Hypersensitivity Flashcards
what is a hypersensitivity reaction?
a condition in which the normally protective immune system has a harmful effect on the body by excessive or inappropriate immune response
Allergy
abnormal immunological response to otherwise harmless environmental stimulus
e.g. food, pollen, animal and dander
Autoimmune disease
abnormal immunological response directed against an antigen within the body
what are the stages of a hypersensitivity reaction?
sensitisation
effect
what is sensitisation?
initial asymptomatic contact with an antigen
what is effect?
harmful immune response following sensitisation and subsequent antigen contact
what are the types of hypersensitivity reaction?
1-4
1-3 = antibody mediated
4 = cell mediated
type 1 hypersensitivity
allergic or immediate
onset within minutes
develop IgE antibodies in response to harmless antigens
can be localised - allergic rhinitis and asthma
can be systemic - anaphylaxis
exposure by ingestion, inhalation, injection or direct contact
pathogenesis of type 1 hypersensitivity
contact with antigen
IgE formed as a result
coats mast cells and basophils - next time your body encounters the allergen it results in an IgE-mediated reaction by preformed IgE antibodies
Free allergen binds to 2 adjacent IgE antibodes - crosslinking
causes degranulation of cells which causes release of histamine and other mediators - prostaglandins, platelet-activating factor, leukotrienes
has varying effects on all these to cause the symptoms associated with allergy/ atopy
what do vasoactive amines effect?
smooth muscle blood vessel mucous gland platelets sensory nerve endings eosinophils
what do vasoactive amines do to smooth muscle?
bronchospasm, abdominal cramping, rhinitis, hypovolemia and hypoxia
what do vasoactive amines do to blood vessels?
cause vasodilation and leaky capillaries
extravasation of capillary blood - causing erythema
fluid shift into the interstitial space - oedema and pulmonary oedema
what do vasoactive amines due to eosinophils?
eosinophilia -
eosinophil and neutrophil chemotaxis induced by basophil and mast cell mediators
what are some common allergies?
drugs foods Insect venom Inhaled or environmental allergens blood transfusion products
examples of type 1 hypersensitivity
anaphylaxis
allergies
is anaphylaxis humoral or cell mediated?
humoral
how to treat anaphylaxis?
adrenaline intramuscularly to lateral thigh airway resuscitate anaesthetics cardiac arrest call antihistamines slow to work
type 2 hypersensitivity reaction
cytotoxic
onset within minutes or few hours
involves IgG and IgM antibodies
5 mechanisms by which these antibodies can cause disease
mechanism 1 for type 2 hypersensitivity
Antigen-antibody complex on host tissue
activates complement cascade which creates a membrane attack complex. Inserts itself into the membrane of the cell it attacks. Allows fluid to rush into cell - swells and bursts cell - cell lysis
mechanism 2 for type 2 hypersensitivity
complement activate complement binds to Fc portion of the antibody. Some of the cascade become cleaved and chemotaxic - attracts neutrophils. Neutrophils undergo degranulation and release enzymes which generate oxygen radicals which cause cytotoxic damage to cell
mechanism 3 for type 2 hypersensitivity
activation of complement cascade causing opsonisation and phagocytosis. The phagocytes engulf cells in the spleen
mechanism 4 for type 2 hypersensitivity
antigen-antibody complex recognised by NKs, they bind to the antibody. NKs release perforins forming pores in the cells. Granzymes and granulysin enter the cell and cause apoptosis
mechanism 5 for type 2 hypersensitivity
antibody mediated cellular dysfunction, antigen-antibody complex blocks normal receptor activator from getting to receptor e.g. myasthenia or simulates a signalling molecule and over activate a receptor e.g. graves disease
type 2 hypersensitivities examples
autoimmune haemolytic anemia good pasture syndrome drug-induced neutropenia immune thrombocytopenia graves disease myasthenia gravis bullous pemphigoid pemphigus vulgaris rheumatic fever acite hemolytic transfusion reaction hemolytic disease of the fetus and newborn hyperacute transplant rejection
distribution of type 2 hypersensitivity diseases
limited to a particular tissue type
diagnosis of type 2 hypersensitivity
autoantibody testing and coombs test
coombs test
used to detect antibodies that act against the surface of cells
hemolytic anemia
form of anemia due to hemolysis, the abnormal breakdown of red blood cells in the blood vessels or spleen
opsonisation and phagocytosis of erythrocytes
Good pasture syndrome
rare, autoimmune disease which antibodies attack the basement membrane in lungs and kidneys, leading to bleeding from the lungs and kidney failure
Complement and Fc receptor mediated inflammation
Nephritis and lung hemorrhage
Autoimmune thrombocytopenic purpura
opsonisation and phagocytosis of platelets causing bleeding
Pemphigus vulgaris
antibody-mediated activation of proteases, disruption of intracellular adhesions . Skin blisters
Vasculitis
Neutrophil degranulation and inflammation. Vasculitis
Acute rheumatic fever
inflammation and macrophage activation. Myocarditis and arthritis
Myasthenia gravis
antibody inhibits acetylcholine binding and down modulates receptors
muscle weakness and paralysis
Graves disease
Antibody mediated stimulation of TSH receptors causing hyperthyroidism
Pernicious anemia
neutralisation of intrinsic factor and decreased absorption of vitamin B12. Abnormal erythropoiesis, anemia, neurologic symptoms
is graves disease local or systemic?
