The Humoral Response Flashcards
(40 cards)
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
Where does affinity maturation occur?
In the germinal center
Where does affinity maturation occur?
What occurs?
In the germinal center
Receptor binding FAB region, random mutations within CD-R-1-3 region (complementarity determining region)
Then test if it got better or worse at binding: FDC
What enzyme is most responsible for affinity maturation and class switching?
AID (similar in function to RAG enzyme for VDJ)
Activation-induced deaminase
Antibody class switching process?
Similar to VDJ
Switch regions are chosen (fold DNA, cut it out, then that switch region is closest)
***this process mediated by AID
T cell tells which to switch to via cytokines
Ones cuz out of DNA can no longer be made
What are the 5 isotopes of antibodies?
IgM (first used) IgD IgG IgE IgA
Which cytokines are needed for IgE, IgG, and IgA?
IL-4 = IgE
IFN-y = IgG
TGF-B = IgA
Antibody effector functions and their natural sequence of expression?
IgD: developmental marker, if presented it is mature, if IgM presented still immature don’t know effector functions
1) IgM: first produced, pentamer (5 Ys linked), BEST one at activating complement
2) IgG: best and most features: best at neutralization, best at opsonization (upregulated phagocytosis), directly responsible for ADCC (tags for NK to kill infected cell), ONLY one that can gross placenta, most abundant in serum
3) IgA: dimer, secretion antibody, for neutralization
4) IgE: allergic response/parasite antibody (helminths) think TH2 (they are connected)
Antibody locations
IgA: transport across epithelium (mucosal tissue immunity: gastrointestinal and respiratory tracts)
IgG: transport across placenta, most abundant in serum, extra vascular sites
IgM: found in blood and lymph (first responder/made)
IgE: body linings: defense against parasites and mast cell de granulation (allergic response)
