Allergic diseases.
Classification, clinical examples.
Lecturer: Professor Vladimir Babadzhan
The Classification of the Hypersensitivity
Type I Type II Type III Type IV a Type IV b Type IV c Type IV d
Immune IgE IgG IgG IFNγ, TNFα IL-5, IL-4/IL- Perforin/ CXCL-8
reactant (TH1 cells) 13 GranzymeB GM-CSF (T-
(TH2 cells) (CTL) cells)
Antigen Soluble Cell-or Soluble Soluble Soluble Cell- Soluble antigen
antigen matrix- antigen antigen antigen associated presented by
associated presented by presented by antigen or cells or direct T
antigen cells or direct cells or direct direct T cell cell stimulation
T cell T cell stimulation
stimulation stimulation
Effector cells Mast-cell FcR+ cells FcR+ cells Macrophage Eosinophils T cells Neutrophils
activation (phagocytes Complement activation
NK cells) immune
complex
Example of Allergic Hemolytic Serum Tuberculin Chronic asthma, Contact AGEP
hypersensitivit rhinitis, anemia, sickness, reaction, chronic allergic dermatitis,
y reaction Behcet disease
asthma, thrombocyto Arthus contact rhinitis, maculopapular
systemic penia reaction dermatitis maculopapular and bullous
exanthema exanthema,
anaphylaxis (with IVc)
with hepatitis
eosinophilia
2
TYPE 1 HYPERSENSITIVITY REACTION
SYNONYMS:
• ALLERGY, ATOPY
• IgE-MEDIATED TYPE HYPERSENSITIVITY
REACTIONS
• IMMEDIATE TYPE HYPERSENSITIVITY (EARLY
PHASE)
TYPE 1 HYPERSENSITIVITY REACTION:
THE SUSCEPTIBILITY OF CERTAIN INDIVIDUALS
TO BE ALLERGENIC TO ENVIRONMENTAL
ALLERGENS
PREDISPOSING FACTORS IN THE
PATHOGENESIS OF ALLERGIC DISEASES
IMMUNOLOGICAL/GENETICAL (Athopy)
• IgA
• Th1:Th2 imbalance
IFNg, IL4
IgE
ENVIRONMENTAL FACTORS ALSO PLAY A ROLE
• ALLERGY CAUSED BY ENVIRONMENTAL FACTORS
• SEASONAL NATURE OF ALLERGIES
• CHILDREN, RAISED IN HOMES OF SMOKERS, AT
INCREASED RISK TO HAVE ASTHMA
• INCREASED RISK OF ALLERGIES IN DEVELOPED
COUNTRIES
ABOUT ALLERGENS
• THEY ARE ANTIGENS THAT EVOKE CD4 +TH2 CELLS
THAT DRIVE AN IgE RESPONSE
• INHALED ALLERGENS ARE SMALL, HIGHLY SOLUBLE
PROTEINS,
CARRIED ON PARTICLES
• ALLERGENS ARE PRESENTED TO IMMUNE SYSTEM AT
VERY LOW DOSES
TYPES OF ALLERGENS
Exogenous Endogenous allergens
Allergens
Inhalant Heteroallergens Autoallergens
(Neoantigens)
1. Non-infectious Normal intact self
antigens characteristic
Contact-type Induced by alteration of young healthy normal
cells that commonly
Ingestant Atypical (senescent cell,
provoke autotolerance
tumor, embryonic)
Injected 2. Infectious
Infectious -virus-induced
Drug -microorganism-induced
Types of exogenous allergens:
Drugs (penicilline, etc)
Inhalative allergens: pollens (ragweed, mugwort,
etc)
animal epithelium (cat, dog,etc)
mites
fungi (mucor, aspergillus, etc)
textile/cotton
Insects bee, wasp
Nutritive allergens: milk, egg, soybeen, etc.
Atopy: pathologic hypersensitivity to allergic reactions. It is a diathesis.
