Hypersensitivity Flashcards
What is hypersensitivity?
Immunological responses with excessive or undesirable consequences >>> that may result in tissue or organ damage
Types of Hypersensitivity
5 types:
- Type-I
- Type-II
- Type-III
- Type-IV
- Type-V
Who did classify hypersensitivity into 4types in 1963?
Gell and Coombs
Names of different types of hypersensitivity
- Type-I: Immediate hypersensitivity, IgE-mediated, Allergy
- Type-II: Cytotoxic hypersensitivity, Cell-bound, Antibody-mediated/dependant
- Type-III: Immune complex mediated hypersensitivity
- Type-IV: Delayed hypersensitivity, Cell mediated, Antibody-independant
- Type-V: Stimulating/Inhibiting hypersensitivity, Stimulatory hypersensitivity
Type-I hypersensitivity: Main pathophysiology
Importants are >>>
- IgE mediated (High IgE level)
- Mast cell degranulation
- Histamine release
Antigen binds to IgE bound to mast cells > degranulation > histamin release
Type-I hypersensitivity: Mechanism
Allergen >>> Antigen presenting cell (APC) presents the allergen on its surface >>> Th2 recognises it >>> releases IL-4, IL-5 >>> they activate B-cells >>> B-cells become plasma cells (class-switching) >>> releases IgE antibody >>> IgE (through its Fc portion) binds to mast cell and basophil >>>
When re-exposue, Antigen binds to Fab portion of IgE >>> Then, Mast cells >>
- Release IL-3, IL-5 >>> Eosinophil recruitment and activation
- Mast cell degranulation >>> release of histamin, histamin-like substance & others
>>> smooth muscle contraction, vasodilation & increased permeability
>>> Bronchospasm, Urticaria, Anaphylactic reaction
Type-I & type IV hypersensitivity: Time period
Immediate (within 24hours)
Delayed (after 24hours)
Type-I hypersensitivity: Types
Immediate hypersensitivity has 2 divisions:
- Early
- Late (But late occurs within 24hours)
Type-I hypersensitivity: Examples
- Anaphylaxis
- Hay fever
- Asthma
- Atopy
- Latex allergy (when acute)
- Eczema
Type-II hypersensitivity: Main pathophysiology
Direct antibody-driven cytotoxicity
(IgG or IgM binds to antigen on the cell surface >> cell destruction)
Type-II hypersensitivity: Mechanism
Target cells have surface antigens >>> Antibodies bind to that surface antigens (with Fab portion) >>> 3 consequences:
- Binds to NK cells or macrophages (by Fc portion)>>> Killing/Degreadation (ADCC = Antibody dependant celullar cytotoxicty)
- Receptor specific auto-antibody >>> interferes with signal transduction
-
Complement activation
- Through MAC (Membrane attack complex) = C5b-9 >>> osmotic lysis of target cells
- Through C3b >>> Opsonisation >>> phagocytosis
Type-II hypersensitivity: Examples
- AIHA (Autoimmune haemolytic anaemia)
- Acute haemolytic transfusion reactions
- ITP (Idiopathic Thrombocytopaenic Purpura)
- Pernicious anaemia
- Goodpasture’s syndrome (Anti-GBM Ab = IgG)
- Rheumatic fever
- Bullous pemphigoid
- Pemphigus vulgaris
Type-III hypersensitivity: Main pathophysiology
Immune complex deposition
Free antigen and antibody (IgG, IgA) combine
Type-III hypersensitivity: Mechanism
Phase-I: immune complex formation:
Free antigen in the circulation >>> Antigen binds on the surface of B cells >>> B cells becomes plasma cells (Class-switching) >>> releases specific antibody IgG >>> IgG bind to antigens (through Fab portion) >>> Formation of ‘immune complex’
Phase-II: Immune complex deposition:
- Deposition in kidneys, joints, small vessels >>> tissue damage
Phase-III: Immune complex mediated inflammation:
- Complement C1 binds to Fc portion of IgG >>> Activation of complement cascade (classical pathway) >>> C3b binds to tissue cells & C5a attracts neutrophils (chemotaxis) >>> tissue damage
- Neutrophil adherence: Neutrophil binds to Fc portion of IgG & C3b on tissue >>> Neutrophil degranulation: secretes lysosomal enzymes >>> fibrinoid necrosis and tissue damage
- So, often hypocomplementaemia is present
Type-III Hypersensitivity: Examples
