Lecture 140: Diagnosis of Immediate Hypersensitivity

Innate vs Adaptive Immune System

Innate:
- macrophages, dendritic cells, NK lymphocytes
- recognize PAMPS by PRRs

Adaptive:
- recent adaptation
- T and B cell mediated
- immune memory and tolerance

3 properties of a normal immune system

- Antigen receptors that recognize a wide range of pathogens
- immune memory to produce rapid recall immune responses
- Tolerance to prevent immune mediated damage to self

Balance maintained in normal immune system

recognize and neutralize pathogens without also attacking benign or self

recognize microbe and microbial virulence factors: don't recognize self or benign

5 steps of normal host response

- Migration of leukocytes to antigen site - Non-specific recognition of antigens by macrophages - specific recognition of antigen by T or B - Amplification of immune response - Neutralization of antigen by destruction and phagocytosis

Hypersensitivity reactions

- exaggerated or inappropriate immune response to benign antigens
- immune response is harmful
- antigen specific: first contact with antigen primes the adaptive immune system
- Subsequent exposure to antigen elicit the hypersensitive allergic response

Gell and Coombs Classification system

Type I hypersensitivity Reaction

skin test
- asthma, arthritis
- already had previous exposures to antigen

Mast cell with IgE bound to surface - Antigen cross links IgE on mast cell surface - Mediators released from mast cells

Phases of Type I hypersensitivities

Immediate Phase of Type I
- onset within minutes
- mast cells + basophils + eosinophils
Late Phase of Type I: eosinophils + mononuclear cells
- Onset 2-4 hours later
- Peak 6-12 hours
- resolves in 12-24 hours

Histamine

major mediator of immune response
- Vasodilation, increased cap permeability, bronchospasm

SRSA (slow reacting substance of Anaphylaxis)

formed after granules released from mast cells and mediates bronchoconstriction
- vascular permeability

ECFA (eosinophilic chemotactic factor)

attracts eosinophils which release enzymes that degrade histamine and SRSA
- release cytotoxic products

Prostaglandins

modulate inflammatory response

Thromboxane

aggregate platelets
- vasoconstrictor, prothrombotic

PAF

platelet aggregation and vasodilation
- hypotension

Cytokines

From T cells: recruit innate cells and increase function
- hypersensitivity

Agents that cause anaphylaxis - IgE dependent

Foods
Dairy, egg, fish
meds
venoms
latex
vaccines
hormones
enzymes

Signs and symptoms of anaphylaxis

Urticaria or angioedema and skin flushing
- cutaneous manifestations absent or delayed
- respiratory
- dizziness, unconsciousness
- Gi symptoms

Type II cytotoxic (IgG) hypersensitivity reaction

Type III immune complex hypersensitivity reaction

Type IV delayed hypersensitivity

(cell) mediated by T cells
3 pathways:
- TH1: IFN gamma - tissue injury - PPd test - cytokines - recruit eosinophils - itching - blistering
- Th17: IL17 - amplify Th2 response
- damage directly to cytotoxic T cells
T cells recognize peptides - secrete IL2, IFN gamma - activation of macrophage + cytotoxic T cells - recognize same antigens bound to target cell - lysis

Angioedema vs urticaria

Urticaria: hives

Angioedema: demarcated nonpitting edema (subcutaneous)

Hereditary angioedema

Hereditary:
- Type 1: C1 esterase inhibitor deficiency
Type 2: functional abnormality of C1 esterase inhibitor
Both have decreased levels of C4 and C1 levels (AD)
Type 3: normal inhibitor: common in females or abnormal plasminogen, angiopoietin

Acquired angioedema

older age with associated disorder
- Idiopathic
- IgE-mediated
- Non-IgE-mediated
- Systemic disease
- Physical causes

Treatment: Replacement therapy C1 inhibitor

Signs of allergies

Turbinate hypertrophy
lymphoid hyperplasia
allergic conjunctivitis

Signs of allergic asthma

hyperinflated lungs
- increased space between ribs, compressed heart, diaphragm flattened
- barrel chest - increased AP diameter
- SCM hypertrophied
- costal retractions

Diagnostic tests used in evaluation of hypersensitivity

Routine Lab tests
- CBC
- Nasal secretions
- UA, Stool
- Ig levels

In Vivo testing
- Skin test
- respiratory test

In Vitro testing
- RAST
- ImmunoCAP

Pulmonary Function Test

lung function
- evaluate dyspnea - assess mechanical function of respiratory system

RAST test vs patch testing

blood drawn and checked for IgE response
- higher class = worse reaction

Patch testing:
- type IV hypersensitivities
- 96 hours

Atopy

- sensitization with casual exposure to specific antigen
- elevated levels of IgE
- genetic transmission involving immune response Ir genes
- Predisposition to common allergic syndromes

Allergic triad

eczema, allergic rhinitis, extrinsic asthma, food allergy

Signs of atopy

allergic salute
allergic facies - allergic shiner, hypertrophied nasal turbinate's

Signs of atopic dermatitis

erythema
- hyperpigmentation
- follicular prominence
- hyperpigmentation in popliteal fossa
- post inflammatory hypopigmentation

Immediate intervention for anaphylaxis

- Assess ABCs
- Administer epi
- IM into anterolateral thigh produces higher and more rapid peak plasma levels versus SQ and IM in arm

General Measures for anaphylaxis

recumbent position and elevate LE
- maintain airway
- oxygen
- normal saline IV for volume expansion especially when person is hypotensive

Venom management

wash area and splint to make sure venom doesn't spread
- if bee sting, remove stinger