hypersensitivity and autoimmunity

Question 1

type 1

Answer 1

allergy
IgE mediated; allergic or anaphylactic

• IgE bound to mast cells and basophils
• allergen binds to IgE forming cross-links which trigger mast cell degranulation

granules release:

• chemoattractants
• activators (vasodilation, complement, platelets)
• spasmogens (SM contraction & mucus secretion)

Question 2

what causes type 1 hypersensitivity

Answer 2

• rhinitis (dust mites, pollens, animal dander)
• insect stings
• food allergies
• small molecules

Question 3

common sites of type 1 hypersensitivity

Answer 3

• respiratory tract
• gut
• skin
• multiple organs = anaphylaxis

Question 4

treatment of type 1 hypersensitivity

Answer 4

(avoid if possible)

• antihistamines
• corticosteroids, especially in asthma
• adrenaline
• densensitisation

Question 5

type 2 hypersensitivity

Answer 5

antibodies against cell surface antigens bind leading to ADCC and complement activation by immune complex formation

• membrane attack complex for lysis
• C3b to help neutrophil attachment

Question 6

what is an example of type 2 hypersensitivity

Answer 6

haemolytic disease of the newborn
- Rh(D) - mother has Rh(D) + child
- baby is born, exposure to Rh(D) + to red cells causes antibody production in mother
- Anti-Rh IgG crosses placenta in sebsequent pregnancy
= complement mediated haemolysis

Question 7

type 3 hypersensitivity

Answer 7

immune complex-mediated

• in chronic infection, period when antibody to antigen is similar, causing formation of large lattice-like immune complexes
• large complexes lodge in small vessels –> micro-thrombus
• neutrophil and complement recruitment can lead to vascular damage

Question 8

type 4 hypersensitivity and tests

Answer 8

CD4 TH1 cell-mediated

mantoux test:

• tests immune memory
• small amount of antigen injected under skin
• if immune memory exists, immune response causes swelling, redness over next 24 hours

contact sensitivity

• small molecules diffusing into skin, attach to normal proteins to change shape
• dendritic cells in skin recognises new shape, then present T cells in node
• memory TH1 cells return from node and provoke inflammation

Question 9

autoimmunity

Answer 9

organ-specific (usually type 2) - antibodies directed against particular tissue

systemic (usually type 3) - antibodies made against soluble antigens

Question 10

development of autoimmunity

Answer 10

• natural IgM low-affinity autoantibodies are common (disease rare)
• anti-nuclear antibody (ANA) seen in systemic lupus erythematosis (SLE) - elderly
• anti-thyroid antibody seen in thyroid disease

Question 11

mechanisms of tolerance in autoimmunity

Answer 11

• clonal deletion in bone marrow and thymus (central)
• clonal regulation (peripheral)
• suppression
• ignorance

Question 12

molecular mimicry mechanism in autoimmunity

Answer 12

• in infection, peptides are presented to immune system. Peptides are similar to self-peptides and therefore response to bacteria attacks tissue and causes autoimmunity phenomenon

Question 13

treatment of autoimmunity

Answer 13

• replacement of insulin, thyroxin, hormones, vitamin B12 etc
• immunosuppressive drugs
  SLE = corticosteroids
  rheumatoid arthritis = corticosteroids, NSAIDs, TNF