Humoral Immunity Flashcards
FAB
Made of Vl and Vh regions…binds the antigen
FC
Constant region that determines function and binds to macrophages, T cells, etc.
Antibody hinge region and how is entire thing held together
Allows flexibility
Disulfide bonds
How many HV regions per chain
3
AB vs. T cell antigen binding
AB can bind tons of stuff
T cell only proteins
Other region besdies HV
Framework…pretty stable
Antigen binding sites composed of
HV regons
AB:antigen interaction due to
Noncovalent forces…means it is reversible
Which region only in heavy chain?
Diversity region
Which region has most functional gene segments?
Variable
Combinatorial diversity
Random joining of D/J regions (example)…other regions can be brought together as well
Junctional diversity and how it happens
RSS brings together junctions…RAG 1 and 2 generate hairpins at region…TdT adds N-nucleotide additions and alters
In absence of TdT
Still some antibodies but lack diversity
Absence of Rag 1 and 2
No recombination…therefore no B cell formation
Cause of SCID
Allelic exclusion of AB
Only one copy of Ig genes are expressed on an individual cell
A heterozygous Ig will only display one specificity on its surface
Alleles for each type of AB
M - M G - G1-4 D - D E - E A - A 1-2
Which activate complement via classical pathway?
IgG1 -3
IgM
Bind to C1q
Whcih transfer placental
IgG
Which bind to marcophage Fc receptors
All but IgM, IgD, and IgG2
Which bind mast and basophils
IgE
Which are reactive with Staph protein A
IgG
Amount of Igs in serum
IgG in serum is most
IgM and IgA present
IgD not in serum
Small IgE
Weird structures of Igs and consequences
Dimeric IgA - 4 binding sites
Pentameric IgM - 10 binding sites
Increases avidity - binding of entire molecule
2 types of determinants
Conformational - need geometry in order to recognize
Linear determinant - may not be able to bind if there is geometry
B cell developmet
Stromal cells aid in development
Go through negative selection in the bone marrow (if bind to self, will try to rearrange and if not, then killing)
Activated outside of bone marrow by lymphoid organs by meeting foreign antigen
Give rise to memory and plasma cells in bone marrow and lymphoid tissue
When B cells first secreted, only have
IgM and IgD
Important IL for B cell development
IL-7 - uses common gamma chain - deficiency leads to SCID
Which chain develops first
Heavy chain…will have IgM before IgD
BK
Bruton’s tyrosine kinase
Deficiency leads to B cell deficiency
IL-7R
Important in expansion of B cells
Arrangement of heavy chain
D-J first
then V-DJ
L-chain arragnement
V-J rearranged
Receptor editing of B cells
If expression in mu chain is to self, will undergo rearrangement of light chain to try to eliminate this effect…if still bind to self, apoptosis
If B cell self-binds to soluble self molecule in bone marrow
Anergic B cell migrates to peripher y
If B-cell binds very low affinity self molecule in bone marrow
Clonally ignorant cell migrates to periphery…could still be activated
In spleen, if B cell recognizes self
Same things as in bone marrow
Will eventually mature if low-affinity (clonal ignorant) or no reaction (mature)
3 things AB does
Neutralization
Opsonization
Complement Activation
Thymus-dependent B cell stimualtion
BCR binds antigen and stimulates signaling…antigen taken in with BCR and processed into class 2 MHC…presented to T cell along with CD40 which binds CD40L…causes class switching from IgM to another type
CD40/CD40L defieincy
Hyper IgM…can’t class switch…susceptible to pyogenic bacteria
T-independent stimulation
2 options
Polyvalent antigen cross linking AB binds…no class switching
TLR binds a mitogen - no class switching
Polysaccharide activation
Is T-independent (no IgG and no memory)…by attaching a protein to the polysaccharide, you can generate memory (IgG)
Hib/pneumococcal conjugate vaccines
Tfh cells
T follicular helper cells
Bind to B cell using CD40L/CD40 interaction and allow proliferation of B cells by producing cytokines
Difference between B and T cell viral activation
T cells recognize things on the inside
B cells recognize surface of virus
T cells can help B cells recognize linked epitopes even if not identical
How do antigens get into lymph node
Via dendritic cells via affarent lymphatics
B cells enter lymph nodes through
HEVs and move through follicles to germinal centers
FDCs have what receptors?
Fc and complement receptors
FcR and Cr1
PLasma cells wil migrate to
Bone marrow
2 things that happen during maturation of AB response and where does it happen?
Somatic hypermutation - mutated genes and expresson of different AA allows variability
Class switch - changes function
Germinal centers
IFN-gamma = which Ig and function?
IgG - opson, complement, placental
IL-4 = which IG and function/
IgE, IgG4 - helminths protection and mast cell degranulation
TGF-B, APRIL, BAFF = which Ig and function?
IgA…mucosal immunity in lungs and gut
Class switching
Nothing changes except for constant region
Requires AID
Somatic hypermutation
Select high-affinity antibodies that change affinity (not specificity)
Requires AID
As number of responses increases
Number of somatic hypermutations increases as well to select for best antibody
If AID is lost then,
Lower affinity B cells with mostly IgM antibodies
IgA function
Secreted into the lumen via pIgR receptor…binds to toxins and pathogens…opsonization for destrution
Distribution of AB through body
IgG and IgM in blood
Dimeric IgA at mucosal
IgE - around the skin …passed to child
Antibody toxin neutralization
Prevents binding of toxin to cell
Antibody virus neutralization
Blocks virus bindign to cell membrane
Antibody bacteria neutralizatio
Block to adhesins of bacteria and prevent association with cell membrane…also complement
Antibody - complement
IgM and IgG bind to and activate C1q
Antibody immune complexes
Get cross linking of antibodies and activate complement…C3b binds to pathogen as well…complement receptor CR1 on erythrocytes binds via C3b…takes ot spleen and liver where phagocytic cells destory
Free Ig will not
Cross-link Fc receptors on macrophages…need to be bound to bacterial surface
Eosinophils attack
IgG and IgA coated schistosome larva
ADCC
AB binds on target…NK cell recognizes and induces apoptosis
Mast cell degranulation
Via IgE…cross-links
In secondayr response, what is differnet?
IgA and IgG more than IgM…high affinity, high somatic hypermutation
If you see more IgM
Then probably early in process and maybe the first time infected
If mostly IgG,
Pathogen is gone or this is not the first time they have seen ti
CD40/CD40L def
CD40L (x-linked)
Hyper IgM
AID def
Hyper IgM
BAFF and APRIL def
No differentiation into Igs in the spleen
TACI def
common variable immunodeficiency
