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Block 1 - Week 5 > Antibody Effector Function > Flashcards

Antibody Effector Function Flashcards

1
Q

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

A

The Fab region

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2
Q

What part of the antibody determines its effector function?

A

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

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3
Q

Generation of antibody diversity

A
  • 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
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4
Q

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

A

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

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5
Q

What types of antigens can antibodies attach to?

A

Proteins, Carbohydrates, or Lipids

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6
Q

BCR vs TCR comparison

A

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
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7
Q

IgM isotype structure

A

Pentamer

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

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8
Q

Iga isotype structure

A

Dimer

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9
Q

IgG, IgD, and IgE structure

A
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10
Q

Memory B-Cells

A
  • 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).
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11
Q

T-Cell Dependent B-Cell Activation (General)

A
  • Protein antigen-only
  • Vigorous response
  • Class switching (IgG, IgA, IgE)
  • Creates Memory Lymphocytes
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12
Q

T-Cell Independent B-Cell Activation (General)

A
  • Non-protein antigen (important for polysaccharide capsules of bacteria and LPS)
  • Releatively weak response
  • Mostly IgM
  • No memory lymphocytes made
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13
Q

Antibody Functions

A
  • Opsonization: Mark pathogens for phagocytosis
  • Neutrallization: Block adherence of pathogen to structures
  • Activate Complimanet: Activates “classical” pathway
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14
Q

IgM

A
  • 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
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15
Q

IgG

A
  • 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
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16
Q

What is the primary location of each antibody?

A
  • IgM and IgG are in the blood and lymph
  • IgA is in the mucus
  • IgE is used on parasites and bind mast cellls/eosinophils
17
Q

IgA

A
  • 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
18
Q

IgE

A
  • 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
19
Q

B-Cell Development Timeline

A
  • Bone Marrow (Pre-Infection) –> VDJ Rearrangement
  • Lymph Nodes (During Infection) –> Class Switching
  • Post-Infection —> Memory B-Cells Remain
20
Q

Follicular B-Cells (AKA B2 Cells)

A
  • 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
21
Q

Marginal Zone B-Cells

A
  • 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
22
Q

B-1 Cells

A
  • 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
23
Q

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

A

In the lymphoid tissue

24
Q

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

A

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
25
Q

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

A
  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)
26
Q

What B-Cell enzyme is involved in isotype switching?

A

Activation Induced Cytidine Deaminase (AID)

27
Q

What cytokine causes isotype switching to IgA?

A

TGF-B produced by Th17

28
Q

What cytokine causes isotype switching to IgG?

A

INF-y produced by Th1

29
Q

What cytokine causes isotype switching to IgE?

A

IL-4 produced by Th2

30
Q

B-Cell Affinity Maturation

A
  • 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
31
Q

Germinal Centers

A

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

32
Q

Summary of the Germinal Center Reaction

A
  • 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
33
Q

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

A

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

34
Q

Neutralizing functions of antibodies

A
  • 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
35
Q

Opsonization function of antibodies

A

Coating microbe with antibodies in preperation for phagocytosis

36
Q

Antibody-dependent cell-mediated cytotoxicity

A
  • IgG binds to antigen on infected cell surface
  • This marks the cell for destruction by NK cells
37
Q

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

A

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

38
Q

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

A

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

39
Q

What do swollen lymph nodes indicate?

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

Block 1 - Week 5 (10 decks)

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