Lecture 15
What are the six categories of antibody effector functions?
Neutralization, opsonization, complement activation, ADCC, mast cell degranulation, agglutination.
What is neutralization?
Antibodies block pathogens or toxins from entering cells.
What is opsonization?
Antibodies coat pathogens to enhance phagocytosis.
What is complement activation?
IgM or IgG trigger complement leading to pathogen lysis.
What is ADCC?
NK cells kill antibody-coated target cells.
What is mast cell degranulation?
IgE triggers release of histamine for allergy and parasite defense.
What is agglutination?
Antibodies clump pathogens together for easier clearance.
What are the characteristics of IgM?
First responder, pentamer, strong complement activation, good at agglutination.
What are the characteristics of IgE?
Involved in allergies and parasites, binds mast cells, low concentration in serum.
What are the characteristics of IgD?
Found on naïve B cells, functions mainly as a B cell receptor.
What are the characteristics of IgA?
Mucosal immunity, dimer, found in secretions like saliva and lungs.
What are the characteristics of IgG?
Main serum antibody, long half-life, crosses placenta, involved in opsonization and ADCC.
What are Fc receptors?
Receptors that bind the Fc region of antibodies and trigger immune responses.
What do Fc receptors do?
Translate antibody binding into cellular responses like phagocytosis or killing.
What are ITAMs?
Activating signaling motifs that trigger immune cell activation.
What are ITIMs?
Inhibitory signaling motifs that suppress immune activation.
Which overrides: ITAM or ITIM?
ITIM overrides ITAM (inhibitory signals dominate).
What is affinity?
Strength of binding between receptor and antigen-MHC.
What is FcγR?
Fc receptor that binds IgG and mediates phagocytosis and ADCC.
What is FcεR?
Fc receptor that binds IgE and triggers mast cell degranulation.
What is FcαR?
Fc receptor that binds IgA and supports mucosal defense and phagocytosis.
What is FcμR?
Fc receptor that binds IgM and regulates IgM responses.
What is FcRn?
Neonatal Fc receptor that binds IgG and protects it from degradation.
What are the two functions of FcRn?
Protect IgG from degradation and transfer IgG to fetus.
What is IgG recycling via FcRn?
IgG is taken into cells, bound by FcRn in endosomes, protected from degradation, and released back into circulation.
What is the significance of FcRn recycling?
Extends IgG half-life (~21 days) and supports long-term immunity.
What is pIgR?
Poly-Ig receptor that transports antibodies across epithelial cells.
Which antibodies use pIgR?
IgA and IgM.
What is the role of the J chain?
Links antibody units together and is required for transport via pIgR.
What is the function of pIgR?
Moves IgA and IgM to mucosal surfaces.
How is pIgR different from FcRn?
pIgR exports antibodies to mucosa, FcRn protects antibodies in circulation.
How is antibody secretion turned off?
Through negative feedback mechanisms.
What is FcγRIIB?
An inhibitory Fc receptor on B cells that binds IgG-antigen complexes.
What is the role of FcγRIIB?
Provides negative feedback to reduce antibody production.
How do ITIMs function in FcγRIIB?
They send inhibitory signals to suppress B cell activation.
What is feedback inhibition in B cells?
Increased IgG leads to increased inhibition of further antibody production.
What are therapeutic antibodies?
Lab-made antibodies used for treatment of diseases.
What is a mouse antibody?
Fully mouse-derived, highly immunogenic.
What is a chimeric antibody?
Mouse variable region with human constant region.
What is a humanized antibody?
Mostly human with only mouse CDR regions.
What is a fully human antibody?
Entirely human, least immunogenic.
What is Rituximab?
A chimeric antibody targeting CD20 to kill B cells, used for lymphoma and autoimmune diseases.
What is Adalimumab?
A fully human antibody targeting TNF-alpha to reduce inflammation in autoimmune diseases.
What is Ipilimumab?
A fully human antibody targeting CTLA-4 to enhance T cell activation in cancer therapy.
What are the general steps of CD8⁺ T cell activation?
Recognition of antigen on MHC I, co-stimulation, cytokine signaling, clonal expansion, differentiation.
What are the three signals for CD8⁺ T cell activation?
TCR + MHC I, CD28-B7 costimulation, cytokines (IL-2).
What is the sequential model of CD8 activation?
CD4 T cells activate first, then help activate CD8 T cells.
What is the simultaneous model?
CD4 and CD8 T cells are activated at the same time by the same APC.
Which model is better supported?
Simultaneous model.
What is dendritic cell licensing?
CD4 T cells activate dendritic cells to better stimulate CD8 T cells.
What is the role of CD40
CD40L? / CD40L on CD4 T cells binds CD40 on dendritic cells to activate them.
What is cross-presentation?
Dendritic cells present external antigens on MHC I to activate CD8 T cells.
What is the role of IL-2?
Promotes T cell growth and proliferation.
Which cells produce IL-2?
Mainly CD4 T cells.
How do cytotoxic T lymphocytes (CTLs) kill target cells?
Using perforin/granzymes and Fas–FasL pathways.
What is perforin?
Protein that forms pores in target cell membranes.
What are granzymes?
Enzymes that enter cells and trigger apoptosis.
What is the Fas–FasL pathway?
FasL on T cells binds Fas on target cells to induce apoptosis.
Why are adhesion molecules important?
They stabilize interaction between CTL and target cell.
What is IFN-γ?
Cytokine that activates macrophages and has antiviral effects.
What is lymphotoxin (LT)?
Cytokine involved in inflammation and cell killing.
What are NK cells?
Innate lymphocytes that kill infected or cancer cells.
What are characteristics of NK cells?
No antigen-specific receptors, rapid response, detect abnormal cells.
What lineage are NK cells from?
Lymphoid lineage.
What cytokines activate NK cells?
IL-12, IL-15, IL-2.
What cytokine do NK cells secrete?
IFN-γ.
How do NK cells decide to kill?
Balance between activating and inhibitory signals.
What is the missing self model?
NK cells kill cells lacking MHC I.
What is the balanced signals model?
NK cell activation depends on net activating vs inhibitory signals.
Which NK model is more accurate?
Balanced signals model.
What are inhibitory NK ligands?
MHC class I molecules.
What are activating NK ligands?
Stress-induced molecules on infected or tumor cells.
What is ADCC in NK cells?
NK cells bind IgG-coated targets and kill them.