Antibody Effector Function

Question 1

What part of the antibody includes the variable and antigen binding site?

Answer 1

The Fab region

Question 2

What part of the antibody determines its effector function?

Answer 2

The Fc region (also called the constant region)

Different cells have specific Fc receptors and can react when bound to the Fc region of an antibody

Question 3

Generation of antibody diversity

Answer 3

• Recombination of VJ (light-chain) or V(D)J (heavy-chain) genes
• Random addition of nucleotides to DNA during recombination
• Random combination of light-chains with heavy-chains

Question 4

What region of the antibody determines the antibody’s isotype?

Answer 4

The Fc region (which is made up of only the heavy chains)

Question 5

What types of antigens can antibodies attach to?

Answer 5

Proteins, Carbohydrates, or Lipids

Question 6

BCR vs TCR comparison

Answer 6

B-Cell Receptors (essentially membrane bound antibodies):

• Can recognize free Proteins, Carbohydrates, or Lipids
• Can be membrane bound or released

T-Cell Receptors:

• Can only recognize Peptides on MHC I or II
• Are always membrane bound

Question 7

IgM isotype structure

Answer 7

Pentamer

Due to its large size it is primarily found in the intravascular space (bloodstream and lymph fluid)

Question 8

Iga isotype structure

Answer 8

Dimer

Question 9

IgG, IgD, and IgE structure

Answer 9

Question 10

Memory B-Cells

Answer 10

• Formed within germinal centers following primary infection
• Can survive for decades
• Generate an accelerated and robust antibody-mediated immune response in the case of re-infection (secondary immune response).

Question 11

T-Cell Dependent B-Cell Activation (General)

Answer 11

• Protein antigen-only
• Vigorous response
• Class switching (IgG, IgA, IgE)
• Creates Memory Lymphocytes

Question 12

T-Cell Independent B-Cell Activation (General)

Answer 12

• Non-protein antigen (important for polysaccharide capsules of bacteria and LPS)
• Releatively weak response
• Mostly IgM
• No memory lymphocytes made

Question 13

Antibody Functions

Answer 13

• Opsonization: Mark pathogens for phagocytosis
• Neutrallization: Block adherence of pathogen to structures
• Activate Complimanet: Activates “classical” pathway

Question 14

IgM

Answer 14

• First antibody secreted during infection
• Excellent activator of complement system (classical pathway)
• Pentemer with 10 binding sites (greatest avidity of the antibodies)
• Prevents attachment of pathogens
• Cannot cross the placenta

Question 15

IgG

Answer 15

• Major antibody of secondary response
• Is the only antibody that can cross the placenta
  
  • Most abundant antibody in newborns
• Excellent opsonin (important for encapsulated bacteria)
• Most abundant class in plasma
• Antibody-dependent cellular cytotoxicity mediated by NK cells

Question 16

What is the primary location of each antibody?

Answer 16

• IgM and IgG are in the blood and lymph
• IgA is in the mucus
• IgE is used on parasites and bind mast cellls/eosinophils

Question 17

IgA

Answer 17

• Found on mucosal surfaces/mucosal secretions
  
  • GI tract, respiratory tract, saliva, tears
• Monomer in plasma (dimer in secretions)
• No complement = no inflammation
• Secreted into milk to protect baby’s GI tract

Question 18

IgE

Answer 18

• Binds to mast cells and eosinophils
• Defense against parasites
  
  • Too large for phagocytosis
  • IgE binds, causing mast cells or eosinophil degranulation
• Does not activate complement
• Mediates allergic reactions

Question 19

B-Cell Development Timeline

Answer 19

• Bone Marrow (Pre-Infection) –> VDJ Rearrangement
• Lymph Nodes (During Infection) –> Class Switching
• Post-Infection —> Memory B-Cells Remain

Question 20

Follicular B-Cells (AKA B2 Cells)

