Hypersensitivity Flashcards
What are the types of hypersensitivity?
A- Allergy/anaphylaxis-Type 1: IgE mediated ( hay fever)
C- cytotoxic- Type 2: IgG or IgM (myasthenia gravis)
I-Immune complex- Type 3: IgG or IgM
D- Delayed type- Type 4: no antibodies
What are some characteristics of Type 1 immediate hypersensitivity?
Symptoms occur second to minutes after contact
Releases histamine
Manifestations can be systemic or local
Treated with epinephrine
What are the effects of histamine release?
Bronchial constriction GI peristalsis Mucus and GI fluid secretion Vasodilation Increase in vascular permeability leading to edema
What are the systemic manifestations of Type 1 hypersensitivity?
Mild cases: itching, erythema, respiratory distress
Severe cases: catastrophic drop in BP, suffocation
What are the local manifestations of Type 1 hypersensitivity?
Local allergies (asthma, hives, rhinitis, atopic dermatitis)
Atopy
Anaphylactoid reactions
What is atopy?
Genetic predisposition to make IgE due to IL-4 polymorphism
Presents with allergic rhinitis, allergic asthma, atopic dermatitis
What is anaphylactoid reaction?
IgE independent mast cells and basophils degranulation
Caused by anaphylatoxins C5a,C4a, C3a, vancomycin, opiates
What are the 3 phases of the pathogenic mechanisms of Type 1 hypersensitivity?
Sensitization
Early phase
Late phase
What are the characteristics of the sensitization phase?
Occurs in a span of 2 weeks Expansion of TH2 subset IL-4 and IL-13 induce class switch to IgE IgE arms cell via Fc epsilon receptor 1 Additional TH2 subset formed
What are the additional TH2 subset formed during the sensitization phase?
IL-5- activates eosinophils
IL-6- mucus secretion
IL-8- neutrophils chemotaxis
IL-9- activates mast cells
What are the characteristics of the early phase of type 1 hypersensitivity?
Occurs within 20 mins of contact with allergen
Bronchoconstriction in smooth muscle and vascular permeability in vascular endothelium (H1)
Mucus, gastric acid in stomach mucosa (H2)
Tryptase generates C3a and C5a leading to mast cell degranulation
Heparin stores peformed mediators and aids in tryptase production
ECF-A attracts eosinophils
What are the characteristics of the late phase of Type 1 hypersensitivity?
Occurs 5-6 hours later
Produced newly formed mediators from arachidonic acid
Thats why it is important to see a health provider even after using an epipen
What are the newly formed mediators?
LTB4- chemotaxis especially PMNs
SRS-A- bronchoconstriction, edema
PGE2 and PGI2- vasodilation, gastric cytoprotection, inhibits platelets aggregation
TXA2- platelets aggregation
What is the cause of reactions in asthma patients?
Leukotriene
What are the clinical presentations of hypersensitivity Type 1?
Urticaria and angioedema Allergic rhinitis- mc atopic disease Food allergies- mc in kids Atopic dermatitis- mostly in kids Allergic asthma Anaphylaxis- mc causes are drugs (penicillin), food (peanuts), bee stings
What is intrinsic asthma?
Reaction where there is no IgE present
Caused by cold air, exercise, stress, anger
What are the clinical test for allergy?
Skin prick test RAST- allergen specific IgE RIST- total serum IgE Nasal provocation Atopy skin patch for eczema Nasal smear Serum tryptase - high in Type 1 compared to other shock
What is the presentation of the skin prick test for allergy?
Histamine causes itchy wheal and flare within 15 min
Late response from arachidonic acid metabolites causes a painful lump 5-6 hour later
How to manage allergy?
Non pharmacological
Pharmacological
What is the non pharmacological therapy?
Prevent exposure by avoidance
Hyposensitization therapy by slowly increasing doses of allergen to induce tolerance
What are the pharmacological therapy of Type 1 hypersensitivity?
Antihistamines-useless for asthmatics Beta agonist bronchodilator (albuterol) Xanthine derivative bronchodilators (theophylline) Mast cell stabilizer (sodium cromolyn)- prophylactic Epinephrine Leukotriene receptors blockers- asthma Leukotriene synthesis inhibitors Omalizumab
What are some characteristics of Type 2 hypersensitivity?
Caused by IgG or IgM that binds to the cell surface antigens
What are the mechanisms of antibody mediated injury?