Anaphylaxy: a lifethretening state when enormously high amouts of the
inflammatory mediators get into the circulation, skin, lung and
gastrintestinal truct
a.) IgE mediated
b.) not IgE mediated forms (mediated by complement and
other factors)
HOUSE DUST MITE
Type I. allergic reaction
The reaction is mediated by allegen specific IgE
The reaction is of immediate type ( the symtoms of inflammation appear
within 4 hours after the allergen challange)
The symptomes are elicited by mediator substances released from mast
cells, basophils, eosinophils, macrophages or platelets.
Mediators of mast cells/basophils eosinophils macrophages platelets
histamine, triptase ECP proteases serotonine
PGD2, LTC4 MBP PGD2, PGE2 histamine
PAF ROS TxA2, LTB4 TxA2
IL-1, IL-4, IL-5 LTC4, PAF LTC4, PAF ROS
TNFa, IFNg IL-5 IL-1, TNF
ROS
ALLERGIC CONDITIONS
ALLERGIC RHINITIS
ALLERGIC ASTHMA
ATOPIC DERMATITIS
FOOD ALLERGY
SYSTEMIC ANAPHYLAXIS
URTICARIA
Definition of anaphylaxis
Ana ( without ) phyalxis ( protection /
guard)
Is an sever life-treating generalized Or
systemic hypersensitivity reaction .
Its commonly ,but not always mediated
by an
allergic mechanism , usually by IgE
Allergic Non IgE mediator anaphylaxis
Non allergic anaphylactic reaction
formerly called anaphylactoid Or
pseudo- allergic reaction
Revised momenclatued for anaphylaxis
Allergic Non allergic
IgE mediator Non IgE mediator
Cell & combos classification of
hypersensitivity
Anaphilaxis
type 1 > Immediate hypersensitivity < 60 mim
Type 2 > cytotoxic reaction < 72 hour
Type 3 > immune complex reaction 1-3 weeks
Type 4 > delayed hypersensitivity > 48
Non allergic anaphslaxis
Anaphylactic reaction are case by
activation of mast cell and release of the
same mediator , but without the
involvement of IgE antibodies
Management is similar to anaphylaxis
Anaphylactic shock
Anaphylaxis associated with systemic
vasodilatation ( hypotension , fainting ,
collapse ) and bronco constriction (
respiratory compromise )
Agent that cause anaphylaxis
IgE –dependent
Food ( peanut, tree nut , seafood)
Medication ( bet-lactam ,antibiotic)
Venoms
Latex rubber
Cause of anaphylaxis
Direct activation of mast cell
Opiates ,tubocurare , radiocontrast dyes
o mediators of arachidonic acid metabolism
Aspirin
Non steroid anti-inflammatory drugs (NsAIDs)
o Mechanism unknown
Sulphites
other causes of anaphylaxis
Exercise – induced
Cold – induced
Idiopathic
Primary symptoms of anaphylaxis
Skin Respiratory
flushing , itching , dysphonia , cough ,
urticaria , angioedema wheezing , dyspnea
,chest tightness
Gastro intestinal
,asphyxiation , death
cardiovascular :
Nausea , vomiting ,
bloating , cramping , Tachycardia ,
diarrhea hypotension , dizziness
Other
,collapse ,death
Felling of impending
doom , metallic taste
Pattern of anaphylaxis
Uniphasic
Symptoms resolve within hour of treatment
Biphasic
Symptoms resolve after treatment but return
between 1 to 72 hour later ( usually 1-3 hour)
Protracted
Symptoms do not resolve with treatment and
may last >24 hour
Medical clinical treatment of
anaphylaxis
Epinephrine
Up to 35% of patient mat need second dose
Antihistamines
Corticosteroids
oxygen
Impair further absorption
local epinephrine ,tourniquet
Supine , elevate legs
ER, ICU monitor /support fluid
1.Drugs for anaphylaxis
Epinephrine
Put the patient in supine position and elevate
his /her leg maintain airway (endotracheal
tube or cricothyrotomy )
Epinephrine
Adult – 1:1000 0,3-0.5ml q 5minutes (or less)
PRN IM in lateral thigh
Child – 0.01 mg /kg ,max 0.3 ml q5minute (or
less) PRN IM in lateral thigh
2. Drug : oxygen
Optimally with all patient with anaphylaxis
Any patient with hypotension or respiratory
distress
Any patient with 02 sat<95%
Any patient requiring more than one
epinephrine injection
Face mask recommended over nasal prongs
Start with 6-8 liter/ minute
Drugs : iv fluids
For hypotension ( systolic <100 ) or any one
who has no responded to first IM epinephrine
When there is shock in spite of increase
vascular resistance
10% sever anaphylaxis not reversible with
epinephrine
select IV Fluids
0.9 % NaCl ( isotonic crystalloid )
Hydroxyethyl starch ( hespan ) (colloid) if
saline not effective
iv fluids
Once IV established
500_1000ml IV bolus in adult
20ml/kg bolus in child
Monitor response – give further bolus as
necessary
Colloid or crystalloid
0.9% sodium chloride or Hartmann's
Avoid colloid ,if colloid thought to have
caused reaction .