Answer 20

• Reside in primary and secondary lymphoid follicles (containing germinal centers) of lymphoid organs, including spleen and lymph nodes.
• Protein antigen + Helper T-Cells cause follicular B-Cells to undergo isotype-switching and produce high-affinity antibodies
• These plasma cells are long-lived

Question 21

Marginal Zone B-Cells

Answer 21

• Noncirculating mature B-Cells that segregate into the marginal zone (MZ) of the spleen and other types of lymphoid tissue
• When bound to antigen lipids, polysacharides, etc. –> become short-lived plasma cells that mainly produce IgM

Question 22

B-1 Cells

Answer 22

• Commonly found in peripheral sites (mucusal tissues and peritoneal cavity)
• After binding to antigen lipids, polysacharides, etc. –> become short-lived plasma cells that mainly produce IgM

Question 23

Where do Naive T and B Lymphocyes primarily gain access to antigens?

Answer 23

In the lymphoid tissue

Question 24

In addition to binding antigen, what additional signal is needed for isotype switching?

Answer 24

Helper T-Cell Signals:

1. ) CD40L on the CD4+ T-Cell binding to CD40 on the B-Cell
2. ) Cytokine signals from the CD4+ T-Cells

Question 25

What signals are required for isotype switching and B-cell proliferation?

Answer 25

1. ) MHC II/antigen on B-Cell binds TCR on T-Cell 2. ) CD40 on B-Cell binds CD40 ligand (AKA CD154) on T-Cell 3. ) T-Cell releases cytokines (these cytokines determine the isotype)

Question 26

What B-Cell enzyme is involved in isotype switching?

Answer 26

Activation Induced Cytidine Deaminase (AID)

Question 27

What cytokine causes isotype switching to IgA?

Answer 27

TGF-B produced by Th17

Question 28

What cytokine causes isotype switching to IgG?

Answer 28

INF-y produced by Th1

Question 29

What cytokine causes isotype switching to IgE?

Answer 29

IL-4 produced by Th2

Question 30

B-Cell Affinity Maturation

Answer 30

* B-Cells migrade to germinal center * The B-Cell enzyme AID causes random mutations of variable regions on antibodies * B-Cells with low-affinity antibodies are selected against (die) * B-Cells with high-affinity antibodies are selected for

Question 31

Germinal Centers

Answer 31

Sites within secondary lymphoid organs (lymph nodes/spleen) where mature B-cells proliferate, differentiate, and mutate their antibody genes

Question 32

Summary of the Germinal Center Reaction

Answer 32

* Activation of B-Cells and migration into germinal center * B-Cell proliferation * Somatic mutation and affinity maturation; isotype switching * Exit of high-affinity antibody-secreting cells and memory B-cells

Question 33

Do memory B-Cells need to undergo isotype switching upon re-infection?

Answer 33

No; memory B-cells have already undergone affinity maturation and isotype switching and are ready to go if there is any reinfection :D

Question 34

Neutralizing functions of antibodies

Answer 34

* Blocks penetration of microbe through epithelial barriers * Blocks binding of microbe to cells that it would otherwise infect * Blocks binding of toxin to cellular receptors

Question 35

Opsonization function of antibodies

Answer 35

Coating microbe with antibodies in preperation for phagocytosis

Question 36

Antibody-dependent cell-mediated cytotoxicity

Answer 36

* IgG binds to antigen on infected cell surface * This marks the cell for destruction by NK cells

Question 37

How do NK cells recognize and kill infected target cells that no longer express MHC I

Answer 37

When NK cells bind to an infected cell's receptor ligand and that cell does not express MHC I, it activates killing of that cell Note: RBCs do not express this ligand nor MHC I as they do not have a nucleus

Question 38

What is the relevance of a splenectomy with relation to immunity?

Answer 38

Patients who have their spleens removed may have reduced protection from previous vaccines and may need to be re-vaccinated

Question 39

What do swollen lymph nodes indicate?

Answer 39

* Adaptive immune response is engaged * T-cells and B-cells are proliferation