B-cells create a mixture of antibody created from 1 pathogen-the larger the antigen the more antibodies generated.

Polyclonal Antibodies

1. Expose animal to microbe
2. Harvest the B cells from spleen
3. fuse B cells with immortal cells=hybridoma ----will have a variety of antibody
4. separate the different B cell types: put antigen in and identify which binds then flow
5. Clone and expand

Cluster of Differentiation

Any antibody reacting specifically with any epitope on the same molecule has the same CD#

What CD do all T cells and NK cells have?

What CD do all T cells have?

CD2

CD3

CD2, CD3, CD4

CD45

What is the difference bw naive B cell DNA and mature B cell DNA?

What does the difference tell us?

Germline DNA has the C and V region on different fragments (far apart), mature B cells have the V and C region on the same fragment.

--->B cells undergo gene rearrangements

heptamer-spacer (either 12 or 23) - nonamer

they follow the 23 to 12 rule

1. RAG1:2 bind the RSS flanking segments.
2. 2 RAG1:2 enzymes come together to join two RSS
3. The flanking segments are cleaved
4. Ku, Artemis, and DNA-PK bind ends and open Hairpin
5. TdT processes and joins the segments

1. The parental chromosomes start rearrangements but most won't be viable bc of stop codons
2. Generate the H-chain from one parent and V-chain from one
3. Successful ones bind epitope and survive

What are Igα and Igβ and what are their roles in the activation of BCRs?

It is present on parasites and destructs the immune system by causing B cells to proliferate without activation signals and create nonspecific polyclonal antibodies with no specific epitopes.

Used in research

antibody is secreted by plasma cells

immunoglobulin is on the surface of B cells

 The heavy C genes have Membrane-Coding (hydrophobic) and Secretion-Coding exons (hydrophilic)- changes in alternative splicing determine which will be transcribed

To make immunoglobulins with different C regions to have a specific function

Achieved by:

Before each isotype C gene there is a Switch Region and the SR regions recombine with Sµ to splice out C genes and the one left will be transcribed 

AID

What is IgG1 good at?

How is further B cell diversity achieved by somatic hypermutation and what is it's purpose?

When does it occur?

After Class Switching the hypervariable regions - CDR1,2,and 3-have a high rate of point mutations and the mutations that increase the affinity for antigen will remain-

whereas B cells whose mutations decrease the affinity for the target antigen will die

MHC class I: closed around epitope, smaller epitope (6-9aas)

MHC class II: groove is open and flexible, epitope is ~25 aas

1. viral protein enter and get degraded in Proteosome
2. fragments enter ER through TAP1/2 protein
3. Calnexin stabilizes MHC components
4. Antigen is inserted
5. ERAP fine tunes the antigen so it fits snug in groove

1. Made in ER,INVARIANT CHAIN is inserted to block antigen groove
2. in endosome chain is cleaved, result in the CLIP fragment plug
3. Endosome fuses with phageolysome containing degraded microbe
4. HLA-DM facilitates CLIP release
5. antigen fins in groove with high affinity
6. transfered to surface

What cells express MHC class I and what cell recognizes them?

What cells express MHC class II and what cell recognizes them?

MHC-I: all cells except rbcs - cytotoxic T cells (CD8)

MHC-II: dendritic cells, B cells, macrophages, thymic epithelium - T helper cells (CD4)

Need 2 signals:

1. TLR recognizes pathogen and is activated
2. cytokine in the environment

Once activated DCs are processed and enter the lymph to node where they encounter Naive T cells - turning them into effector T-cells by Clonal selection

there is a high diversity of the MHC complexes due to diverse gene families with multiple alleles

HLA-heterozygous important for AIDS

MHC-I: 6 complete genes with many alleles

MHC-II: 5 genes

Vary in population to protect against different pathogens - one person's 6 will be dif than another's

after a transplant non-self MHC molecules are rejected bc T cells respond to them as non-self can happen with fetus too

avoided by supressing the immune system (decreasing t cells)

Co stimulatory molecules; B7 on DC must bind CD28 on T cell

----->clustering of several activated together TCRs, one activated won't do the trick

connection bw T cell and Dendritic Cells:

c-SMAC in middle connecting with high affinity:

TCR, CD2, 4, 8, 28

p-SMAC around the focus where adhesion molecules bind together to stabilize the connection

1. TCR and CD4 (or CD8) with MHC
2. Costimulatory molecules B7 to CD28
3. cytokines released by DC

A cytokine that can work in an autocrine fashion to begin clonal expansion and proliferation

Another piece of the receptor is made after activation of T cell to increase the affinity for IL-2 and have max effect

What is the purpose of T cell Co stimulation between B7 and CD28 in activation of T cell and how do pathogens alter this?

What is an anergic response?

it decreases the threshold of TCR activation needed for activation

some pathogens down regulate customatory molecules to decrease T cell activation

Anergic- TCR is activated but CD28 isn't=no activation

cytokine environment will lead to different T helper cell subsets with different functions

Th1

Th2

Th17

Treg cell

What is the function of:

Th1

Th2

Th17

Treg cells?

Th1: secretes IFN-γ that opsonizes, activates macrophages, and increases B cells

Th2: increase B cell antibody secretion

Th17: secretes IL-17 to recruit neutrophils and inc inflammation

T reg cells: balance response by supressing Th1/2/17