OVER-REACTIONS OF THE IMMUNE SYSTEM

1
OVER-REACTIONS OF THE IMMUNE SYSTEM
Hypersensitivity Reactions and Allergic Diseases
2
OVER-REACTIONS OF THE IMMUNE SYSTEM

• Hypersensitivity reactions
• Adaptive immune response to harmless molecules
• Sensitization of immune system required
• Mediated by antibody and effector T cells
• Allergic diseases
• Disease following immune response to allergens
• Allergens
• Harmless molecules which cause type 1
  hypersensitivity reactions

3
(No Transcript)
4
(No Transcript)
5
(No Transcript)
6
(No Transcript)
7
CLASSIFICATION OF HYPERSENSITIVITY REACTIONS
(GELL AND COOMBS)

• Based on immune reactant, antigen and effector
  mechanism
• Type I
• Mediated by IgE against soluble antigens with
  mast cells, basophils and eosinophils
• Type II
• Mediated by IgG and IgM against cell surface /
  matrix antigens with complement and phagocytes

8
CLASSIFICATION OF HYPERSENSITIVITY REACTIONS
(GELL AND COOMBS)

• Based on immune reactant, antigens and effector
  mechanism
• Type III
• Mediated by IgG against soluble antigens with
  complement and phagocytes
• Type IV
• Mediated by CD4 and CD8 cells against soluble and
  cell surface antigens with macrophages and CD 8 T
  cells

9
(No Transcript)
10
(No Transcript)
11
TYPE I HYPERSENSITIVITY REACTIONS

• Normal physiological role of IgE
• Defense against parasites
• Pathophysiological role of IgE
• Allergy
• Greater knowledge
• Type I reactions follow sensitization to
  allergens
• Sensitization
• First exposure to allergen elicits an IgE
  response
• Genetic predisposition (Atopy)

12
TYPE I HYPERSENSITIVITY REACTIONS THE IgE
RECEPTOR

• IgE binds (Fc fragment) with high affinity to
  FceRI receptor
• FceRI receptor
• Mast cells, basophils, activated eosinophils
• Binding of IgE results in sensitization of cells
• IgE functions as allergen receptor

13
ANTIGEN RECEPTORS ON MAST CELLS, BASOPHILS AND
ACTIVATED EOSINOPHILS

• Different from receptors on T and B cells
• Effector function becomes operational immediately
  following antigen binding
• Cell proliferation and differentiation not
  required
• Receptors are not restricted to a single antigen
  specificity
• Features provide a strong and quick response to
  antigens for a sensitized person

14
MAST CELLS (MASTOCYTES)

• Originate in bone marrow from CD34 progenitor
• Basophils may have same progenitor
• Development of immature cells at tissue sites
• Types
• Mucosal
• Tryptase production
• Development T cell dependent
• Connective tissue
• Chymotryptase production
• Express high levels of IgE receptor

15
(No Transcript)
16
MECHANISM OF TYPE I HYPERSENSITIVITY REACTIONS

• FceRI receptor expressed constitutively
• Mast cells and Basophils
• Activated eosinophils
• Allergen binding results in cross-linking of
  receptors
• Cross-linked receptors signal degranulation of
  cytoplasmic granules
• Degranulation results in release and synthesis
• Inflammatory mediators, toxins, enzymes

17
(No Transcript)
18
Figure 10-5
19
HISTAMINE (BIOGENIC AMINE)

• Exerts a variety of physiological effects
  following binding to specific receptors (H1, H2,
  H3)
• Allergic reactions
• Histamine binds to H1 receptors
• Physiological effects
• Constriction of bronchial / intestinal smooth
  muscle
• Increased permeability of blood vessels
• Increased secretion of mucus by goblet cells
• Leukocyte chemotaxis

20
LEUKOTRIENES

• Classified as lipid mediators of inflammation
• Derived from arachidonic acid via lipoxygenase
  pathway
• Produced by mast cells, monocytes and
  granulocytes
• Leukotrienes (LTA4 LTE4)
• Sustain inflammatory response in allergic disease
• Autocrine and paracrine mechanisms
• C, D and E are cysteinyl leukotrienes
• Increased levels induce anaphylaxis
• Physiological effects similar to histamine
• More potent / longer lasting than histamine
• Vasodilation, bronchoconstriction, neutrophil
  chemotaxis

