The Humoral Response Flashcards
What mediated effector functions of humoral response?
Antibodies produced by activated B cells: they neutralize the extracellular microbes
Overview of humoral response!
mature B cell: IgM and IgD being expressed
Activate when helper T cell signals to activate (3signals)
Clonal expansion
Differentiation:
1) some become plasma cells
2) some class switch and affinity mature
3) sub pop becomes memory B cells
The differentiation possibilities of B cells?
1) become plasma cells: active antibody secretion, IgM (IgM is first produced)
2) class switch and affinity mature under direction of helper T cells Affinity mature: change FAB region so it binds stronger --> HIGH AFFINITY IgG****
3) sub pop becomes memory B cells to activate in a secondary response
What are the three signals of B cell activation?
1) BCR complex recognizes antigen (NOT MHC DEPENDENT, FREE ANTIGENS ONLY)
2) complement receptor CR2 binds C3d (complement activation product)–> drives activation
* esp strong if both signal 2) and antigen recognition
3) t-dependent antigen signal provided by TH cells = CD40-CD40 ligand (CD40 is on B cell, ligand on helper T)
Humoral response deals with:
Extra cellular microbes
Humoral response must neutralize and eliminate extra cellular microbes
Overview of B cell antigen recognition (what needs to bind?)
Cd3 bound to microbe binds CR2
Microbial antigen binds BCR
Together= recognition
Single receptor complex binding is usually not enough to actually activate B cell, need signals from Ig and Cr2 complex
What happens after B cell activation?
Proliferates Plasma, class switch, affinity mature, and memory cells
IgM secretion is eventually replace by IgG (class switching)–> population of IgG making cells outgrows IgM producing population
B cell responses to antigen? And significance?
Entry into cell cycle= clonal expansion
INC expression of cytokine receptors= can respond to Helper T cell secreted cytokines
Migration out of lymphoid follicles= interaction with helper T cells
Secretion of low levels of IgM= early phase of humoral response
T-dependent versus T-independent B cell antigens?
T-dependent (thymus):
- proteins (think how T cells only recognize proteins, and this type of activation depends on T cell function
- ***if recognizes protein–> needs T cell help
- isotope switching YES
- affinity maturation YES
- memory cells made YES
T-independent:
- polysaccharides, nucleic acids, glycolipids, polymeric antigens
- low level isotope switching
- little to no affinity maturation
- memory cells only made when dealing with some polysaccharide antigens
What are polymeric antigens and how can they activate T cells?
What is the downside to this type of activation?
Antigens with same repeating unit, long polymers bind and cross link BCR ‘s, bringing them together and causing a large signal
Downside: T cell cannot communicate so cannot class switch or affinity mature, so only IgM is made
How do B cells activate via t-dependent antigens?
Recognizes globular protein, only engages one receptor of Y: no cross linking
Cell takes that receptor, pulls it in, makes MHC class II and becomes APC
T cell must then recognize and tell it to activate
Most are t dependent
B cell antigens are large or small complexes?
Large complexes!!
3 types of B cells: location and antibody production? Main antigen? Effector functions?
Follicular B cells (B2):
- location: follicles of secondary lymph nodes, adult humoral response
- antigen: recognize T- dependent antigens
- can do all antibody isotopes
- effector function: long lived plasma cells
B-1 cells:
- location: peritoneal and pleural cavity fluid AND mucosal tissue
- formed early in life, short lived, self populate
- antigens: polymorphic, T-independent
- only IgM
- express CD5
- plasma cells
Marginal zone:
- location: marginal zone of splenic white pulp
- resting mature cells
- antigens: T-independent
- IgM only
- plasma cells
T and B cell interaction
B cell binds globular protein, internalizes and presents as APC
B cell enters border T-B cell region
Dendritic cell activates T cell
Activated T cell activates B cell w/same antigen
B cell makes IgM, back to follicle, makes germinal center: also starts class switching and affinity maturing
What does the follicular dendritic cell do?
Holds antigens so B cells can retest receptors after affinity maturing (sits in follicle)
IF doesn’t bind: does
IF works better: lineage expanded for that cell
T and B cell interaction simple version
B cell encounters its antigen
Processes via MHC2
Presents to active T cell (CD4)
T cell recognizes: if CD40 (on B) and CD40 ligand (on T) AND MHC/antigen interaction both match
Cytokines secreted by T cell signal antibody class switching to B cell