5: Hypersensitivity Flashcards
Types of hypersensitivity
Type :
I - IgE mediated, anaphylactic/immediate
II - antibody mediated
III - immune complex mediated
IV - delayed or T-cell mediated
In hypersensitivity reactions, the immune system
reacts in a way that damages the body rather than protecting it
Exaggerated immune reactions can lead to
Sepsis
Hypercytokinaemia (cytokine storm)
Organ dysfunction
Fatal tissue damage
Type I hypersensitivity
Mediated by IgE antibodies against environmental allergies
Immediate hypersensitivity - within mins
Targeted to multivalent environmental agents - allergens
Tested for by skin prick test - wheal and flare reaction to specific known allergens
Test for Type I hypersensitivity
Skin prick test, looking for wheal and flare reaction to specific allergens
two phases :
1. sensitisation phase
2. re-exposure leading to anaphylaxis
Sensitisation phase
Complex - mechanism not exactly understood, influenced by genetics, environment and age
Th2-cells and follicular Th cells produce IL-4 and IL-3
B cell class switching from IgM to IgE production
Th2 cells recruit eosinophils
IgE by B cells not found in circulation, loaded onto Fc receptors of mast cells and basophils
Allergen encountered again, cross-linking of two IgE bound on membrane of mast cell and basophils, leading to rapid immune reaction - sensitisation
Crosslinking causes
rapid degranulation, release of inflammatory mediators
- occurs at lower antigen concentrations than normal immune reactions
Phases of T1 hypersensitivity
3 phases :
Early phase- degranulation of mast cells, within minutes
Later response - within a few hours, recruitment of neutrophils
Late response - 3/4 days, eosinophils recruited, Th2 cells present
Anaphylaxis is a
medical emergency
Anaphylaxis can be treated by
- adrenaline injection ; counteracting vasodilation, EpiPen
- antihistamines
- feet up to maintain brain perfusion
- Monitor for biphasic anaphylaxis
Biphasic anaphylaxis
Unknown anaphylactic shock following first anaphylactic shock
Type II hypersensitivity
IgG or IgM mediated cytotoxicity reactions
Self-antibodies produced by self-reactive B cells (escaped tolerance)
Secrete self-reactive IgM or IgG when activated by self-reactive T cells
By which mechanisms can hypersensitivity II result in disease
Anti-receptor activity; blocking or activating its function
Antibody dependent cell-mediated cytotoxicity (ADCC)
Classical activation of complement cascade
Cytotoxic mechanisms of Type II hypersensitivity
Complement neutrophil activation
Membrane Attack Complex
Antibody opsonisation and phagocytosis
Natural Killer cells against antibodies
Receptor binding in Type II hypersensitivity
Blocking receptors e.g Myasthenia gravis
Activating receptors e.g. Graves’ disease
Type III hypersensitivity
Small soluble antigens make immune complexes less immunogenic, not removed by spleen
Self reactive B cells switched from IgM to IgG Production
immune complexes become deposited in blood vessel walls
In type 3 hypersensitivity, immune complex deposition in blood vessel walls can lead to:
Activation of complement system
Activation of neutrophil degranulation
leads to tissue damage at site of deposition
Example of Type 3 hypersensitivity
Systemic Lupus Erythematosus
Systemic Lupus Erythematosus
Auto-antibodies against DNA and nuclear proteins
Complement activated by immune complexes, leading to :
damage by MAC formation
oedema by anaphylatoxins
neutrophil recruitment
In Lupus (T3 hypersensitivity) immune complexes are deposited in
kidneys (blood filtration)
joints (synovial fluid, filtered from blood vessel walls)
Compare Complement in Type 2 and Type 3 hypersensitivity
T2: Complement used in small amounts- because damage is localised
T3: Complement used in large amounts (C3 & C4 can be used as diagnostic markers)
Compare Antigens in Type 2 and Type 3 hypersensitivity
T2: antigens cell-surface bound
self-antigens / foreign antigens e.g drugs
T3: antigens soluble
mostly self-antigens (except serum sickness)
Compare damage in Type 2 and Type 3 hypersensitivity
T2: damage where immune complexes are formed (tissue specific)
T3: Damage where immune complexes are deposited (not tissue specific)
Type IV hypersensitivity
T-cell mediated
Delayed-type hypersensitivity; T cell recruitment takes time
NOT antibody mediated
damage occurs through both CD4+ Th cell or CD8+ cytotoxic T cell
Reactions of type 4 hypersensitivity
Sensitisation phase
Re-exposure and immune response
Use of T4 hypersensitivity in testing
Can be used in Mantoux skin test for TB
(poison ivy)
Haptens
small proteins functioning as antigens when bound to proteins
Sensitisation phase of T4 hypersensitivity
Exposure leads to dendritic cell uptake
DC present to specific naive T cells in lymph node
T cells differentiate into mature Th1-cells –> form memory cells
Re-exposure in T4 hypersensitivity
Specific memory T cells respond, induce inflammation in tissue
leads to Th1-cell expansion
leads to Macrophage activation - incr. vascular permeability, causing swelling (oedema) and redness
Involvement of T cells in T4 hypersensitivity
Dependant on signals T cells receive from phagocytes
- differentiation to Th17 cells; IL-17 secretion that recruits neutrophils
-CD8+ self-specific cytotoxic T cells directly kill cells within antigens
