Transcript What are hypersensitivities?

Immune Hypersensitivity
Chapter 18
Self-Test
Questions:
Intro: all
A1-2: all
A3: 1, 3, 5
A4: all
B: 1, 2, 4, 5
C: 1 - 4
D: 1 - 4
Hypersensitivities
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What characteristics are shared by all
hypersensitivies?
Immune responses:
Primary (sensitization) response
Secondary (activation) response
Abnormal (hyper-) response to antigens (allergens)
Symptoms: localized or systemic
Onset can be: Early, Late or Chronic
Hypersensitivities
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What are hypersensitivities?
4 types of hypersensitivities (Gel and Combs classification)
Immune
Name
system involved
Effectors
Type 1 “Atopic”
Humoral (IgE)
mast cells
eosinophils
Effects
inflammation
(anaphylaxsis)
Onset
seconds
Type II “Cytotoxic”
Humoral/
Complement
macrophages
complement
cell destruction
(hemolysis)
hours
Type III “Im. Complex”
Humoral/
Complement
granulocytes
inflammation
hours
Type IV “Delayed type”
Cell-mediated
-- TH1
macrophages
inflammation
days
Hypersensitivities
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Type I – Atopic hypersensitivities
AG presentation
DCs, even Basos & Eosinos
activate TH2 cells
IgE production
class switching to IgE
Mast cell sensitization
IgE binding to Fc receptors
Mast cell activation
Degranulation
secretion
synthesis
Early phase
& late phase
responses
McGraw-Hill
Type-I
Hypersensitivities
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Early phase responses
Molecular Mediators:
Primary – in granules
Secondary – synthesized later
(w/in 1- few minutes)
Localized clinical response (Atopy)
atopic asthma:
urticaria (hives)
eczema (skin lesions)
atopic rhinitis
food allergies
Systemic clinical response (anaphylaxis)
anaphylatic shock
Hypersensitivities
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Late phase responses
-- 4-6 hours later
e.g.,
Erythema, etc
“peak flow rate” measurements
Due to:
Early phase
Late phase
-- Cytokines from mast cells
-- Recruited eosinophils & TH2
-- degranulation
Chronic Type I
-- eosinophilia
-- inflammation: damaged
airways & mucous membranes
Hypersensitivities
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What factors affect predisposition toward Type I
hypersensitivities?
Genetic factors
Environmental factors
Hygiene hypothesis
Hypersensitivities
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Treatment
Skin testing
-- carries some risk
Drugs therapies
-- Theophylline (blocks degranulation)
-- antihistamines (block histamine receptors)
-- epinephrine (reverses trachael & bronchiole SM
and contracts arteriole SM)
Desensitization Therapy
Desensitization
Hypersensitivities
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Type II hypersensitivity
-- “Cytotoxic”
Ig binding to AG on cells
-- triggers cell lysis
Complement mediated
Macrophage mediated
Various types of hemolytic disorders
e.g., Blood transfusion incompatibility
{see section in chapter 17}
Autoimmune disorders
e.g.. Goodpasture’s syndrome
RBC being phagocytosed
in fetal erythroblastosis
1967 Science 158: cover
Hypersensitivities
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Type III hypersensitivity
-- “immune complex”
Localized: (Arthus reaction)
-- could result from an insect bite
1)
Ag-Ab complex
Excess AG  small complexes
 complement activation
2) mast cell degranulation
3) neutrophil recruitment
4) Triggering of inflammation
C3a, C5a
Systemic:
Serum sickness
Vasculitis
Hypersensity pneumonitis
-- Pigeon breeders disease (pigeon feces dust)
-- Farmers lung (Actinomycetes)
-- Mushroom picker’s…
-- Cheese washer’s…
-- Chicken plucker’s…
-- etc., … disease
Type III Hyper
Hypersensitivities
Adapted from Majno and Joris, 2004, Cells,
Tissues and Disease
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Type IV hypersensitivity
“Delayed-type”
-- slow onset
~day(s) (if sensitized)
TH1-cell mediated
Sensitization phase -- week(s) onset
-- TH1 expansion
Effector stage – day(s) onset
-- TH1 & macrophage activation
-- inflammation
Latex type IV hypersensitivity
Hypersensitivities
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Type IV hypersensitivities, con’t
Contact dermatis reactions
Often involves hapten production
e.g. to: hair sprays, plant toxins, turpentine
TH1
Hypersensitivities
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Tuberculosis
(see Chapter 14 pp 212-213)
-- Persistent Mycobacterium tuberculosis
Granuloma (tubercule) formation
TH1 cells and activated macrophages
‘caseous’ regions
extended tissue destruction
Hypersensitivities
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