HI19 Type I Hypersensitivities

What is the defining characteristic of a Type I Hypersensitivity reaction?

immediate reaction mediated by IgE antibodies to non-self antigens

what is the evolutionary purpose theorized for IgE-mediated reactions?

to defend against parasites, particularly helminth worms

where are mast cells predominantly located within the body?

at the boundaries between tissues and the external environment, such as in mucosal membranes and the dermis

allergens

environmental antigen that causes an unnecessary overreaction of the immune system, also known as a hypersensitivity reaction

Atopy

a genetic and environmental predisposition to develop allergies

what are the four main types of hypersensitivity reactions, classified by their primary mediator?

1. IgE-mediated

2. IgG/Complement-mediated (Cytotoxic)

3. Immune complex/complement-mediated

4. Cell-mediated

mast cells, which contain cytoplasmic granules with biologically active chemicals, are located at the body’s portals of entry and are considered ____ cells

sentinel

what type of receptor, found on mast cells and basophils, binds IgE with high affinity?

high affinity IgE Fc receptor

what event triggers histamine release from mast cells?

cross-linking of IgE Fc receptors by an allergen?

How do basophils differ from mast cells in terms of their location in the body?

Basophils circulate in the blood, whereas mast cells are located in tissues

Up to what percentage of the global population is sensitized to at lease one environmental allergen?

Up to 40%

Type I Hypersensitivity reaction has a biphasic response. What are the two phases?

Phase 1 is the immediate response, and Phase 2 is the late phase response

how quickly can the immediate response phase of a Type I Hypersensitivity reaction occur?

It can be as fast as a few seconds, typically occurring within 15-30 minutes

when does the late phase response of a Type I Hypersensitivity reaction typically occur?

hours after the immediate response subsides

why cant helminth worms and multicellular parasites be phagocytosed by immune cells?

they are too large to be engulfed by phagocytes

what is the primary mechanism the body uses to eject large parasites like helminths, driven by Type I reactions?

physical means such as coughing, sneezing, vomiting, diarrhea, and scratching

the crosslinking of IgE on mast cells, basophils, and eosinophils triggers ___, which produces an explosive inflammatory reaction

degranulation

what is the core tenet of the hygiene hypothesis regarding allergies?

reduced exposure to pathogens and the environment in the developed world has led to misguided immune responses against harmless antigens

the hygiene hypothesis notes an inverse correlation between parasitic infection and allergies. what does this mean?

areas with high incidence of parasites have a low incidence of allergies and vice versa

how does the antigen reactivity of a single mast cell compare to that of a single B cell?

single mast cell can react to a wide range of antigens, whereas a single B cell is specific to only one antigen

why cant helminth worms be eliminated by phagocytosis or CD8+ T cells?

they are too large to be phagocytosed and are extracellular pathogens, so they cannot be targeted by CD8+ T cells

According to the hygiene hypothesis, what is the relationship between the incidence of parasitic infections and allergies?

inverse correlation; regions with higher incidence of parasites has a lower incidence of allergies, and vice versa

what is the main idea of the biodiversity hypothesis?

contact with natural environments enriches the human microbiome, which promotes immune balance and protects from allergies and inflammatory disorders

According to the biodiversity hypothesis, how is the loss of contact with the natural environment linked to allergies?

it leads to a less diverse human microbiome, which is associated with an increased prevalence of allergies and inflammatory diseases

what type of molecule are most allergens, and why is this important for generating an IgE response?

most allergens are proteins, which is necessary to get T cell help for B cells to class-switch and produce IgE

besides being proteins, what are three common characteristics of allergens?

typically small, soluble, and stable (resistant to degradation)

some allergens possess ___ activity, which can disrupt epithelial cell junctions and allow them to access underlying immune cells

protease

describe the key events that occur during the initial sensitization phase of a Type I hypersensitivity reaction

upon first exposure to an allergen, B cells are activated with T-helper cell assistance, leading to class-switching and the production of allergen-specific IgE antibodies

does an allergic reaction occur on the first exposure to an allergen?

No, an allergic reaction occurs only on subsequent encounters with the allergen after the initial sensitization phase

why is cellular proliferation not required for an immediate allergic response to occur upon re-exposure to an allergen?

because mast cells and other granulocytes are already present in the tissues and have been ‘armed’ with IgE during the sensitization phase

explain why a single mast cell is capable of responding to multiple, distinct allergens

coated with IgE antibodies that have many different antigen specificities, allowing it to be cross-linked by various allergens

what is the typical timeframe for the onset of the immediate phase of an allergic reaction?

it can be as fast as a few seconds, but usually occurs within 15-30 minutes of allergen exposure

when does the late phase of an allergic reaction typically occur?

it occurs hours after the immediate response subsides

what are the major pre-made inflammatory mediators released during the immediate response phase from mast cell degranulation?

histamine and TNF-alpha

what are the major inflammatory mediators that are synthesized and released during the late phase response?

Leukotrienes, cytokines, chemokines, and prostaglandins

what are the major effects of histamine that contribute to allergy symptoms?

bronchiole constriction, increased GI motility, vasodilation, increased capillary permeability, and increased mucosal secretion

what is the primary role of leukotrienes in the late phase response, especially concerning asthma?

they cause prolonged bronchospasm, increased vascular permeability, and stimulate mucus secretion

which late-phase mediators are responsible for vasodilation, vascular permeability, bronchoconstriction, and increased pain sensitivity?

prostaglandins