Complement dependent lysis of host cells
Frustrated phagocytosis especially by PMNs
ADCC by NK cells ( CD16)
Agonistic or antagonistic signals sent by receptor antibodies
What are some of the hypersensitivity Type 2 reactions?
Autoimmune diseases ( graves, myasthenia, addison)
Reactions against RBC (ABO,Rh)
Reactions against platelets (drug induced thrombocytopenia)
Rheumatic fever
What are the antibodies present based on blood type?
A—>anti B: agglutinate B and AB
B—>anti A: agglutinate A and AB
AB—> no antibodies, will not agglutinate
O—> anti A and B: agglutinate A,B and AB
What are the characteristics of transfusion reactions against ABO antigens?
Isohemaglutinins develop by 8 months
Elicited by contact with food or microbial antigens
Anti-A antibodies cross react with influenza
Anti- B antibodies cross react with E coli
Present with fever, hypotension, lower back pain, nausea and vomiting
What are the characteristics of hemolytic disease of the newborn or erythroblastosis fetalis?
Maternal IgG antibodies cross placenta and bind to the Rh(D) antigen of the babys RBCs
Presents with anemia, CHF, kernicterus ( bilirubin in CNS), jaundice, fetal hydrops, enlarged liver
How to treat erythroblastosis fetalis?
Rhogam therapy
Anti Rh injected postpartum to eliminate Rh positive and prevent sensitization
Rhogam works by IgG negative feedback
What are the types of autoimmune hemolytic anemias?
Warm reactive autoantibodies react with RBCs @ 37C - coombs test (SLE)
Cold reactive autoantibodies react with RBCs under 37C- complement activating IgM and cold agglutinins ( mycoplasma pneumoniae)
What are the characteristics of drug induced thrombocytopenia?
Drugs attached to platelets induce antibodies
Can be idiopathic
Present with purpura
What are the characteristics of rheumatic fever?
Can follow a throat infection with group A streptococcus
M protein reacts with cardiac myosin leading to rheumatic heart disease and myocarditis
What are the characteristics of the Type 3 hypersensitivity?
Immune complexes containing IgM and/or IgG and complement form in the bloodstream then get lodged in certain tissues or the vasculature
What are the areas most affected by Type 3 hypersensitivity?
Kidneys Skin Joints Choroid plexus Ciliary artery of the eye
What are the examples of Type 3 hypersensitivity?
Systemic lupus erythematosus (SLE) Post streptococcal glomerulonephritis Serum sickness Arthus reaction Extrinsic allergic alveolitis Polyarteritis nodosa (PAN)
What are the characteristics of post streptococcal glomerulonephritis?
Immuno complex formed by S. Pyogenes, antibodies and complement
Lumpy-bumpy immunofluorescence
Glomerulonephritis begins within 1-2 weeks after pharyngitis or 3-6 weeks after pyoderma
Dark urine may be first sign
What is the treatment for Post streptococcal glomerulonephritis?
Water and salt intake restriction
Administer diuretics
Antibiotics
What are the characteristics of serum sickness?
Patient forms antibodies to passively transferred xenogeneic immunoglobulins
Due to horse serum for snake bites, murine monoclonal antibodies to treat cancer and graft rejections
What are the causes of serum sickness?
Penicillin- most common cause
NSAIDs
What are the characteristics of Arthus reaction?
Seen when boosters are administered to persons with high antibody titers
wheal greater or equal 50mm with a poorly defined edge
Reaction peaks 5-12 hours
Platelets may clump, leading to vascular occlusion and necrosis
What are the persistent infections of Type 3 hypersensitivity?
Streptococcal infections Staphylococcal infective endocarditis Viral hepatitis Leprosy Malaria Dengue
What are the characteristics of extrinsic allergic alveolitis of Type 3 hypersensitivity?
Inhaled antigens from molds, plants and animals complex to specific IgG in the alveoli of the lungs
Fixed complement
Induce inflammation and fibrosis
What are some of the extrinsic allergic alveolitis ( occupational pneumonitis)?
Farmer’s lung- fungi in moldy hay
Pigeon fancier’s lung- avian antigens
What are the presentations of Type 3 hypersensitivity?
Acute hypersensitivity pneumonitis
Subacute hypersensitivity pneumonitis
Chronic hypersensitivity pneumonitis
What are the characteristics of the acute hypersensitivity pneumonitis?
Develop 4-6 hours following heavy exposure
Symptoms often resolve spontaneously within 12 hours to several days upon cessation of exposure
Presents with abrupt fever, chills, malaise, cough, chest tightness, dyspnea
What are the characteristics of subacute hypersensitivity pneumonitis?
