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Hypersensitivity: Types, Mechanisms, and Treatments, Study Guides, Projects, Research of Immunology

An in-depth exploration of hypersensitivity, its different types (I, II, III, and IV), mechanisms, and treatments. It covers topics such as allergens, sensitization, IgE and FcεR, effector stage, and delayed-type hypersensitivity. Real-life examples and illustrations are used to enhance understanding.

What you will learn

  • What are the different types of hypersensitivity?
  • How does the immune system respond during the sensitization stage of hypersensitivity?
  • What are the effects of Type I hypersensitivity on the body?

Typology: Study Guides, Projects, Research

2021/2022

Uploaded on 09/12/2022

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Hypersensitivity
Robert Beatty
MCB150
Type I
IgE Mediated
Classic Allergy
Type II
IgG/IgM
Mediated
rbc lysis
Type III
IgG Mediated
Immune
complex
Disease
Type IV
T cell
Delayed
Type
Hypersensitivity
Gel and Coombs classification of hy persensitivities.
TYPE I Hypersensitivity
Classic allergy
Mediated by IgE attached to Mast cells.
The symptoms resulting from allergic responses
are known as anaphylaxis.
Includes: Hay fever, asthma, ec zema, bee stings, food
allergies.
Allergens
Allergens are nonparasite antigens that can
stimulate a type I hypersensitivity response.
Allergens bind to IgE and trigger
degranulation of chemical mediators.
Allergens
In the US ---
36 million people
said to have hay fever!
Characteristics of allergens
Small 15-40,000 MW proteins.
Specific protein components
Often enzymes.
Low dose of allergen
Mucosal exposure.
Most allergens promote a Th2 immune.
pf3
pf4
pf5
pf8

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Hypersensitivity

Robert Beatty

MCB

Type I IgE Mediated Classic Allergy Type II IgG/IgM Mediated rbc lysis Type III IgG Mediated Immune complex Disease Type IV T cell Delayed Type Hypersensitivity Gel and Coombs classification of hypersensitivities.

TYPE I Hypersensitivity

Classic allergy

Mediated by IgE attached to Mast cells.

The symptoms resulting from allergic responses

are known as anaphylaxis.

  • Includes: Hay fever, asthma, eczema, bee stings, food allergies.

Allergens

Allergens are nonparasite antigens that can

stimulate a type I hypersensitivity response.

Allergens bind to IgE and trigger

degranulation of chemical mediators.

Allergens

In the US --- 36 million people said to have hay fever!

Characteristics of allergens

Small 15-40,000 MW proteins.

Specific protein components

  • Often enzymes.

Low dose of allergen

Mucosal exposure.

Most allergens promote a Th2 immune.

Allergens

Dermatophagoides pteronyssinus (common dust mite) Example: Der P Der P1 is an enzyme allergen from the fecal pellets of the dust mite. Allergen is easily aerosolized and inhaled. Der P1 breaks down components of tight junctions which helps it to cross mucosa.

Der P1 Allergen

Atopy

 Atopy is the term for the genetic trait to have a

predisposition for localized anaphylaxis.

Atopic individuals have higher levels of IgE and

eosinophils.

Genetic Predisposition

Type I hypersensitivity

Candidate polymorphic genes include:

  • IL-4 Receptor.
  • IL-4 cytokine (promoter region).
  • FcεRI. High affinity IgE receptor.
  • Class II MHC (present peptides promoting Th2 response).
  • Inflammation genes.

Mechanisms of allergic response

Sensitization

Repeated exposure to allergens initiates

immune response that generates IgE

isotype.

Th2 cells required to provide the IL-

required to get isotype switching to IgE.

Mechanisms of allergic response

Sensitization

Th2/B cell interaction

IL-

IL-4R

CD

Drive B cell

Activation and IgE

isotype switch.

Busse and Lemanske NEJM Feb 2001. 344:

Immediate vs Late Effects

(early mediators) Early/Late Effect on lung airflow OR Wheezing

Mediators of Type I Hypersensitivity

Primary Mediators

Pre-formed mediators in granules

Histamine

Cytokines TNF-α, IL-1, IL-6.

Chemoattractants for Neutrophils and

Eosinophils.

Enzymes

  • tryptase, chymase, cathepsin.
  • Changes in connective tissue matrix, tissue breakdown. Type I Hypersensitivity Secondary mediators Mediators formed after activation

Leukotrienes

Prostaglandins

Th2 cytokines- IL-4, IL-5, IL-13, GM-CSF

Continuation of sensitization cycle

Mast cells control the immediate response.

