Hypersensitivity reactions

Question 1

Hypersensitivity Definition

Answer 1

excessive, harmful reactions produced by the normal immune system
hypersensitivity reactions require a pre-sensitized immune state of the host

occur in response to:

• infectous agent (f.ex. streptococci)
• environmental substances (f.ex. pollens)
• self antigens

Question 2

Type I (IgE mediated)

Initiation
Exposure
Time of onset after exposure

Answer 2

immediate hypersensitivity (allergic reactions)

• initiated by an ALLERGEN - antigen leading to the production of specific IgE antibodies
• antigen/allergen: pollen, food, insect stings, drugs

mediated by degranulation of mast cells, eosinophils and basophils

onset: seconds - minutes after exposure

Question 3

(additional info to lecture): First step of allergic reaction at the example of Type I Hypersensitivity

Answer 3

Sensitazation/ first exposure

allergen is picked up by antigen presenting cells in the airways and carried to lymph nodes

• APC present it to T-helpers
• T-helper transforms from naiive to (usually) Th2
• this process is triggered by cytokines: usually interleukins IL-4, IL-5, IL-10
• Th2 cells release IL-4, which causes B cells to produce IgE molecules specific to the allergen
• IgE antibodies attach to surface of mast cells
• Th2 cells also release IL-5, which stimulates production and activation of EOSINOPHILS (granulocytes)

Question 4

Second step of allergic reaction at the example of Type I Hypersensitivity

Answer 4

• allergen binds to mast cells/ basophils with IgE antibodies on the surface
• degranulate and release pro-inflammatory mediators, f.ex. histamine (causes contraction of smooth muscle in bronchi - difficult breathing, blood vessel dialation - edema) in strong cases: Anaphylaxis (allergic shock)

!Unklar ob nur für eosinophils oder auch mast cells:
- destroy cells by releasing toxic granules and free radicals
- produce mediators like prostaglandins
perform ADCC
(Antibody‐dependent cell‐mediated cytotoxicity, the killing of an antibody‐coated target cell by a cytotoxic effector cell through a nonphagocytic process, characterised by the release of the content of cytotoxic granules or by the expression of cell death‐inducing molecules.)

Question 5

Type II

Initiation
Mediation
Examples

Answer 5

cytotoxic, antibody dependent reactions
- antibody mediated destruction of own healthy cells or cells from blood transfusion

Initiation: Antibodies (IgM, IgG) bind antigen on the surface of target cells

Mediation: Cytolysis due to:

• phagocytosis
• activation of the complement
• ADCC (Antibody‐dependent cell‐mediated cytotoxicity)

Examples:

• incompatible blood transfusions
• autoimmune hemolytic anemia (destruction of own red blood cells)
• thrombocytopenia (destruction of own thrombocytes: cytoplasmic blood components which react to bleeding injuries by clumping)
• Drug allergies (haptens: antibiotics, tranquillants)

additional info:

• normally, self-reactive lymphocytes are already destroyed in the lymphoid organs
• but if some of them escape, they become activated and produce IgG antibodies which finally induce the distruction of healthy cells

Question 6

Type III

initiation
mediation
examples

Answer 6

immune complex reactions

Initiation:
- Antibody-antigen complex

Mediation:
- cause damage at site of production, then circle and cause damage elsewhere
- deposit on basal membrane of capillaries
cause:
- complement activation
- cytolysis

Examples

• rheumatoid arthritis (autoimmune arthritis)
• poststreptococcal glomerulonephritis (kidney disease after infection with streptococcus bacteria)
• SLE (type of autoimmune disease)

Question 7

Type IV

mediation
examples
Time of onset after exposure

Answer 7

delayed hypersensitivity (cell mediated reactions)

• activated by APC
• mediated by T cells (Th1 or Tc)

if the Ag is presented again in the future:
- memory Th1 cells activate Maf
- cause inflammation and tissue damage,
due to cytokines and and chemokines released by Th1

• 2-3 days after exposure to Ag

examples:

• Tuberculosis
• Contact dermatitis (f.ex. to nikel)
• multiple sclerosis
• chronic transplant rejection

Question 8

Type V

mediators
function
Examples

Answer 8

receptor mediated autoimmune diseases
(additional type used as a distinction from Type 2)

Mediators: IgM, IgG, Complement

• Instead of binding to cell surfaces, antibodies bind to the cell surface receptors
• this either prevents the intended ligand from binding with the receptor or mimics the effects of the ligand
  consequence: impaired cell signaling.

examples:

• Graves disease: activation of receptors for TSH, hyperthyroidism (Schilddrüsenüberfunktion)
• Mystenia gravis (Muskelschwäche): decrease of acetylcholine receptors due to complement depending cytolysis, decrease of action potential