hypersensitivity Flashcards
what are hypersensitive reactions?
excessive immune responses that cause damage
what are examples of antigens involved in hypersensitive reactions?
- infectious agents
- environmental substances
- self-antigens
what are the 4 different types of hypersensitivity?
- type I (Immediate)
- type II (cell-bound antigen)
- type III (immune complex)
- type IV (delayed)
describe the process of influenza causing hypersensitivity?
- damaged respiratory tract epithelial cells
- exaggerated immune response
- cytokine storm
- attract leukocytes to the lungs (hypotension and coagulation)
severe influenza
- inflammatory cytokines spill into systemic circulation causing effects in remote parts of body, such as brain
describe the process of dust causing hypersensitivity?
enters lower extremities of respiratory tract and mimics parasites to stimulate an antibody response
IgE: triggers immediate hypersensitivity → allergy symptoms (asthma or rhinitis)
IgG: different kind of hypersensitivity eg farmer’s lung
describe the lower extremities of respiratory tract
rich in adaptive immune response cells
what are haptens?
small molecule irritants that bind to proteins and elicit immune response
example is nickel causing contact dermaititis
describe type I hypersensitivity
immediate hypersensitivity reaction to environmental antigens
degranulation of mast cells and eosinophils
how quick is the onset of type I hypersensitivity?
within minutes of exposure
what is type I hypersensitivity basically?
an allergy
what is another word for allergy?
atopy
presentations of type I hypersensitivity?
- anaphylaxis
- angioedema
- asthma
- dermatitis, eczema, urticaria
- rhinitis
atopic march
different presentations of type I hypersensitivity come and go at different ages
allergens
antigens that trigger allergic reactions
how can people be exposed to allergens
- inhalation
- ingestion
- contact
- administered as drugs
what immunoglobulin mediates type I hypersensitivity?
IgE
what is IgE produced by
B cells when co-stimulated with IL-4 (secreted by TH2 cells)
describe the mechanism of type I hypersensitivity?
- release of mediators that cause allergic symptoms
- mast cells are resident in many tissues
- eosinophils migrate to tissues
- mast cells initiate allergic symptoms after allergen and IgE interact
- mast cells have receptors for IgE and FcεRI
anaphylaxis symptoms
- low blood pressure
- angioedema
- airway obstruction
asthma symptoms
reversible airway obstruction in bronchi
rhinitis symptoms
- discharge
- sneezing
- nasal obstruction
urticaria symptoms
acute, itchy oedema of subcutaneous tissue
angioedema symptoms
acute, non-itchy oedema of subcutaneous tissue
atopic eczema symptoms
chronic, itchy inflammation of skin
epidemiology of allergies
very common, up to 40% population
describe the genetics of allergies
filaggrin is expressed by keratinocytes
- maintains epithelial barrier
- moisturises surfaces
- controls pH
polymorphism in filaggrin → allergy
what is the role of environmental factors in allergy
- urbanisation
- hygiene hypothesis: reduced exposure to microorganisms in early life
- infections: increase/decrease risk of allergies
what is the most serious type of allergy?
anaphylaxis
describe the mechanism of anaphylaxis
mast cells degranulate to produce histamine and leukotrienes
- vasodilation
- increased vascular permeability → hypotension
describe the mechanism of rhinitis
mast cells degranulation and leukotrienes
- vasodilation & oedema (nasal stuffiness and sneezing)
- mucous secretion (nasal discharge)
describe the mechanism of asthma
leukotrienes cause smooth muscle contraction → airflow reduction
describe the treatment of allergies?
prevention
desensitisation (allergen immunotherapy)
drug treatment
- beta 2 adrenergic agonists
- epinephrine
- antihistamines
- corticosteroids
test to determine what antigen someone is allergic to
skin prick test
what immunoglobulins mediate type II hypersensitivity
IgG or IgM
react with antigen present on surface of cell
bound IgG then interacts with complement or with Fc receptor on macrophages
effects of type II hypersensitivity
damage to red cells
damage to solid tissues
functional effects
examples of damage to red blood cells
autoimmune haemolytic anaemia
- rhesus disease
- mismatched blood transfusion (ABO compatibility)
- infections: hep c, hiv, cmv, vzv
- diseases: SLE, CVID
- drugs
examples of damage to solid tissues
good pastures syndrome
examples of functional effects
graves disease
what are the different variations of blood type?
- rhesus positive or negative
- I positive or negative
- group A, B or O
what is a consequence of A and B blood group antigens being oligosaccharides which are similar to molecule exposed by bacteria?
antibodies recognise A and B blood group
- anti A and anti B are IgM antibodies naturally occurring
group O have antibodies against both A and B
People who are group O have antibodies against what groups?
A and B
People who are group AB have antibodies against what groups?
None
What type of antibodies are anti-A and anti-B?
IgM antibodies
What is unique about IgM?
IgM antibodies are multivariant (can combine to multiple antigens)
What is a complication of IgM being multivariant?
