Lecture 18 Flashcards
(24 cards)
Antibodies can do what against microbes and their toxins?
- neutralize these agents
- opsonize them for phagocytosis
- sensitize them for Ab- dependent cellular cytotoxicity
- activate the complement system.
Different effector functions can be mediated by:
different antibody isotypes
Antibodies are produced by__________, and where does this happen?
Abs are produced by plasma cells in primary (bone marrow) and secondary (LNs) lymphoid organs.
What is the difference between between short-lived plasma cells vs. long-lived plasma cells?
• Short-lived plasma cells
– are generated during T-independent responses.
– may well be generated early during T-dependent responses in extrafollicular B cell foci.
– are generally found in secondary lymphoid organs and in peripheral non- lymphoid tissues.
• Long-lived plasma cells
– are generated in T-dependent germinal center responses to protein Ag.
– Are generated by signals from the BCR and IL-21 via a stage of their precursors called plasmablasts.
Plasmablasts are generated where, and what do they differentiate into?
in germinal centers enter the circulation and home to the bone marrow where they differentiate into long-lived plasma cells.
It is estimated that almost 50% Ab in the blood of a healthy adult is produced by long-lived plasma cells and is specific for Ags that were encountered in the past.
After a person is immunized, how long does it take for the Ab production to being?
- Typically 2 to 3 weeks after immunization with a T cell-dependent Ag, the bone marrow becomes a major site of Ab production.
- Plasma cells may continue to secrete Abs for months or even years after the Ag is no longer present.
- These Abs can provide immediate protection if the Ag is encountered later.
Memory cells:
Memory cells are generated mainly in germinal centers for T-dependent protein Ags.
Memory B cells express
high levels of the anti-apoptotic protein Bcl-2.
Memory cells typically express
high-affinity (mutated) Ag receptors and Ig
molecules of switched isotypes.
Explain why a secondary exposure to an antigen causes a faster immune response?
Abs production is greatly accelerated after secondary exposure to Ags, and this
can be attributed to the activation of memory cells in germinal centers.
• Some memory B cells may remain in the lymphoid organ where they were generated, whereas others exit germinal centers and recirculate between the blood and lymphoid organs.
Vaccine-induced humoral response for infectious disease: POLIO, TETNUS, DIPHTHERIA
What is the mechanism of protective immunity?
Neutralization of virus by mucosal IgA Ab
Vaccine-induced humoral response for infectious disease:
HEP A or B
What is the mechanism of protective immunity?
Neutralization of virus by mucosal IgA or systemic IgG Ab
Vaccine-induced humoral response for infectious disease:
Pneumococcal pneumonia, Haemophilus
What is the mechanism of protective immunity?
Opsonization and phagocytosis mediated by IgM and IgG Abs, directly or secondary to complement activation
How do influenza viruses behave in an infected cell?
And how do antibodies affect this process for host protection?
Influenza viruses use their envelope hemagglutinin to infect respiratory epithelial cells, and Gram- negative bacteria use pili to attach to and infect a variety of host cells.
Abs that bind to these microbial structures interfere with the ability of the microbes to interact with cellular receptors by means of steric hindrance and may thus prevent infection.
Abs against microbes and microbial toxins block the binding of these microbes and toxins to cellular receptors
Antibodies inhibit the spread of microbes from an infected cell to an adjacent uninfected cell.
Ab-Mediated Opsonization and Phagocytosis
Antibodies of the IgG isotype coat (opsonize) microbes and promote their phagocytosis by binding to Fc receptors on phagocytes.
FcR: FcγRI (CD64)
AFFINITY:
CELL DISTRIBUTION:
FUNCTION:
FcγRI (CD64) :
High affinity for IgG1 and IgG3
Cell Distribution: Mφ, neutrophils eosinophils
Function: Phagocytosis Cell activation
FcR: FcγRII (CD32)
AFFINITY:
CELL DISTRIBUTION:
FUNCTION:
FcR: FcγRII (CD32)
Low affinity for IgG1 and IgG3
Cell distribution: Mφ, neutrophils DCs, B cells, NK cells
Function: Phagocytosis Cell activation; Feedback inhibition
FcR: FcγRIII (CD16)
AFFINITY:
CELL DISTRIBUTION:
FUNCTION:
FcR: FcγRIII (CD16)
Low affinity for IgG1 and IgG3
Cell distribution: NK cells
Function: Ab-dependent cell-mediated cytotoxicity
FcεRI
AFFINITY:
CELL DISTRIBUTION:
FUNCTION:
FcεRI
AFFINITY: High Affinity for binds monomeric IgE
CELL DISTRIBUTION: Mast cells, basophils eosinophils
FUNCTION:Cell activation (degranulation)
Ab-Mediated Phagocytosis
- Binding of Fc receptors on phagocytes to multivalent ab-coated particles leads to phagocytosis and the activation of phagocytes.
- IgG1 and IgG3 are the most efficient opsonins for promoting phagocytosis via high-affinity FcγRI (CD64).
- Signals from the Fc receptors activate the phagocytes to destroy these microbes.
Inhibitory Signaling by FcγRIIB Receptor
- Ag-Ab complexes can simultaneously bind to membrane Ig (through Ag ) and the FcγRIIB receptor through the Fc portion of the antibody.
- As a consequence of this simultaneous ligation of receptors, phosphatases associated with the cytoplasmic tail of the FcγRIIB inhibit signaling by the BCR complex and block B cell activation.
SHIP – SH2-Containing Inositol Phosphatase
FcR Mediated Ab Feedback
• Is a physiologic control mechanism in humoral immune responses.
• It is triggered by secreted Ab and blocks further Ab production as apposing the
activation via CR2.
- It is not clear under which circumstances secreted Abs provide complement-mediated amplification or Fc receptor–mediated inhibition.
- A likely scenario is that IgM which activate complement but do not bind to the FcγR are involved in amplification, whereas increasing production of IgG leads to feedback inhibition.
- Uncontrolled Ab production seen in mice in which the FcγRIIB gene has been knocked out.
- A polymorphism in the FcγRIIB gene has been linked to susceptibility to the autoimmune disease systemic lupus erythematosus in humans.
Ab-Dependent Cell-Mediated Cytotoxicity (ADCC)
- Ab of certain IgG subclasses bind to infected host cells), and the Fc regions of the bound Ab are recognized by an FcγRIII on NK cells.
- The NK cells are activated and kill Ab-coated cells.
- This process is called antibody-dependent cell-mediated cytotoxicity (ADCC)
IgE-FcεRI in Killing of Helminths
.