local as it only effects thyroid tissue but shows systemic effects because of role of thyroid
type 3 hypersensitivity
immune complex hypersensitivity
onset between 2 and 6 hours
can be local or systemic
antigens causing it can be exogenous or endogenous
pathogenesis of type 3 hypersensitivity
formation of antigen antibody immune complexes with slight antigen excess
complement is activated by the immune complexes via the classical pathway . This causes basophils to degranulate, releasing mediators that increase vascular permeability.
complexes circulate and are trapped in the basement membrane of small blood vessels
activated complement attracts neutrophils and causes them to degranulate
neutrophils release enzymes responsible for much of the tissue damage
what is an immune complex?
antigen-antibody complex formed when the antigen is found in the blood stream, so is soluble .
clinical examples of type 3 hypersensitivities
systemic lupus erythematosus drug-induced hypersensitivity vasculitis poststreptococcal glomerulonephritis polyarteritis nodosa wegeners granulomatosis arthus reaction hypersensitivity pneumonitis - Farmer's/ pigeon fanciers lung serum sickness serum sickness-like reaction
wegners granulomatosis
rare condition in which blood vessels become inflamed, affecting the ears, nose, sinuses, kidneys and lungs
arthus reaction
post tetanus vaccination
hypersensitivity pneumonitis
triggered by exposure to proteins present in bird droppings . The lungs become inflamed with granuloma formation - farmers lung
serum sickness
a reaction to medications or often serums - such as antivenom
systemic lupus erythrmatosus
nephritis
arthritis
vasculitis
polyarteritis nodosa
vasculitis
poststrptococcal glomerulonephritis
nephritis
type 4 hypersensitivity
delayed hypersensitivity reaction, inflammation by 2-6hours and peaks at 24-48hrs
result from interaction of T cell-initiated inflammation and doesnt involve antibodies
the inflammatory responses result from the manner in which the T cells encounter and respond to the antigen
can be transferred by sensitised T cells but not serum
Pathogenesis of type 4 hypersensitivity reactions
foreign antigen enters the body
uptake by langerhans cell
migration to lymph nodes and formation of sensitised T lymphocytes
secretion of lymphokines and cytokines - IFN gamma and TNF alpha by sensitised T lymphocytes
macrophage attaches to antigen
macrophage presents antigen to T lymphocytes
forms a cytotoxic T cell
autoimmune reaction - cytotoxic T cell attaches to similar antigen in healthy tissue
killer T cells release perforin and granzymes
tissue destruction
examples of type 4 hypersensitivities
contact dermatitis drug reactions - stevens-johnson syndrome Graft-versus-host disease Mantoux tuberculin skin test for latent TB rheumatoid arthritis IBD MS Guillain-Barre syndrome Hashimoto's thyroiditis type 1 diabetes mellitus
rheumatoid arthritis
inflammation mediated by TH1 and TH17 cytokines
MS
inflammation mediated by TH1 and TH17 cytokines
myelin destruction by macrophages
Type 1 diabetes
T cell mediated inflammation and destruction of islet cells
killer T cells
IBD
inflammation mediated by TH1 and TH17 cytokines
Psoriasis
inflammation mediated by T cell derived cytokines
Stevens Johnson drug reaction
affects skin and mucus membranes
flu-like symptoms, rash and blistering . the skin eventually dies
common drug allergies
penicilin and muscle relaxants
common food allergies
nuts, shellfish, eggs, soy and wheat
common insect venom allergies
Insect venom - bee and wasp
common environmental allergies
Inhaled or environmental allergens - dust mites, animal dander, pollen, latex