- EAA (Extrinsic Allergic Alveolitis)- Acute phase
- SLE (Systemic Lupus Erythematosus)
- Serum sickness
- PSGN (post-streptococcal glomerulonephritis)
Type-IV hypersensitivity: Main pathophysiology
Cell mediated (T cell driven/mediated)
Type IV hypersensitivity: Main goal
Early elimination of responsible agent
Type-IV hypersensitivity: Mechanism
Sensitization phase: (1-2 weeks after primary contact)
Pathogen/foreign body >>> APCs (Macrophages, Langerhans cells) recognise & presents antigen to T-helper cells >>> releases IL-12, IL-6 >>> activates CD4+ T-helper cells >>> Further activation of type-I T-helper cells (Th-1): generally (Occasionally CD8+ cytotoxic T cells)
Effector phase:
Sensitised (Effective) Th-1 cell produces IFN-gamma (also TNF-beta, IL-1, IL-2, IL-8, MCAF, GM-CSF, MIF) >>> resting macrophage >>> Activated macrophage >>> Effect of macrophage activation: high MHC/HLA class II, TNF receptor, oxygen radicals, Nitric oxide, lysosomal enzymes >>> tissue damage
Type-IV hypersensitivity: Examples
- Tuberculosis
- BCG-immunisation
- Tuberculin skin test reaction
- Allergic contact dermatitis
- Scabies
- EAA (Extrinsic Allergic Alveolitis)- Chronic phase
- Graft-vs-host disease (GVHD)
- Latex allergy- when delayed
- Multiple sclerosis
- GBS
(BCG = Bacille Calmette-Guerin)
Type-V hypersensitivity: Main pathophysiology
Stimulating/Inhibiting
(Antibodies stimulate cells they are directed against)
Type-V hypersensitivity: Mechanism
Antibody >>> binds to cell surface receptors (instead of cell surface) >>> either:
- mimics the effects of ligands >>> stimulates hormone receptors OR
- Prevents intended ligand binding >>> inhibits receptors
Type-V hypersesnsitivity vs Type-II hypersensitivity
Some suggests type-V to be under type-II hypersensitivity
- As both are antibody driven
But most suggests it to be an independant type (type-V), because >>>
- Type-II causes tissue damage/destruction
- Type-V do NOT cause damage/destruction (only stimulates/inhibits)
Type V hypersensitivity: Examples
Grave’s disease
Myasthenia gravis
Antibody types in Type I, II, III, V hypersensitivity
- Type I hypersensitivity >> IgE
- Type II hypersensitivity >> IgG or IgM
- Type iii hypersensitivity >>> IgG or IgA
- Type V hypersensitivity >>> IgG
- Type IV is NOT antibody mediated. It is T cell mediated
Which type of hypersensitivity are related to cell and which are NOT?
Antibodies bind to cell:
- Type I (IgE binds to mast cells)
- Type II (IgG or IgM bind to antigen on cell surface)
- Type V (IgG bonds to receptor on cell surface)
NO cell involvement;
- Type III (NO cell, free Ag-Ab immune complex)
- Type IV (NO cell, NO antibodies)
Type of hypersensitivity that does not depend upon antibody at all
Type-IV (Delayed, Cell mediated, Antibody independant) hypersensitivity
Type of hypersensitivity with NO tissue damage or NO cytotoxicity
Type V (Stimulating/inhibiting) hypersensitivity
What are cell-mediated and cell-bound hypersensitivities?
- Cell mediated hypersensitivity is type IV (delayed, cell mediated, antibody-independant hypersensitivity)
- Cell bound is type II (cytotoxic, antibody-mediated/dependant) hypersensitivity
Type of hypersensitivity in Grave’s disease/Grave’s thyroid disease and Grave’s eye disease
- Grave’s disease = Grave’s thyroid disease >>> Type-V hypersensitivity
- Grave’s eye disease (ophthalmopathy) >>> Type-II hypersensitivity
Why do Grave’s disease and Grave’s eye disease have different types of hypersensitivity?
We know,
Type-V hypersensitivity has antibody-mediated stimulation/inhibition (no destruction)
Type-II hypersensitivity has antibody-mediated cytotoxicity/cell destruction
As,
In Grave’s disease/Grave’s thyroid disease >>> Ab binds & stimulates hormone receptors (NO cell destruction/cytotoxicty) >>> So, Type-V
In Grave’s eye disease >>> Ab binds & causes cytotoxicity/cell destruction >>> So, Type-II
Hypersensitivity with immediate onset-?
