2 types of immunity
innate and adaptive
innate immunity involves these types of cells
neutrophils, macrophages
adaptive immunity involves these types of cells
B cell, T cells, macrophages, dendritic cells
FYI: a few scientists were discussed and their contributions to immunology - look at the slides if you want to learn them
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the kinetics of an Ig response - if you immunize someone with an ___, after about 10 days you get a small ___ first response followed by a small ___ response - then the response goes back to normal - then if you wait 3 weeks and you are exposed to the sam
antigen, IgM, IgG, IgM, IgG
this is the specific Ig that gives a large response upon secondary exposure to an antigen
IgG
this theory is the main one in immunology
clonal selection theory
clonal selection theory says that each cell has a unique __ on the surface and the __ selects which cell would be stimulated, stimulated cells ___ and ___ and secrete identical antibodies to those on the cell surface that they binded
antibody, antigen, expand, differentiate
these cells produce antibodies (Ig)
plasma cells
plasma cells produce ___
antibodies
plasma cells are the result of differentiation of ____
lymphocytes
lymphocytes have a ___ (smaller/larger) cytoplasm than plasma cells
smaller (plasma cells have large cytoplasms packed with ER and mitochondria b/c they produce antibodies)
development of B and T cells starts in __ ___ as hemopoietic stem cells - then preT cells move to the ___ where they differentiate and preB cells move to the ___ (in birds) where they differentiate
bone marrow, thymus, bursa of Fabricius
this lymphocyte is involved in cell mediated immune response
T cells
this lymphocyte is involved in antibody response
B cell
this portion of Ig binds to antigen
Fab (variable region)
this is the functional part of Ig
Fc (constant region, effector function)
what is an easy way to describe antigen-antibody binding?
lock and key mechanism (antigens can bind in pockets, grooves, or on extended surfaces in the antibody binding site)
T/F: antigen binding to antibody is all about surface features
true
Ig molecules are composed of __ disulfide-linked polypeptide chains
4
there are 5 classes of Ig which are defined by the type of ___ chain they have: G,A,M,E,D
heavy
each heavy chain has ___ variable domain and __ constant domains (slide 18)
1,3 (except IgM)
IgM has ___ constant domains
4
there are 2 kinds of light chains: __ and __
lambda and kappa
on a single Ig there will be __ kind of light chain
1 (either lambda or kappa)
how are the heavy and light chains of Ig held together?
disulfide bonds (4 of them)
what are the precursors to plasma cells?
mature B cells and memory B cells
mature B cells can either become ___ ___ or ___ __
memory B cells, plasma cells
secondary immune responses occur due to presence of these cells
memory B cells
as stem cells differentiate into B cells they gain receptors - immature B cells have __ receptors and mature (true) B cells have ____
IgM, IgM and IgD
will immature B cells respond to antigen?
no
do memory cells secrete Ig?
no
____ recombination during B cell development generates diversity
VDJ
VDJ recombination during ___ development generates diversity
B cell
the variable region genes of Ig are assembled by somatic recombination of ____ segments for the heavy chains and __ segments for the light chains
VDJ (D=diversity), VJ
which chain is more diverse, heavy or light?
heavy (VDJ)
selection of gene segments is a ___ process which is key to ___
random, diversity
is organization of V,D, J encoded in the germline?
no (cells randomly express these proteins and they have unique and unpredictable binding)
T/F: combinatorial genetics occurs in the absence of antigens
true
transmembrane and secreted forms of Igs are derived from identical ___ by alternative ___
mRNA, splicing
can membrane Ig be different than secreted Ig?
yes (they are derived by alternative splicing from identical mRNA)
if you look at gene sequence, there are structures in the sequence with 2 kinds of ___, one that codes for a tail that inserts itself onto plasma ___ or that's a code for a ____ tail - both are in primary DNA transcript - then the cell decides which is ha
tails, membrane, secretor, mRNA
co-expression of IgD and IgM is regulated by ___ processing
RNA
co-expression of __ and __ is regulated by RNA processing
IgD, IgM (the initial gene transcript contains both and it depends on how the mRNA is spliced for which one it ends up having)
these cells have expression of both IgM and IgD
mature B cells
V,J, D are regulated by ___ slicing while the expression of IgD or IgM is regulated by ___ splicing
DNA, mRNA
during the development of B cells, any cells that have the potential to recognize self structures are ____
eliminated
during the development of B cells, those lymphocytes that DON'T respond to self Ag live and can proliferate and differentiate into ___ ___ that secrete Ig to recognize those pathogens
plasma cells
the surface of a pathogen is a mosaic of ____ that B cells can respond to, this response is ___ ___
epitopes, clonal proliferation
Using the ____ molecule as its receptor, the B cell recognizes _____ on the surface of the antigen. If it is stimulated by this contact, the B cell ____, and the resulting clones can secrete antibody whose specificity is the same as that of the cell-surfa
antibody, epitopes, proliferates
FYI: for each epitope there may be several different lymphocyte clones with different B-cell receptors, each of which recognizes the epitope in a slightly different way and therefore with a different binding strength (affinity).