21
PROSTAGLANDINS

• Classified as lipid mediators with a variety of
  physiologic effects
• Normal
• Inflammation
• Derived from arachidonic acid
• Cyclooxygenase pathway
• Act locally and rapidly metabolized
• Produced by all nucleated cells except lymphocytes

22
(No Transcript)
23
CYCLOOXYGENASE PATHWAY

• Prostaglandins produced by two different enzymes
• Cyclooxygenase-1 (Cox-1)
• Cyclooxygenase-2 (Cox-2)
• Cox-1 involved in normal physiological functions
• Stomach mucus production
• Kidney water excretion
• Platelet function
• Cox-2 involved in inflammatory response

24
(No Transcript)
25
NONSTEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS)

• Reduce pain, inflammation and fever by inhibition
  of cyclooxygenase pathway
• Non-Selective (Cox-1 and Cox-2 inhibitors)
• Acetylsalicyclic acid (Aspirin)
• Ibuprofen (Motrin, Advil)
• Indomethacin (Indocin)
• Naproxen (Naprosyn, Aleve)
• Selective (Cox-2 inhibitors)
• Celecoxib (Celebrex)
• Rofecoxib (Vioxx)
• Valdecoxib (Bextra)

26
(No Transcript)
27
(No Transcript)
28
EOSINOPHILS

• Granulocytic leukocytes (1 6 in blood)
• Level variation (down in am, up in pm)
• Granules
• Orange to reddish-orange in color
• Uniform in size and evenly distributed
• Toxins, enzymes, cytokines and inflammatory
  mediators
• Mature cells reside in
• Blood and lower GI tract

29
Figure 10-9
30
EOSINOPHILS

• Eosinophil response
• Parasites (Helminths)
• Main effector cell in allergy and asthma
• Induced by drugs, diseases and radiation
• Eosinophilia potentially toxic to host
• Control mechanism for host toxicity
• Limiting bone marrow production
• Regulated expression of Fc-epsilon-RI
• IgE receptor not expressed in resting state

31
CASE STUDY 58 YEAR OLD FEMALE

• Presents to family physician with 1 month history
• Fever
• Cough
• Weight loss
• Dyspnea
• Past and present medical history
• Non-smoker
• Childhood asthma
• Rheumatoid arthritis

32
CASE STUDY 58 YEAR OLD FEMALE

• Laboratory
• CBC with differential
• 12,000 leukocytes with 10 eosinophils
• Sputum for eosinophils
• Unable to produce
• Radiology
• CXR and CT
• Endoscopy
• Fiberoptic bronchoscopy with bronchoalveolar
  lavage (BAL)

33
(No Transcript)
34
(No Transcript)
35
(No Transcript)
36
CASE STUDY EOSINOPHILIC PNEUMONIA

• Pulmonary eosinophilia or eosinophilic lung
  disease
• Classification
• Primary (idiopathic)
• Secondary
• Parasitic or fungal infection
• Immunological or systemic disease
• Asthma, HIV, malignancy
• Drugs
• Antibiotics, NSAIDS, L-tryptophan
• Mechanism of disease is unknown

37
CASE STUDY 23 YEAR OLD MALE

• Presents to family physician with 2 year history
  of
• Dysphagia
• Episodes of food impaction
• Breads and meats
• Past and present medical history
• Seasonal allergic rhinitis
• Non-smoker

38
CASE STUDY 23 YEAR OLD MALE

• Laboratory
• CBC with differential
• 12,000 leukocytes with 11 eosinophils
• Endoscopy with esophageal biopsy
• Endoscopy showed ringed esophagus
• Surgical Pathology Report
• gt 20 eosinophils/HPF (proximal and distal)
• Areas of basal cell hyperplasia suggests reflux
• No viral CPE, dysplasia or malignancy

39
(No Transcript)
40
(No Transcript)
41
CASE STUDY EOSINOPHILIC ESOPHAGITIS

• Etiology is unknown
• Associated with food allergy
• Milk, eggs, soy, corn, wheat, beef, chicken
• Acid reflux
• Medications stuck in esophagus
• Mechanism
• Decrease stretching of esophagus
• Treatment is evolving
• Prednisone, antihistamines, Mast cell stablizers
• Avoidance of implicated food
• Proton pump inhibitors (Nexium) ?

