Hypersensitivity

Question 1

What is hypersensitivity?

Answer 1

• Group of disorders
• normally beneficial components of the immune system response act
• in an exaggerated or inappropriate fashion to environmental antigens which don’t normally cause tissue damage.
• Exaggerated response itself is actually responsible for the tissue damage.

Question 2

What is the ACID Pneumonic and how does it relate to Hypsensitivty?

Answer 2

• A - Allergic (Atophy/Anaphalxis) - Type 1
• C - Cytotoxic - Type 2
• I - Immune Complex - Type 3
• D - Delayed - Type 4

Question 3

Generally, outline Type 1 Hypersensitivity

Answer 3

• The type of reaction involved in (most) allergies
• Mediated by IgE immunoglobulins.
• Resulting in an immediate reaction
• Associations are also seen to hypersensitive T Helper Cells.

Question 4

What are the 2 phases of Type 1 Hypersensitivity?

Answer 4

Sensitisation Phase

Reaction Phase

Question 5

Describe what is occurring in the sensitisation phase of Type 1 Hypersensitivity.

Answer 5

• APC (Antigen Presenting Cell) - picks up a hapten (non-human protein source/allergen)
• Activated APC
  
  • Go to the lymph nodes where they see T Helper Cells
  • These recognise the foreign antigen - and bind to the abnormal HLA
  • Interleukins are released.
    
    • IL-4 - encourage B cell activation - IgM -> IgE
    • IL-5 Granulcyte Activation
• B cells change to produce IgE rather than IgM
• Changes also seen in Basophils, Eoisinophils and mast cells.

Question 6

What happens in the reactive phase of a Type 1 Hypersensitivity Reaction?

Answer 6

Mass cells degranulate

• Histamine release
• Inflammation seen (- Oedema and Urticaria)

Other + inflammatory mediators released too

• • Basophils
• Th2
• Eosinophils etc.
• Interleukins released
  
  • bringing more WCs & Basophils

Question 7

What is Atophy?

Answer 7

Genetic predisposition to develop allergic diseases.

• Eczema
• Hayfever
• Asthma

Question 8

Bascially outline Atopic Dermatitis in terms of a Type 1 Hypersensitivity?

Answer 8

Eczema

• Common in children
• Seen on exposed and flexor surfaces
• Degranulation of basophils and mast cells in response to sensitised IgE.
• Leaky skin allows more allergen in.

Question 9

What are the treatment options for Type 1 Hypersensitivity?

Answer 9

• Antihistamines
• Corticosteroids
• Adrenaline (anaphlaxis)
• Allergen avoidance

Question 10

What is Type 2 Hypersensitivity?

Answer 10

Also known as Cytotoxic Hypersensitivity.

• Antibody-mediated destruction of cells, by tissue-specific antibodies.
• Antigen-antibody complexes lead to activation of the complement system.
  
  • Neutrophil degranulation
  • MAC formed
  • NK degranulation - apoptosis of marked cells.

Question 11

What is Intrinsic and Extrinsic causes of Type 2 Hypersensitivity?

Answer 11

• Intrinsic - Reacting to HLA (human cells)
• Extrinsic - Reacting to something not normally found in the body - such as penicillin.

Question 12

What is Type 3 Hypersensitivity?

Answer 12

“Complex”

• Antigen-Antibody/Immune complex formation.
  
  • With soluble antigens
• Deposition in tissues and BV
• Activating phagocytes and causing damage in these areas
• Complement activation causes inflammation

Tends to be systemic.

An example of Type 3 Hypersensitivity is in Lupus.

Question 13

Briefly outline how Lupus is a type 3 Hypersensitivity

Answer 13

Systemic Lupus Erythematosis

• Failure of Tolerance, allowing ”self-reactive” B/T cells to circulate
• Leaked auto-antigen is presented to B-cell, passed to T Helper cells and antibodies to DNA made

Question 14

What is Type IV Hypersensitivity?

Answer 14

• “Delayed” - reaction to none harmful hapten.
• T Cell Mediated
  
  • Cytotoxic (CD8+) and Helper (CD4+)
• Quite similar to Atophic disease - but occurs much slower because there is a lack of genetic disposition
• Activation of the Complement cascade happens too.
• Tc Cells themselves also at atach MHC1 (foreign)
  
  • Release perfroins - directly damages surface.

Question 15

Generally outline Contact Dermatitis.

Answer 15

Type 4

• Haptens cross stratum corneum of skin
• Langerhans cells present to TH1 cells
  
  • TNF alfa and IL 1, 13 and 18
• LCs become differentiated Dendritic cells presenting allergenic epitope and multiply
• More aggressive response 2nd time

Question 16

To summarise - Define Type 1

Answer 16

Allergic, IgE mediated reaction leading to rapid and later smooth muscle contraction, bronchoconstriction and inflammation

Question 17

To summarise - Define Type ​2

Answer 17

Cell surface antigens bound by circulating antibodies, activating opsionisation, complement fixation and macrophages

Question 18

To summarise - Define Type ​3

Answer 18

Reactive cells create Immunoglobulins, that clump with fragments of lysed products to form complexes in tissues

Question 19

To summarise - Define Type ​4

Answer 19

Th1 Cell recruitment in response to adaptive immune response, often taking up to 48 hours to react to pathogen.