Eosinophils and neutrophils drive late or

chronic response.

More IgE production further driven by

activated Mast cells, basophils, eosinophils.

Continuation of sensitization cycle

Eosinophils

Eosinophils play key role in late phase

reaction.

Eosinophils make

  • enzymes,
  • cytokines (IL-3, IL-5, GM-CSF),
  • Lipid mediators (LTC4, LTD4, PAF)

Eosinophils can provide CD40L and IL-

for B cell activation.

Localized anaphylaxis

Target organ responds to direct contact with allergen.

Digestive tract contact results in vomiting,

cramping, diarrhea.

Skin sensitivity usually reddened inflamed

area resulting in itching.

Airway sensitivity results in sneezing and

rhinitis OR wheezing and asthma.

Systemic anaphylaxis

Systemic vasodilation and smooth muscle

contraction leading to severe bronchiole

constriction, edema, and shock.

Similar to systemic inflammation.

Treatment for Type I

Pharmacotherapy

Drugs.

  • Non-steroidal anti-inflammatories
  • Antihistamines block histamine receptors.
  • Steroids
  • Theophylline OR epinephrine -prolongs or increases cAMP levels in mast cells which inhibits degranulation.

Treatment for Type I

Immunotherapy

  • Desensitization (hyposensitization) also known as allergy shots.
  • Repeated injections of allergen to reduce the IgE on Mast cells and produce IgG.

Treatment for Type I

Effect of allergy shots Allergen Specific Antibodi es Change in amount of each isotype from more IgE to more IgG. TYPE II Hypersensitivity Antibody mediated cytotoxicity

Blood Transfusion reactions

Innocuous antigens on red blood cells. EXAMPLE: ABO blood group antigens A and B carbohydrate antigens

Antibody against rbc antigen binds and

mediates killing of rbcs via C’or ADCC

causes systemic inflammation.

ABO Blood Groups Quex: Why do we have antibodies to these innocuous antigens even before we get blood transfusion?

TYPE III Immune Complex Disease

Localized disease

Deposited in joints causing local inflammation =

arthritis.

Deposited in kidneys = glomerulonephritis.

TYPE III Immune Complex Disease

Serum sickness from large amounts of antigen

such as injection of foreign serum.

 Serum sickness is usually transient immune complex disease with removal of antigen source.

Serum Sickness

Systemic immune complex disease

Days after Antigen Injection Large amounts of antigen such as injection of foreign serum. Delayed type hypersensitivity Th1 cells and macrophages

DTH response is from:

  • Th1 cells release cytokines to activate macrophages causing inflammation and tissue damage.
  • Continued macrophage activation can cause chronic inflammation resulting in tissue lesions, scarring, and granuloma formation. Delayed is relative because DTH response arise 24- hours after exposure rather than within minutes.

Stages of Type IV DTH

Sensitization stage

Memory Th1 cells against DTH antigens

are generated by dendritic cells during the

sensitization stage.

These Th1 cells can activate macrophages

and trigger inflammatory response.

Stages of Type IV DTH

Effector stage

Secondary contact yields what we call DTH.

 Th1 memory cells are activated and produce

cytokines.

  • IFN-γ, TNF-α, and TNF-β which cause tissue destruction, inflammation.
  • IL-2 that activates T cells and CTLs.
  • Chemokines- for macrophage recruitment.
  • IL-3, GM-CSF for increased monocyte/macrophage

Stages of Type IV DTH

Effector stage

Secondary exposure to antigen

Inflamed area becomes red and fluid filled can

form lesion.

  • From tissue damage there is activation of clotting cascades and tissue repair.

Continued exposure to antigen can cause chronic

inflammation and result in granuloma formation.

Type IV DTH

Contact dermatitis

The response to poison oak is a classic Type IV.

  • Small molecules act as haptens and complex with skin proteins to be taken up by APCs and presented to Th cells to get sensitization.
  • During secondary exposure Th1 memory cells become activated to cause DTH.

Contact dermatitis

Delayed type hypersensitivity

(DTH)

DTH is a type of immune response classified by Th1 and macrophage activation that results in tissue damage. DTH can be the result of Chronic infection or Exposure to some antigens. Granuloma Formation from DTH Mediated by Chronic Inflammation

Drug reactions can be any Type

of Hypersensitivity