14 - Hypersensitivity Flashcards by Karlo Sison

Initial Exposure to Allergen

Type 1 Hypersensitivity:
ALLERGIC REACTION

Allergen –> ATOPIC individual
VVV
IgE Antibody
that recognizes that allergen is produces
VVV
Mast Cell Receptors
bind to the IgE

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Subsequent Exposure to Allergen
Type 1 Hypersensitivity:
ALLERGIC REACTION

Allergen –> MAST CELL (in mucosa)
VVV
Allergen CROSS LINKS IgE-Fc receptors
VVV
Triggers Mast cell to Degranulate
VVV
Mediators Released
Histamine / Prostaglandins / Leukotrienes / TNF-a / IL-4
&
Basophils are recruited from blood

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LATE PHASE REACTION
Type 1 Hypersensitivity:
ALLERGIC REACTION

Caused by the MEDIATORS released from mast cell degranulation
Histamines / Prostaglandins / Leukotriens / TNF-Aa / IL-4

the RECRUIT Inflammatory cells such as:
EOSINOPHILS + NEUTROPHILS

take ~6 hours

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WHICH MEDIATOR?
rom the granules of MAST CELLS
Type 1 HYPERsensitivity

Vasodilation

INCREASED Capillary Permeability

Smooth Muscle Contraction** = **BronchoSpasm

HISTAMINE

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WHICH MEDIATOR?
from the granules of MAST CELLS
Type 1 HYPERsensitivity

BronchoCONSTRICTION

PROSTAGLANDINS

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WHICH MEDIATOR?
from the granules of MAST CELLS
Type 1 HYPERsensitivity

Capillary PERMEABILITY

LEUKOTRIENES

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WHICH MEDIATOR?
from the granules of MAST CELLS
Type 1 HYPERsensitivity

Inflammation

Cytokine Release

Stimulate Th2

TNF-A

IL-4

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What makes an EFFECTIVE ALLERGEN?

Small inhaled proteins that stimulate
IgE production in atopic individuals

Small / Highly Soluble

Low Dose

Carried on DRY PARTICLES (Pollen)

Ex.
Mold Spores / Dust Mites / Pets / Cockroaches

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Why do ATOPIC INDIVIDUALS have
IgE ALLERGY PRODUCTION?

MORE TH2
allergen-specific cells

IL-4

IL-5

IL-10

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HOW does MORE TH2-allergen-specific cells in atopic individuals
result in
MORE IgE Production?

IL-4
induce CLASS SWITCHING –> B-cell produces IgE

IL-5
produce EOSINOPHILS

*IL-10**
INHIBIT production of* TH1 cells

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Why is there more TH2 vs Th1 in atopic individuals?

4 Reasons

FETUS + PLACENTA
express freign paternal AG, must be protected from maternal CTL+NKcells
TNF-A –> stimulates NK/CTL –> Th2 Bias
Placenta secretes IL-4 & IL-10 –> more Th2 bias

CHILDHOOD INFECTION
Th1 response –> memory cells remember allergen & TH1 response
Hygiene Hypothesis

HEREDITY
Genes / Mutant IgE receptors / Mutation in Il-4 Promotor gene

TREG CELLS

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FETUS

Why is there more TH2 vs Th1 in atopic individuals?

Placenta & Fetus express FOREIGN Paternal Ag
must be protected from the MATERNAL CTL & NK cells

Th1 –> TNF-a –> stimulates NK & CTL
Th2 Bias Preferred

*Placenta** secretes IL-4 & IL10
*Th2 Bias** in mother & fetus

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Childhood Infection

Why is there more TH2 vs Th1 in atopic individuals?

Childhood infection = TH1 RESPONSE

*Memory cells** remember:
*Allergen & Th1 Response** to allergen

HYGIENE HYPOTHESIS
early microbial infections important
Higher Hygiene = lower infections = Higher Allergies
>3 older siblings or < 6mo at daycare = protection vs allergies

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HEREDITY
Why is there more TH2 vs Th1 in atopic individuals?

Certain Genes have been linked with certain allergic disease
(bias towards Th2)
Asthma & Atopic Dermatitis

*Mutant IgE receptors**
*CROSS-LINKING** = STRONG signal –> IL-4 Release

Mutation in IL_4 Promoter Gene
Increase IL-4 Production
TH2 stimulated IL-4 –> B-cell produces IgE instead

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T-REG CELLS
Why is there more TH2 vs Th1 in atopic individuals?

Repeat stimulation of T-helper Cells –> TREG production

TREGS suppress immune response to allergen by producing:

*IL-10**
inhibits* pro-inflammatory Th1 cells

TGF-B
bias towards IgG / IgA production
AWAY from IgE production!

In Atopic Individuals:
their T-REGS are DEFECTIVE in supressing Th2 cytokine production

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Which Treatment for Allergies?

Treats BRONCHOCONSTRICTION

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BRONCHODIALATORS

B- Agonist

Albuterol

Xanthine Derivatives = Theophylline

Which Treatment for Allergies?

Block CYTOKINE production by HELPER T-CELLS
↓B-cell activation = ↓AB production

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CORTICOSTEROIDS

What Treatment for Allergies?

*ANTIBODY** which grasps Fc Region of IgE Ab
blocking binding to* Mast Cells

Reliieves allergic symptoms & ↓severity of asthma attack

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OMALIZUMAB

What Treatment for Allergies?

Decrease or Prevents
MAST CELL DEGRANULATION

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MAST CELL MEMBRANE STABILIZERS

Cromolyn Sodium

What Treatment for Allergies?

