Humoral immunity (b cell response) dwinell Flashcards
humoral immune responses are an arm of the (adaptive/innate) immune system and is activated by and recognize _, _, _, and _ (which types of molecules)
adaptive
proteins, polysaccarides, lipids, and small chemicals
Humoral immunity is mediated by _ lymphocytes and secreted _
B lymphocytes, secreted antibodies
When _ molecules recognize antigens, signals are delivered to the lymphocytes by proteins associated w/ the antigen receptors
B cell receptor (BCR) immunoglobulin (Ig) molecules (two or more!)
Iga and Igβ proteins
TCR and BCR consist of domains that mediate immune recognition and are different between clones of lymphocytes
Constant (C) region- genetically _
Variable (V) region- genetically _
C, concerved receptor domain
V, variable, diverse antigen recognition domain
Variable region of Ig is focused among _
Constant region in the BCR can change but TCR is fixed
Which has a higher affinity for antigen? TCR or BCR?
CDRs
BCR has higher initial affinity, increases during response
TCR affinity is fixed
commitment of progenitor cells to develop for B cells-
Heavy chain protein expression
(In T cells it was the TCR Beta chain)
_ produced by bome marrow and stromal cells provides the mitogenic signal for developing lymphocytes (B and T) to proliferate
IL7
IL7
Lymphocyte precursor proliferation
Variable region of heavy chain (IgH) is composed of three gene segments that recombine during cellular differentiation and maturation. They are:
v (variable)
D (diversity)
J(joining)
heavy chain transcript VDJC (also contains constant Cμ) is processed and then expressed at the cell surface
B cells are mature (but still naive) in the peripheral immune tissues (follicles) when they express_ and _ on the cell surface
IgM and IgD
The BCR is a dimeric protein that confers Antigen Specificity (variable region) and effector function specificity (constant region)
Where would you find the heavy chain, light chain, variable region, constant region, Fab region, and Fc region on a secreted IgG?
Where is the antigen binding site?
mechanisms of antigenic diversity
_-variation amongst possible vdj and vj exon combinations
_-removal of nucleotides, addition of nucleotides by TdT enzyme, strand repair during recombination process
Combinatorial, junctional
each variable region of the IgH and IgL chain has three regions of hypervariability known as _
CDR (cdr1, cdr2, cdr3)
when a naive IgM IgD B cell becomes activated by a helper T cell or another stimuli, it undergoes _ _ and _
Types of B cell outcomes possible include:
clonal expansion
differentiation
Antibody secreting plasma cells, IgG expressing B cells, High-affinity Ig-expressing B cell
In the LN follicle, antigens are presented by _ to membrane bound _ on _
follicular dendritic cells (potentially)
IgM, naive B cells
Naive b cells require 2 signals for activation
1)
2)
1- bcr binds antigen
2)
a) CR2/CD21 (complement receptor) activated by Cd3 complement protein OR
B) TLR activated by microbial pathogen association molecule (PAMP)
BCR activation
Two or more BCRs
ITAM: immunoreceptor tyrosibe based activation movif
Activates a battery of transcription factors that drive clonal expansion, differentiation
Four b cell responses to antigen after activation-
name 4 things
mitosis, increase cytokine receptors to respond to T cell’s cytokines, migration out of lymphoid follilcles, secretion of IgM
if a b cell phagocytoses an antigen, it will present it on Class 2 mhc peptide complex. For the T cell to recognize it, the b cell must express _ and the T cell must express _
B7, cd28
T cell-mediated differentiation of activated B cells involves _ ligand from T cell interacting with B cell surface protein _.
Cytokines from T cell also attach to the cytokine receptor on B cell.
Cd40L, CD40
B lymphocytes differentiate into antibody secreting _ cells and _ cells
Plasma, memory B
in effector b cells, class switching results in antibodies with:
Affinity maturation produces antibody with _
fc regions capable of diverse effector functions
higher affinities for antigen binding (triggered by booster stimulation)
B cell differentiation in a secondy exposure causes changes in antibody structure. three changes that can occur:
Affinity maturation (increases affinity)
Switch from membrane to secreted form (change from b cell receptor function to effector function)
Isotype switching (different set of effector functions)
isotype switching- antibody mediated mechanisms in host defense
_ activation leading to opsonization and/or microbial killing
_ enhanced by antibody and/or complement components bound to the infectious agent (opsonization)
-_
complement activation
phagocytosis
neutralization
different immunoglobulin heavy chains have evolved to carry out different functions. The _ region is inially found of IgM and IgD, but is switched onto other _ regions during the course of the response, hence “isotype switching”
Switching is controlled by _ cells and _
Heavy chain variable (VH) initially,
Heavy chain constant (CH)
T helper cells and varying cytokines
Define idiotype
Define isotype
Idiotype: shared characteristic between a group of Ig molecules with shared antigen binding specificity and variable region (VH and VL) structure
Isotype: type of antibody as defined by the constant heavy (Ch) region
T independent class switching results in Ig_
T dependent? Ig_ and Ig_
M,
G and E
The principal effector function of the T-independent production of IgM is _
complement activation
T dependent isotype switching.
Helper T cells with CD40L and Cytokines
If there is IFN-y present, make B cells turn into plasma cells that secrete _
If there is IL-4 present, make B cells turn into plasma cells that secrete _
If there are cytokines in mucosal tissues such as TGF-B present, they make B cells turn into plasma cells that secrete _
IgG- Fc receptor-dependent phagocyte responses; complement activation; neonatal immunity (placental transfer)
IgE- immunity against helminths, mast cell degranulation (immediate hypersensitivity)
IgA- Mucosal immunity (transport of IgA through epithelia)
