Humoral Immunity Flashcards
How do B cells in the blood and in the lymph enter into 2ndary lymphoid tissue?
B cells in the blood enter through HEV and cells from the lymph enter through the subcapsular sinus
What is the process by which antigens moving through the lymph are captured and presented to B cells in the lymph nodes?
Antigens are caught by specialized macrophages in the subcapsular sinus; capture is mediated by the antigen being coated with complement fragments which macrophages and follicular dendritic cells have receptors for
What complement receptors are found on follicular dendritic cells and what are their ligands?
CR1- C3b; CR2,3,4- iC3b; CR2 also C3dg
How does a B cell that enters a lymph node from the blod travel through the node?
Enters through HEV into the T cell zone and then move into a B cell zone (follicle)
What attracts naive B cells to follicles?
B cell express CXCR5 which is attracted to CXCL-13
How is a B cell activated by strictly antigen?
Cross linking over numerous (at least 2) BCR
What are the 3 principal functions of the BCR?
1) Recognition and binding of pathogen 2) Intracellular signaling for activation 3) Internalization of the antigen for processing and presentation via MHC II
What are thymus-independent antigens? What is a common example?
They are antigens that can generate an antibody response without T cell co-activation of the B cell; Usually highly repetative determinants (e.g., polysaccharides of bacterial coat) that can bind to very many BCR and amplify the signal
What are the two signals required for B cell activation with thymus-dependent antigens?
1) cross-linking of BCR and 2) CD40 and CD40L ligation [Interactions between the MHC and TCR also augment the activation signal
How do B cells and Tfh cells move from their respective areas in the lymph node to one another
Signal 1 of BCR activation induces CCR7 expression on the B cell drawing it to the CCL19, CCL21 gradient in the T cell zone; Tfh cells activated by dendritic cells reduce their expression of CCR7
What results from full activation of a B cell in a lymph node?
Formation of a germinal center
What is the process of affinity maturation?
The process by which an activated B cell undergoes somatic hypermutation in which there is rapid proliferation, producing clones that can have mutations in the antigen binding site which improve or decrease the affinity. Those clones with improved affinity continue to die, but the decreased affinity clones die such that the resulting population has a higher and higher affinity to the antigen
What is the cause of X-linked Hyper IgM?
CD40L deficiency
What is the intermediate stage between activated B cells and plasma cells?
Plasmablasts
Where does terminal differentiation of plasmablasts to plasma cells occur?
In the tissue
Where are the majority of serum antibodies produced?
Plasma cells living in the bone marrow
What is the approximate length of time after a primary infection that a antibody can be measured in the serum? At what time point does the production peak?
1 week ; 2 weeks
Which portion of the antibody confers effector function?
Fc region
How does a neutralizing antibody work? Which classes are the best neutralizers?
The Ab binds to the outer surface determinant that is required by the pathogen (or toxin) to enter the cell; IgA, IgG, and IgM
How do antibodies facilitate the elimination of soluble immune complexes? Which Ab classes are used for this?
Antibody:antigen complexes form and complement deposition occurs due to the affinity of Cb3 to the Fc portion of IgG or IgM. RBCs express CR1 which binds the C3b and transports the connected IC to Kupffer cells for phagocytosis
Which Ab classes are best at fixing complement? Why?
IgG and IgM- They have a C1q binding site on their Fc portion
Which Ab classes are best at Opsonization?
IgA or IgG
Which Ab class is used against parasites? How does it work?
IgE Fc portion binds to FceR on eosinophils and binding triggers degranulation
Which cells are always coated with noncomplexed IgE and why? How are these cells activated?
Mast cells and basophils because they express high affinity FceR; Activated by cross-linking the IgE
What is immunological ADCC?
Antibody-dependent cellular cytotoxicity by NK cells
What is the process by which ADCC occurs?
An infected cell expresses a pathogenic antigen that is recognized by and binds to IgG; Cross-linking of the Fc(gamma) receptors overrides the NK cell brakes and they destroy the IgG bound host
How do NK cells kill?
Release of perforin and granzymes
What is the mechanism by which Rituximab works?
Rituximab is a IgG MOAb against CD20 (on B cell lymphoma)which activates NK cell Fcgamma receptors and kills the cancer cells
Which cells are considered most important for Fc-mediated destruction of bacteria?
Macrophages/monocytes and neutrophils
Which cells are considered most important for Fc-mediated destruction of parasites?
Eosinophils, Mast cells, and basophils
Which cells are considered most important for Fc-mediated destruction of virus-infected cells?
NK cells
What is the function of FcRn?
Transports maternal IgG across the placenta to the fetus
What is the function of pIgR?
Transportation o dimeric IgA antibodies acrocc epithelial barriers and into secretions
What is the most prevalent form of Ig in breast milk?
IgA
