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Hypersensitivity Flashcards

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1
Q

What is hypersensitivity?

A

Immunological responses with excessive or undesirable consequences >>> that may result in tissue or organ damage

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2
Q

Types of Hypersensitivity

A

5 types:

  • Type-I
  • Type-II
  • Type-III
  • Type-IV
  • Type-V
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3
Q

Who did classify hypersensitivity into 4types in 1963?

A

Gell and Coombs

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4
Q

Names of different types of hypersensitivity

A
  • 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
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5
Q

Type-I hypersensitivity: Main pathophysiology

A

Importants are >>>

  • IgE mediated (High IgE level)
  • Mast cell degranulation
  • Histamine release

​Antigen binds to IgE bound to mast cells > degranulation > histamin release

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6
Q

Type-I hypersensitivity: Mechanism

A

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

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7
Q

Type-I & type IV hypersensitivity: Time period

A

Immediate (within 24hours)

Delayed (after 24hours)

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8
Q

Type-I hypersensitivity: Types

A

Immediate hypersensitivity has 2 divisions:

  • Early
  • Late (But late occurs within 24hours)
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9
Q

Type-I hypersensitivity: Examples

A
  • Anaphylaxis
  • Hay fever
  • Asthma
  • Atopy
  • Latex allergy (when acute)
  • Eczema
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10
Q

Type-II hypersensitivity: Main pathophysiology

A

Direct antibody-driven cytotoxicity

(IgG or IgM binds to antigen on the cell surface >> cell destruction)

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11
Q

Type-II hypersensitivity: Mechanism

A

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
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12
Q

Type-II hypersensitivity: Examples

A
  • 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
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13
Q

Type-III hypersensitivity: Main pathophysiology

A

Immune complex deposition

Free antigen and antibody (IgG, IgA) combine

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14
Q

Type-III hypersensitivity: Mechanism

A

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
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15
Q

Type-III Hypersensitivity: Examples

A
  • EAA (Extrinsic Allergic Alveolitis)- Acute phase
  • SLE (Systemic Lupus Erythematosus)
  • Serum sickness
  • PSGN (post-streptococcal glomerulonephritis)
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16
Q

Type-IV hypersensitivity: Main pathophysiology

A

Cell mediated (T cell driven/mediated)

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17
Q

Type IV hypersensitivity: Main goal

A

Early elimination of responsible agent

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18
Q

Type-IV hypersensitivity: Mechanism

A

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

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19
Q

Type-IV hypersensitivity: Examples

A
  • 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)

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20
Q

Type-V hypersensitivity: Main pathophysiology

A

Stimulating/Inhibiting

(Antibodies stimulate cells they are directed against)

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21
Q

Type-V hypersensitivity: Mechanism

A

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
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22
Q

Type-V hypersesnsitivity vs Type-II hypersensitivity

A

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)
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23
Q

