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PH2502- immunology > Lec 10-Hypersensitivity I > Flashcards

Lec 10-Hypersensitivity I Flashcards

1
Q

Undesirable effects

A

-Many disease and conditions are caused by inappropriate immune responses
Response to
-Innocuous Ag- Allergies
-Self- Autoimmunity
-Transplants- Rejection different Ag being present on organ

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2
Q

Hypersensitivity

A

-Increasing incidence in the developing world
Why
-Clean world (hygiene, vaccination and antibiotics)
-Poor development of immune system
-Immune system less able to deal with proper infections
-Responds to imaginary foes

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3
Q

What is hypersensitivity

A
  • An over reaction of the adaptive immune system
  • First exposure= sensitisation
  • Repeated exposure= reaction (very strong)
  • This is similar to how vaccines work
  • Ag are often common e.g. pollen, dust mite poo
  • 10-40% of people in developed countries are allergic to 1+ environmental Ag’s
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4
Q

Common sources of allergens

A 
Inhaled materials 
-Plant pollen 
-Mold spores
-Feces of dust mites 
Injected materials 
-Insect venoms 
-Vaccine
-Drugs 
Ingested 
-Food 
-Oral drugs- penicillins 
Contacted materials 
-Plant leaves 
-Synthetic chemicals 
-Metals
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5
Q

Hypersensitivity reactions

A
  • Grouped according to effector mechanism that generate the reactions
  • Some Ag cause different types of reaction depending on how they are encountered
  • 4 types: classified by Coombs and Gell
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6
Q

Four classes of hypersensitivity
1-3
-Allergies are type 1

A

-Types I-III are Ab mediated
Type I
-IgE, soluble Ag, mast cell activation
-Occurs in Allergic rhinitis, asthma and anaphylaxis
Type II
-IgG
-Cell or metric Ag or cell surface receptor
-Complement FcR cells (phagocytes, NK cells) or Ab alters signalling
-Some drug allergies or Rash
Type II
-IgG, soluble Ag, complement phagocytosis, Serum sickness, Arthus reaction

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7
Q

Four classes of hypersensitivity

4

A 
Th1 cells 
-Soluble Ag, macrophage activation 
-Contact dermatitis, tuberculin
Th2 cells 
-Soluble Ag, eosinophil activation
-Chronic asthma, allergies 
CTL 
-Cell-associated Ag, cytotoxicity
-Contact dermatitis
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8
Q

Type 1 hypersensitivity

A

-Immediate-type hypersensitivity
-Ab (IgE) mediated
-Soluble Ag
-Effector mechanism- mast cell degranulation
Allergy
+The symptomatic reaction to innocuous Ag
Atopy- Tendency in susceptible individuals to produce immediate hypersensitivity reactions against innocuous Ag

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9
Q

IgE

A

-Protection against parasites (in the less developed world were paracites are more common there are less allergies)
+Developed world-parasites rare; allergies common
-Present in tissue
-Sensitise mast cells
+Poor opsonising, neutralising function (cross linking)
+Binds to Fc’epsilon’R1 (Very high affinity Receptor)- also on basophils and activated eosinophils

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10
Q

Mast cells

A

-Contains preformed inflammatory mediators (granules
-Trigger miscelar contraction for physical expulsion from lungs or gut
-Carry Fc’epsilon’R1
+Rapid response (Unlike B and T cells)
-Multi-tasking-each cell can carry multiple IgE
-There is a length Ag where multiple IgE can bind to it, with multiple Ab binding to the mast cells this causes degranulation

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11
Q

Inappropriate response

A 
-Primary exposure 
\+sensitisation 
\+Ab response --> 
\+IgE binds mast cells via Fc'epsilon'RI 
\+No problem... yet 
-Repeated exposure- Allergen cross-links Fc'E'RI 
-Degranulation
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12
Q