IgM antibodies are multivariant (can combine to multiple antigens):
- causes agglutinate of red blood cells
- IgM activates complement
- membrane attack complex destroying RBC
How does IgG lead to destruction of red cells?
IgG does not damage circulating red cells:
- Fc receptors on splenic macrophages bind IgG coated red cells, which are then destroyed
What can autoimmune haemolysis occur due to?
- Rhesus antigen (IgG develops during pregnancy and crosses the placenta and causes haemolytic disease
- Incompatibility in the ABO system during blood transfusion
What can autoimmune haemolytic anaemia be caused by?
- Induced by infections or drugs
- Part of systematic autoimmune disease (SLE)
- Autoantibodies produced by malignant B cells
Describe the pathophysiology of Goodpasture syndrome?
- IgG autoantibodies bind a glycoprotein in basement membrane of lung and glomeruli
- Anti-basement membrane antibody activates complement, triggering inflammatory response
Describe the genetics of Graves disease?
- Family history
- HLA allele DR3
Describe the epidemiology of Graves disease?
- Most common cause of hyperthyroidism
- Young woman
Describe the pathophysiology of Graves disease?
thyroid-stimulating autoantibody binds TSH receptors and stimulates thyroxine secretion
What is type III hypersensitivity?
- IgG responsible
- Immune complexes of antigen and antibody form and cause damage at site of production or circulate and cause damage elsewhere
- Take time to form and initiate tissue damage
What Ig mediates type III hypersensitivty?
IgG
Antigens that form complexes must be what?
- Polyvalent
- Present long enough to start an antibody response
Why is the antigen:antibody ratio important for type III hypersensitivity?
- At low levels of antibody, each antigen binds several immunoglobulin molecules
- When antibody and antigen levels are equal, or antibody in slight excess, large complexes can form
- When antibody exceeds antigen small complexes form
When do small and when do large complexes form?
- When antibody and antigen levels are equal, or antibody in slight excess, large complexes can form
- When antibody exceeds antigen small complexes form
Describe the process of clearing complexes?
- Done by compliment system
- Complement receptor 1 (CR1) transfers complexes to phagocytes
What does failure of clearance of complexes lead to?
Failure of clearance leads to immune complex disease:
- Activation of innate immune system
What are two diseases type III hypersensitivty is involved in?
Glomerulonephritis
Farmer’s lung
What is the presentation of glomerulonephritis due to hypersensitivity?
- 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
What is Farmer’s lung?
Hypersensitivity reaction to fungal spores:
- Precipitating IgG antibodies against mold proteins
- If patient inhales mold protein, insoluble immune complexes form in lung tissues
What is type IV hypersensitivity?
Delayed hypersensitivity reaction:
- Mediated by T cells
- Takes 2-3 days to develop
What mediates type IV hypersensitivity?
T cells
How long is the onset of type IV hypersensitivity?
- Takes 2-3 days to develop
What are the main diseases of type IV hypersensitivity?
- Rheumatoid arthritis
- Multiple sclerosis
Describe the mechanism of type IV hypersensitivity?
- Initiated when tissue macrophages recognise danger signals and initiate an inflammatory response
- Dendritic cells loaded with antigen migrate to local lymph node, where present antigen to T cells
- Specific T-cell clones proliferate in response to antigens, which migrate to site of inflammation
- Tumour necrosis factor (TNF) is secreted by both macrophages and T cells and stimulates much of the damage in delayed hypersensitivities
Describe the presentation of rheumatoid arthritis?
- Symptoms arise in joints and tendons, but also affects skin, lungs and eyes
Describe the mechanism behind rheumatoid arthritis?
- Antigens that drive RA are citrullinated proteins (citrullination is the conversion of amino acid arginine to the amimo acid citrulline)
- Autoreactive T and B cells recognise citrullinated proteins, causing production of antibodies against the protein
- Referred to as anti-cyclic citrullinated peptide (CCP) antibodies
- Synovium becomes infiltrated by T cells (TH1 and TH17) and macrophages
- TNF and IL-17 attracts and activates neutrophils that cause damage to synovium
- Osteoclasts are activated and destroy bone at the joint margins, creating erosions
- Persistent IL-6 secretion triggers an acute-phase response
What are risk factors for rheumatoid arthritis?
- Family history
- Associated with HLA-DR4
- Smokers
- Infection with porphyromonas
Describe the mechanism behind MS?
- Initially, acute attacks occur during which inflammatory lesions consisting of TH1 and TH17 cells and macrophages develop in the affected nervous tissue
- Lesions are reversible, relapsing disability typical of early MS
- Myelin loss impairs ability of neurons to conduct impulses, resulting in neurological symptoms
- Once inflammation settles the disability improves
Describe the treatment for delayed hypersensitivity?
- Prevention through avoiding antigens
- Anti-inflammatory drugs
- NSAID
- Corticosteroids
- Drugs that block TNF and IL-6
- Antibodies against B cells
- Immunosuppressive drugs
