exam 2 simplified

how does genetic recomb of BCR regions occur

HC, VDJ → RSS + RAG1/2 → Hairpin + artemis → P + exonucleotides → TdT + N →

P, N nucleotides, and exonuclease activity

additional mechs for diversity

P nucleotides

palindromic nucleotides

generated when Artemis cleaves hairpin

N nucleotides

non-templated random nucleotides

added by TdT to open strands of DNA

after Artemis cleaves

exonuclease activity

removes nucleotide form ssDNA

results after Artemis cleavage

BCR HC

single

use J,D,V

P and N nucleotides

TdT

BCR LC

kappa and lambda

V and J

order of BCR expression

Generate HC

pre-BCR stability w/ SLC

test w/ kappa LC → Lambda LC if both kappas dont work

allelic exculsion = chain expression order (HC → KC → LC) and expression of one alleles for each chain

autoreactive BCR

induce further LC V,J rearrangement

mRNA can generate how many different antibodies from what

4 from a single RNA transcript

IgM and D

splicing

can select either IgM (u) or IgD (S) constant regions

determines if BCR is mem bound or secreted

future gene DNA recomb = dif AB classes

BCR and TCR

hc → VDJ → RSS, RAG1/2 → artemis → P → exo → TdT → N → chain testing

BCR

HC and LC

Surrogate LC

mRNA splicing

TCR

HC = Beta, Delta

LC = alpha, gamma

± selection

MHC I

expressed by most cells

cytoplasmic Ag 8-10 aa

binding cleft = 1 a chain

B2 microglobulin

CD8

Tc

req cytosolic/endogenous processing

immunoproteasome

TAP

MHC II

expressed by APCs

13-18 aa

binding cleft = 2 chains a/B

CD4 Th

extracellular Ag

presentation req exogenous processing

invariant chain

cross presentation

results in MHC I presentation of extracellular peptide by dend cell

MHC I and II

both present pathogen and self peptides

encoded w/in MHC locus

encoded by multiple genes w/ mutated binding sites

involved w/ B cells

secretes cytokines

detects MHC on thymus epithelial cells

antigen loading pathway MHC I

TAP: transports Ag into RER

B2 microglobulin: on RER

ER

immunoproteasome: cleaves Ag for better MHC binding

MHC I + peptide

antigen loading pathway MHC II

phagocytosed protein

invariant chain blocked MHC II ER → endosome → degraded chain

MHC II + peptide

influence factors of MHC expression

PRR-Stimulated transcription

cytokine stimulate transcription

viral inhibition

CD1 and MR1

present non-peptide antigens to TCR

MHC polymorphisms and Haplotypes

anchor residues w/in binding pockets = presented peptides

mutation w/in binding site (poly) = new MHC (haplo)

MHC present dif peptides = simultaneously expressed

transplantation of dif MHC lead to rejection

why transplantation of dif MHC lead to rejection

if MHC dont match they will reject and see the transplant as anti self

order of TCR expression testing

B chain + pre Ta → Pre-TCR

test for CD3 signaling

a chain → expressed CD4/8

testing

+ selection

TCR interacts w/ particular MHC

non-binding cells = anergy = death 95%

- selection

TCR doesn’t interact w/ MHC and self too strongly

too strong = autoimmunity

non-central tolerance

Treg cells

peripherial tolerance

Treg cells

arise from TCR binding self peptides but not too strongly

depletes cytokines

produce inhibitoy cytokines

inhibit APC

kills T cells

peripheral tolerance

not accompanied by other signals prevent T cell activation

lineage commitment mechs

instructive

stochastic

kinetic

instructive

it knows

depends on which MHC DP cells interact w/ more strongly

stochastic

random, it doesnt know

either CD4 or 8 downgraded and + = cell survival - = cell death

kinetic

it doesn’t know but tests both

one is tested and if no response other is tested

- selection in the medulla

cells tested on dend cells and mTECs

both express MHC I and II

tests both types of cells

mTEC

express AIRE regulator = other tissue presentation for - selection (skin)

NKT cells

CD4 or DN

cannot develop mem cells

express TCR interacts w/ lipid presenting MHC CD1

secrete cytokines and kills cells

gamma delta (yS) Tcells

DN for CD4/8

less TCR diversity

detects lipids like NKT

process of naive T cell activation by dend cells

3 signals for activation

cross presentation for Tc

signal 1

TCR CD3 and CD4 or 8 contact w/ peptide + MHC

signal 2

CD28 binding w/ CD 80/86

if missing = clonal anergy

signal 3

cytokines from dend cell in response to PRR = dif into effector cells

superantigens subvertion

antigen that binds on the side and not in the MHC pocket so no ID = body throws everything at it in an attempt to kill the unknown

can lead to T cell activation/cytokine storms

detrimental in infections and autoimmunity

CTLA-4 subvertion

a negative receptor, regulated T cell activity

maintains homeostasis

if blocked = T cell overstimulation = possible autoimmune diseases

T cell activation outcomes

increased proliferation, IL-2

increased diff, generation of mem cells at each diff step

final diff into effector cells through activation of master regulators

Th1

intracellular

increase macrophage, enhance phagocytosis/MHCII → increased Tc activation

Bs switch from IgM/D → IgG, better against intracellular pathogens

IFN-y

Th2

extracellular (IL-4, 5, 13)

IL-4: Bs → IgE fro allergic response

increase antibodies and granulocytes

fights parasites/allergens

Treg

anti-immune response

low inflammation

Th17

extracellular

high inflammation

Th9

extracellular

cancer autoimmunity

Th22

extracellular

skin

TFH

activate B cells w/in secondary lymphoid organ follicles

naive Tc require

same three signals as Th

TCR/MHC-I

CD28, CD 80/86

cytokines

Th activation req first, dend cel cross-presentation to MHC I

CTL mech to kill infected cells

perforin/granzyme

Fas/FasL

Th and Tc dif class similarities

Th and Tc memory formation

NKT and what they sense

how NK know a cell is compromised

how NK and NKT respond to activation

mem T cells

occur at each step on dif pathway

localize:

central cells

localized: