Hypersensitivity Flashcards
Hypersensitivity
Inappropriate stimulation of the adaptive immune system, resulting in tissue damage from inflammatory reactions, and even death.
Types I-V mechanisms:
types I, II, III, V – antibody mediated
type IV – T-cell mediated
Immediate hypersensitivity
- initiated in a sensitised recipient (from previous contact with Ag) within minutes of further exposure to Ag
- Ab-mediated eg Type
Delayed hypersensitivity
appears only after some days (48-72hr)
T-cell mediated – Type IV
Types of hypersensitivity
- immediate hypersensitivity IgE
- antibody mediated IgM, IgG
- immune complex mediated
- T cell mediated
Genetic susceptibility to immediate hypersensitivity
Polymorphs in genes (chr.5q31) IL-4, IL-5, IL-13
Hygiene hypothesis
Related to decrease in infections in early life
pre-natal/childhood infections train immune system => less likely to respond to environmental allergens
(Fewer allergies in children brought up on farms than city children)
Allergic response- sensitisation phase
Allergic response- effector phase
Mast cell degranulation
Mast cells release inflammatory mediators
Trigger mechanisms
- allergen cross-linking
- IgE on surface
- FceRI receptors
Mast cell activation causes…
Late reaction (immediate hypersensitivity)
Eosinophils
Immediate hypersensitivity stages
Mast cells and non-atopic allergy
triggered by temperature extremes & exercise
IgE and Th2 not involved
mast cells hypersensitive to activation
~20%-30% of immediate hypersensitivity
Direct triggers of mast cell degranulation
Opiates, contrast media, vancomycin
C5a, C3a anaphylatoxins
Anaphylaxis
Systemic exposure to allergen (even small doses)
- injections (drugs eg, penicillin)
- insect bites (eg bee venom)
- absorption across epithelia
- - mucosa gut (peanut, shellfish; skin
Clinical manifestations
- drop in blood pressure (vascular shock)
- difficulty in breathing (airway constriction)
- widespread oedema
- Vomiting, abdominal cramps, diarrhoea
Allergy treatment
Antihistamines
Mast cell stabilisers (stop histamine release)
Decongestants (shrink swollen membrane sin nose)
Corticosteroids
Epipen (adrenaline)
Anti IL-4 Omalizumab
type 2: cytotoxic
Antibody formed against antigen on cell surfaces → cell lysis by:
1) activation of the classical complement pathway IgG, IgM Abs
2) ADCC – antibody-dependent cell-mediated cytotoxicity by NK cells binding IgG Ab via their Fc receptors
3) phagocytosis of RBCs, platelets – mediated by
Fc receptors on macrophages and C3b
(from complement activation)
Type 2: Haemolytic disease of newborn
Ab response to RhD on foetal rbc, when mother RhD-ve
Sensitisation -> no sensitisation (anti-D) -> haemolytic disease (rhesus prophylaxis introduced)
What type of hypersensitivity is Grave’s?
Type 2/V
hyperthyroidism
Type 3 immune complex mediated hypersensitivity
Ag/Ab (IgG, IgM) complexes form in excess and deposit on (or near) blood vessel walls in tissues causing local inflammation and tissue damage (immune complex disease)
Streptococcus Staphylococcus Malaria Leprosy Viruses
Inhaled antigens – Pigeon fancier’s lung (pigeon antigens
Farmer’s lung (fungi in mouldy hay)
Hep B
autoimmune- RA, SLE
Goodpasture’s syndrome vs systemic lupus
Goodpastures- type 2
Lupus- 3
Mechanism of inflammation
complement activation →
C5a, C3a
→ release of mediators from
mast cells,macrophages
→ attract neutrophils etc
(C5a)
neutrophils → FcRs, C3bR
→ enzymes, ROI, NO
basophil, platelet binding by FcgR
→ further release of vasoactive amines
platelets → microthrombi
Type 4 cell mediated , delayed
T cell mediated eg TB, Listeria, herpes, measles
Mechanism of type IV hypersensitivity
What type of cells mediate type IV?
CD4+ Th1 cells
Granuloma formation
- Mycobacterial, TH1-type granulomas
Mycobacterium tuberculosis, M leprae infections
eg TB – bacteria persist in alveolar macrophages
Ag presented on MHCII to CD4+ TH1 cells macrophages activated (IFNg)
influx of monocytes to infection site
differentiate to macrophages, activated, retained
form granuloma (healed tubercule) to ‘seal off’ infected macrophage
The process is cytokine driven:
Th1 cell -> RANTES (chemokine for monocytes)
-> MIF (retention of macrophages)
macrophage -> MCP-1 (chemokine for monocytes)
-> TNF-alpha, IL1 (= ↑ adhesions for extravasation)
Granuloma structure
persistent Ag in centre macrophages – necrosis
macrophages (from blood monocytes) form concentric rings of ‘epithelioid’ cells
other cell types – eosinophils, T-cells
giant cells – multinucleate
fibrous connective tissue (fibrosis)
calcification
CD8+ T cells:
possible source of cytokines
lyse bacterial-infected macrophages
produce granulysin – bactericidal
gamma-d-T cells: cytokine producing; cytotoxic
Tuberculin reaction
skin test for memory TH1 cells against mycobacterial Ag
purified protein derivative (PPD) from culture filtrate
→ skin
presented on dendritic cells
→ firm red swelling at 48-72hr; T cells, macrophages
Type V - stimulatory
modification of type 2
Persistent activation of target cell membrane receptor by autoAb, normally responding to hormone
-> TSH (thyroid stimulating hormone) receptor by auto Ab in thyrotoxicosis (Graves’ Disease) → continuous thyroxine release