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3 ways that immature B cells which react to self-antigens are eliminated
deletion, anergy, receptor editing
immature B cells that react to self ___ are eliminated
antigens
when immature B cells that react to self antigens are NOT eliminated as they should be, it can cause ____ ___
autoimmune disease
when immature B cells that react with self antigen die by apoptosis the process is called ___
deletion
when immature B cells that react with self antigen are inactivated long term the process is called ___
anergy
when immature B cells that react with self antigen undergo reactivation of VDJ recombination so that the B cell now has a receptor for non-self antigen the process is called ____
receptor editing
what is a probable issue with anergy?
autoimmune disease can arise when immature B cells that interact with self antigen get inactivated by anergy but then are reactivated sometime later
most antigens are T ____ (dependent/independent)
dependent (in order for B cells to respond it has to cooperate with a T cell)
antigens that can activate B cells in the absence of T cells are called ____
T-independent antigens
T-independent antigens tend to be associated with bacteria that have highly ___ subunits - they can ___ the receptor and it's the clustering of receptor that gives signal to proliferate
repetitive, crosslink
Ig response to T-independent antigens is primarily ___ and no __ ___ are produced
IgM, memory cells
are memory cells produced in response to T-independent antigens?
no (maybe a few)
will there be IgA or IgG response to T-independent antigens?
no (just IgM)
Since Ig doesn't have a large cytoplasmic domain it needs assistance to get info to move from outside to inside a cell - what are the 2 major players that help?
Ig-alpha and Ig-beta (they have extensive cytoplasmic domains and will noncovalently interact with Ig to help with signaling)
clustering of antigen receptors allows receptor-associated kinases to phosphorylate ___
ITAMs (immune tyrosine activation motif)
when Ig are clusterd and noncovalently interacting with Ig-alpha/beta, there are ____ kinases that ___ the cytoplasmic regions of the associated Ig-alpha/beta
tyrosine, phosphorylate
once tyrosine kinases phosphorylate the cytoplasmic regions of the associated Ig-alpha/beta a second family of kinases, __, phosphorylate regions further and bind to these regions - the regions on Ig-alpha/beta that are phosphorylated are called ___
Syk, ITAMs
Syk binds to __ phosphorylated ___ and is activated on binding
doubly, ITAMs
T/F: most antigens are T-dependent - they require help from T cells to stimulate B cells
true
most B cells require 2 signals:
1. through the ___
2. various, but most common is through ____
antigen, CD40 (T cells have a CD40 ligand that binds to CD40 on B cells)
this a protein on the surface of B cells that is often a part of the 2nd signal to stimulate B cells (T cells have a ligand that will bind to it on the B cells)
CD40
triggering stimulation of B cells starts with __
antigen
T/F: even with segments of the network blocked, signal transduction still is possible; but perhaps not as efficiently
true (fishing net image)
what is the only primary lymphoid organ?
thymus
antigens usually require help from ___ ___ ___ in the germinal center or ____ to stimulate B cells
follicular dendritic cells, TLRs
B and T cells interact with Ag in defined structure called ___ ___ ____ which have special cells within them called ____ ____ cells - T dependent Ag bind
first to ___ ____ cells and they present the Ag to the B cell
secondary lymphoid organs, follicular dendritic, follicular dendritic
__ and ___ (endotoxin) both can also function to stimulate B cells in
secondary lymphoid organs - can substitute for 2nd signals for T dependent Ag
TLRs, LPS
what presents the antigen to the B cell in the germinal center?
follicular dendritic cells
are follicular dendritic cells absolutely necessary for stimulation of B cells?
no
B cells develop in the lymph node in the __ ___, T cells, helper T cells, B cells and follicular dendritic cells found there also - Lymphocytes come into the organ and if they don't ___ they will die by apoptosis. Those cells that bind to an Ag (+ selecte
germinal center, bind, proliferate, plasma, memory
during development of B cells in the germinal center - selection of B cells with high affinity for antigen is called ___ which can take place in IgV genes. This process generates diversity by forming random gene segments - when stimulated, the sequence ch
hypermutation, variable
name 2 ways diversity is created
recombination of DNA, somatic hypermutation (during development of B cells)
what does hypermutation of B cells do essentially?
create more diversity (makes further alterations in the Ig variable regions of receptor gene to increase affinity to antigen)