42
BASOPHILS

• Granulocytic leukocytes (0 1 in blood)
• Granules
• Violet-blue in color
• Variable in size and unevenly distributed
• Contents similar to mast cells
• Mature cells reside in blood
• Basophils similar to mast cells
• Constitutive expression of IgE receptor
• Significant source of IL-4
• Both interact with eosinophils

43
(No Transcript)
44
IgE MEDIATED ALLERGIC REACTIONS

• IgE production is favored following
• Chronic exposure to proteins or chemicals bound
  to proteins
• Low molecular weight, soluble, glycosylated
  proteins
• Allergens promote CD4 TH2 response when
  interleukin-4 is present
• Interleukin-4 promotes IgE isotype switch in
  cognate interaction with B cells
• IgE response amplified following release of IL-4
  by activated mast cells and basophils

45
SENSITIZATION TO AN INHALED ALLERGEN

• Majority of allergens are components of dried
  particles derived from plant and animals
• Majority of allergens in US are proteases
• Cysteine protease in feces from house dust mite
• Dermatophagoides pteronyssimus
• Papain from papaya fruit
• Significance of enzymatic activity of allergens
  is unknown

46
(No Transcript)
47
(No Transcript)
48
GENETIC PREDISPOSITION TO TYPE I
HYPERSENSITIVITY

• Atopy
• Genetic propensity to produce IgE antibodies in
  response to allergens
• Atopic response characterized by elevated levels
• IgE and eosinophils
• Multiple genes are involved
• Chromosome 2
• Regulation of T cell activation
• Chromsome 5
• Gene cluster for IL-3, IL-4 and IL-13
• Chromosome 11
• Beta chain of FceRI receptor

49
TWO STAGES OF TYPE I HYPERSENSITIVITY REACTIONS

• Immediate reaction (Stage 1)
• Appears within 30 minutes
• Subsides within 30 minutes
• Late phase reaction (Stage 2)
• Appears 6 to 8 hours after immediate reaction
  has subsided
• Subsides within 24 hours
• Examples
• Wheal and flare (skin)
• Breathing capacity (lungs)
• Forced expiratory volume in 1 second (FEV1)

50
(No Transcript)
51
(No Transcript)
52
SPECTRUM OF TYPE I ALLERGIC DISEASES

• Allergic rhinitis (hay fever)
• Allergic conjunctivitis
• Allergic rhinoconjunctivitis (ARC)
• Allergic asthma
• Eczema
• Atopic dermatitis
• Allergic contact eczema (dermatitis)
• Allergic urticaria (hives) and angioedema
• Food allergy
• Anaphylaxis (Anaphylactic shock)

53
ALLERGIC RHINITIS (HAY FEVER)

• Inflammation of mucous membranes of
• Nose
• Eyes, eustachian tubes, ears, sinuses, pharynx
• Symptoms
• Sneezing, itching, rhinorrhea, nasal congestion,
  fatigue
• Tearing, postnasal drip, earache, sinus pressure
• Genetic predisposition for offspring
• 1 (30) or 2 (50) parents with AR
• Classification
• Seasonal (tree, grass, ragweed pollens)
• Perennial (dust mites, cockroaches, animal
  dander)

54
ALLERGIC RHINITIS (HAY FEVER)

• Prevalence in US of 20
• Diagnosis
• History and physical
• Laboratory studies
• Differential diagnoses
• Sinusitis
• Viral rhinosinusitis
• Vasomotor or non-allergic rhinitis
• Hormonal rhinitis
• Rhinitis medicamentosa
• NARES

55
LABORATORY DIAGNOSIS OF ALLERGIC RHINITIS (HAY
FEVER)

• Nasal cytology
• Wright stained smear of nasal secretions
• CBC with differential
• Serum IgE (total)
• Allergy testing
• Skin test
• Prick or puncture techniques
• Blood test
• ImmunoCAP system

56
(No Transcript)
57
(No Transcript)
58
(No Transcript)
59
(No Transcript)
60
(No Transcript)
61
IMMUNOCAP SPECIFIC IgE BLOOD TEST