Urticaria
Common Causes of Acute Urticaria
Idiopathic
Immune-mediated (IgE)
foods (shellfish, nuts)
drugs
Nonimmune-mediated
opiates
Nonspecific
viralinfections (influenza)
bacterial infections (occult abscess, mycoplasma)
Etiology of Urticarial Reactions: Allergic Triggers
Acute Urticaria
Chronic Urticaria
– Drugs
Physical factors
– Foods
–cold
– Food additives –heat
– Viral infections –dermatographic
hepatitis A, B, C –pressure
Epstein-Barr virus
–solar
– Insect bites and stings
Idiopathic
– Contactants and inhalants
(includes animal dander and Avtoimmune reactions
latex)
Role of Mast Cells in Chronic Urticaria:
Lower Threshold for Histamine Release
Release threshold decreased by:
– Cytokines & Cutaneous mass cell
chemokines
in the cutaneous
microenvironment Release threshold
– Antigen exposure increased by:
– Histamine-releasing Corticosteroids
factor Antihistamines
– Autoantibody Cromolyn (in vitro)
– Psychological factors
The Pathogenesis of Chronic Urticaria: Cellular Mediators
An Autoimmune Basis for Chronic
Idiopathic Urticaria: Antibodies to IgE
Initial Workup of Urticaria
Patient history Physical exam
– Sinusitis Skin
– Arthritis Eyes
– Thyroid disease Ears
– Cutaneous fungal infections Throat
– Urinary tract symptoms Lymph nodes
– Upper respiratory tract infection Feet
(particularly important in children) Lungs
– Travel history (parasitic infection) Joints
– Sore throat Abdomen
– Epstein-Barr virus, infectious
mononucleosis
– Insect stings
– Foods
– Recent transfusions with blood products (hepatitis)
– Recent initiation of drugs
URTICARIA or HIVES
Острая крапивница. Уртикарные высыпания, первые
часы.
URTICARIA or HIVES
Острая крапивница. Уртикарные высыпания с элементами гиперемии
на коже спины.
URTICARIA or HIVES
URTICARIA or HIVES
Laboratory Assessment for
Chronic Urticaria
Initial tests
Possible tests for selected
CBC with differential
patients
Erythrocyte sedimentation rate
– Stool examination for ova Urinalysis
and parasites
– Blood chemistry profile
UNICAP for specific IgE
– Antinuclear antibody titer
Complement studies: CH50
(ANA)
Cryoproteins
– Hepatitis B and C
Thyroid microsomal antibody
– Skin tests for IgE-mediated
Antithyroglobulin
reactions
Thyroid stimulating hormone
(TSH)
Urticaria Associated With
Other Conditions
– Collagen vascular disease (eg, systemic lupus
erythematosus)
– Complement deficiency, viral infections (including
hepatitis B
and C), serum sickness, and allergic drug eruptions
– Chronic tinea pedis
– Pruritic urticarial papules and plaques of pregnancy
(PUPPP)
– Schnitzler’s syndrome is characterized by chronic, nonpruritic
urticaria in association with recurrent fever, bone pain, arthralgia or
arthritis, and a monoclonal immunoglobulin M (IgM) gammopathy in a
concentration of usually less than 10 g/L.
