Hypersensitivity and chronic inflammation

Question 1

Hypersensitivity

Answer 1

occurs when the immune system responds to foreign antigens but in too vigorous a manner

Question 2

Name the types of hypersensitivity reactions.

Answer 2

I
II
III
IV

Question 3

Allergy

Answer 3

a reaction to environment antigens and is usually a type I response but sometimes type III or IV

Question 4

HR type I

Answer 4

~ allergy and atopy

~ mediated by IgE

Question 5

HR type II

Answer 5

~ antibody-mediated hypersensitivity
~ IgG + IgM antibodies binding to antigen on RBC and inducing cell destruction –> recruits complement or antibody-dependent cell cytotoxicity (ADCC) by NK cells and granulocytes

Question 6

HR type III

Answer 6

~ immune complex-mediated hypersensitivity
~ immune complexes of antibody + antigen when they cannot be cleared by phagocytes due to antigen structure or phagocytic malfunction
~ uncleared complexes cause mast cell degranulation + inflammation

Question 7

HR type IV

Answer 7

~ delayed type hypersensitivity (DTH) + is cell mediated
SENSITISATION PHASE: contact with allergen promotes T(H)1 type response
EFFECTOR PHASE: re-exposure stimulates T(H)1 cytokine release + inflammation due to activation/recruitment of macrophages
~ symptoms occur 2-4 days later = delay

Question 8

IgE

Answer 8

~ tightly regulated (lowest abundance)
~ shortest half-life of all Ig isotopes (2 days comp. 20 for IgG)
~ low steady-state level of serum IgE + transient nature = help to minimise IgE cross-reactivity that trigger unwanted allergic reactions
~ HR type I

Question 9

What receptors does IgE bind to?

Answer 9

FCERI

FCERII

Question 10

Primary mediators

Answer 10

substances released from intracellular granules by degranulation with direct effects

Question 11

Secondary mediators

Answer 11

synthesised or released from membranes following stimulation

Question 12

Atopic

Answer 12

individuals predisposed to allergic responses

Question 13

FCERI

Answer 13

~ high affinity
~ mast cells + basophils –> responsible for type 1 responses
~ eosinophils –> contibute to allergy, stimulated by chemokine and cytokines released by mast cells
~ dendritic cells + macrophages –>internalises IgE-antigen complexes for antigen presentation + stimulation of T(H)2 responses

Question 14

FCERII

Answer 14

~ low affinity
~ B-cells, macrophages + epithelial cells –> antigen presentations,
~ not involved in allergy

Question 15

Name the primary mediators of type 1 hypersensitivity.

Answer 15

~ Histamine - act rapidly by binding to hist. receptors = contraction of intestinal and bronchial smooth muscle
~ Eosinophil chemotactic factor (ECF-A)
~ Neutrophil chemotactic factor (NCF-A)
~ all released from granules

Question 16

Name the secondary mediators of type 1 hypersensitivity.

Answer 16

~ Platelet-activating factor (PAF) + leukotrienes + bradykinins - increase vascular permeability and smooth muscle contraction
~ range of cytokines + chemokine = increases inflammation and IgE production by B-cells

Question 17

Why are allergies increasing?

Answer 17

~ hygiene hypothesis

~ diet hypothesis

Question 18

Hygiene hypothesis (allergies)

Answer 18

~ decreased exposure to certain pathogens + allergens during early life = immune systems becomes unbalanced and biased in a T(H)2 direction
~ Type 1 hypersensitivities occur e.g. asthma –> driven by T(H)2 type responses

Question 19

Diet hypothesis

Answer 19

~ maternal diet can influence immune response of breastfed child
~ breast milk contains food allergens and aeroallergens
~ imbalances in diet that can lead to obesity/micronutrient deficiency = suggested as factors influencing susceptibility to allergic diseases and asthma