Lecture 2A - Antibodies and Complements (Quan)

Question 1

What are the important features of antibodies? (4)

Answer 1

1. Bind a variety of antigenic structures.
2. Discriminate between similar antigens
3. Bind antigen with strength
4. Recognize antigen in its native form.

Question 2

***What are the functions of antibodies? (3)

Answer 2

1. Neutralization of bacteria/toxin
2. Opsonization (tagging) for phagocytosis
3. Complement Fixation (recruit complement system to destroy)

Question 3

*** What is the major immunoglobulin (Ig) in the serum?

Answer 3

IgG (70-75% of all Igs) - “work horse”

Question 4

*** What is the first antibody produced for a new antigen?

Answer 4

IgM

Question 5

***What is the primary antibody in the oral cavity?

Answer 5

IgA

Question 6

Why is IgE important?

Answer 6

Important for killing large parasites.

Contributes to allergic reaction.
found on basophils and mast cells

Question 7

What is “complement?”

Answer 7

something that fills up, completes, or makes perfect

Question 8

There are 30+ complement serum molecules that make up 10% of the serum proteins. Why are they so important?

Answer 8

They are a major DEFENSE SYSTEM of the body that contributes to:
control inflammatory reactions
chemotaxis
clearance of immune complexes
cellular activation
antimicrobial defense

Question 9

Which complement “family member” is the CENTRAL COMPONENT?

Answer 9

C3

Question 10

Which complement “family members” are the LATE COMPONENTS?

Answer 10

C5
C6, C7, and C8
C9

Question 11

***Are complements active in their normal state?

Answer 11

They must first undergo proteolytic cleavage to “unmask” their active site. Therefore FRAGMENTS OF COMPLEMENT MOLECULES ARE THE ACTIVE COMPLEMENTS.

Question 12

What are the 3 functions of the complement system?

Answer 12

1. Opsonization and cell activation
2. Chemotaxis
3. Lysis of target cells (assembly of membrane attack complex (MAC) that creates holes in cell membrane

Question 13

What complements are powerful CHEMOTAXIS factor?

Answer 13

C5a and C3a

Question 14

Why is C5b important?

Answer 14

activation leads to membrane attack complex (MAC) formation

Question 15

There are 2 complement activation pathways.

Answer 15

1. Antigen-Antibody Complex (CLASSIC PATHWAY)
   
   • adaptive immune response
2. WITHOUT ANTIBODY, microbial cells walls have surface components that active complements
   
   • innate immune response
   A.) LECTIN PATHWAY ACTIVATORS
   -terminal mannose groups
   B.) ALTERNATIVE PATHWAY ACTIVATORS
   -microbial cell walls

Question 16

What activates the complements system through the lectin pathway?

Answer 16

terminal mannose groups

Question 17

What activates the complement system through the alternative pathway?

Answer 17

microbial cell walls

Question 18

How does the innate immune response activate the complement system?

Answer 18

1. lectin pathway (terminal mannose groups)

2. alternative pathway (microbial cell walls)

Question 19

How does the adaptive immune response activate the complement system?

Answer 19

Classic pathway (antigen-antibody complex)

Question 20

Break down the ALTERNATIVE PATHWAY that the innate immune system uses to activate the complement system.

Answer 20

1. C3 floats, inactive, in the blood. It is spontaneously cleaved into C3b and C3a.
2. C3bH (“host” or “self”) found on self surface.
   
   • deactivated by FACTOR I
3. C3bB (“bacteria”) found on bacterial surface.
   
   • activated by FACTOR D (now C3bBb)
4. C3bBb is a very active enzyme, C3 CONVERTASE.
5. C3 Convertase cut C3 to make more C3b. (positive feedback loop) –> C3 ACTIVATION

Question 21

Break down the CLASSICAL PATHWAY that the adaptive immune system uses to activate the complement system.

Answer 21

C1 is involved in the classical pathway.

1. C1 cleaves C2 and C4 to create C4b2a.
2. C4b2a is the classical C3 convertase (C3 into C3a and C3b)
3. C4b2a3b is the classical C5 convertase
4. once C5 is cut into C5b, C5b links to cell membrane. Then C5b, C6, C7, C8, and multiple C9 form MAC