Immunology 3 - Hypersensitivity Flashcards
What are CD8+ cells?
T killer cells
What are CD4+ cells?
T helper cells
What is Type 1 hypersensitivity reaction?
Allergy/immediate hypersensitivity
Allergies are mediated by what?
IgE
Hypersensitive T helper cells
What are the phases of type 1 hypersensitivity?
Sensitisation Phase
Reaction phase
What is the atopic triad?
Atopic dermatitis
Atopic asthma
Allergic rhinitis
What is atopic dermatitis?
Eczema
What is the pathophysiology of atopic dermatitis?
Degranlation of basophils + mast cells in response to sensitised IgE
“leaky” skin lets allergen in and water out
How are allergies investigaed?
Skin testing
Patch testing
Serum Tryptase
How are allergies treated?
Antihistamines
Corticosteroids
Adrenaline
Allergen avoidance
What blood antibodies do type A blood individuals have in their plasma?
Anti B
What blood antibodies do type O blood individuals have in their plasma?
Anti-A and anti-B
What is a hypersensitivity reaction?
Excessive immune response to an antigen that causes harm
What pathogens are associated with hypersensitivity reactions?
Influenza - cytokine storm
How does Influenza cause hypersensitivity reaction?
Cytokine storm
Cytokines attract leukocytes and trigger vascular changes
Hypotension and coagulation
Cytokines can spill into systemic circulation
How can dust trigger hypersensitivity?
Dust can mimic parasites and stimulate an antibody response
How do small molecules trigger hypersensitivity?
Act as haptens - bind to proteins and elicit immune response
Type 1 hypersensitivity is mediated by what?
Immediate response by IgE
Mast cells, Eosinophil degranulation
What is a Type 2 hypersensitivity reaction?
Previous exposure causing antibody generation
Reaction on SECOND exposure
What is a Type 3 hypersensitivity reaction?
Immune complex
Like type 2 but takes hrs
What is a Type 4 hypersensitivity reaction?
2-3 day delayed hypersensitivity
- autoimmunity associated
Type 2 hypersensitivity is mediated by what?
IgG
Complement, phagocytes
Type 3 hypersensitivity is mediated by what?
IgG
Complement, neutrophils
Type 4 hypersensitivity is mediated by what?
T-cells
Macrophages
Outline the pathway of Type 1 hypersensitivity
Th2 cells release IL-4
IL4 stimulates B-cells to release IgE
IgE binds to the allergen
What are the typical atopic symptoms?
Anaphylaxis Angioedema Urticaria Rhinitis Asthma Eczema
Peanut allergy is associated with which proteins?
Ara h2 - stable protein
Ara h8 - unstable
Which peanut protein is associated with cross-reactivity?
Ara h8
What allergen is associated with penicillin?
beta-lactam
What is the role of filaggrin in allergies?
Expressed by keratinocytes
Maintains epithelial barriers (moisture and pH)
Polymorphisms in Filaggrin associated with allergy
How does the time of allergy development affect allergies?
Developing an allergy whilst young increases the risk of developing another
What is the hygiene hypothesis?
Increase in allergies in developing world caused by reduced early exposure to microorganisms
Outline anaphylaxis?
Mast cells produce prostaglandins and leukotrienes
This causes vasodilation and vascular permeability
Fluids shift from vascular to extravascular space
This causes a severe BP drop
Histamine release in skin causes swelling
What pathways of mast cells cause prostaglandin and leukotriene release?
Cyclooxygenase
Lipoxygenase
Outline Allergic rhinitis
Allergens stimulate mast cells in nasal mucosa
Vasodilation and oedema causes nasal stuffiness
Leukotrienes cause mucus secretion
What is the affect of leukotrienes on the lungs?
Smooth muscle contraction leading to reduced airflow
This causes wheeze
How are allergies treated?
Desensitisation (immunotherapy) B2-adrenergic agonists Epinephrine Antihistamines Anto-leukotrienes Corticosteroids
How do B2-adrenergic agonists work?
(salbutamol)
Prevents bronchial smooth muscle contraction
How does Epinephrine work?
Stimlates alpha and beta adrenergic receptors
Increase blood pressure and decrease vascular permeability
How do antihistamines work?
Block histamine receptors in skin, nose and mucus membranes
What is Type 2 hypersensitivity?
Antibody mediated hypersensitivity
IgG or IgM reacting with antigen on cell surface
Causes immune mediated haemolysis
Anti B and Anti A antibodies are which type of antibodies?
IgM
What is Alloimmune haemolysis?
Rhesus antigen
IgG crosses placenta and causes haemolytic disease in SECOND child
What are the main types of Immune mediated haemolysis?
Autoimmune
Alloimmune
Type 2 autoimmune
What is Goodpasture’s syndrome?
Type II Autoimmune Hypersensitivity Against Solid Tissue
IgG autoantibodies bind to long and glomeruli - inflammatory response
What is the mechanisms of penicillin allergy?
Penicillin binds to proteins on RBC surface - acts as hapten
Causes that RBC to be destroyed by FcR on splenic macrophage
What mutation is associated with Graves Disease?
HLA allele DR3
What is Type 3 hypersensitivity?
Immune complex disease - take time to form
IgG mediated
What is required for antigens to form complexes?
Antigens must be polyvalent
Ratio of antibodies:antigens is vital
How are complexes cleared?
Complement Receptor 1 transfers complexes to phagocytes
Failure of complex clearance leads to what?
Activation of the innate immune system (mast cells and platelets)
What is Immune complex disease of the kidney?
Glomerulonephriits - immune complexes form in epithelial lining causing infiltrate
What are the mechanisms for immune damage of the glomerulus?
Autoantibodies against the glomerular basement membrane (Goodpasture’s)
Immune complex deposits in the glomerulus (Lupus)
Outline type 4 hypersensitivity?
Slowest - T-cell mediated
Dendritic cells with antigens migrate to lymph nodes > Present to T cells
T cell clones proliferate and migrate to site of inflammation
TNF secreted by Macrophages and T cells and stimulate damage
RA is what type of hypersensitivity?
Type 4
Th1, Th17 and TNF mediated
What antigens drive RA?
Citrullinated proteins (arginine > citrulline
Outline the pathophysiology of RA?
Citrullinated proteins act as antigens which are recognised by T and B cells, these produce antibodies
(Anti-cyclic citrullinated peptide antibodies)
Synovium infiltrated by T(h1,17) cells, macrophages
TNF and IL-17 activate neutrophils and osteoclasts, creating erosions
What are the risk factors for RA?
Smoking
HLA-DR4
Porphyromonas infections
Outline the pathophysiology of MS?
Th1, 17 cells and macrophages develop inflammatory lesions of the CNS
Myelin loss causes neurological symptoms
Recovery between attacks
Chronic disability due to AXONAL loss
Name 3 T-cell mediated delayed hypersensitivity (type 4) conditions?
RA MS T1DM IBD Psoriasis Coeliac
How is delayed hypersensitivity treated?
Anti-inflammatory drugs NSAIDS, Corticosteroids Anti-TNF Anti-IL-6 B-cell antibodies Immunosuppressants
Name 3 type 3 hypersensitivity conditions?
Farmer’s lung
Post-streptococcal glomerulonephritis
Lupus
Name 3 type 2 hypersensitivity conditions?
Graves’ Disease
Blood transfusion reactions
Haemolytic disease of the newborn
Drug-induced haemolysis