• Quantitative measurement of specific IgE levels
  to numerous allergens by FEIA
• Fluoresence Enzyme Immunoassay (FEIA)
• Consists of reaction chamber with solid phase of
  cellulose sponge matrix
• Specific allergens covalently linked to solid
  phase
• Specific IgE levels expressed as kU/L
• Interpretation
• Seven concentration classes (0-6) from lt 0.35 to
  gt 100.00
• Negative, equivocal, positive (2), strongly
  positive (3)

62
(No Transcript)
63
PREVENTION AND TREATMENT OF ALLERGIC RHINITIS

• Prevention
• Avoidance of offending allergens
• Treatment / Prevention
• Antihistamines
• Decongestants
• Leukotriene receptor antagonists
• Anti-inflammatory agents
• Mast cell stabilizing agents
• Immunotherapy (Hyposensitization /
  Desensitization)

64
ANTIHISTAMINES (ORAL) FOR ALLERGIC RHINITIS

• Mechanism of action
• Prevent binding of histamine to H1 receptors
• Blood vessels, GI tract, respiratory tract
• Antihistamines (1st generation)
• Sedating
• Chlorpheniramine (Chlortrimeton)
• Diphenhydramine (Bendryl)

65
ANTIHISTAMINES (ORAL) FOR ALLERGIC RHINITIS

• Antihistamines (2nd generation)
• Low-sedating or non-sedating
• Cetirizine (Zyrtec)
• Levocetirizine (Xyzal)
• Fexofenadine (Allegra)
• Loratadine (Claritin)
• Loratadine (Alavert)
• Desloratadine (Clarinex)

66
NASAL ANTIHISTAMINE FOR ALLERGIC RHINITIS

• Azelastine (Astelin, MedPointe Pharmaceuticals)
• First intra-nasal antihistamine
• Reduces nasal congestion
• Indicated for seasonal allergic rhinitis
• 1 to 2 sprays per nostril BID
• Adverse events
• Bitter taste, headache, somnolence
• Precaution
• Avoid concurrent use with alcohol and other CNS
  depressants

67
(No Transcript)
68
DECONGESTANTS FOR ALLERGIC RHINITIS

• Mechanism of action
• Decrease hyperemia by vasoconstriction
• Activate alpha-adrenergic receptors of
  respiratory tract
• Decongestants (oral)
• Pseudoephedrine (Sudafed)
• No longer OTC but BTC
• Phenylephrine (Sudafed PE)
• Phenylpropanolamine
• AR of hemorrhagic stroke
• Decongestants (intranasal)
• Oxymetazoline

69
(No Transcript)
70
(No Transcript)
71
(No Transcript)
72
(No Transcript)
73
(No Transcript)
74
ANTIHISTAMINE / DECONGESTANT COMBINATIONSFOR
ALLERGIC RHINITIS

• First generation
• Chlorpheniramine pseudoephedrine
• (Chlortrimeton-D)
• Diphenhydramine pseudoephedrine (Bendryl-D)
• Second generation
• Cetirizine pseudoephedrine (Zyrtec-D)
• Fexofenadine pseudoephedrine (Allegra-D)
• Loratadine pseudoephedrine (Claritin-D)

75
ANTI-LEUKOTRIENE AGENTS FOR ALLERGIC RHINITIS

• Leukotriene receptor antagonists
• Montelukast (Singulair)
• Mechanism of action
• Binds to CysLT1 receptor with no agonist activity
• Precautions
• Avoid aspirin (NSAIDS) if aspirin sensitive
• Neuropsychiatric events
• Changes in behavior and mood
•  

76
NASAL STEROIDS FOR ALLERGIC RHINITIS AND ARC

• Considered most effective for prevention and
  treatment
• Mechanism of action is unknown
• Wide range of effects on many inflammatory cells
  and mediators
• Control all major symptoms
• Corticosteroids
• Fluticasone propionate (Flonase)
• Fluticasone furoate (Veramyst)
• Mometasone furoate (Nasonex)
• Triamcinolone acetonide (Nasacort)
• Beclomethasone dipropionate (Beconase)

77
(No Transcript)
78
MAST CELL STABILIZING AGENTS FOR ALLERGIC RHINITIS

• Cromolyn sodium
• Cromolyn (Nasalcrom) by nasal spray
• Mechanism of action
• Calcium ion channel blocker
• Intracellular Ca essential for degranulation
• Not as effective as corticosteroids
• Frequent dosing (1 spray q6h)

