9) Lymphs Flashcards
main 4 characteristics of the immune response
- specificity
- memory
- adaptiveness
- discrimination between self and nonself
parts of clonal selection theory (4)
- lymphs of all specificities exist prior to ag contact
- each lymph carries Ig/TCR of only one specificity
- lymphs create progeny with identical specificity
- self-reactive lymphs are eliminated
marker on pluripotential cell
CD34
old way to ID lymphs
rosette formation between T cells and sheep RBCs
current methods used to ID lymphs
flow cytometry
monoclonal Ab to epitopes
CD stands for…
cluster determination
named for Ab that reacts to protein; numbered in order of discovery
developmental stages of B cells
- pro-B
- pre-B
- immature B
- mature B
- B-cell blast/immunoblast
- plasma cell/memory cell
most immature committed B-cell
pro-B
activity of pro-B
starts to rearrange heavy chains
no Ig made
activity of pre-B
mu polypeptide forms
(heavy chain of IgM)
activity of immature B-cell
light chain genes rearrange
sIgM produced
Ag binding to sIgM on the ——— cell results in deletion, not expansion
immature B
in BM, only self antigens are present
activity of mature B-cell
expresses IgM, IgD
ready to respond to Ag
antigen dependent B-cell development begins with the ——– stage
B-cell blast/immunoblast
formed when Ag triggers IgM+, IgD+ cells to proliferate
B-cell blast/immunoblast
——— cells can become ———- cells, but not vice versa
memory
plasma
express high level of CD44 (homing)
memory B-cells
memory cells found in…
secondary lymph tissue
2 ways for B-cells to class switch
- T-cell cytokines
- T-B surface interactions via CD40 (B) and CD40 ligand (T)
class switching from IgM to…
IgG
IgA
IgE
affinity maturation
clonal selection of B-cells with mutations for higher affinity Ab to Ag in germinal centers of spleen/lymph nodes
B-cell programmed death occurs in cells with…
low affinity for Ag
allows a continuously replenished library of B-cell Ag specificities to exist
- affinity maturation
- programmed cell death
negative selection of B-cells
immature B-cells in contact with self antigens are removed/inactivated
2 reasons to remove/inactivate B-cells
- low affinity for Ag
- self reactivity
B-cells that do not possess sIg
- pro B
- plasma
allow us to ID B-cells
sIg
Ig noncovalently bound to sIg, and found in all stages of B-cells
Ig𝛼
Igβ
function of Ig𝛼, Igβ
linked to kinases inside B-cell
lead to transcrption of genes and B-cell activation
function of CD40 (B-cell)
links to CD40 ligand on T-cells to mediate class switching
disorder involving mutation of CD40 ligand (missing)
human X-linked hyper-IgM syndrome
only make IgM
males
first B-cell to express MHCII
pre-B
function of B7 (CD80 + CD86)
costimulatory molecule found on APCs
binds CD28 on T-cells
allows T-cell to be turned on by contact with Ag
what if T-cell does not receive B7 costimulation?
turned off by contact with Ag
poor APCs with low levels of costimulatory molecules
mature resting B-cells
where is FcR (CD32) found?
all mature B-cells
function of FcR (CD32)
if it binds to the Fc portion of an IgG involved in an Ag-Ab complex – while Ag binds sIg on the same cell – the B-cell is inactivated
(negative feedback)
function of CD21 (B-cell)
- receptor for C3d
- receptor for EBV
why do we have T and B lymphs?
T: antigens inside cells
B: antigens outside cells
T-cells only recognize antigen when it is…
- presented on an APC
- complexed with MHC
general structure of TCR
- disulfide linked
- 2-polypeptide chain (𝛼β or 𝛾𝜹)
- globulin structure
- short cytoplasmic tail
function of CD3
noncovalently associated with the TCR to form the TCR complex
linked to a kinase inside the cell, which leads to gene transcription when TCR binds Ag
CD3 structure
- 3 polypeptides (gamma, delta, epsilon)
- associated with 2 zeta chains (or zeta + eta)
- found on all T-cells
totally intracellular proteins on T-cell
2 zeta chains associated with CD3
composition of TCR complex
- TCR
- CD3
- 2 zeta chains (or zeta + eta)
accessory/coreceptor molecules noncovalently linked to TCR
CD4 and CD8
express CD4 and CD8
immature T-cells
𝛾𝜹 T-cells mostly express CD—
CD8
3 functions of CD4/CD8
- adhesion molecules; tighten binding of T-cell to APC (on constant portion of MHC)
- signal trasducer, phosphorylated when TCR binds Ag
- CD4 binds HIV
possible functions of 𝛾𝜹 T-cells
defense against common bacterial antigens and malaria
self-MHC restriction
only able to bind to self MHC
steps in T-cell maturation in thymus
- precursors enter thymus
- TCR genes rearranged (pre-T)
- 𝛾𝜹 cells separate from 𝛼β cells
- thymocytes (T-cells) move from cortex to medulla
- most mature T-cells enter circulation
selection process steps for T-cells
- positive selection
- negative selection
- cells become either CD4+ or CD8+
T-cell positive selection
cells must bind with a certain critical affinity for epithelials’ MHC
cells that survive are “educated”
MHC restriction
T-cells only respond to type of MHC to which they bound with critical affinity in thymus (pos selection)
T-cell negative selection
cells interact with interdigitating dendritic cells at cortico-medullary junction, and those reacting with self Ag are removed/inactivated
dendritic cells in thymus are involved with…
T-cell negative selection
—–% of developing T-cells apoptose
90
reasons for T-cell apoptosis
- TCR genes fail to rearrange successfully
- precursor not positively selected for
- cell negatively selected against
function of CD28
binds to B7 on APC
crucial for IL-2 generation
function of CTLA-4
- expressed on activated T-cells
- binds B7 on APC
- negative signal; inhibits IL-2 production
function of CD2
- T-cells
- binds LFA-3 (CD58) found on many cells, enhancing binding
function of LFA-1
binds ICAM-1 (CD54), enhancing binding
lymphocyte trafficking
“homing” of lymphs to areas where they can interact with Ag
where do different lymphs home to?
- naive cells: peripheral nodes
- activated and memory cells: skin and mucosa
function of L-selectin (CD62L)
- homing receptor on T-cell, especially naive
- homes to peripheral nodes
downregulated after T-cell is activated so that it can home to skin, mucosa
L-selectin