Algoritm for the evaluation of urticaria
Therapy for Urticaria
Abbreviated search for triggers
treat the treatable causes
Anti-histamines
Short-acting (Clemastine)
Long-acting (Loratadine, Cetirizine)
Corticosteroids
start around 1 mg/kg/day (single or divided doses)
Treatment of Urticaria:
Pharmacologic Options
Antihistamines, others
Corticosteroids
– First-generation H1
Severe acute urticaria
– Second-generation H1
–avoid long-term use
– Antihistamine/decongestant –use alternate-day regimen
combinations when possible
– Tricyclic antidepressants Avoid in chronic urticaria
(eg, doxepin) (lowest dose plus
– Combined H1 and H2 agents antihistamines
might be necessary)
Beta-adrenergic agonists Miscellaneous
– Epinephrine for acute PUVA
urticaria Hydroxychloroquine
(rapid but short-lived
Thyroxine
response)
– Terbutaline
H1-Receptor Antagonists:
Pros and Cons for Urticaria and Angioedema
First-generation antihistamines (diphenhydramine
and hydroxyzine)
– Advantages: Rapid onset of action, relatively inexpensive
– Disadvantages: Sedating, anticholinergic
Second-generation antihistamines (cetirizine, loratadine)
– Advantages: No sedation (except cetirizine); no adverse
anticholinergic effects; bid and qd dosing
– Disadvantages: Prolongation of QT interval; ventricular
tachycardia (astemizole only) in a patient subgroup
Third-generation antihistamines (levocetirizine, fexofenadine,
desloratadine)
An Approach to the Treatment of
Chronic Urticaria
Angioedema
Characteristics
Similar process to urticaria
Occurs deeper in subcutaneous tissue
“Swelling” due to extravastation of
fluid into tissues from vasodilators
Typically seen in areas with little
connective tissue such as lips, face,
mouth, uvula and genitalia
Can occur in bowel wall which
manifests as colicky abdominal pain
Characteristics (cont)
Rapid onset (typically minutes to hours)
Often asymmetric in distribution
Often in non-gravitationally dependent
areas such as lips, mouth, face, tongue
Can be associated with urticaria,
sometimes with allergic reaction or part of
anaphylaxis, or may occur in isolation
*Can be life-threatening if associated
with airway compromise
Classification of Angioedema
Mast cell-related angioedema
– Can begin within minutes of exposure of
trigger like food, drug, sting
– May occur with other allergic type symptoms
such as urticaria
– Usually resolves within 24-48 hours
Bradykinin-induced angioedema
– Develops more gradually
– Often longer to resolve 2-4 days
– Example: ACE induced angioedema
Medications Associated with
Angioedema
ACE Inhibitors
ARBs
Ca2+ Channel Blockers
Estrogens
Fibrinolytics
Epidemiology of
Angioedema
Uptodate. Angioedema
Angioedema of eyelid
Hereditary Angioedema
Usually presents in second decade of life
– May be seen in younger children or even into 30’s
Edema can be present in different organs and can
alter presentation:
– Tongue – most serious as can cause obstruction
Face
Trunk
Genitals
– GI track – can resemble SBO and have pt go for
emergent surgery
– Extremities
Attacks usually last 2-5 days
Common triggers of hereditary
angioedema attacks
Trauma Menstruation
Angioedema
Angioedema
attack
Infection
Medications
Stress
Aleena Banerji, MD. Overview of Hereditary and Acquired Angioedema. 2010.
