Allergy and asthma Flashcards
Innate immunity timeline
6-12 hours
Adaptive immunity timeline
12 hours to week
Helper T cell activation and action
Antigen recognition - MHCII and CD4+
Clonal selection to effector cells and memory T cells
How do Treg cells form?
CD4+
IL-2 and TGF-beta
What do Treg cells do?
Release TGR-beta, IL-10, IL-35, STAT6 and FOXP3
Suppresses tumour immunity
Promotes immune tolerance
Maintains lymphocyte homeostasis
How do TH1 cells form?
CD4+
IL-12
What do TH1 cells do?
IFN-gamma LT-alpha STAT4 T-bet Promotes tumour immunity Intracellular pathogens Drives autoimmunity
How do TH2 cells form?
CD4 cells
IL-4
What do TH2 cells do?
IL-4, IL-5, IL-13, STAT6, GATA3
Extracellular pathogens
Allergy
Asthma
How do Th17 cells form?
CD4 cells
TGF-beta
IL-6
IL-21
What do TH17 cells do
IL-17A IL-17F IL-22 IL-21 CCL20 STAT3 Controversial tumour immunity Breaks immune tolerance Extracellular bacteria Autoimmunity
How do Treg cells maintain balance between TH1 and TH2
Release IL-10 and TGF-beta
TH1 and TH2 suppress eachother
What happens in allergic reaction
- TH2 dominant to TH1
- Humoral response is IgE secretion
- IgE = death of helminth cells
- Eosinophils destroy helminths and get rid of worms
How are eosinophils activated?
TH2 + IL-5 -> IgE
What happens when you encounter an antigen for the first time?
DC present on MHC ii to naive T cell
Differentiation and clonal expansion occurs
Produce IL-4, IL-13 which acts on B cells to produce IgM
IL-4 and IL-13 cause class switching to produce IgE and memory B cells by clonal expansion
B cells can activate T cells to enter system
Where are IgE Fc receptors found?
Mast cells in tissue (most)
Basophils in blood
B-lymphocytes but less so
What happens when you are re-exposed to an antigen?
IgE on mast cells and basophils
Cross links with at least 2 Fc-e0R1 receptors to prevent misfiring
When this happens, mast cells/basophils degranulate
What does histamine do?
Vasodilation, vascular leakage, bronchoconstriction
Second phase of allergic reaction
- Calling in basophils and eosinophils by increased inflammatory cell migration and activation
- Takes basophils up to 6 hours to appear at site of exposure - biphasic reaction at 6 hours
- Keep children who have allergic reaction in hospital for 6 hours
- Can lead to chronic inflammation because of leaky vessels from TNF-alpha
Eosinophils
- Elevated in lungs and blood in asthma
- Allergy and parasitic infections
- Activated by cytokines
- Release toxins, leukotrienes and cytokines
- Activation causes bronchial hyperactivity
Chronic allergic reaction
Persistant inflammation
Prolonged/repetitive exposure to antigens
Large numbers of innate and adaptive immune cells
Fibroblasts - implicated in normal healing process and scar formation, thickening of basement membrane
Cause IgE response
- Hives - drug, hormones, genetics, illness, food, stress
- Drugs - antibiotics, NSAIDs, biological treatments, contrast agents, blood
- Infection, chronic parasites, cutaneous fungal infections
- Viruses - acute viral syndrome, hepatitis, Ebstein Barr virus, HSV
- Bacteria - streptococcal, Coxsackie, H. pylori
- Foods - nuts, milk, eggs, wheat, soy, fish, shellfish, sesame
Clinical presentation of asthma
- SOB (exercise, interval)
- Expiratory wheeze
- Nocturnal cough
- Episodic
- Reversible
- Diagnosis based on likelihood and assessment
- Rationale for diagnosis needs documentation
Asthma triggers
- Hyperventilation in teenagers
- Viral induced wheeze
- Primary ciliary dyskinesia
- Bronchiectasis
- CF
- Vocal cord dysfunction
- Persistent bacterial bronchitis