79
IMMUNOTHERAPY (ALLERGY SHOTS) FOR ALLERGIC
RHINITIS

• Immunotherapy (allergy shots) indications
• Allergic rhinitis, allergic asthma and insect
  stings
• Allergy shot phases
• Build-up (1-2 visits a week for 3-6 months)
• Maintenance (1 visit every 2-4 weeks for 3-5
  years)
• Mechanism
• Generation of allergen-specific regulatory T
  cells
• Secretion of IL-10 and TGF-beta
• Suppression of IgE and stimulation of IgG4 and
  IgA by B cells

80
ASTHMA

• Disease of the lower respiratory tract
• Types
• Allergic (extrinsic) asthma
• Symptoms triggered by inhalation of allergens
• Non-Allergic (intrinsic) asthma
• Symptoms triggered by factors not related to
  allergy
• Anxiety, stress, exercise, viruses, smoke and
  other irritants
• Symptoms for two types are similar

81
ALLERGIC AND NON-ALLERGIC ASTHMA

• Symptoms
• Shortness of breath (SOB), wheezing, chest
  tightness, cough, fatigue
• Pathophysiology
• Characterized by inflammation, constriction and
  mucus in tracheobronchial tree
• Prevalence in US
• 1 in 15 (20 m)

82
(No Transcript)
83
(No Transcript)
84
(No Transcript)
85
MANAGEMENT AND TREATMENT OF ALLERGIC ASTHMA

• Bronchodilators (beta-antagonists)
• Albuterol (Proventil)
• Short acting
• Salmeterol (Serevent)
• Long acting
• Mast cell stabilizing agents
• Cromolyn (Intal) for inhalation
• Corticosteroids (oral, IV, inhaled)
• Prednisone (PO), Methylprednisolone (IV), inhaled
  fluticasone (Flovent)

86
MANAGEMENT AND TREATMENT OF ALLERGIC ASTHMA

• Leukotriene receptor antagonists
• Montelukast (Singulair)
• Zafirlukast (Accolate)
• Leukotriene synthesis inhibitors
• Zileuton (Zyflo)
• Anti-IgE monoclonal antibody
• Omalizumab (Xolair)

87
OMALIZUMAB (XOLAIR) IN ALLERGIC ASTHMA

• Indication
• Persons gt12 years with moderate to severe disease
  not controlled with ICS
• Positive for perennial aeroallergen
• IgG1 kappa monoclonal antibody to IgE
• Mechanism of action
• Reduces binding of IgE to FceRI receptors
• Reduces number of receptors on basophils
• Administration
• Subcutaneous every 2 to 4 weeks
• Bioavailability of 62

88
(No Transcript)
89
(No Transcript)
90
(No Transcript)
91
(No Transcript)
92
(No Transcript)
93
ALLERGIC REACTIONS IN SKIN

• Urticaria (Hives)
• Red and itchy swelling of superficial skin
• Allergic and non-allergic etiology
• Acute and chronic (idiopathic) onset
• Chronic idiopathic urticaria
• 35 have autoimmune etiology
• Angioedema
• Swelling of skin with pain and burning
• Mouth, lips, tongue, hands
• Lower dermis and subcutaneous
• Allergic and non-allergic etiology

94
ALLERGIC REACTIONS IN SKIN

• Reactions occur following mast cell activation
• Direct inoculation into skin
• During systemic anaphylaxis
• Following ingestion of food or drug carried
• to skin by bloodstream

95
(No Transcript)
96
(No Transcript)
97
ALLERGIC REACTION TO FOOD

• Food allergy
• A reaction involving the immune system
• IgE
• Prevalence of 2 of adults and 6 of children
• Symptoms
• Tingling in mouth
• Swelling of lips, tongue, throat and face
• Abdominal pain, N/V/D
• Urticaria, eczema
• Dizziness, syncope
• Wheezing, SOB

98
ALLERGIC REACTION TO FOOD

• Top eight foods
• Milk, eggs, peanut, tree nuts (almonds,
  pecans,walnuts), soybean, wheat, fish and
  shellfish
• Shellfish allergy
• Usually develops in young adults and is life-long
• Types of shellfish
• Crustaceans (shrimp, crab, lobster)
• Mollusks (clams, oysters, scallops)