Recurrent Angioedema - Familial
HAE due to ↓ C1 Type I Functional def –
inhibitor def bradykinin mediated
Type II Functional def –
Bradykinin mediated
HAE w/normal Factor XII Assoc w/Factor XII
C1 inhibitor Mutation mutation, likely
(prev Type III) bradykinin mediated
Unknown Mutation unknown,
cause likely bradykinin
mediated
Recurrent Angioedema -
Sporadic
Acquired C1 inhibitor Assoc w/underlying malignancy or
anti C1 inhibitor antibodies likely
deficientis
bradykinin mediated
ACE - I Related Decreased catabolism of
bradykinin – likely
bradykinin mediated
Allergic Mast Cell degranulation
Laboratory Evaluation (cont)
When you refer, we may order
– Tryptase where anaphylaxis might
be present
– Immunocap testing to particular
trigger
– C1 inhibitor antigen and function
Medical Management HAE
C1 inhibitor concentrates - direct C1-esterase
inhibitors that decrease bradykinin production
– Berinert
20 units/kg intravenous infusion
Half life Berinert: 22 hours
Time to peak: ~4 hours
– FDA approved 2009
– Cinryze
1000 units/patient BID weekly dosing for prophylaxis
Half life Cinryze: 56 hours
Time to peak: ~4 hours
– FDA approved 2008
Medical Management of HAE
Firazyr (Icatibant)
– 30mg SC q6h for max of 3 doses
– Bradykinin B2 receptor antagonist therefore stopping bradykinin
action
– Adverse Reactions:
>10%: Local: Injection site reaction
1% to 10%: Central nervous system: Pyrexia, dizziness
Hepatic: Transaminase increased
<1% Anti-icatibant antibody production, headache, nausea,
rash
– Pregnancy Class: C
Medical Management of HAE
Kalbitor (Ecallantide)
– 30mg SC
– Reversibly inhibits plasma kallikrein therefore decreasing
bradykinin levels
– Adverse Reactions:
>10%: Central nervous system: Headache, fatigue;
Gastrointestinal: Nausea, diarrhea
1% to 10%: Central nervous system: Fever; Dermatologic:
Pruritus, rash, urticaria; Gastrointestinal: Vomiting, upper
abdominal pain; Local: Injection site reactions; Respiratory: Upper
respiratory infection, nasopharyngitis; Miscellaneous: Antibody
formation, anaphylaxis
<1% Hypersensitivity
Medical Management of HAE
Lysteda (Tranexamic acid)
– Oral, I.V.: 25 mg/kg/dose every 3-4 hours (maximum: 75
mg/kg/day)
– 1000 mg 4 times/day for 48 hours
– Displaces plasminogen from fibrin irreversibly to cause a decrease in
fibrinolysis; also inhibits proteolytic activity of plasmin
– Pregnancy category: B
– Adverse Reactions:
IV Form: Cardiovascular: Hypotension (with rapid I.V. injection)
Central nervous system: Giddiness; Dermatologic: Allergic
dermatitis; Endocrine & metabolic: Unusual menstrual
discomfort; Gastrointestinal: Diarrhea, nausea, vomiting; Ocular:
Blurred vision
OralForm: >10%: Central nervous system: Headache;
Gastrointestinal: Abdominal pain; Neuromuscular & skeletal: Back
