Test 3: Immune Complex Clearance and Diseases

Question 1

What are the important cell surface receptors necessary for opsonization?

Answer 1

• CR1 which binds to C3b

- Fc(gamma or mu)R: binds to Fc portions of IgG and IgM

Question 2

What are the functions of C5a from the complement system?

Answer 2

• recruit more neutrophils to the area

- increase number of CR1 on phaygocytes to facilitate phagocytosis

Question 3

What type of phagocytic cell is typically recruited when an immune complex forms in tissue?

Answer 3

Tissue macrophages (histiocytes)

Question 4

How are the small and soluble immunogen/ab complexes removed from circulation?

Answer 4

-Too small for Fc receptors, removed by complement system (C3b and C4b)

Question 5

Where are most CR1’s found?

Answer 5

On the surface of RBCs bc they are more prominent in the blood (700/cell)

Question 6

How does C3b reduce the probability of contact of an immune complex with endothelial cells?

Answer 6

It intercalates with the complex and sterically hinders Ig binding

Question 7

How are immune complexes removed from RBCs?

Answer 7

• transported to liver or spleen and removed by tissue macrophages (liver Kupffer cells), CR1s removed as well
• Factor I cleaves C3b

Question 8

What remains when C3b is cleaved by Factor I?

Answer 8

C3dg is left attached to CR1–so no other complexes can bind (reduces # of active CR1s)

Question 9

When can small immune complexes leave axial blood flow and come into contact with endothelial cells?

Answer 9

• Excess antigen (early in disease process)
• complexes are efficiently removed by spleen/liver
• deficiency of complement
• net loss of CR1s

Question 10

When complexes attach to endothelium, what complement is generated?

Answer 10

C3a and C5a (anaphylatoxins)

Question 11

What are the functions of C3a and C5a?

Answer 11

• attract neutrophils which release degradative enzymes and oxidizing agents (reactive oxygen species)
• degranulate basophils

Question 12

What is released from basophils?

Answer 12

Histamine (exposes basement membrane and tissue) and Platelet Activating Factor (forms thrombus and ischemic necrosis)

Question 13

What factors favor immune complex deposition in tissue?

Answer 13

• small complex sizes with antigen excess (remain in circulation longer)
• increased vascular permeability
• vessels with high pressure/turbulent flow

Question 14

Which of these does not have high pressure/turbulent flow?

• glomerulus
• capillaries
• synovial membranes
• bifurcations and vascular filters

Answer 14

Capillaries

Question 15

Where do you typically see an arthus response, animal or humans?

Answer 15

Animals

Question 16

What does the lesion near the immunogen injection site with an arthus response look like?

Answer 16

• Edema, hemorrhage, necrosis
• moderately delayed response (4-10 hrs)
• typical histological evidence of inflammation

Question 17

What can cause an arthus response in humans?

Answer 17

• Non protein drugs (beta-lactams)
• Booster vaccines (tetanus, diptheria)
• Allergens for allergy desensitization

Question 18

An acute, self-limited disease caused by
immune complex-activated, complementgenerated
inflammation after injection of a protein
or haptenic drug

Answer 18

Serum Sickness

Question 19

What are causes of serum sickness?

Answer 19

• Heterologous serum (equine)

- ‘gamma globulin and antilymphocyte/thymocyte globulin (ALG, ATG) for immunosuppressive therapy

Question 20

Is serum sickness induced after a second exposure?

Answer 20

No, it is induced by a single, first time administration (about 7-10 days later)

Question 21

What is the first sign of serum sickness?

Answer 21

Puritic (itchy) rash

Question 22

Other signs of serum sickness

Answer 22

Angioedema of the face, fever, lymphadenopathy, athralgia, myalgia

Question 23

What are predisposing properties of immune complexes that could lead to glomerulonephritis?

Answer 23

• Large size
• Cationic
• Long, persisting complexes

Question 24

What are predisposing properties of Kidney glomeruli that could lead to glomerulonephritis?

Answer 24

• high hydrostatic pressure

- fenestrated endothelial lining

Question 25

What are some signs/symptoms of glomerulonephritis?

Answer 25

• high serum creatinine
• low serum complement
• slight proteinuria
• hematuria (blood in urine)

Question 26

How does Rheumatoid arthritis progress through the body?

Answer 26

-starts in joints of hands and feet and progress centripitally (towards center) and symmetrically

Question 27

What type of autoantibodies are found in the synovial fluid and serum with Rheumatoid arthritis?

Answer 27

-ones for the Fc portion of IgG (rheumatoid factors)