5: Adaptive Immunity - B cells, gene rearrangement + function 🏁 Flashcards
How do adaptive immunity directs innate immunity? Give an example
Activation of naive B cell leads to antibody secretion of plasma cell.
These soluable antibodies can bind to Fc receptor of innate immune cell so innate immune cell acts in an antigen specififc way
Name the 3 different lymphocyte poulation and their major function
B cell or plasma cells
have B cell receptor that activates B cell once antigen binds:
plasma cells then produce 1000x the amount of antibodies
T helper (CD4+) cells
help B cells + innate immune cells by producing IFN-gamma that upregulates innate immune functions
T cytotoic (CD8+) cells
kill other cells to control infection
Clonal selection theory of lymphocytes
clonal distribution of antigen receptors means that lymphocytes that are specififc for the invading pathogen are too infrequent
Clonal selection after activation of antigen specific lymphocytes leads to proliferation
Once reaching a threshold (takes time), this leads to an effective immune response
Clonal nature of adaptive immune response also allows removal of harmfull cells via immunological tolerance
- deletion or anergizing (silencing) of cells that are specific to self-antigen
Developement of B cells (8)
from germline to plasma cell
Germline
- All gene segments present for each segment class (variable, diversity, joining, constant)
Early pro-B cell
- D to J recombination of heavy chain segments
- checkpoint if sucessfull on one chromsome (no = cell death)
Late pro-B cell
- DJ to V recombination of heavy chain segments
- checkpoint if sucessfull on one chromsome (no = cell death)
Large pre-B cell
- Transient Expression of pre-B cell receptor with functional heavy chain (VDJ and C) and surrogate light chain (VpreB) that is necessary for surface expression
- if cell receives a positive signal, heavy chain recombination was successfull and further maturation can occur
- Allelic exlusion: Supression of further H chain rearrangement so there is only 1 h chain gene on one gene (specificity)
- Proliferation
Small pre-B cell
- proliferation stops, there is no pre-receptor on surface
- recombination of VDJC of heavy chain and V to J of light chain
- check point if successfull light chain (lambda or kappa version possible) on one chromosome (cell death)
Immature B cell
- first cell with fully rearranged antibody on surface
- able to sense Ag enviroment so check for self reactivity is possible
Steps of tolerance
- Central (bone marrow): if immature B cell does not recognize any self antigen, it is exported to periphery
- peripheral (spleen): non-self reactive B cell further matures to naive B cells in spenic follicles
- if self-reactive: deletion, anergy or receptor editing
Differentiation in periphery
- Naive peripheral B cell recognizes non self antigen in periphery
- Activation leads to differentiation into plasma cell to secrete 1000x of antibodies
What’s the main difference in the 2nd checkpoint for B and T cells?
B cells: bone marrow, many possible antigen not checked, so another important check in the periphery is necessary
T cells: thymus contains almost every antigen in the body, so this step is stricter for T cells and peripheral step isnt that important
Main difference of antigen receptors for B and T cells and main similariry
Difference
- B cell antigen receptor is membrane bound antibody (surface immunoglobulin)
- B cell directly recogizes 3D structures like proteins, lipids, polysaccharides
- T cell antigen receptor is not mebrane bound but highly related to antibodies
- T cell recognizes peptides, protein antigen presented by MHC molecules
Similarity
- each antigen receptor binds to different antigen
- each cell has only one antigen specificity
3 signals for strong B response
- B cell receptor signal (necessary)
- CD40 signal activated by ligand produced by T helper cells (necessary)
- cytokine signals can modulate response (not essential)
Name 2 different types of antigens that can activate B cells without T helper cells. Give 2 examples for each type and which signals are necessary.
TI-1 antigen (T cell independent)
- e.g. Lipids, Polysaccharides
- 1st: strong singnal of B cell receptor
- 2nd: signal of TLRs on B cells necessary for activtion
- with a very high concentration even signalling without B cell receptor is possible using the TLRs for polyclonal b cell activation
TI-2 antigen
- repetitious molecules like proteins for bact. flagella
- 1st: masive B cell receptor crosslinking that leads to very strong signal
Different B cell subpoulations, their properties and B cell response type
What are natural antibodies?
- A fraction of IgM,IgA and IgG3 antibodies derived from TI-antigen dependent B cells that bind polyreactive and with low affinity to many antigens
- Induced by B-1 cell stimulation by microbial antigens or mitogens of gut flora and stimulation by autoantigens
- part of innate immune response
Developement of B cell subpopulations
- Immature B cell differentiates into transitional (T1) B cell in spleen
- T1 B cell differentiates into T2 B cell (B cell activating factor)
If self reactive:
- anergic T3 B cell
otherwise:
- development into:
- folicular B cell (follicular,B-2 subpoulations)
- Marginal zone cell (B-2,MZ subpopulations)
- B-b B cell (B-1 subpopulation)
T cell dependent B cell response and difference between 1st and 2nd exposure
- Memory antibodies reflect infection to which an individual has been exposed
- pathogen specific immunity
- basis of diagnostics for infection and vaccination
1st exposure: similar IgM and IgG (later) response
2nd exposure: less IgM, but very fast long lasting IgG response
Characteristics of B cell memory (5)
selectiv
against pathogens recognized by T AND B cells
specific
against one specific antigen
strong
increased number and reactivity
fast
lower activation thresholds
optimized
affinity maturated antibodies
Antibody classes and main functions
IgM, IgG, IgE, IgA
IgM
- complement system
IgG
- several functions including neutralization, opsonization, sensitization of NK cells, complement system, different subclasses
IgE
sensitization of mast cells
IgA
neutralization
How is an antibody class switch mediated?
Is a re-switch possible?
Does the antibody class switch alter antigen specificity?
Mediated by gene recombination:
1. Removal of DNA segments by enzyme activity between switch regions
2. Non-homogous end joing leads to newly joined genes
3. Transcript for different antibody class
Re-switch to IgM or IgD is not possible
There is no altering of antigen specificity, so immune response against same antigen with different antibody classes possible
