Chapter 4 Micro

Created by dvirwin 

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RAG:

• Binds between D & J to 12 and 23 and splices

TdT (terminal deoxynucleotical transferase):

• Adds N nucleotides

Surrogate light chain:

• Bind to heavy chain to check for correctness of chain before cloning

VLA-4:

• Integrin on B cell
• Binds VCAM on bone marrow stromal cell

VCAM:

• Integrin on bone marrow stromal cell
• Binds VLA4

KIT:

• Binds to SCF on stromal cell

SCF:

• Binds to KIT
• Stimulates IL-7 release

IL-7:

• Stimulates growth and proliferation when surrogate chain is bound

CCL19 &CCL21:

• Chemokine released by stromal cells to attract B cells to HEV

CCL13:

• Chemokine released by FDC to attract B cells to primary follicle

TNF-α

• Is secreted in follicles
• BAFF (B-cell activating factor in TNF)
• LT (lymphotoxin)

BAFF (B-cell activating factor in TNF):

• Produced by FDCs
• Binds to B cell receptor and promotes survival and maturation in follicle

LT (lymphotoxin):

• Produced by B cells
• Binds to FDC to preserve integrity of FDC network

2 processes happening in germinal centers:

• Isotype switching
• Hypermutation

Isotype switching:

• Changing of the constant region

AID:

• Deaminates Cytosine to Uracil at the switch sequence

UNG (Uracil-DNA-glycosylase):

• Uracil is removed leaving a nucleotide that lacks a base

APE1:

• Excises the abasic nucleotide and leaves a nick in DNA

Hypermutation:

• Undergone by B cells in germinal center after the recognition of an antigen
• Attempt to better match antigen

AID (Activation-induced cytidine deaminase):

• Deaminates Cytosine to Uracil

Immunoglobulin (Ig)

• All proteins which structurally resemble Abs.

Antibodies (Abs)

• Proteins made by lymphocytes and plasma cells, which specifically react with molecules termed antigens (Ags).

Papain:

• Cleaves before (above) disulfide bond
• Leaves 3 fragments

Pepsin:

• Cleaves after (below) disulfide bond
• Leaves 3 fragments

B cell ITAMs:

• Blk
• Fyn
• Lyn
• Syk
• Activate CD19 co-receptor

CD19

• B cell surface protein
• Activated by B cell ITAMs after crosslinking
• Responsible for intracellular cascades to produce transcription factors

IP3:

• Activates the transcription factor NFAT

DAG

• Activates the transcription factor NFkB

GEFs:

• Activate AP-1 transcription factor.

NF-kB, NFAT, and AP-1:

• Transcription factors that induced by crosslinking antibodies
• Encourage B cell proliferation and differentiation to plasma cells

CR2 AKA CD21:

• Binds C3d or iC3b for opsonization
• Stimulates B cell through CD 19 (make transcription factors)

CD40:

• B cell protein
• Expressed naturally on B cell surface

CD40L:

• T cell protein
• Expressed after T cell recognizes MHC:peptide complex (foreign) that B cell presents from ingestion of a pathogen
• Binding with CD40 causes T cell to release cytokines

Medullary cords:

• B cells migrate here to produce IgM and exit to site of infection

Primary follicle (germinal center):

• B cells migrate here to undergo hypermutation and antibody switching

CR1 on stromal cells:

• Breaks down C3b to iC3b or C3d

CR2 on stromal cells:

• Binds iC3b or C3d and drags pathogen for presentation

B cell low affinity interaction with stromal cell:

• Apoptosis

B cell high affinity interaction with stromal cell:

• Stromal cell interaction (BAFF & LT)
• T cell interaction (CD40L and cytokines)

IL10:

• Produced by TH cells
• Induces B cell to differentiate into plasma cell which migrate to bone marrow

IL4:

• Produced by TH cells
• Induces B cell to differentiate into memory cells (IgG & IgE)

IL5:

• Produced by TH cells
• Induces B cells to differentiate into IgA

TGF-β:

• Th2
• Induces IgG2b and IgA

IFN-γ:

• Th1
• Induces IgG3 and IgG2a (Fc)

LPS presentation to T cell:

• Is not done
• Instead TLR is used to signal B cell to make IgM

TI-2 activation:

• Activates B cells by having a high number of crosslinks with antigen

FcRn:

• Recognizes IgG and pulls it across the placenta

pIgR:

• Receptor on BM side of cell
• Binds to J chain and pulls it into lumen (intestine)

Monomeric IgA location in body:

• Bloodstream
• Extracellular fluid

IgG location in body:

• Bloodstream
• Extracellular fluid
• Transferred to fetus (FcRn)

IGM location in body:

• Bloodstream

Dimeric IgA location in body:

• Mucosal surfaces
• Breast milk

IgE location in body:

• Beneath epithelial surfaces (skin, resp tract, GI tract)

FcγRI:

• High affinity Fc receptor that recognizes IgG1 and IgG3

FcγRIII:

• NK cell receptor that recognizes Fc portion of antibody
• NK cells release cytotoxic granules

FcγRIIB1:

• Inhibitory receptor on B cell that shuts down Rh response when too much IgG is present

FcεRI:

• IgE receptor on mast cells

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