Type V hypersensitivity: Examples

A

Grave’s disease

Myasthenia gravis

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24
Q

Antibody types in Type I, II, III, V hypersensitivity

A
  • 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
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25
**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)
26
**Type of hypersensitivity that does not depend upon antibody at all**
**Type-IV (Delayed, Cell mediated, Antibody independant) hypersensitivity**
27
**Type of hypersensitivity with NO tissue damage or NO cytotoxicity**
**Type V (Stimulating/inhibiting) hypersensitivity**
28
**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**
29
**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**
30
**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**
31
**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)**
32
**Type of Hypersensitivity that has hypocomplementaemia (low complement levels in blood)**
**Type 3 (Immune complex mediated) hypersensitivity**
33
**Anaphylaxis \>\> Type of hypersensitivity**
**Type-I (Immediate hypersensitivity, IgE mediated)**
34
**Autoimmune haemolytic anaemia (AIHA) \>\> Type of hypersensitivity**
**Type II (Antibody-driven/mediated, cytotoxic) hypersensitivity**
35
**Extrinsic Allergic Alveolitis \>\> Type of hypersensitivity**
* **Acute phase \>\> Type III (immune-complex mediated) hypersensitivity** * **Chronic phase \>\> Type IV (delayed, cell mediated, antibody-independant) hypersensitivity**
36
**BCG immunisation \>\> Type of hypersensitivity**
**Type- IV (Delayed, Cell mediated, Antibody-independant) hypersensitivity**
37
**Grave's disease \>\> Type of hypersensitivity**
**Type V (Stimulatory) hypersensitivity**
38
**Myasthenia Gravis \>\> Type of hypersensitivity**
**Type V (Stimulatory) hypersensitivity**
39
**Graft vs Host disease (GVHD) \>\>\> Type of hypersensitivity**
**Type IV (Delayed, Cell mediated, Antibody-independant) hypersensitivity**
40
**SLE (Systemic Lupus Erythematosus) \>\> Type of hypersensitivity**
**Type III (Immune-complex mediated) hypersensitivity**
41
**Goodpasture syndrome \>\> Type of hypersensitivity**
**Type II (Cytotoxic, Antibody-mediated/dependant) hypersensitivity** **Anti-GBM antibody (IgG)**
42
**Hay fever \>\> Type of hypersensitivity**
**Type I (Immediate, IgE mediated) hypersensitivity**
43
**Asthma \>\> Type of hypersensitivity**
**Type I (Immediate, IgE mediated) hypersensitivity**
44
**Latent TB \>\>\> Type of hypersensitivity**
**Type IV (Delayed, cell mediated, antibody-independant) hypersensitivity**
45
**Atopy \>\> Type of hypersensitivity**
**Type I (immediate, IgE mediated) hypersensitivity**
46
**Eczema \>\> Type of hypersensitivity**
**Type I (Immediate, IgE mediated) hypersensitivity**
47
**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**
48
**Acute haemolytic transfusion reactions \>\>\> Type of hypersensitivity**
**Type II (Cytotoxic, antibody-mediated/dependant) hypersensitivity**
49
**ITP (Idiopathic Thrombocytopaenic Purpura) \>\> Type of hypersensitivity**
**Type II (cytotoxic, antibody-mediated/dependant) hypersensitivity**
50
**Pernicious anaemia \>\> Type of hypersensitivity**
**Type II (Cytotoxic, cell-bound, antibody-mediated/dependant) hypersensitivity**
51
**Rheumatic fever \>\> Type of hypersensitivity**
**Type II (Cytotoxic, cell-bound, antibody mediated/dependant) hypersensitivity**
52
**Bullous pemphigoid OR Pemphigus vulgaris \>\> Type of hypersensitivity**
**Both \>\> Type II (cytotoxic, cell-bound, antibody-mediated/dependant) hypersenisitivity**
53
**PSGN (Post-streptococcal glomerulonephritis) \>\> Type of hypersensitivity**
**Type III (imuune complex mediated) hypersensitivity**
54
**Serum sickness \>\>Type of hypersensitivity**
**Type III (Immune-complex mediated) hypersensitivity**
55
**Tuberculosis \>\> Type of hypersensitivity**
**Type IV (Delayed, cell mediated, antibody-independant) hypersensitivity**
56
**Tuberculin skin test reaction \>\> Type of hypersensitivity**
**Type IV (Delayed, cell-mediated, antibody-independant) hypersensitivity**
57
**Allergic contact dermatitis \>\> Type of hypersensitivity**
**Type IV (delayed, cell-mediated, antibody-independant) hypersensitivity**
58
**Scabies \>\> Type of hypersensitivity**
**Type IV (Delayed, Cell-mediated, antibody-independant) hypersensitivity**
59
**Multiple sclerosis \>\> Type of hypersensitivity**
**Type IV (Delayed, cell-mediated, antibody-independant) hypersensitivity**
60
**GBS (Guillain-Barre syndrome) \>\> Type of hypersensitivity**
**Type IV (Delayed, cell-mediated, antibody-independant) hypersensitivity**

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