1: Hypersensitivty and allergy Flashcards
(31 cards)
When do hypersensitivity reactions occur?
Occur when immune responses are mounted against
- Harmless foreign antigens
- Autoantigens
- Alloantigens
What are the 4 types of hypersensitivity reactions?
Type 1 = IMMEDIATE hypersensitivity
Type 2 = Antibody-dependent Cytotoxicity
Type 3 = Immune complex mediated
Type 4 = Delayed Cell Mediated
What is type 1 hypersensitivity? Give clinical examples
Anaphylaxis, asthma, rhinitis, food allergy
1st antigen exposure: Develop sensitivity, NOT tolerance
IgE produced, binds to mast cells & basophils
2nd antigen exposure: MORE IgE produced, antigen CROSS-LINKS IgE molecules on mast cells/basophils, leading to DEGRANULATION
What is type 2 hypersensitivity? Give clinical examples
Auto-antibodies
Clinical presentation depends on target tissue
Organ-specific autoimmune diseases - Myasthenia Gravis (Ab to Ach receptors) , Pemphigus vulgaris (Ab to epithelial cell cement protein)
Autoimmune cytopenias - haemolytic anaemia, thrombocytopenia, neutropenia
Tests for antibodies?
Immunoflourescence
ELISA (e.g. anti-CCP for rheumatoid arthritis)
What is type 3 hypersensitivity? Give clinical examples
Antigen-antibody complexes in blood get deposited in blood vessels/tissues and leads to complement/cell activation (+clotting)
Results in TISSUE DAMAGE (Vasculitis)
SLE (lupus)
Other vasculitides
What is type 4 hypersensitivity? Give clinical examples
Antigens presented by antigen presenting cells to Th1 lymphocytes
Th1 produces interferon gamma (IFN gamma)
Activates macrophages that release Tumour necrosis factor (TNF)
Activates fibroblasts causing angiogenesis/fibrosis
Activates Cytotoxic T lymphocytes (CTL) by production of IL-2.
Most tissue damage from CTL + TNF
Th1 mediated: Chronic graft rejection GVHD Coeliac disease Contact hypersensitivity (skin) Many autoimmune diseases
Th2 mediated:
Asthma, rhinitis, eczema
Features of inflammation
Give examples of mediators
Vasodilation
Increased vascular permeability (caused by complement activation/histamine release)
Inflammatory mediators/cytokines (IL-1/2/6, TNF, IFNgamma)
Inflammatory cells + tissue damage
Main cells involved in inflammation?
Neutrophils, macrophages, lymphocytes, mast cells
Prevalence of atopy in UK?
50%
Genetic risk factors of allergy?
80% of atopics have family history
Polygenic (many genes linked to asthma/atopy)
Examples of genes:
- IL-4 gene cluster (linked to raised IgE)
- Genes on chromosome 11q (IgE receptor)
- Genes linked to structural cells (filaggrin linked to eczema, IL-33 linked to asthma)
Environmental risk factors of allergy?
- Age - increases in infancy, peaks in teens, decreases in adulthood
2.Childhood - more common in males
Adulthood - more common in females
- More common in small families
- Early life infections protect from allergy
- Animals - early exposure protects from allergy
- Diet (anti-oxidants/breast-feeding, fatty acids protect)
Prevalence of allergies in UK?
Asthma, eczema, hay fever all RISING
Types of inflammation?
Asthma, rhinitis, eczema = MIXED inflammation (type 1+4 hypersensitivity) so both IgE mediated and chronic inflammation
Anaphylaxis, urticaria, angiodema = Type 1 hypersensitivity (IgE mediated)
Idiopathic/chronic urticaria = Type 2 (IgG mediated)
What does expression of these diseases require?
Primary response (early life) = Development of SENSITISATION to allergens rather than tolerance
Memory/secondary response = FURTHER allergen exposure causing disease
Explain the process of an allergic reaction
Allergen sampled by dendritic cells in epithelial layer
Dendritic cells processes allergen and presents peptides to naive T cell
Naive T cells differentiate into Th2 cells to produce allergic response (Th1 = autoimmune, regulatory T cells = tolerance)
Th2 proliferate and release IL-4/13 that signal B cells to produce IgE
IgE binds to plasma cells
On second exposure:
Processed allergen presented to memory Th2 cells
Leads to more IgE production
Antigens bind to IgE on MAST CELLS, causing degranulation of inflammatory mediators
Th2 also release IL-5 which activates EOSINOPHILS
Structure of eosinophils?
Mostly reside in tissues, some in blood
Bi-lobed nucleus
Have large granules containing toxic proteins (can lead to tissue damage)
Structure of mast cells?
Present in tissue
Single-lobe nucleus, also granulated
IgE receptors on surface
Crosslinking of IgE by allergen causes release of mediators:
- Pre-formed histamines, cytokines, toxic proteins
- Newly synthesized prostaglandins, leukotrienes
What kind of allergic diseases are neutrophils important in? Describe their structure.
Important in SEVERE or VIRUS-INDUCED ASTHMA + ATOPIC ECZEMA
Multi-lobed nucleus
Granules containing digestive enzymes
Synthesise oxidant radicals, cytokines, leukotrienes
Pathogenesis of Acute inflammation in asthma
ACUTE Inflammation of airways due to:
MAST cell activation/degranulation
Release of pre-stored (histamine) and newly synthesized (prostaglandins, leukotrienes) mediators
Vascular leakage -> Airway wall oedema
Mucus secretions
SM contraction
TWO phase response - acute early response + late response (hrs later, lesser narrowing)
Pathogenesis of Chronic inflammation in asthma
Chronic inflammation due to: Dense cellular infiltrate (Th2, eosinophils) Smooth muscle hypertrophy Mucus plugging Epithelial shedding Sub-epithelial fibrosis
List important clinical features of asthma
- Reversible generalised airway obstruction
- Chronic episodic wheeze
- Bronchial hyperresponsiveness (irritability)
- Cough
- Mucus production
- Breathlessness, chest tightness
- Reduced/variable Peak flow (PEF)
Give Clinical features of allergic rhinitis?
Seasonal (hay fever) or Perennial (pets)
Sneezing
Rhinorrhoea
Itchy nose/eyes
Nasal blockage, sinusitis, loss of smell/taste
Clinical features of allergic eczema?
Chronic itchy skin rash
Usually at flexures of arms/legs
Caused by House dust mite sensitisation, dry cracked skin
Can be complicated by bacterial/viral infections
50% clears by 7 years
90% clears by adulthood
