hypersensitivity Flashcards
Dust
can mimic parasite and stimulate antibody response
if dominant is IgE- allergy symptoms
if stimulate IgG -different kind f hypersensitivity, eg farmer’s lung
haptens
Smaller molecules sometimes diffuse into the skin triggering a delayed hypersensitivity reaction.
small molecule irritants that bind to proteins and elicit an immune response
Contact dermatitis caused by nickel.
Drugs administered orally, by injection, or onto the surface of the body can elicit hypersensitivity
type 1 hypersensitivity
Mediated through the degranulation of mast cells and eosinophils.
The effects are felt within minutes of exposure.
Immediate hypersensitivity, allergy
IL-4 (TH2 cells)production induces Ig E antibody
Atopy
Immediate hypersensitivity reaction to environmental antigens mediated by IgE. Develops within minutes of exposure Family history with atopy traits. Anaphylaxis Angioedema urticaria rhinitis
Allergens
Peanut allergy is the most common cause of severe allergic reactions.
Allergy to peanut protein Ara h2, Ara h8, cross reactivity with other foods.
latex
Penicillin allergy, the allergen is β-lactam
degranulating cells
release of mediators
mast cells
eosinophils migrate
basophils stay in circulation appear like mast cells
MCs initiate allrgic symptoms
-receptors for IgE and FcεRI (high affinity IgE receptor)
skin allergy
urticaria
angioedema
atopic eczema
genetics of allergies
Filaggrin is expressed by keratinocytes and involved in maintaining epithelial barriers and moisturizing surfaces and controlling pH.
Polymorphisms in the gene encoding is established as a cause of allergy and implicated in 50% of severe eczema.
Exposure to environmental factors
timing
hygiene hypothesis
: increase in allergies in the developed world is caused by reduced exposure to microorganisms in early life
polymorphisms
variants of different alleles in the same gene
anaphylaxis
vasodilation and increased vascular permeability
shift fluids from vascular to extra vascular space resulting in a fall in vascular tone
severe drop in blood pressure
in skin, mast cells release histamine- fluid shift and oedema
allergic rhinitis
inhaled allergens stimulate mast cells in the nasal mucosa.
Subsequent vasodilation and oedema in the nose causes nasal stuffiness and sneezing.
Leukotrienes increase mucus secretion,
Asthma
Increased mucus secretion and contributes to the airflow obstruction.
In the lungs, leukotrienes cause smooth muscle contraction, which has the most dramatic effects on airflow reduction
Several hours after the acute episode, the airflow in the bronchi may deteriorate again, reflecting the migration of leukocytes into the bronchi in response to chemokines
drug treatment
β2-adrenergic agonists, mimic the effects of the sympathetic nervous system and work mainly by preventing smooth bronchial muscle contraction in asthma
Epinephrine (adrenaline) lifesaving where blood pressure falls dramatically. Epinephrine stimulates bothα- andβ-adrenergic receptors, decreases vascular permeability, increases blood pressure, and reverses airway obstruction
Antihistamines block histamine receptors and have allergies that affect the skin, nose, and mucus membranes.
Specific receptor antagonists block the effects of leukotrienes. Montelukast reduces airway inflammation in asthma
Corticosteroids can prevent the immediate hypersensitivity reaction, the late phase, and chronic allergic inflammation
type II hypersensitivity
Antibody mediated hypersensitivity IgG or IgM reacting with antigen present on the surface of cells. The bound Ig interacts with complement or with Fc receptor macrophages. Opsonisation of target cells Immune mediated haemolysis. Takes several hours. Drug-induced haemolysis. Rhesus ABO
immune mediated haemolysis
Alloimmune Haemolysis
Rhesus antigen (IgG develops during pregnancy and crosses the placenta and causes haemolytic disease).
Incompatibility in the ABO system
Autoimmune Haemolysis
systematic autoimmune disease (SLE)
Autoantibodies produces by malignant B cells
Type II Autoimmune Hypersensitivity Against Solid Tissue
Goodpasture syndrome, IgG autoantibodies bind a glycoprotein in the basement membrane of the lung and glomeruli. Anti–basement membrane antibody activates complement, which can trigger an inflammatory response
graves disease
Most common cause of hyperthyroidism Mainly young women Family history HLA allele DR3 Thyroid is stimulated with an autoantibody that binds into the THS receptor
type III hypersensitivity
Immune complex disease
IgG is also responsible
Immune complexes of antigen and antibody form and cause damage at the site of production or circulate and cause damage elsewhere.
Immune complexes take some time
form complexes must by polyvalent.
Present long enough to start an antibody response
At low levels of antibody, each antigen molecule binds several immunoglobulin molecules.
When antibody and antigen levels are approximately equal, or antibody levels are slightly in excess, large complexes can form.
When antibody exceeds antigen, small complexes form.
clearance of complexes
Complement breaks down large complexes
Complement Receptor 1 Transfers Complexes to Phagocytes
immune complex disease in kidney
Glomerulonephritis
Nephrotic syndrome (protein leaks into urine) with gradual development of renal failure
Nephritis with rapid onset renal failure, blood and protein in the urine and hypertension
type IV hypersensitivity
This can take 2 to 3 days to develop
Delayed hypersensitivity
Delayed hypersensitivity reactions are initiated when tissue macrophages recognize danger signals and initiate an inflammatory response.
Dendritic cells loaded with antigen migrate to local lymph nodes, where they present antigen to T cells.
Specific T-cell clones proliferate in response to antigens, which migrate to the site of inflammation.
Tumour necrosis factor (TNF) is secreted by both macrophages and T cells and stimulates much of the damage in delayed hypersensitivity
Rheumatoid arthritis
Many features of delayed hypersensitivity with persistent TH1 and TH17 reactions and TNF secretion.
antigens that drive RA appear to be citrullinated proteins. Citrullination is the conversion of the amino acid arginine to the amino acid citrulline.
Autoreactive T cells and B cells can recognize citrullinated proteins. The result is production of antibodies against citrullinated protein. These are referred to asanti–cyclic citrullinated peptide(CCP) antibodies
The synovium becomes infiltrated by T cells (TH1 and TH17) and macrophages.
TNF and IL-17 attract and activate neutrophils that cause damage to the synovium.
Osteoclasts are activated and destroy bone at the joint margins, creating erosions.
Persistent IL-6 secretion triggers an acute-phase response.
Family history.
Association with HLA-DR4.
MS
Chronic, disabling neurologic disease.
Initially in MS, acute attacks occur during which inflammatory lesions consisting of TH1 and TH17 cells and macrophages develop in the affected nervous tissue.
The inflammatory lesions cause the reversible, relapsing disability typical of early MS.
Although active inflammation is present in the vicinity, myelin loss impairs the ability of neurons to conduct impulses, resulting in neurologic symptoms.
Once the inflammation settles, the disability improves.
Between attacks, there is usually good recovery of function, at least early in the disease.
The chronic disability that usually occurs later results from axonal loss.
