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PATH201 lectures > Lecture 9 - hypersensitivity > Flashcards

Lecture 9 - hypersensitivity Flashcards

1
Q

What is hypersensitivity

A

Inappropriate or exaggerated immune response against antigen or allergen
includes allergy and autoimmunity

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2
Q

What is consequence of hypersensitivity

A

Reactions against self antigen
Inappropriate reactions against microbes
Against environmental antigens
Occurs on second and subsequent exposures

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3
Q

Describe hypersensitivity type 1

A

Allergy
- Rapid
- IgE-mediates degranulation of mast cells

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4
Q

Describe hypersensitivity type 2

A

Initiated by binding of antibody to cell membrane or EM

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5
Q

Describe hypersensitivity type 3

A

Antibody binding to soluble molecules - form immune complexes

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6
Q

Describe hypersensitivity type 4

A

Attack by immune cells in absence of antibody

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7
Q

What initiates type 1 hypersensitivity

A

Activation of Th2 cell -> cytokines (IL-4, IL-5, IL13)
Drive down-stream production of IgE - binds to FcER on mast cells (degranulate)

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8
Q

Describe second exposure in type 1 hypersensitivity

A

allergen binds to IgE already on mast cells - FcER crosslinking antigen -> degranulation - release mediators (histamine)

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9
Q

Describe immediate response in type 1 hypersensitivity

A

Cause - mast cell degranulation
Peaks @ 30 mins then subsides
systemic manifestation - anaphylactic shock

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10
Q

Describe late response in type 1 hypersensitivity

A

Recruitment of effector cells - Th lymphocytes, eosinophils and neutrophils

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11
Q

What are eosinophils role in type 1

A

Release cytotoxic cationic granule proteins
- skin itching and bronchial irritability
- induce mast cell degranulation

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12
Q

What cytokines do Th2 cells produce

A

IL-4 - stimulate B cell to produce IgE
IL-5 activates eosinophils
IL-13 stimulates mucus secretion - amplifies response
TNF-alpha - promotes inflammation

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13
Q

What is atopy

A

Genetic tendency to develop allergic diseases

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14
Q

What are the predisposing factors to atopy

A

More IgE molecules/mast cells
High affinity Fc receptors for IgE on mast cells
Higher IgE levels
Genetic predisposition (80% at least 1 affected parent)

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15
Q

What is the ‘hygiene hypothesis’

A

Link between lack of exposure to infectious disease in early childhood and increase in allergy incidence
Attributed to less exposure (controversial)

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16
Q

What is the difference between hypersensitivity and autoimmunity

A

Hypersensitivity - mechanisms of how the body reacts
Most hypersensitivities manifest in autoimmune disorders (type 2 - 4)

17
Q

What are the features of autoimmune diseases

A

Breakdown of immunologic tolerance
Systemic - affect tissues through body or localised to specific sites
Lymphocyte, macrophage and plasma cell infiltrate into lesions
More than one autoimmune condition
Female bias - familial - HLA associations - lesions classified by hypersensitivity types 2,3 & 4

18
Q

What is immunologic tolerance

A

Billions of antigen receptors developing B and T lymphocytes - some recognise self antigen
unresponsiveness to antigen induced by exposure
prevent our bodies reacting against self antigen

19
Q

What is central tolerance

A

Antigen induced death of self-reactive T and B cells

20
Q

What is peripheral tolerance

A

Anergy - functional inactivation of lymphocytes
Suppression by regulatory T cells
Activation-induced cell death

21
Q

Examples of local autoimmune disorders

A

Multiple sclerosis
Hashimoto’s thyroiditis
type 1 diabetes
chron’s disease
Myasthenia gravis
Grave’s disease

22
Q

Examples of systemic autoimmune disorders

A

SLE
Sjogren’s syndrome
Scleroderma
Rheumatoid arthritis

23
Q

describe type 2 hypersensitivity

A

Antibody-mediated
- targets on cell surface
- Tissue components

24
Q

What are the mechanisms of tissue injury in type 2

A

Opsonisation and phagocytosis
Complement and Fc-mediated inflammation
Anti-body-mediated cellular dysfunction

25
Q

Describe Sjogren’s syndrome

A

Destruction of exocrine glands (lacrimal and salivary - dry eyes and mouth)
- common in older women
Autoantibodies - FcR and induction of apoptosis and inflammation - inflammation of CD4 T cells - cytokines that contribute to inflammation

PATH201 lectures (15 decks)

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