pain, muscle pain; Respiratory: Nasal/sinus symptoms; 1% to
10%
DISTINCTION BETWEEN TYPES OF ASTHMA
ALLERGIC ASTHMA
•FAMILY HISTORY OF ATOPY (ALLERGY)
•GENERALLY DEVELOP DISEASE EARLY IN LIFE
(USUALLY IN INFANCY & CHILDHOOD)
•HIGH CIRCULATING IgE
•POSITIVE SKIN TEST
•SEASONAL OR EPISODIC NATURE
NON-ALLERGIC ASTHMA
•NOT ASSOCIATED WITH ATOPY
•A FAMILY HISTORY OF ASTHMA ONLY)
•GENERALLY OCCUR IN ADULT LIFE
•NORMAL LEVELS OF IgE
CHARACTERISTICS OF TYPE 1 HYPERSENSITIVITY
2 PHASES:
EARLY PHASE:
• WITHIN MINUTES
• INITIATED BY IgE STIMULATION OF MAST CELLS,BASOPHILS
LATE PHASE
• WITHIN 6-24 HOURS
• INFLUX OF Th2, EOSINOPHILS
LATE PHASE
INFLAMMATORY RESPONSE WITH:
• Th2 lymphocytes
• Eosinophils
ENZYMES DAMAGE LEUKOTRIENES, PROSTAGLANDINS
AIRWAY EPITHELIUM EFFECTS (Previous Slide)
FOODS THAT CAUSE ALLERGIES
TRUE FOOD ALLERGIES PRESENT IN:
1-4% OF GENERAL POPULATION
6% IN CHILDREN
NON-ALLERGIC FOOD INTOLERANCE
TOXICITY, FOOD ADDITIVES
CHEMICAL REACTIONS, NOT TRUE ALLERGIC
REACTIONS
HAPTENS
MOLECULAR MASS <1000: NOT TRUE AGs (ALLERGENS)
•BIND TO LARGER MOLECULE
(CARRIER MOLECULE)
IMMUNOGENIC/ALLERGENIC
HAPTEN
+ AMINO ACIDS
CARRIER
MOLECULE
HAPTENIC DETERMINANT
LOCALISED ALLERGIC REACTIONS
AREA CONDITION ALLERGEN
LUNG Allergic bronchial asthma Grass, house dust, animal hair,
pollen, fungal AG’s, foodstuffs
NOSE Allergic rhinitis(hayfever) Same
EYES Conjunctivitis (hayfever) Same
SKIN Atopic dermatitis, urticaria Foodstuffs, drugs, bee venom,
chemicals
GIT Vomiting, cramps, diarrhoea Food Allergens
DIAGNOSIS OF ALLERGIC CONDITION 1
• SKIN TEST SENSITIVITY
POSITIVE SKIN TEST
WHEAL & FLARE REACTION
Laboratory diagnosis:
Determination of serum total IgE (nephelometry, turbidimetry)
Determination of allergen specific IgE (ELISA, FIA, dot-blot, ImmunoCAP)
Determination of activity markers: increased levels of eosinophil cationic
protein (ECP) and tryptase
Determination of blood film: eosinophylia
PENICILIN ALLERGY
(HAPTEN= not an AG)
TRANSFORMED IN VIVO AND BIND TO
PROTEINS TO BECOME ALLERGENIC:
PENICILIN
PENICILLENIC ACID PENICILIOIC ACID
(haptenic form) (haptenic form)
REACTS WITH FREE NH2-GROUPS ON PROTEINS
TO FORM A HAPTENIC DETERMINANT
EVOKE ALLERGY
TESTS FOR PENICILIN SENSITIVITY
SKIN TEST
IMMUNOCAP TEST (specific IgE determent)
NB: PREPARATION USED IS SYNTHETIC HAPTENIC DETERMINANT FORM:
Penisilloyl:polylysine
PHARMACOLOGICAL TREATMENT
• Anti-histamine
• -adrenergic stimulants
• cAMP-phosphodiesterase inhibitors
• Chromoglycates
• Corticosteroids
• Leukotriene receptor antagonists
• Anti-IgE monoclonal antibodies
HYPOSENSITISATION
• CONTROLLED INJECTION OF INCREASING AMOUNTS OF CAUSATIVE
ALLERGEN FOR MONTHS->YEARS.
• THIS DIVERTS IgE RESPONSE DRIVEN BY Th2 Th1
DOWN REGULATION OF IgE
• PURIFIED MIXTURES OF ALLERGEN USED
WHO CAN BE DESENSITISED?