99
ALLERGIC REACTION TO FOOD

• Fish allergy
• One of most common and most dangerous
• Tendency to be life-long
• Canned fish (tuna, salmon) less antigenic than
  fresh
• Peanut allergy
• One of most common and most dangerous
• Tendency to be life-long
• 35 show allergy to tree nuts

100
ALLERGIC REACTION TO FOOD

• Egg allergy
• One of most common in children
• Tendency to outgrow
• White contains allergenic proteins
• Milk (cow) allergy
• The most common in infants and young children
• Majority outgrow
• Not to be confused with lactose intolerance

101
ALLERGIC REACTION TO FOOD

• Oral allergy syndrome
• Fruits and vegetables trigger a mild allergic
  reaction due to protein cross-reactivity
• Allergy to ragweed pollen
• Reaction to melons, bananas, tomatoes
• Allergy to grass pollens
• Reaction to melons, kiwis, tomatoes
• Allergy to birch pollen
• Reaction to apples, peaches, plums, cherries,
  nectarines, carrots, celery

102
FOOD INTOLERANCE AND MALADSORPTION

• A reaction to foods (containing lactose and
  fructose) not involving the immune system
• Same signs and symptoms as food allergy
• Lactose intolerance
• Results from lactase deficiency
• Fructose
• Intolerance
• Results from Adolase B deficiency
• Maladsorption
• Results from defective intestinal transport
  mechanism

103
ALLERGIC REACTION TO FOOD

• Food Allergy Initiative (www.faiusa.org)
• National 501 (c) non-profit organization founded
  in 1998 by concerned parents and grandparents
• Played major in passage of
• Food Allergen Labeling and Consumer Protection
  Act (FALCPA) of 2004
• FALCPA (August, 2004)
• Under FDA
• January 1, 2006 start date
• August of 2008 to include gluten

104
ALLERGIC REACTION TO FOOD

• Gluten
• Proteins in wheat, barley, rye and sometimes oats
• Mixture of prolamins and glutelins
• Prolamins trigger reaction in small intestine
• Celiac disease
• Celiac disease
• Autoimmune disease
• Inflammation of mucosa leads to atrophy of villi
• Maladsorption

105
(No Transcript)
106
(No Transcript)
107
ANAPHYLAXIS

• Acute, systemic (multi-system) reaction
• Caused by allergens which reach bloodstream
• Venomous insect stings
• IV and IM drugs
• PO drugs (rapid absorption and high
  bioavailability)
• Foods
• Anaphylactoid reactions
• Non-IgE mediated
• Clinical manifestations are same
• Cause is NSAIDS, radiographic dyes or idiopathic

108
(No Transcript)
109
SIGNS AND SYMPTOMS OF ANAPHYLAXIS

• Appear within minutes to hours of exposure
• Order of appearance
• Skin and soft tissue
• Flushing, pruritis, urticaria and angioedema
• Cardiovascular
• Syncope, tachycardia, irregular or no pulse
• Nervous
• Apprehension, convulsions
• Gastrointestinal
• Vomiting, diarrhea, abdominal cramps
• Respiratory
• Wheezing, dyspnea

110
TREATMENT OF SYSTEMIC ANAPHYLAXIS

• Epinephrine is drug of choice
• Catecholamine drug (stress hormone) acting on
• Alpha receptors of vascular endothelium
• Beta receptors of bronchial smooth muscles
• Administered by IM injection into anterolateral
  thigh
• Do not inject into buttock
• Do not inject IV
• Cerebral hemorrhage
• Epinephrine Auto-Injector (EpiPen)
• Adult (0.3 mg) and pediatric (0.15)

111
(No Transcript)
112
(No Transcript)
113
ALLERGY TESTING

• Methods of testing
• Skin and blood
• Skin testing
• Prick, puncture or scratch technique
• Skin reaction (wheal and flair) within 15 minutes
  
• Blood testing
• Measure serum IgE level
• Measure serum IgE level for allergen(s)
• CBC with differential

114
TYPE II HYPERSENSITIVITY REACTIONS

• Antibody mediated (IgG and IgM) cell destruction
• Mechanisms of cell destruction
• Activation of complement
• ADCC
• Opsonization
• Clinical settings
• Blood transfusion reactions
• Hemolytic disease of the newborn
• Drug-induced hemolytic anemia

