deposit - problems start where they deposit - cant bind to receptor start a pathway - c3b can opsonise the tissue - can release chemoattractatt v3a which attracts neutrophils - stick to c3b - signal start degradation, releasing toxic material - tissue damage. Neutrophils are essential in driving the damage
Gve 2 example of diseases caused by type 3 reactions
• Rheumatoid arthritis (self-antigen) • Antigen = Fc portion of IgG (75%) • Articular and extra-articular features • Episodes of inflammation/remission • Poor prognosis factors - <30year-old - High-titreofRF - Female - DR4allele - Joint erosions
• Glomerulonephritis (infectious)
- Bacterial endocarditis
- Hepatitis B infection
• Systemic lupus erythematosus • Antigen = Ds-DNA • Most prevalent immune complexes disease • Ratio female:male (9:1) • 40-60% patients with cardiac, respiratory, renal, joint and neurological features • Repeated miscarriage • Every patient is unique!!!!!!
Give an overview of type 4 reactions
- Usually develops within 24-72hr
- Involves lymphocytes and macrophages
- Different subtypes (clinical outcomes)
- Contact hypersensitivity
- Tuberculin hypersensitivity
- Granulomatous hypersensitivity
Give an overview of the pathogeneis of type 4
First encounter . APC meets bacteria, activates TH1 - specific against this trigger/TB is a good example. A set of effector cells and memory T cells against (eg) TB, first encounter nothing happens. Re encounter - effector chase where you get damage. Macrophages are reactivated by th cells - recognise the bacteria. Activated th, then activate macrophage, these try to clear microbe (but Tb cannot be cleared). Macrophages release toxins, ROS, etc, but this locally damages the tissue and recruite more th cells then activate cd8 -. Pathway -> tissue damage. Triggers local inflammatory response
What are some disease caused y type 4
Contact hypersensitivity • Occurs 48-72 hr postexposure • Epidermal reaction • Require endogenous proteins • Examples o Nickel (common) o Poison ivy o Organic chemicals
Granulomatoushypersensitivity • Occurs 21-48 days post-exposure • Tissue damage • Examples: o Tuberculosis o Leprosy (tuberculoid) o Schistosomiasis o Sarcoidosis
• Pancreatic Islet cells: o Insulin-dependent diabetes mellitus • Thyroid gland: o Hashimoto’s thyroiditis • Fc portion of IgG: o Rheumatoid arthritis
Describetype 3 and4 therapy
Anti-inflammatory drugs • Non-steroidals • Corticosteroids (oral prednisolone) • Second drugs as steroid-sparing agents (<10 mg oral steroid) - Azathioprine - Mycophenolate mofetil - Cyclophosphamide
Monoclonal antibodies
• B Cells and T cells
• Cytokine network
• APCs
