Antibody Effector Function Flashcards
What part of the antibody includes the variable and antigen binding site?
The Fab region
What part of the antibody determines its effector function?
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
Generation of antibody diversity
- 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
What region of the antibody determines the antibody’s isotype?
The Fc region (which is made up of only the heavy chains)
What types of antigens can antibodies attach to?
Proteins, Carbohydrates, or Lipids
BCR vs TCR comparison
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
IgM isotype structure
Pentamer
Due to its large size it is primarily found in the intravascular space (bloodstream and lymph fluid)
Iga isotype structure
Dimer
IgG, IgD, and IgE structure
Memory B-Cells
- 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).
T-Cell Dependent B-Cell Activation (General)
- Protein antigen-only
- Vigorous response
- Class switching (IgG, IgA, IgE)
- Creates Memory Lymphocytes
T-Cell Independent B-Cell Activation (General)
- Non-protein antigen (important for polysaccharide capsules of bacteria and LPS)
- Releatively weak response
- Mostly IgM
- No memory lymphocytes made
Antibody Functions
- Opsonization: Mark pathogens for phagocytosis
- Neutrallization: Block adherence of pathogen to structures
- Activate Complimanet: Activates “classical” pathway
IgM
- 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
IgG
- 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
What is the primary location of each antibody?
- IgM and IgG are in the blood and lymph
- IgA is in the mucus
- IgE is used on parasites and bind mast cellls/eosinophils
IgA
- 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
IgE
- 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
B-Cell Development Timeline
- Bone Marrow (Pre-Infection) –> VDJ Rearrangement
- Lymph Nodes (During Infection) –> Class Switching
- Post-Infection —> Memory B-Cells Remain
Follicular B-Cells (AKA B2 Cells)
- 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
Marginal Zone B-Cells
- 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
B-1 Cells
- 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
Where do Naive T and B Lymphocyes primarily gain access to antigens?
In the lymphoid tissue
In addition to binding antigen, what additional signal is needed for isotype switching?
Helper T-Cell Signals:
- ) CD40L on the CD4+ T-Cell binding to CD40 on the B-Cell
- ) Cytokine signals from the CD4+ T-Cells
What signals are required for isotype switching and B-cell proliferation?
- ) MHC II/antigen on B-Cell binds TCR on T-Cell
- ) CD40 on B-Cell binds CD40 ligand (AKA CD154) on T-Cell
- ) T-Cell releases cytokines (these cytokines determine the isotype)
What B-Cell enzyme is involved in isotype switching?
Activation Induced Cytidine Deaminase (AID)
What cytokine causes isotype switching to IgA?
TGF-B produced by Th17
What cytokine causes isotype switching to IgG?
INF-y produced by Th1
What cytokine causes isotype switching to IgE?
IL-4 produced by Th2
B-Cell Affinity Maturation
- 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
Germinal Centers
Sites within secondary lymphoid organs (lymph nodes/spleen) where mature B-cells proliferate, differentiate, and mutate their antibody genes
Summary of the Germinal Center Reaction
- 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
Do memory B-Cells need to undergo isotype switching upon re-infection?
No; memory B-cells have already undergone affinity maturation and isotype switching and are ready to go if there is any reinfection :D
Neutralizing functions of antibodies
- 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
Opsonization function of antibodies
Coating microbe with antibodies in preperation for phagocytosis
Antibody-dependent cell-mediated cytotoxicity
- IgG binds to antigen on infected cell surface
- This marks the cell for destruction by NK cells
How do NK cells recognize and kill infected target cells that no longer express MHC I
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
What is the relevance of a splenectomy with relation to immunity?
Patients who have their spleens removed may have reduced protection from previous vaccines and may need to be re-vaccinated
What do swollen lymph nodes indicate?
- Adaptive immune response is engaged
- T-cells and B-cells are proliferation
