9) Lymphs Flashcards by Samantha Boyer

main 4 characteristics of the immune response

specificity
memory
adaptiveness
discrimination between self and nonself

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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

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marker on pluripotential cell

CD34

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old way to ID lymphs

rosette formation between T cells and sheep RBCs

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current methods used to ID lymphs

flow cytometry
monoclonal Ab to epitopes

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CD stands for…

cluster determination

named for Ab that reacts to protein; numbered in order of discovery

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developmental stages of B cells

pro-B
pre-B
immature B
mature B
B-cell blast/immunoblast
plasma cell/memory cell

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most immature committed B-cell

pro-B

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activity of pro-B

starts to rearrange heavy chains
no Ig made

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activity of pre-B

mu polypeptide forms
(heavy chain of IgM)

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activity of immature B-cell

light chain genes rearrange
sIgM produced

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Ag binding to sIgM on the ——— cell results in deletion, not expansion

immature B

in BM, only self antigens are present

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activity of mature B-cell

expresses IgM, IgD
ready to respond to Ag

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antigen dependent B-cell development begins with the ——– stage

B-cell blast/immunoblast

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formed when Ag triggers IgM+, IgD+ cells to proliferate

B-cell blast/immunoblast

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——— cells can become ———- cells, but not vice versa

memory
plasma

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express high level of CD44 (homing)

memory B-cells

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memory cells found in…

secondary lymph tissue

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2 ways for B-cells to class switch

T-cell cytokines
T-B surface interactions via CD40 (B) and CD40 ligand (T)

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class switching from IgM to…

IgG
IgA
IgE

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affinity maturation

clonal selection of B-cells with mutations for higher affinity Ab to Ag in germinal centers of spleen/lymph nodes

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B-cell programmed death occurs in cells with…

low affinity for Ag

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allows a continuously replenished library of B-cell Ag specificities to exist

affinity maturation
programmed cell death

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negative selection of B-cells

immature B-cells in contact with self antigens are removed/inactivated

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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

1. positive selection 2. negative selection 3. 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

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