Patients gradually develop productive cough, dyspnea, fatigue, anorexia and weight loss
What are the characteristics of chronic hypersensitivity pneumonitis?
Patient may lack a history of acute episodes
Insidious onset of cough, progressive dyspnea, fatigue and weight loss
Removing exposure results in only partial improvement
What are the characteristics of Polyarteritis nodosa (PAN)?
Systemic necrotizing vasculitis of medium and small muscular arteries
Livedo reticularis: reddish blue mottling of the skin especially of the extremities upon cold exposure
Treated with steroids, cyclophosphamide, antivirals and plasmapheresis
What are the characteristics of complement deficiency in Type 3 hypersensitivity?
Patients with complement deficiency affecting C1,C2 and C4 immune complex remain large and bind to erythrocytes
Inability to carry immune complexes to spleen and liver for destruction
Immune complexes don’t get destroyed and are deposited in the tissues and induce inflammatory reactions
How to detect immune complexes?
PEG precipitation
Cryoglobulins precipitation upon refrigeration
RIA using C1q as ligand
Immunofluorescence assay for immune complexes containing antibody and complement
What are the characteristics of Type 4 hypersensitivity?
Delayed Type hypersensitivity Cell mediated hypersensitivity Antibody plays no role Mediated by CD4+ TH1 cells TH1 recruit TH17,macrophages,PMNs, Tc cells and NK cells Can be beneficial or harmful
What are the stages of TYPE 4 hypersensitivity?
Sensitization
Elicitation
What are the characteristics of the sensitization phase in Type 4 hypersensitivity ?
Langerhans cells present antigen to lymph node T cells
T cells undergo clonal selection and proliferation over 10-14 days
What are the characteristics of the elicitation phase of Type 4 hypersensitivity?
Sensitized T cells activated b subsequent contact with same antigen
T cells produce inflammatory cytokines
IFN gamma activates macrophages
IL-2 activates NK, Tc
What are the variants of Type 4 hypersensitivity?
Contact hypersensitivity/dermatitis
Tuberculin Type hypersensitivity
Granulomatous hypersensitivity
What are the characteristics of contact hypersensitivity/ dermatitis of Type 4 hypersensitivity?
Poison Ivy is a classic example
Present with eczema and blister formation
Maximal @ 48-72h
DNCB sensitizes all individuals and can be used to assess cell mediated immunity
Diagnosed with skin patch test
Treated with corticosteroids
What are the characteristics of tuberculin Type hypersensitivity of Type 4?
Characterized by an area of firm red (erythema) swelling of the skin(induration)
Maximal 48-72 h after challenge
PPD Mantoux test is classic example
How to interpret the PPD Mantoux test ?
In the USA positive test is indicative of M. tuberculosis exposure
Read after 48-72 h
No risk factors-induration of greater or equal 15mm is positive
Healthcare workers positive is induration greater or equal 10mm
HIV- induration of greater or equal 5 mm
How to distinguish between positive Mantoux test and vaccination with BCG?
In other countries a positive Mantoux test may be indicative of vaccination with BCG
Quantiferon-TB Gold can distinguish TB from BCG vaccination
What are the characteristics of granulomatous hypersensitivity of Type 4?
Clinically the most important form of DTH
Continuous accumulation of macrophages leads to clusters of epithelioid cells
Epithelioid cells fuse and form multinucleate giant cells in granulomas
Maximal @ 21-28 days
What are the characteristics of sarcoidosis?
Unknown etiology Usually affects young adults Chronic or self resolving Lung is most often affected Presents with hilar lymphadenopathy, Pulmonary infiltration, ocular lesions, cutaneous lesions ( erythema nodosum)
What are the characteristics of inflammatory bowel disease?
Crohn’s disease and ulcerative colitis are the main diseases
Present with intestinal inflammation, abdominal pain, diarrhea
Flare and symptoms free periods
Diagnosed by endoscopy
What are the antibodies in Crohn’s and Ulcerative colitis?
Crohn’s——> ASCA
UC——> P- ANCA
What are the characteristics of Berylliosis?
Chronic lung disease caused by exposure to beryllium (hapten)
Non necrotizing granulomas
Present with crackles, lymphadenopathy, rash, enlarged liver and spleen
Treated with corticosteroids,methotrexate, Lung transplantation
What is the treatments for IBD?
Diet Aminosalicylates Corticosteroids Biologic therapies: TNF alpha inhibitors(adalimumab,infliximab),integrins Control diarrhea Surgery
