Transcript misdirected reactions of the immune system autoimmunity

OVER-REACTIONS OF THE
IMMUNE SYSTEM
Hypersensitivity Reactions and
Allergic Diseases
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
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
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
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)
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
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
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
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
Figure 10-5
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
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
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
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
NONSTEROIDAL ANTIINFLAMMATORY 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)
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
Figure 10-9
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
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
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)
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
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
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
– > 20 eosinophils/HPF (proximal and distal)
– Areas of basal cell hyperplasia suggests reflux
– No viral CPE, dysplasia or malignancy
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) ?
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
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
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
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
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)
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)
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)
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
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
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 < 0.35 to > 100.00
* Negative, equivocal, positive (2), strongly positive (3)
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)
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)
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)
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
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
ANTIHISTAMINE / DECONGESTANT
COMBINATIONS
FOR 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)
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
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)
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)
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
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
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)
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)
MANAGEMENT AND TREATMENT OF
ALLERGIC ASTHMA
* Leukotriene receptor antagonists
* Montelukast (Singulair)
* Zafirlukast (Accolate)
* Leukotriene synthesis inhibitors
* Zileuton (Zyflo)
* Anti-IgE monoclonal antibody
* Omalizumab (Xolair)
OMALIZUMAB (XOLAIR) IN ALLERGIC
ASTHMA
* Indication
* Persons >12 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%
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
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
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
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)
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
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
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
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
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
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
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
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
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)
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
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
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
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
Figure 10-27
Figure 10-28
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
TYPE III HYPERSENSITIVITY
REACTIONS
*
Pathophysiology related to portal of entry of
antigen
1. Subcutaneous injection (Arthus reaction)
* Localized erythema and induration
2. IV administration (Serum sickness)
* Occurs 7 to 10 days following
* Horse serum, mouse monoclonal antibodies
* Characterized by fever, chills, skin rash….
3. Inhalation (Hypersensitivity pneumonitis)
*
Continued exposure to antigen with IC formation and
deposition on alveolar membranes
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
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)
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)
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