Hypersensitivity reactions and Asthma

Question 1

Hypersensitivity reactions

Answer 1

• Immune reactions that lead to tissue injury.
• may be antibody or T cell mediated
• may lead to autoimmune diseases.
• classified based on the principal immunological mechanism that is responsible for tissue injury.

Question 2

Immediate hypersensitivity (Type 1 )

Answer 2

• against environmental antigens (allergens)
• mediated via IgE which then binds to FcɛRI on the surface of mast cells.
• Upon second exposure to the antigen, mast cells degranulate leading to rapid vasodilation and inflammation at the site of exposure
• hay fever, food allergies, bronchial asthma, skin allergies, and anaphylaxis if systemic.

Question 3

atopic

Answer 3

Individuals who are prone to develop allergic diseases

Question 4

Omalizumab

Answer 4

• Anti-IgE antibody
• neutralize and eliminate IgE

Question 5

Syndrome : Anaphylaxis

Answer 5

• Therapy : Epinephrine
• MOA : Vascular smooth muscle contration; increases cardiac output to counter shock; inhibits further mast cell degranulation.

Question 6

Bronchial-Asthma

Answer 6

Therapy & MOA

• COC-steroids ( reduce inflammation)
• Leukotriene anta ( reduce inflammation)
• Phosphodiesterase inhibitors ( relax bronchial smooth muscles)

Question 7

Antihistamines

Answer 7

block actions of histamine on vessels and smooth muscles

Question 8

Cromolyn

Answer 8

inhibits mast cell degranulation

Question 9

Type II

Answer 9

• IgG-mediated cytotoxic Hypersensitivity
• Antibody directed against cell surface antigens mediates cell destruction via complement activation
• Ex: Acute rheumatic fever; Blood transfuion reactions, erthroblastosis fetalis, autoimmune hemolytic anemia; Myasthenia Gravis; Graves’ Disease (hyperthyroidism); pernicious anemia

Question 10

Type III

Answer 10

• Immune complex-mediated
• Antigen-Antibody complexes deposited in various tissues induce complement activation and resulting in inglammatory response mediated by massive infiltration of neutrophils
• RA; Lupus; poststreptococcal glomerulonephiritis

Question 11

therapies for Type II and III

Answer 11

• IVIG (intravenous IgG from healthy donors) - may block Fc recetors on phagocytes so pathogenic antibodies do not bind
• Antibodies specific to CD20 on B cells result in their depletion or antibodies that block CD40 OR CD40L can inhibit B cell activation.

Question 12

T cell mediated diseases (Type IV or delayed hypersensitivity reactions )

Answer 12

• the result of autoimmunity or due to persistent responses to environmental antigens
• against cellular antigens with restricted tissue distribution and thus reactions are localized and not systemic
• Th1, Th17 or CTLs
• Sensitized Th1 ce;;s re;ease cytokines that activate macrophages of Tc cells which mediate direct cell damage
• Ex: Contact dermatitis, TB lesions and graft rejection.

Question 13

Treatments of Type IV hypersensitivity:

Answer 13

1. Steroids
2. Anti-TNFs in RA or IBD
3. Drugs that block B7 molecules
4. IL-1, IL-6, or IL-17 antagonists

Question 14

Granulomatous hypersensitivity

Answer 14

• occurs as a defense against intracellular infections such as T.B.
• macrophages + other immune cells form a core of inflammatory cells that include lymphocytes, eosinophils, plasma cells, giant cells, and epithelioid cells to localize the infection.
• These collections of cells develop into a ball-like mass called granuloma.

Question 15

Mechanisms by which autoantibodies cause disease

Answer 15

1. Inflammation
2. Opsonization and Phagocytosis
3. Abnormal cellular responses

Question 16

Inflammation

Answer 16

• auto-antibody binds to soluble antigen
• phacocytes activated through Fc receptor
• activated complement system ⇒ inflammation and leukocyte recruitment
• released ROS and lysosomal enzymes that cause tissue damage

Question 17

Opsonization and phagocytosis

Answer 17

Antibodies that bind to cells such as erythrocytes or platelets may lead to phagocytosis of these cells by phagocytes.

Question 18

Abnormal cellular response

Answer 18

• Antibodies against hormonal receptors or acetylcholine receptor may block its function.
• Antibodies may serve as ligands and activate receptors such as thyroid stimulating hormone

Question 19

Effector Functions of Antibodies

Answer 19

• Neutralizing of microbes and toxins
• Opsonization
• complement activation
• Mucosal immunity

Question 20

Mast Cells produce _____

Answer 20

• Histamine
• Leukotrienes
• Prostaglandins
• TNF-alpha (early)

Question 21

Immune cells involved in asthma

Answer 21

• Th2 cell
• Neutrophil
• Mast cell
• Eosinophil
• B cell
• IgE

Question 22

Superantigens

Answer 22

• induce T-cell activation by binding the TCR and MHC simultanseously
• class of antigens which cause non-specific activation of T-cells resulting in polyclonal T cell activation and massive cytokine release
• Anti-CD3 and Anti-CD28 antibodies are highly poten super antigend
• I.E. Toxic Shock Syndrome