Lecture 2- Hypersensitivity 2 Flashcards Preview

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1

Type I hypersensitivity=

allergy

2

Allergy

Allergy is usually an immediate effect (<30 mins)that can affect different organs resulting in different clinical manifestations.

Allergy requires IgE and mast cells to be activated against an antigen that the host encounters.

Can occur as both local and systemic reactions.

3

local reaction

ingested or inhaled allergen

4

systemic reaction

insect sting or IV adminsitration

5

allergy antigens can be

environmental and non-infectious antens (proteins)

6

Insect sting

- reaches systemic circulation- bad news- massive mast cell activation and degranulation- systemic reaction

7

Types of allergens

  • Seasonal exposure
    • Tree and grass pollens
  • Perennial exposure
    • House dust mite
    • Animal dander= cats and dogs
    • Fungal spores
  • Accidental exposure
    • Insect venom (wasp and be stings)
    • Medicines e.g. penicillin
    • Chemicals such as latex
    • Foods: milk, peanuts, nuts etc

8

Mechanisms of allergy

 

  •  

  • Abnormal adaptive immune response against the allergens
    • T helper 2 (TH2) response (IL-4, IL-5, IL-13)
    • IgE production
  • Mast cell activation  (IgE dependent)
    • Sensitized individuals
    • Different clinical allergic disorders depending of on mast cell location

9

The development of allergy can be influenced two factors:

genetics and environmental exposure.

10

outline immune mechanism of an allergic response

  1. Upon first exposure to the allergen (sensitisation phase) a TH2 response is initiated and allergen specific IgE produced which binds to the mast cell via the FcRεRI.
  2. Upon repeated exposure to the antigen (effector phase) the allergen will crosslink with 2 IgE and activate the mast cells causing degranulation resulting in tissue reaction.

11

Why do people have allergies?

 

  • Hygiene hypothesis
    • This hypothesis suggests that the critical post-natal period of immune response is derailed by the extremely clean household environments often found in the developed world
  • Old friends hypothesis” or “biodiversity hypothesis”

12

 

  • Trigger= bee
  • Timing = very acute
  • Symptoms
    • Respiratory
    • CV
    • Skin
    • Face
  • Therapy= epinephrine (2nd dose required)
  • Outcome= likely fatal

 

Probably had been stung before but didn’t get bad reaction- sensitisation reaction (no anaphylaxis)- however when he is stung again he is in the effector stage that drives hypersensitivity reaction (effector stage)

13

whyy are allegries increasing in prevalence in the western world

Western lifestyle associated with a reduced infectious burden

“Hygiene hypothesis”

  • Children exposed to animals, pets and microbes in the early postnatal period appear to be protected against certain allergic diseases
  • Strachan study (1989) found that children who grew up in large family had a lower risk of hay fever and eczema compared with children in small families
  • Illi study (2001) found in a prospective birth cohort study that infections of the upper respiratory tract before the age of 3 was protecting against allergic sensitisation and asthma later in life

14

The western lifestyle is associated with microbial dysbiosis

 

Old friends hypothesis” or “biodiversity hypothesis”

  • Western lifestyle induces alteration of the symbiotic relationships with parasites and bacteria leading to “dysbiosis” of the microbiome at mucosal surfaces (gut)
    •  Dysbiosis = compositional and functional alterations of microbiome
    •  Microbiome = The complete genetic content of all the microorganisms that typically inhabit in the body, such as the skin or the gastrointestinal tract.

15

The culprit of allergic reactions

Content of mast cell granules will drive allergic reaction- triggered by IgE

Mature mast cell has:

  • FceRI
  • IL-3R
  • react to SCF

16

Origin of mast cell and tissue distribution

 

  • Strategic location
    • Most mucosal and epithelial tissue = GI tract, skin, resp epithelium
    • In connective tissue surrounding blood cells

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Mast cell activation in: the epidermis

=Urticaria

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mast cell activation: Deep dermis

= Angioedema

19

Mast cell mediators

20

Immune mechanism of allergic reaction

 

  • First exposure= sensitisation phase
    • TH2 response
  • TH2 stimulates B cells to produce IgE
  • IgE binds to FC receptor on the mast cell
  • When antigen (e.g. re-exposed to allergic) mast cells already have antibodies  - Effector phase
  • 1 allergen activated 2 antibodies attached to mast cell and cause degranulation of the mast cell
    • release of Histamine and chemokines

21

Histamine and chemokines

  • Increased vascular permeability
  • Vasodilation
  • Bronchoconstriction (unwanted function)

22

skin manifestations of allergic reaction : urticaria

Caused by mast cell activation within the epidermis (mediators= histamine and leukotrienes/cytokines)

- prloned and chronic exposure= atopic dermatitis and eczema

23

Skin manifestation of allergic reactions: angiodema

  • In the deep dermis
    • Angioedema
      • medical emergency due to airway obstruction risk e.g. swollen tongue or pharynx

24

Systemic manifestations of allergic reaction: Anaphylaxis

anaphylaxis

systemic release of histamine and chemokines:

  • increased vaslar permeability- hypotension, cvs collapse, generalised urticaria
  • vasodilation- angiodema 
  • bronchial constriction- breathing problems

 

Lose 30% of circulating blood in 10 mins

25

summary of anaphylaxis

Anaphylaxis Systemic mast cell activation resulting in:

• Hypotension

• Cardiovascular collapse

• Generalised Urticaria

• Angioedema

• Breathing problems

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treatment of anaphylaxis

IM adrenaline (give second dose sometime after to prevent reaction continuing)

27

how to deliver IM dose of adrenaline via epipen

28

Type I hypersensitivity therapy

 

 

  • Abnormal adaptive immune response against the allergens
    • TH2 response = Allergen desensitization (oral immunotherapy)
    • Omalizumab = Anti-IgE monoclonal antibody
    • Mepolizumab – Anti-IL5 monoclonal antibody
  • Mast cell activation
    • Anti-histamine
    • Leukotriene receptor antagonists
    • Corticosteroids (most important anti-inflammatory drugs

29

Allergen desensitization or immunotherapy

 

  • “It involves the administration of increasing doses of allergen extracts over a period of years, given to patients by injection or drops/tablets under the tongue (sublingual)”
    • 90% effective in patients with bee and wasp venom anaphylaxis
    • Potential mechanisms
      • CD4+CD25 Regulatory T cells
      • Shift from TH2 to TH1
      • Inhibitory anti-inflammatory cytokines

Allergen specific blocking

30

Other allergic disease

  • Anaphylaxis is the worst