INDICATIONS CONTRA-INDICATIONS
ALLERGIC RHINITIS BRONCHIAL ASTHMA
BEE-STING ANAPHYLAXIS ATOPIC DERMATITIS
FOOD ALLERGIES
SLIT (SUB LINGUAL IMMUNOTHERAPY
(ALLERGEN DROPS UNDER TONGUE)
USED IN CERTAIN PARTS OF THE WORLD.
THEY CLAIM THAT SLIT CAN BE USED FOR:
CHILDREN
HIGHLY REACTIVE PATIENTS
ASTHMATICS
THOSE WITH FOOD ALLERGIES
Type II. allergic reaction
Mechanism: cytolytic and cytotoxic reactions induced by IgG and IgM,
causing tissue damages:
- complement mediated cytolysis (classic pathway)
- stimulation of PMN, Eo cells and monocytes/macrophages by
activated C3
- IgG bindig to effector cells: killer cells, PMN, Eo cells and
monocytes/macrophages
Allergens: drugs: chinine, furosemide, gold salt, indomethacine,
sulphonamides, salicylate, chloramphenicole
Laboratory diagnosis:
measurement of complement activity
demonstration of the activation of PMN, Eo,
monocytes/macrophages
ADCC
EXAMPLES OF ONLY TYPE II
• AUTO-IMMUNE HAEMOLYTIC ANAEMIA
• GOOD PASTURE SYNDROME
• DRUG-INDUCED HAEMOLYTIC ANAEMIA
THE TISSUE DAMAGE IN OTHER AUTO-IMMUNE DISEASES IS CAUSED BY
COMBINATIONS OF TYPES II, III & IV
AUTO-IMMUNE HAEMOLYTIC ANAEMIA
COLD & WARM VARIANTS OF AIHA
I ANTIGEN Rh ANTIGEN
ON SURFACE OF RBC
LYSIS OF RED BLOOD CELLS
TREATMENT OF TYPE II
• PHARMACOLOGICAL: IMMUNOSUPPRESSIVE AGENTS:
CORTICOSTEROIDS & CYTOTOXIC AGENTS
INHIBIT AB PRODUCTION
• PLASMA PHERESIS
• DRUG-INDUCED: STOP USING DRUG
PLASMAPHERESIS
BLOOD PUMPED AGAINST PERMEABLE
MEMBRANE WHICH ALLOW Ig TO
MOVE THROUGH
PERMEABLE MEMBRANE
TYPE III TYPE HYPERSENSITIVITY
SYNONYM; IMMUNE COMPLEX-MEDIATED REACTIONS
Type III. allergic reaction
Mechanism: tissue damages caused by immunocomplexes
sedimentation of IC in circulation
sedimentation of IC in tissues
Allergens: drugs, antibiotics, benzotiazine, hidantoine,
bacteria: streptococcus, etc
viruses: hepatitis B,C, etc.
Laboratory diagnosis:
Measurement of IC level in serum
Measurement of complement factor activity in serum
Histology: microscopic IC verification
FAILING IF IC REMOVAL
IMMUNE COMPLEX DEPOSITION
CHRONIC PRODUCTION OF IC ACUTE & EXCESSIVE PRODUCTION OF
DURING AUTO-IMMUNE DISEASES IC DURING INFECTIONS & SERUM SICKNESS
(INSOLUBLE COMPLEXES) (SOLUBLE IC WITH AG EXCESS
EXHAUSTION OF MONOCYTE/ POOR PHAGOCYTOSIS
MACROPHAGE SYSTEM
ACCUMULATION OF IC IN THE BLOOD VESSELS & ORGANS,
PARTICULARLY KIDNEY
EXAMPLES OF TYPE III CONDITION
VASCULITIS-BLOOD VESSEL
ALVEOLITIS- LUNG
GLOMERULONEPHRITIS- KIDNEY
ARTHRITIS-JOINTS
SERUM SICKNESS
DEVELOP AFTER INJECTION OF LARGE QUANTITIES OF FOREIGN SERUM
(EG PASSIVE IMMUNISATION WITH HYPERIMMUNE SERUM)
RECIPIENT PRODUCES AB’s TO AG IN SERUM
IC FORMATION
SPREADING & DEPOSITION OF IC THROUGHOUT THE BODY
(BLOOD VESSELS, SKIN, KIDNEY, JOINTS)
GENERAL REACTION
CLINICAL PICTURE OF SERUM SICKNESS
• RAISED TEMPERATURE
• ENLARGED LYMPH GLANDS
• ARTHRITIS
• URTICARIA
• COMPLEMENT LEVELS
TREATMENT
•CORTICOSTEROIDS
•CYTOSTATIC AGENTS
•PLASMAPHERESIS
Type IV. allergic reaction
SYNONYM:
CELL MEDIATED HYPERSENSITIVITY REACTIONS
DELAYED TUPE HYPERSENSITIVITY REACTION
Mechanism: „delayed type” hypersensitivity induced by the cytokines of
Th1 cells. The symptoms appear within 12-24 hours after the allergen
challange.
