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Immunology > Hypersensitivity > Flashcards

Hypersensitivity Flashcards

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
Q

What are the antibodies present based on blood type?

A

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

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26
Q

What are the characteristics of transfusion reactions against ABO antigens?

A

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
Q

What are the characteristics of hemolytic disease of the newborn or erythroblastosis fetalis?

A

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
Q

How to treat erythroblastosis fetalis?

A

Rhogam therapy
Anti Rh injected postpartum to eliminate Rh positive and prevent sensitization
Rhogam works by IgG negative feedback

29
Q

What are the types of autoimmune hemolytic anemias?

A

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
Q

What are the characteristics of drug induced thrombocytopenia?

A

Drugs attached to platelets induce antibodies
Can be idiopathic
Present with purpura

31
Q

What are the characteristics of rheumatic fever?

A

Can follow a throat infection with group A streptococcus

M protein reacts with cardiac myosin leading to rheumatic heart disease and myocarditis

32
Q

What are the characteristics of the Type 3 hypersensitivity?

A

Immune complexes containing IgM and/or IgG and complement form in the bloodstream then get lodged in certain tissues or the vasculature

33
Q

What are the areas most affected by Type 3 hypersensitivity?

A 
Kidneys
Skin
Joints
Choroid plexus 
Ciliary artery of the eye
34
Q

What are the examples of Type 3 hypersensitivity?

A 
Systemic lupus erythematosus (SLE)
Post streptococcal glomerulonephritis
Serum sickness
Arthus reaction
Extrinsic allergic alveolitis
Polyarteritis nodosa (PAN)
35
Q

What are the characteristics of post streptococcal glomerulonephritis?

A

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
Q

What is the treatment for Post streptococcal glomerulonephritis?

A

Water and salt intake restriction
Administer diuretics
Antibiotics

37
Q

What are the characteristics of serum sickness?

A

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
Q

What are the causes of serum sickness?

A

Penicillin- most common cause

NSAIDs

39
Q

What are the characteristics of Arthus reaction?

A

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
Q

What are the persistent infections of Type 3 hypersensitivity?

A 
Streptococcal infections
Staphylococcal infective endocarditis
Viral hepatitis
Leprosy
Malaria
Dengue
41
Q

What are the characteristics of extrinsic allergic alveolitis of Type 3 hypersensitivity?

A

Inhaled antigens from molds, plants and animals complex to specific IgG in the alveoli of the lungs
Fixed complement
Induce inflammation and fibrosis

42
Q

What are some of the extrinsic allergic alveolitis ( occupational pneumonitis)?

A

Farmer’s lung- fungi in moldy hay

Pigeon fancier’s lung- avian antigens

43
Q

What are the presentations of Type 3 hypersensitivity?

A

Acute hypersensitivity pneumonitis
Subacute hypersensitivity pneumonitis
Chronic hypersensitivity pneumonitis

44
Q

What are the characteristics of the acute hypersensitivity pneumonitis?

A

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
Q

What are the characteristics of subacute hypersensitivity pneumonitis?

A

Patients gradually develop productive cough, dyspnea, fatigue, anorexia and weight loss

46
Q

What are the characteristics of chronic hypersensitivity pneumonitis?

A

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
Q

What are the characteristics of Polyarteritis nodosa (PAN)?

A

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
Q

What are the characteristics of complement deficiency in Type 3 hypersensitivity?

A

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
Q

How to detect immune complexes?

A

PEG precipitation
Cryoglobulins precipitation upon refrigeration
RIA using C1q as ligand
Immunofluorescence assay for immune complexes containing antibody and complement

50
Q

What are the characteristics of Type 4 hypersensitivity?

A 
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
Q

What are the stages of TYPE 4 hypersensitivity?

A

Sensitization

Elicitation

52
Q

What are the characteristics of the sensitization phase in Type 4 hypersensitivity ?

A

Langerhans cells present antigen to lymph node T cells

T cells undergo clonal selection and proliferation over 10-14 days

53
Q

What are the characteristics of the elicitation phase of Type 4 hypersensitivity?

A

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
Q

What are the variants of Type 4 hypersensitivity?

A

Contact hypersensitivity/dermatitis
Tuberculin Type hypersensitivity
Granulomatous hypersensitivity

55
Q

What are the characteristics of contact hypersensitivity/ dermatitis of Type 4 hypersensitivity?

A

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
Q

What are the characteristics of tuberculin Type hypersensitivity of Type 4?

A

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
Q

How to interpret the PPD Mantoux test ?

A

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
Q

How to distinguish between positive Mantoux test and vaccination with BCG?

A

In other countries a positive Mantoux test may be indicative of vaccination with BCG
Quantiferon-TB Gold can distinguish TB from BCG vaccination

59
Q

What are the characteristics of granulomatous hypersensitivity of Type 4?

A

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
Q

What are the characteristics of sarcoidosis?

A 
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
Q

What are the characteristics of inflammatory bowel disease?

A

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
Q

What are the antibodies in Crohn’s and Ulcerative colitis?

A

Crohn’s——> ASCA

UC——> P- ANCA

63
Q

What are the characteristics of Berylliosis?

A

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
Q

What is the treatments for IBD?

A 
Diet 
Aminosalicylates
Corticosteroids 
Biologic therapies: TNF alpha inhibitors(adalimumab,infliximab),integrins
Control diarrhea
Surgery

Immunology (8 decks)

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