Hypersensitivity with delayed onset-?
- Hypersensitivity with immediate onset >>> Type-I (IgE mediated, Allergy)
- Hypersensitivity with delayed onset >>> Type-IV (Cell mediated, Antibody-independant)
Type of Hypersensitivity that has hypocomplementaemia (low complement levels in blood)
Type 3 (Immune complex mediated) hypersensitivity
Anaphylaxis >> Type of hypersensitivity
Type-I (Immediate hypersensitivity, IgE mediated)
Autoimmune haemolytic anaemia (AIHA) >> Type of hypersensitivity
Type II (Antibody-driven/mediated, cytotoxic) hypersensitivity
Extrinsic Allergic Alveolitis >> Type of hypersensitivity
- Acute phase >> Type III (immune-complex mediated) hypersensitivity
- Chronic phase >> Type IV (delayed, cell mediated, antibody-independant) hypersensitivity
BCG immunisation >> Type of hypersensitivity
Type- IV (Delayed, Cell mediated, Antibody-independant) hypersensitivity
Grave’s disease >> Type of hypersensitivity
Type V (Stimulatory) hypersensitivity
Myasthenia Gravis >> Type of hypersensitivity
Type V (Stimulatory) hypersensitivity
Graft vs Host disease (GVHD) >>> Type of hypersensitivity
Type IV (Delayed, Cell mediated, Antibody-independant) hypersensitivity
SLE (Systemic Lupus Erythematosus) >> Type of hypersensitivity
Type III (Immune-complex mediated) hypersensitivity
Goodpasture syndrome >> Type of hypersensitivity
Type II (Cytotoxic, Antibody-mediated/dependant) hypersensitivity
Anti-GBM antibody (IgG)
Hay fever >> Type of hypersensitivity
Type I (Immediate, IgE mediated) hypersensitivity
Asthma >> Type of hypersensitivity
Type I (Immediate, IgE mediated) hypersensitivity
Latent TB >>> Type of hypersensitivity
Type IV (Delayed, cell mediated, antibody-independant) hypersensitivity
Atopy >> Type of hypersensitivity
Type I (immediate, IgE mediated) hypersensitivity
Eczema >> Type of hypersensitivity
Type I (Immediate, IgE mediated) hypersensitivity
Latex allergy >> Type of hypersensitivity
- When acute/immediate (within 24hours) >>> Type I (immediate, IgE-mediated) hypersensitivity
- When delayed (After 24hours) >>> Type IV (delayed, cell-mediated, antibody-independant) hypersensitivity
Acute haemolytic transfusion reactions >>> Type of hypersensitivity
Type II (Cytotoxic, antibody-mediated/dependant) hypersensitivity
ITP (Idiopathic Thrombocytopaenic Purpura) >> Type of hypersensitivity
Type II (cytotoxic, antibody-mediated/dependant) hypersensitivity
Pernicious anaemia >> Type of hypersensitivity
Type II (Cytotoxic, cell-bound, antibody-mediated/dependant) hypersensitivity
Rheumatic fever >> Type of hypersensitivity
Type II (Cytotoxic, cell-bound, antibody mediated/dependant) hypersensitivity
Bullous pemphigoid OR Pemphigus vulgaris >> Type of hypersensitivity
Both >> Type II (cytotoxic, cell-bound, antibody-mediated/dependant) hypersenisitivity
PSGN (Post-streptococcal glomerulonephritis) >> Type of hypersensitivity
Type III (imuune complex mediated) hypersensitivity
Serum sickness >>Type of hypersensitivity
Type III (Immune-complex mediated) hypersensitivity
Tuberculosis >> Type of hypersensitivity
Type IV (Delayed, cell mediated, antibody-independant) hypersensitivity
Tuberculin skin test reaction >> Type of hypersensitivity
Type IV (Delayed, cell-mediated, antibody-independant) hypersensitivity
Allergic contact dermatitis >> Type of hypersensitivity
Type IV (delayed, cell-mediated, antibody-independant) hypersensitivity
Scabies >> Type of hypersensitivity
Type IV (Delayed, Cell-mediated, antibody-independant) hypersensitivity
Multiple sclerosis >> Type of hypersensitivity
Type IV (Delayed, cell-mediated, antibody-independant) hypersensitivity
GBS (Guillain-Barre syndrome) >> Type of hypersensitivity
Type IV (Delayed, cell-mediated, antibody-independant) hypersensitivity