Mast cell activation

A

1) Enzyme- Tryptase; chymase; Cathepsin G; carboxypeptidase
-Remodelling of connective tissue metrix
-Activate other enzymes–> MMP (metric metallo proteases)
-Breakdown metric and cause tissue destruction
2) Toxic mediator- Histamine, heparin
-Toxic to paracites, increase vascular permeability, cause smooth muscle contraction
3) Chemokine- CCL3- chemotactic for monocytes, macrophages and neutrophils
4) Lipid mediators
-LT C4,D4,E4
-Cause smooth muscle contraction, increase vascular permeability, mucus secretion
+Platelet activating factor
+Chemotactic for leukocytes
+Amplifies production of lipid mediators
+Activates neutrophils, eosinophil, platelets

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13
Q

Mast cell activation-5) Cytokines

A

TNF-a
-Promotes inflammation, stimulates cytokine production by many cell types, activates endothelium
IL-4, 13
-Stimulates and amplify Th2 cell response
IL-3, 5, GM-CSF
-Promote eosinophil production and activation

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14
Q

Histamine

A
  • Toxic mediators
  • Very rapid release
  • Short-lived vasoactive amine
  • Increases permeability of vessels (endothelial cell) = swelling
  • Smooth muscle contraction
  • Mucus secretion (airway mucosa)
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15
Q

Cytokines and chemokine

A
  • Range of function
  • Promotes- inflammation
  • IgE production
  • Amplify Th2
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16
Q

Lipid mediators

A
  • PGd2 and PGe2
  • LTb4, LTc4
  • Cause many symptoms
17
Q

Eosinophils

A

-Granulocytes
-Few in circulation
-Activation= increase in Fc’E’RI degranulation
-Hypereosinophilia can lead to tissue damage
-Presence indicates inflammation
Mast cell, basophils and eosinophils can amplify IgE response

18
Q

Basophils

A

-Granulocytes- similar to mast cells
-Few in circulation
-Secrete Th2 cytokines
+IL-4, 13
+Polarise T cells to Th2
-Promotes class switching to IgE
Mast cell, basophils and eosinophils can amplify IgE response

19
Q

Allergic reactions mediated by IgE

A

1) Systemic anaphylaxis: Allergens= drugs, serum, venom, food
- Route of entry: IV (following oral)
- Response:edema, vascular permeability, laryngeal edema
2) Acute Urticaria (wheel and flare): Animal hair, insect bites
- route of entry: Skin
- Local increase in blood flow and vascular permeability
3) Hayfever: Pollens
- Inhalation
- Edema of nasal, Mucosa, sneezing
4) Asthma: Dander; pollen; mite feces
- Inhalation
- Bronchial constriction, increases mucus, airway inflammation
5) Food allergy: milk, eggs, fish
- Oral
- Vomiting, diarrhoea, pruritus (itching), anaphylaxis

20
Q

Allergen characteristics

A

-Most allergens are small, stable, soluble, proteins, often proteases
+Pollen grains, animal dander, HDM faeces
+Drugs modify proteins
-Once inhaled/Ingested particles rehydrate in mucus, from here it can bind to receptors
-Antigens processed and presented to CD4 Th cells- stimulate Th2 response- IgE
+Driven by IL4 from basophils
->20% allergies are to the cysteine protease from HDM

21
Q

What happens (sensitisation)

A
  • 1st exposure
  • Extraction of Ag
  • Activation of Ag specific T cells
  • Production of IgE and binding to mast cells on Fc’E’RI
22
Q

Early v Late

A

Immediate reaction
-Effects of histamine, PG and other pre-made or rapidly synthesised mediators

Late-phase reaction

  • In up to 50% of patients
  • Effects of induced synthesis of mediators (cytokines) causing inflammation
23
Q

Allergic reactions have 2 phases

A

Immediate phase- wheal and flare- mast cells degranulation; histamine
-Late phase is 6-8 hours later (this is bad because they may have recovered from immediate and may be away from help) - more widespread welling; LT and cytokines
-Asthma- allergic reaction to inhaled allergen
+Breathing tests to diagnose
+Late phase reaction is more damaging- leads to chronic inflammation

24
Q

Allergic asthma

A

-L/min of O2
Immediate: at optimum then goes to its lowest point but after 45 minutes it is returned to normal
Late phase: At optimum then lowers (not as low as immediate about 3/4) but the level of O2 stays low for hours as oppose to minutes for immediate so late phase is more severe

