13. Lung Immunology: Allergic Airway Diseases Flashcards
Outline hypersensitivity
Hypersensitivity is an exaggerated response that may be immunological or non-immunological:
- Immunological - i.e. allergy; may be IgE-mediated (e.g. atopic diseases including hayfever, eczema, asthma) or non-IgE-mediated (e.g. farmers’ lung)
- Non immunological - intolerance (e.g. food), enzyme deficiency (e.g. lactate dehydrogenase / LDH), pharmacological (e.g. aspirin hypersensitivity)
Outline allergy
Allergy is an exaggerated immunological response to a foreign substance (allergen) which is either inhaled, swallowed, injected, or comes in contact with the skin or eye
An allergy is a mechanism, not a disease, but the mechanisms often play a temporary or permanent role in disease
It can be subdivided into different categories:
o Asthma o Drug reactions o Food reactions o Rhinitis o Eczema, urticaria (hives), angioedema (swelling similar to hives, but not on surface of skin)
Outline atopy
Atopy means ‘out of place’; the hereditary predisposition to produce IgE antibodies against common environmental allergens
The atopic diseases are allergic rhinitis, asthma and atopic eczema
Allergic tissue reactions in atopic subjects are characterised by infiltration of Th2 cells and eosinophils
The term ‘allergic match’ is used to describe the common progression from atopic dermatitis to allergic asthma
Contrast Th1 and Th2 cells
Proliferating helper T cells that develop into effector T cells differentiate into two major subtypes of cells known as Th1 and Th2 cells (also known as Type 1 and Type 2 helper T cells, respectively)
Th1 cells’ main partner cells are Macrophages and CD8+ T cell
Th2 cells’ main partner cells are B-cells, Eosinophils and Mast cells
Outline IgE-mediated allergic reactions in the upper and lower airways
May present with either acute or chronic symptoms of allergy
Acute symptoms result from the binding of allergen to IgE-coated mast cell, which causes mast cell degranulation and histamine release
Chronic symptoms present from the interaction of the allergen with antigen-presenting-cells, involving the release of Th2 cytokines and chemokines
Outline Th2 responses with regards to IgE-mediated allergic reactions in the upper and lower airways
Involves the collaboration between innate and adaptive immune responses
PAMPs present on allergen interact with barrier cells e.g. epithelial cells lining airway - stimulates secretion
of IL-33 and IL-25
Interleukins attract natural helper cells, nuocytes and MPPtype2 cells (which differentiate to form mast cells, basophils and macrophages)
These cells then secrete IL-4, IL-5 + IL-13, which induces Th2 cell differentiation, B1 cell proliferation and anti-allergen effector functions; this is where the adaptive immune response is involved
Th2 cells are CD4+, therefore release:
o IL-4 –> IgE synthesis
o IL-5 –> Eosinophil development
o IL-9 –> Mast cell development
o IL-13 –> IgE synthesis and airway hyper-responsiveness
Outline nuocytes
The nuocyte is a cell of the innate immune system that plays an important role in type 2 immune responses that are induced in response to helminth worm infection or in conditions such as asthma and atopic disease
What are MPPtype2 cells?
Multipotent progenitor type 2 cells
Contrast totipotency, multipotency, pluripotency, oligopotency and unipotency
Totipotency is the ability of a single cell to divide and produce all of the differentiated cells in an organism; spores and zygotes are examples of totipotent cells; in the spectrum of cell potency, totipotency represents the cell with the greatest differentiation potential
In cell biology, pluripotency refers to a stem cell that has the potential to differentiate into any of the three germ layers: endoderm (interior stomach lining, GI tract, the lungs), mesoderm (muscle, bone, blood, urogenital), or ectoderm (epidermal tissues and nervous system)
Multipotency describes progenitor cells which have the gene activation potential to differentiate into discrete cell types; for example, a multipotent blood stem cell is a hematopoietic stem cell (HSC), and this cell type can differentiate itself into several types of blood cell types like lymphocytes, monocytes, neutrophils, etc., but it is still ambiguous whether HSC possess the ability to differente into brain cells, bone cells or other non-blood cell types
In biology, oligopotency is the ability of progenitor cells to differentiate into a few cell types; it is a degree of potency; examples of oligopotent stem cells are the lymphoid or myeloid stem cells; a lymphoid cell specifically, can give rise to various blood cells such as B-cells and T-cells, however, not to a different blood cell type like a red blood cell; examples of progenitor cells are vascular stem cells that have the capacity to become both endothelial or smooth muscle cells
In cell biology, a unipotent cell is the concept that one stem cell has the capacity to differentiate into only one cell type; it is currently unclear if true unipotent stem cells exist; hepatoblasts, which differentiate into hepatocytes (which constitute most of the liver) or cholangiocytes (epithelial cells of the bile duct), are bipotent; a close synonym for unipotent cell is precursor cell.
Outline allergic diseases
Allergic diseases include:
Atopic allergy (IgE mediated):
- Allergic asthma - including occupational asthma
- Allergic rhinitis - including hay fever
- Anaphylaxis - e.g. food, insect stings, drugs, latex
- Skin allergies - e.g. urticaria, angioedema, atopic eczema
Non-atopic allergy (IgG mediated/T-cell mediated):
- Contact dermatitis
- Extrinsic allergic alveolitis
- Coeliac disease
Outline non-allergic hypersensitivity/intolerance responses
Usually apply to food intolerance
Non-immunological mechanisms
E.g. include enzyme deficiency (Lactase DH), migraine (triggered by coffee, wine), IBS (exacerbated by
various foods), bloating due to wheat intolerance
Also idiopathic environmental intolerance (also known as multiple chemical hypersensitivity; cause unknown)
Outline allergic rhinitis
Can be either seasonal or perennial (triggered indoors); prevalence is up to 17% of the population
It is characterised by a blocked or runny nose, sneezing, itching and streaming eyes
Seasonal allergic rhinoconjunctivitis (more commonly referred to as hayfever), is caused by allergenic substances contained within pollen
o Commonly the causative factor is grass pollen but allergy to tree and weed pollen is also on the
increase
Worst symptoms usually at the height of summer when vast clouds of grass pollens become airborne; due
to mild winters and warmer springs, pollination of grasses in the UK is now starting earlier,
therefore the worst symptoms can be well established by the first week in June and tend to peak around mid-June to early July
When the pollen counts are very high, some wheeziness can also co-exist with rhinitis, in a condition known as seasonal allergic asthma
Perennial allergic rhinitis involves troublesome chronic symptoms such as a blocked, runny nose and sneezing
Can have non-allergic causes of perennial rhinitis such as infection and structural abnormalities, and a small
minority of patients have underlying immunodeficiency problems too
Allergy to the house dust mite (Dermatophagoides species) and allergens derived from animals such as cats,
dogs, horses and pet rodents are the most important causes
Define asthma
A chronic disorder characterised by episodes of wheezy breathlessness, but which may also present as an isolated cough, particularly in children
It affects 8-12% of the population
Outline the aetiology of asthma
The aetiology os still uncertain, but the pathology involves inflammation of the large and small airways (bronchi and bronchioles)
The consequence is an irritable or twitchy airway in which airflow obstruction results from exposure to a variety of non-specific irritants (bronchial hyper-responsiveness)
Define aetiology
The cause, set of causes, or manner of causation of a disease or condition