115
TRANSFUSION REACTIONS

• Transfusion of blood is a type of transplantation
• ABO blood group antigens
• Glycoproteins on surface of erythrocytes
• Blood types based on ABO and Rh antigens
• A, B, AB, O
• Rh or
• Natural antibodies associated with ABO antigens
• Isohemagglutinins
• Mechanisms
• IgM mediated response to ABO antigens
• IgG mediated response to Rh antigen

116
(No Transcript)
117
(No Transcript)
118
(No Transcript)
119
(No Transcript)
120
DRUG-INDUCED HEMOLYTIC ANEMIA

• Drugs (soluble, small molecules) covalently
  linked to cell surface proteins of human cells
• Drugs and cells
• Penicillin to erythrocytes
• Sulfamethoxazole to platelets
• Results in altered antigen and IgG response with
  cell lysis
• Hemolytic anemia
• Thrombocytopenia

121
(No Transcript)
122
Figure 10-27
123
Figure 10-28
124
TYPE III HYPERSENSITIVITY REACTIONS

• Mediated by immune complexes
• Formed by IgG and soluble antigens
• IC cleared by phagocytes following complement
  fixation
• Complement fixation influenced by size of IC
• Small
• CF is inefficient
• Circulate in blood and deposited in tissues
• Large
• CF is efficient
• Removed from blood with no tissue deposition
• Size of IC influenced by concentration of antigen
  and antibody

125
(No Transcript)
126
(No Transcript)
127
TYPE III HYPERSENSITIVITY REACTIONS

• Pathophysiology related to portal of entry of
  antigen
• Subcutaneous injection (Arthus reaction)
• Localized erythema and induration
• IV administration (Serum sickness)
• Occurs 7 to 10 days following
• Horse serum, mouse monoclonal antibodies
• Characterized by fever, chills, skin rash.
• Inhalation (Hypersensitivity pneumonitis)
• Continued exposure to antigen with IC formation
  and deposition on alveolar membranes

128
(No Transcript)
129
TYPE IV HYPERSENSITIVITY REACTIONS

• Delayed-type hypersensitivity reactions (DTH)
• Occur 1 3 days following antigen contact
• Large amount of antigen required
• Mechanism of action
• Presentation of antigen to memory T cells
• CD4 TH1, CD4 TH2 and CD8
• Effector T cells secrete cytokines
• Macrophage activation, inflammation, tissue
  destruction
• Examples
• Tuberculin skin test
• Contact with poison ivy

130
(No Transcript)
131
TUBERCULIN SKIN TEST (TST)

• Synonym
• PPD (purified protein derivative) skin test
• Identify infection with Mycobacterium
  tuberculosis
• Test procedure and interpretation
• Injection of TB protein intradermally
• Read reaction at 48 to 72 hours for induration
  (mm)
• Interpret induration based on risk factors
• 5 mm (high risk)
• 10 mm (moderate risk)
• 15 mm (low risk)

132
(No Transcript)
133
(No Transcript)
134
(No Transcript)
135
(No Transcript)
136
(No Transcript)
137
QuantiFERON-TB GOLD TEST (Interferon-gamma
release assay)

• Blood test for
• Tuberculosis
• Latent tuberculosis infection (LTBI)
• Test procedure
• Whole blood mixed with M. tuberculosis antigens
  (peptides)
• ESAT-6
• CFP-10
• TB7.7 (p4)
• Incubation for 16 to 24 hours
• Measure quantity of interferon-gamma (IFN-gamma)
• Interpretation
• IFN-gamma indicates CMI (memory T cells)

138
(No Transcript)
139
CONTACT WITH POISON IVY

• A contact dermatitis
• Involves both CD4 TH1 and CD8 T cells to
• Pentadecacatechol (urushiol oil)
• Langerhans cells process and present modified
  proteins
• Extracellular
• CD4 TH1 cells
• Intracellular
• CD8 cells
• Transfer of pentadecacatechol from initial site
  of contact
• Delayed nature of reaction

140
(No Transcript)
141
(No Transcript)
142
(No Transcript)
143
(No Transcript)
144
(No Transcript)
145
(No Transcript)
146
(No Transcript)