MTB W1 Flashcards
Inheritance pattern of allergies
Inheritance pattern of propensity to allergy development is multigenic
T/F. Target organ of atopic disease will be the same in each member of the same family
False, it is variable
How are plasma IgE levels in individuals with hereditary atopy?
Higher than average
What are the potential effects of mutations or variations in the FCER1A gene?
Effects on expression or function of the FCeRI receptor, potentially affecting an individual’s susceptibility to allergic diseases
Where is susceptibility locus for atopy located?
Chromosome 5q
Chromosome located near the site of gene cluster encoding for IL-4, IL-5, IL-9, IL-13 and IL-4
Chromosome 5q
The function and/or expression of this receptor can be influenced by variations in the IL4RA gene
IL-4 receptor
Polymorphisms in this gene appear to have the strongest association with asthma:
IL33 gene
What does normal IL-33 do?
It is released by damaged epithelial cells and induces type 2 inflammation
The loss of expression or function of this protein results in significant risk for development of atopic dermatitis in early childhood + subsequent allergic diseases, including asthma
Filaggrin
What is the function of filaggrin protein?
Skin barrier functions and water retention
What are the effects of a lack of filaggrin?
Promotion of keratinocyte damage
Cytokine release
Allergen entry into dermis
Genes in cytokine cluster, CD14 and B2 adrenergic receptor are associated with…
Asthma
Defects on this encoded protein located in chromosome 6p are associated with asma:
Class II MHC
This encoded protein mediates mast cell activation, it is located in chromosome 11q and involved in asthma:
FCERI B chain
Stem cell factor, IFN-y and STAT6 mutations (located on chromosome 12q) are involved in this disease:
Asthma
IFN-y (chromosome 12q) action
Opposes action of IL-4
STAT6 (chromosome 12q) action
Mediates IL-4 signal transduction
Defects on IL-4 receptor alpha chain are associated with ______ development, as it is a subunit of both IL-4 and IL-13 receptors.
Asthma
Metalloproteinase involved in airway remodeling
ADAM33
Defects on ADAM33 metalloproteinase (chromosome 20) are associated with the development of…
Asthma
Component of terminally differentiated keratinocytes important for epithelial barrier functions
Filaggrin
Gene that, if mutated, is associated with the development of atopic dermatitis (also mention its location)
Filaggrin
Chromosome 1q
This protein is in charge of the induction of type 2 cytokines in T cells, mast cells, eosinophils and ILCs; defects in it are associated with asthma
IL-33
IL-33 receptor
ORMDL3 gene defects are associated with
Asthma
This protein degrades cAMP and regulates airway smooth muscle contractility; defects in it are associated with asthma.
Phosphodiesterase 4D
This protein is in charge of the activation of dermal dendritic cells; when mutated, it is associated with asthma development.
TSLP
Doing this during early childhood may reduce the risk for developing allergies
Exposure to microbes during early childhood may
Exposure to microbes during early childhood
Role of respiratory viral and bacterial infections in asthma
These infections are a predisposing factor in the development of asthma and exacerbations of preexisting asthma
What immune shift is associated with the hygiene hypothesis?
A skewing toward Th2 immune responses, which are linked to allergic diseases.
What environmental factors support the hygiene hypothesis?
Growing up with older siblings, in rural areas, on farms, or attending daycare.
How might early-life infections affect immune development?
They may train the immune system and promote a more balanced Th1/Th2 response.
What is the “Old Friends” extension of the hygiene hypothesis?
It suggests that exposure to ancient microbes (e.g., gut flora, soil microbes) is critical for immune tolerance.
What is the role of the microbiome in the hygiene hypothesis?
A diverse microbiome may help regulate immune function and reduce inflammation.
Early-life infections or certain vaccinations (like BCG) may modulate immune responses towards…
A Th1 response
CD14 is a component of these receptors:
LPS receptor
TLR2
TLR4
What do polymorphisms in CD14 and TLR4 affect?
Recognition and clearance of bacterial endotoxin LPS —> triggers innate immune responses
Research links CD14 polymorphisms with microbial exposure factors like farm living, farm milk consumption and household dust endotoxin levels, what is the overall impact of these interactions?
Elevated serum IgE levels
Allergen sensitization
Asthma development
This type of mutation in TLR4/CD14 can modify early immune system development and influence allergic disease risk
Single nucleotide polymorphisms
What does TSLP stand for?
Thymic Stromal Lymphopoietin
What is the role of TSLP in allergic inflammation?
It’s an epithelial-derived cytokine that helps initiate allergic inflammation by activating dendritic cells and other immune cells.
Which disease is associated with TSLP genetic susceptibility loci?
Asthma
Where is TSLP released from in the airways?
From the airway epithelium
What is FLG and its function in the skin?
Filaggrin is a protein essential for skin barrier function; it helps regulate water loss and blocks microbes/allergens.
Where is the FLG gene located?
On chromosome 1q21 in the epidermal differentiation complex
What diseases are associated with FLG mutations?
Ichthyosis vulgaris, atopic dermatitis, and asthma
What happens in homozygous or compound heterozygous FLG mutations (e.g., R501X, 2282del4)?
Causes severe ichthyosis vulgaris
What happens in heterozygous FLG mutations?
Leads to milder ichthyosis vulgaris
What is the carrier frequency of FLG null mutations in Caucasian populations?
Approximately 9%
What is ST2 (IL1RL1) and its role in asthma?
It’s a receptor elevated in human asthma, induced by proinflammatory stimuli, possibly involved in T helper cell function and disease exacerbation.
What does IL-13 do in the airway?
It drives IgE production by B cells, goblet cell differentiation, and mucus production by the airway epithelium.
Which cytokine is strongly associated with asthma and Th2 responses?
IL-13
What role does IL4RA play in immunity?
It binds IL-4 to initiate Th2 lymphocyte polarization and is associated with atopy and disease severity.
What is the significance of IL4RA gene polymorphisms?
They affect risk and severity of atopic diseases by influencing Th2-type immune response.
What do CD14 and TLR4 encode?
Proteins involved in the LPS response pathway, key in innate immunity.
What is the interaction between CD14/TLR4 and the environment?
Gene-environment interaction: polymorphisms in CD14/TLR4 alter host responses to bacterial endotoxins like LPS.
How do CD14 and TLR4 contribute to innate immune responses?
They recognize and clear LPS by activating innate immune cascades.
