Immunology 101B

How to turn on adaptive immune response?

Activated APC present to T cell

CD4 bind to:

MHC II , exogenous Ag

CD8 bind to:

MHC I, endogenous Ag

exception to MHC I presentation

DC present exogenous Ag

MHC are _______

Do-dominantly expressed

MHC I made up of

1 a-chain (b-2 microglobulin attached)

MHC I expressed by which cells?

all nucleated cells

MHC II made up of

2 chains, 1 alpha/1 beta chain

MHC II has _______ for more diversity

heterozygous complementation

MHC II only expressed by ______

APCs

What’s V(D)J recomb mediated by for ALL lymphocytes (B/T cells)

RAG1/2

failure to successfully rearrange TCR/BCR of developing lymphocyte results in _______

deletion

T and B cell Ag-receptor rearrangement occurs ______

independently

def: allelic exclusion

lymphocyte only expresses one allele for TCR/BCR

if cell was given transgene for TCR/BCR, cell will ________

not rearrange its own TCR/BCR loci

TCR associates with ____

CD3

def: CD3

complex of multiple chains containing ITAM motifs

Def: ZAP-70

tyrosine kinase for TCR signaling

the 2 TCR types (alpha/beta + delta/gamma) are ________

mutually exclusive

T cell activation requirements:

Signal 1, 2, 3

def: TCR signal 1

TCR engagement w/ MHC-peptide

def: TCR signal 2

co-stimulatory interaction

CD28 on T cell engage w/ APC CD80/86 or B7

def: anergy

T cell unresponsiveness due recieving signal 1 without signal 2

anergy caused by ________

APC CD80/86 bind to T cell CTLA-4 or T cell bind to non-APC

Def: TCR signal 3

cytookine signaling

cytokine signals T cell activated by:

autocrine cytokine and APC cytokine (IL-12)

Order of T cell development:

DN, DP, SP

def: B-selection

test functionality of B-chain first (pairs with pTa)

def: positive selection

failure to bind to MHC results in deletion

What step do T cells mainly fail?

positive selection

Where does positive selection take place?

cortex of thymus

what cell (from cortex) present self-peptide to T cell progenitors?

cTEC

def: negative selection

binding too strongly to MHC results in deletion (or sometimes Treg development)

where does T cell negative selection take place?

medulla of thymus

what cell (from medulla) present self-peptide to T cell progenitors?

mTEC or DC

lineage commitment requires _________

MHC binding

def: T_reg cells

regulatory T cells that are result of strongly binding to MHC

BCR structure involves:

2 copies of H chain and light chains

Both H + L chains include _______

variable region

The Fc region of BCR only contains __________

heavy chain

Different _______ have different F_c

isotypes

BCR equivalent of CD3

Ig alpha Ig beta

def: CD19/21

BCR co-receptors that enhance BCR signal 1

def: BCR signal 1

Ag cross-links BCR on surface

def: BCR signal 2

B cell CD40 binds to T cell’s CD40L

def: BCR signal 3

cytokines

def: Pre-BCR testing

H chain pairs with SLC (surrogate L chain)

def: negative selection I

binding to self-Ag in bone marrow result in deletion or receptor editing

def: receptor editing

further rearrangements of light chain

where does negative selction I take place?

bone marrow

def: negative selection II

bind to Ag in spleen results in deletion

def: peripheral tolerance

loss of self-reactive BCR in periphery (blood or spleen)

def: central tolerance

loss of self-reactive BCR in bone marrow

B cells that bind to cell-surface Ag are _______

deleted

B cell anergy occurs when _______

B cell binds to soluble Ag

def: B-1 B cell

in periphery

self renewing

innate-like (PRR for polysaccharide Ag)

TI

makes IgM

def: B-2 cell

in blood/follicles

adaptive-like

TD

respond to peptide Ag

cognate T/B cells do what?

return to follicle and begin proliferating to generate germinal center

Linked T/B pairs are ________ but _____________.

specific for same Ag, not for same epitope

somatic hypermutation requires __________

AID

somatic hypermutation does what? and where?

proliferate cells in dark zone

def: affinity maturation

B cell compete for Tfh help by binding to Ag on FDC in light zone

Affinity maturation helps __________

select for highest affinity BCR

Class switiching requires __________ and _______ and _____________

AID
T cell help
cytokine presence

All cell types are helped by

cytokines from CD4

Th1 function

cell mediated response and secreate inflammatory cytokine (IFN-gamma)

Th2 function

humoral response

Tfh found in _________, and do what?

follicle, provide B cell help

Treg purpose

secrete immunosupressive cytokines to promote peripheral tolerance

CD8s do what?

kill infected and tumor cells

examples of CD8 cytotoxic cytokines:

perforin
granzymes
Fas/FasL