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Hypersensitivity Flashcards

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1
Q

What are the types of hypersensitivity?

A

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

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2
Q

What are some characteristics of Type 1 immediate hypersensitivity?

A

Symptoms occur second to minutes after contact
Releases histamine
Manifestations can be systemic or local
Treated with epinephrine

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3
Q

What are the effects of histamine release?

A 
Bronchial constriction
GI peristalsis 
Mucus and GI fluid secretion
Vasodilation
Increase in vascular permeability leading to edema
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4
Q

What are the systemic manifestations of Type 1 hypersensitivity?

A

Mild cases: itching, erythema, respiratory distress

Severe cases: catastrophic drop in BP, suffocation

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5
Q

What are the local manifestations of Type 1 hypersensitivity?

A

Local allergies (asthma, hives, rhinitis, atopic dermatitis)
Atopy
Anaphylactoid reactions

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6
Q

What is atopy?

A

Genetic predisposition to make IgE due to IL-4 polymorphism

Presents with allergic rhinitis, allergic asthma, atopic dermatitis

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7
Q

What is anaphylactoid reaction?

A

IgE independent mast cells and basophils degranulation

Caused by anaphylatoxins C5a,C4a, C3a, vancomycin, opiates

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8
Q

What are the 3 phases of the pathogenic mechanisms of Type 1 hypersensitivity?

A

Sensitization
Early phase
Late phase

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9
Q

What are the characteristics of the sensitization phase?

A 
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
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10
Q

What are the additional TH2 subset formed during the sensitization phase?

A

IL-5- activates eosinophils
IL-6- mucus secretion
IL-8- neutrophils chemotaxis
IL-9- activates mast cells

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11
Q

What are the characteristics of the early phase of type 1 hypersensitivity?

A

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

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12
Q

What are the characteristics of the late phase of Type 1 hypersensitivity?

A

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

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13
Q

What are the newly formed mediators?

A

LTB4- chemotaxis especially PMNs
SRS-A- bronchoconstriction, edema
PGE2 and PGI2- vasodilation, gastric cytoprotection, inhibits platelets aggregation
TXA2- platelets aggregation

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14
Q

What is the cause of reactions in asthma patients?

A

Leukotriene

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15
Q

What are the clinical presentations of hypersensitivity Type 1?

A 
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
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16
Q

What is intrinsic asthma?

A

Reaction where there is no IgE present

Caused by cold air, exercise, stress, anger

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17
Q

What are the clinical test for allergy?

A 
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
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18
Q

What is the presentation of the skin prick test for allergy?

A

Histamine causes itchy wheal and flare within 15 min

Late response from arachidonic acid metabolites causes a painful lump 5-6 hour later

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19
Q

How to manage allergy?

A

Non pharmacological

Pharmacological

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20
Q

What is the non pharmacological therapy?

A

Prevent exposure by avoidance

Hyposensitization therapy by slowly increasing doses of allergen to induce tolerance

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21
Q

What are the pharmacological therapy of Type 1 hypersensitivity?

A 
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
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22
Q

What are some characteristics of Type 2 hypersensitivity?

A

Caused by IgG or IgM that binds to the cell surface antigens

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23
Q

What are the mechanisms of antibody mediated injury?

A

Complement dependent lysis of host cells
Frustrated phagocytosis especially by PMNs
ADCC by NK cells ( CD16)
Agonistic or antagonistic signals sent by receptor antibodies

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24
Q

What are some of the hypersensitivity Type 2 reactions?

A

Autoimmune diseases ( graves, myasthenia, addison)
Reactions against RBC (ABO,Rh)
Reactions against platelets (drug induced thrombocytopenia)
Rheumatic fever

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25
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
26
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
27
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
28
How to treat erythroblastosis fetalis?
Rhogam therapy Anti Rh injected postpartum to eliminate Rh positive and prevent sensitization Rhogam works by IgG negative feedback
29
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)
30
What are the characteristics of drug induced thrombocytopenia?
Drugs attached to platelets induce antibodies Can be idiopathic Present with purpura
31
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
32
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
33
What are the areas most affected by Type 3 hypersensitivity?
``` Kidneys Skin Joints Choroid plexus Ciliary artery of the eye ```
34
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) ```
35
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
36
What is the treatment for Post streptococcal glomerulonephritis?
Water and salt intake restriction Administer diuretics Antibiotics
37
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
38
What are the causes of serum sickness?
Penicillin- most common cause | NSAIDs
39
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
40
What are the persistent infections of Type 3 hypersensitivity?
``` Streptococcal infections Staphylococcal infective endocarditis Viral hepatitis Leprosy Malaria Dengue ```
41
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
42
What are some of the extrinsic allergic alveolitis ( occupational pneumonitis)?
Farmer’s lung- fungi in moldy hay | Pigeon fancier’s lung- avian antigens
43
What are the presentations of Type 3 hypersensitivity?
Acute hypersensitivity pneumonitis Subacute hypersensitivity pneumonitis Chronic hypersensitivity pneumonitis
44
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
45
What are the characteristics of subacute hypersensitivity pneumonitis?
Patients gradually develop productive cough, dyspnea, fatigue, anorexia and weight loss
46
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
47
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
48
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
49
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
50
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 ```
51
What are the stages of TYPE 4 hypersensitivity?
Sensitization | Elicitation
52
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
53
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
54
What are the variants of Type 4 hypersensitivity?
Contact hypersensitivity/dermatitis Tuberculin Type hypersensitivity Granulomatous hypersensitivity
55
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
56
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
57
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
58
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
59
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
60
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) ```
61
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
62
What are the antibodies in Crohn’s and Ulcerative colitis?
Crohn’s——> ASCA | UC——> P- ANCA
63
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
64
What is the treatments for IBD?
``` Diet Aminosalicylates Corticosteroids Biologic therapies: TNF alpha inhibitors(adalimumab,infliximab),integrins Control diarrhea Surgery ```

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