25
Q

Allergic reactions vary by site

A
  • mast cell activation and granule release
    1) GI tract- increased fluid secretion, increased peristalsis
  • Expulsion of GI tract contents (vomiting and diarrhoea)
    2) Airways- decreased diameter, increased mucus secretion
  • Expulsion of airway contents (Phlegm, coughing)
    3) Blood vessels- increased blood flow, increased permeability
  • Oedema, inflammation, increased lymph flow and carriage of Ag to lymph nodes
  • This is systemic
26
Q

Allergens in blood can cause systemic anaphylaxis

A

-Stings, food and drugs can call cause anaphylaxis
-Disseminated mast cell activation
-Rapid
+Systemic effects
+Increased vascular permeability –> hypotension –> Shock
+Smooth muscle contraction –> bronchiole constriction –> swelling of epiglottis –> Asphyxiation
-Rare: many may be at risk
-Treat with adrenaline
+reduces vascular permeability
+Relaxes constricted smooth muscle
+Stimulates the heart
-Penicillin allergy
+ B-lactam ring opens, modifies proteins, IgE response

27
Q

Allergen in blood can cause systemic anaphylaxis

A
  • Ag in bloodstream enters tissues and activates connective tissue mast cells throughout the body
  • Mast cell degranulation and release of inflammatory mediators this effects
    1) Heart and vascular system: Increased capillary, permeability and entry of fluid into tissues
  • Swelling of tissues including the tongue
  • Loss of blood pressure
  • Reduced O2 to tissue
  • Irregular heartbeat
  • Anaphylaxtic shock
    2) Respiratory tract- contraction of smooth muscle and constriction of throat and airway
  • Difficulty in swallowing
  • Difficulty in breathing wheezing
    3) GI tract- Contraction of smooth muscle
  • Stomach cramps
  • Vomitting and diarrhoea
  • Fluid outflow into gut
28
Q

Clinical effects- localised

A

Allergic Rhinitis

  • Hayfever
  • Airborne allergens
  • Sensitised mast cells in nasal and conjunctival mucosal
  • Sneezing, coughing, exudate
29
Q

Allergic Rhinitis

A
  • Allergens enter the respiratory tract, Ag activates mucosal mast cells
  • Mast cell degranulation
  • Histamine affects capillaries and epithelium
  • Eosinophils are attracted and activated
  • Mucus production and oedema
30
Q

Clinical effects localised- asthma

A
  • Mast cells of lower respiratory tract
  • Broncho-constriction
  • Airway oedema, mucus secretion, inflammation
  • Mucosal mast cell captures Ag
  • Inflammatory mediators contract, smooth muscle, increase mucus secretion from airway epithelium and increase blood vessel permeability
  • Chronic response mediated by cytokines and eosinophil production
31
Q

Asthma

A
  • Mucus plug in bronchus

- They cannot breath

32
Q

Clinical effects localised- Atopic dermatitis (allergic eczema)

A
  • Skin inflammation
  • Common presentation in families with atopy
  • Subcutaneous Ag, low dose
  • Mast cell activation
  • Increased vascular permeability leads to localised swelling
33
Q

Clinical effects localised- food allergies

A
  • Mast cells of upper or lower GI tract
  • Smooth muscle contraction
  • Allergen to blood stream –> asthma; urticaria (Hives)- allergen carried elsewhere to sensitised mast cells
  • Rarely anaphylaxis
  • Ingestion of Ag activates mucosal mast cells
  • Activated mast cells release histamine, which acts on epithelium, Blood vessels and smooth muscle
  • Ag diffuses into blood vessels and is widely disseminated causing urticaria; smooth muscle concentration induces vomiting and diarrhoea
34
Q

3 approaches to treating allergy

A

1) prevention- modify behaviour or environment to avoid contact with allergen
2) Pharmacology- Anti-inflammatory drugs
- Anti-histamine (block histamine receptors)
- Corticosteroids (suppress leukocyte function)
- Sodium cromoglycate (Mast cell stabilisers)
- Adrenaline
3) Immunology- prevent IgE production by shifting to IgA or IgG production
- Desensitisation (Controlled allergen exposure)

PH2502- immunology (16 decks)

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