Forms:
a.) Contact sensitivity
Hapten-carreir complexes processed by Langerhans cells to Th1
lymphocytes: cytokine release
antigens: nickel, gutta percha, oils, Hg salts, stains, drugs, cosmetics
EXAMPLES OF TYPE IV HYPERSENSITIVITY-
MEDIATED TISSUE DAMAGE
• GRANULOMATOUS LESIONS: LEPROSY, TB
• CAVITATION & CASEATION (IN LUNG) IN TB
• TISSUE DAMAGE ASSOCIATED WITH FUNGAL & PARASITIC
INFECTIONS
• REJECTION OF TRANSPLANTED ORGANS
• DESTRUCTION OF HOST TISSUE’S IN AUTO-IMMUNE DISEASES
• SKIN DAMAGE IN CONTACT DERMATITIS (DYES, MINERALS,
CHEMICALS)
• BRONCHIAL OBSTRUCTION IN ASTHMATIC INDIVIDUALS
CONTACT HYPERSENSITIVITY REACTION
(CONTACT DERMATITIS)
IMMUNE RESPONSE BY CD4+Th1 OR CD8+ T LYMPHOCYTES,
DEPENDING ON THE ROUTE OF AG PROCESSING.
ANTIGENS ARE HIGLY REACTIVE SMALL MOLECULES THAT EASILY
PENETRATE SKIN,
ESPECIALLY IF ITCHING CAUSE SCRATCHING.
AG IS A HAPTEN THAT BIND TO CARRIER PROTEIN MOLECULES IN SKIN.
EXAMPLES:
METALS , CHROMATE& NICKEL
CHEMICALS
POISON PLANTS
NICKEL ALLERGY
Contact Dermatitis
Contact dermatitis
with Nickel.
Reddish marking
and itching will
occur.
TREATMENT OF SERIOUS TYPE IV REACTIONS
TREATMENT BASED ON INHIBITION OF
• PHAGOCYTE ACCUMULATION
• RELEASE OF HIGHLY REACTIVE OXIDANTS AND PROTEOLYTIC
ENZYMES
• PROLIFERATION OF CD4+ & CD8+ T-LYMPHOCYTES
CORTICOSTEROIDS general and local
CYTOSTATIC DRUGS
CLINICAL APPLICATIONS OF TYPE IV SKIN TEST.
MULTITEST CMI
MULTITEST-CMI
USED TO TEST GENERAL STATUS OF THE CMI IN INDIVIDUALS WITH
SUSPECTED ACQUIRED OR CONGENITAL ABNORMALITIES OF CMI.
APPARATUS CONTAINS 7 ANTIGENS + CONTROL
INJECTED INTO SKIN
TETANUS TOXOID, DIPHTHERIA TOXOID, STREPTOCOCCAL AG, PPD,
CANDIDA ALBICANS
TRICHOPHYTON MENTAGROPHYTES
PROTEUS MIRABILIS
IF POSITIVE TO AT LEAST 4 AG’S, CMI INTACT.