Binds to LEUKOTRINE RECEPTORS
or
INHIBITS the formation of Leukotrines

Prevents:
Airway Edema
Bronchoconstriction
Inflammation

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LEUKOTRIENE MODIFIERS

ZAFIRLUKAST

Specific ImmunoTherapy
for
Treatment for Allergies

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ONLY APPROACH FOR ALLERGY CURE

*Several Years of** **maintanence injections
-> TOLERANCE**

Can induce the
shift Th1 instead of Th2

IgG:IgE ratio
can increase 100 fold
Repeated injections –> TREGS which produce TGF-B
which suppress IgE Ab production

ICU DRUG DESENSITATION

Done when a
Drug NEEDS to to be given to a patient who has that DRUG ALLERGY

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EVALULATION
indication / ICU BED / plan / IV access

ORDERING
Allergy consult / PRN meds / CRASH CART / Phamacist dilution assist

MONITORING
watch for: HypoTension / TachyCardia / Tightness / Wheezing
Dyspnia / Hives / other allergies

PREPARATION
prepares ALL DILUTION and clearly labeled doses

ADMINISTRATION
each dose given over 30 min via pump @ specific times
30 min after IV dose –> 60 min monitoring after PO dose

Which TYPE OF HYPERSENSITIVITY?

Immediate & Anaphylactic

Mediated by IgE

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*TYPE 1**
*The Allergic Reaction**

IgE induced by allergen & binds to mast cells + basophils
VVV
Re-Exposure to allergen –> allergen CROSS LINKS bound IgE
VVV
Degranulation & Mediator Release

Which TYPE OF HYPERSENSITIVITY?

Mediated by IgG

Antigens on cell-surface combine w/ AB

COMPLEMENT-mediated lysis

PMN-mediated cell dmg

Ab-Ag induced cell dysfunction

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TYPE 2
CYTOTOXIC

**Which TYPE OF HYPERSENSITIVITY?** Mediated by **IgG** **Ag-Ab** **immune complex** deposited in tissue **Complement activated** --\> **PMNs attracted to site** VVV **release LYSOSOMAL ENZYMES** VVV **TISSUE DMG**

**_TYPE 3 IMMUNE COMPLEX_**

**Which TYPE OF HYPERSENSITIVITY?** **_CELL MEDIATED_** **Helper T-Cell** **sensitized** by antigen --\> **re-exposure to Ag** VVV **Lymphokine Release** VV **Inflammation & MACROPHAGE activation** w/ mediator release

* *_TYPE 4_** * *DELAYED**

**Type 2: CYTOTOXICITY** **3 Mechanisms**

**IgG Mediated Reaction** **Complement** --\> **_MAC --\> LYSE_** **Complement** --\> **_PMN to site**_ --\> _**PHAGOCYTOSIS_** * *IgG** binds to **Ag on membrane** --\> * *_Ab-Ag induced cell DYSFUNCTION_**

**Examples of TYPE 2 HYPERSENSITIVITY: CYTOTOXICITY**

_RBC CELL:_ * *Hemolytic Anemia** / **ABO Transfusion Reactions** * *Drugs (PLT also) / Rh Hemolytic Disease** _Cardiac Cell_ **Infections = Rheumatic Fever** _Kidney + Lung Cells_ **Goodpasture's Syndrome**

**Type 3: IMMUNE COMPLEX**

**FREE FLOATING AG** + **AB** **complexes form in BLOOD** VVV Deposit into **blood vessel** = **_COMPLEX DESPOSITION_** VVV Activate **COMPLEMENT** = **C5a** *does not go all the way to MAC* VVV Attracts **NEUTROPHILS** --\> release **enzymes** to **DESTROY endothelium**

Which type of **TYPE 4 HYPERSENSITIVITY disease?** **_Localized Inflammation_** immune complexes @ local site **Repeated Ag Admin =** **HIGH IgG** then **SC injection of Ag**

**_ARTHUS REACTION_**

**What disease? Type 3 Hypersensitivity** Immune complexes deposited **throughout the body** **SYSTEMIC INFLAMMATORY RESPONSE** * *_Foreign Drug serum_** injected = *SLOW Ag Excretion* * *AB production** --\> **Immune complex formation & deposition**

**_SERUM SICKNESS_**

**What disease? Type 3 Hypersensitivity** **_Post-Streptococcal_** **Ag-Ab complexes** along the basement membrane of **KIDNEY** VV **Complement Active --\> Neutrophil recruitment**

**_GLOMERULONEPHRITIS_**

**What disease? Type 3 Hypersensitivity** **_Rh Factor_** binds with **AB** VV Immune complex deposit in **Synovial membranes VV Complement Activation -\> Neutrophil Recruitment**

**_RHEUMATOID ARTHRITIS_**

**What disease? Type 3 Hypersensitivity** Ab targetted against **DNA of Face/Kidney/Joints**

**_Systemic LUPUS ERYTHREMATOUS_**

**_Type 4: DELAYED_**

only **CELL-MEDIATED** type of hypersensitivity **Macrophage** + **Ag** (on MHC2) --\> **_IL-1**_ + _**IL-12_** **^^^** VV **_T-HELPER CELL_** **TH1** --\> **_INF-Y_** Activates Macrophage **Delayed = Takes hours or days after contact** & **lasts for days**

Examples of **TYPE 4 HYPERSENSITIVITY**

* *_CONTACT HYPERSENSITIVITY_** * *POISON OAK** ## Footnote **_TUBERCULIN = TB_**

14 - Hypersensitivity Flashcards

(36 cards)