immunology quiz 3

What are antibodies and where do they come from

the secreted form of the B cells antigen receptor. Come from plasma cells. they coat mucosal surfaces

What region of the Abs determins isotype/ class function?

C region or buisness end

What Immunoglobulin forms a pentamer?

IgM

What immunoglobulin forms a dimer?

IgA

what is so special about IgM?

IgM can bind to 10 PAMPS which recurits C1Q to activate the classical complement pathway, lots of binding sites means good at opsonizin, it is the first antibody produced by the immune system

What makes Antibodies stable?

Disulfide bond helps stability; they can survive the acidity of the stomach due to these bonds

Where does the varability come from in the Light chain?

H3 region is where the DNA gets mutated for antigen specificity (bulk of changes)

what is the epitope?

the exact nucleotide that an antigen binds to an antibody

when and where does VDJ/somatic recombination happen?

Prior to infection; bone marrow

When and where does somatic hypermutation happen?

post encounter with pathogen; in the lymph node; always B-cells

what happens when an infant produces too little B cells?

cannot produce enough antibodies to protect themselves which makes them suseptible to infection; treated with IVIG

What processes happen in the bone marrow prior to infection?

VDJ recombination, H3 Junctional diversity (P and N insertion)

What processes happens in the Lymph nodes after antigen encounter?

Somatic hypermutation (this is why B cells are good at clearing infections) ; Class/isotype switching

What must occur before heavy and light chain loci are transcribed?

They must undergo rearrangement (VDJ recombination)

Whats the logic of VDJ recombination in the heavy chain?

A randomly chosen D will be put next to a randomly chosen J, a randomly chosen V will be put next to the DJ

Whats the logic of VDJ recombination in the light chain?

A randomly chosen V will be put next to a randomly chosen J

What do the RAG-1/2 complexes do?

cleave the gene segment into the signal joint and the coding joint which remains in the chromosome

Where does Rag -1 bind to on the gene segment?

7 mer

Where does rag-2 bind to on the gene segment?

V1

When does junctional diversity occur?

In the bone marrow, prior to infection, alongside VDJ recombination, H3 region

what is the first step in Junctional diversity?

After Rags make the cleavage(dsDNA), there is a DNA hairpin it creates and RAG opens the hairpins (ssDNA) results in the palindrome

What are the next steps in junctional diversity?

once the palindrome is formed, TdT will insert random nucleotides and the gaps will be filled in by DNA synthesis and ligases.

How to the H1,2,3 correspond to the VDJ regions?

V = H1 and 2, J and DJ = H3

H and L association

Until a functional heavy chain is made, VDJ will continue to occur. VDJ recom, happens on one chromosome at a time enforcing allelic exclusion - restricting a cell to one receptor prevents competing signals and maintains a precise, targeted immune response

where does class switching happen?

lymph node at the same time as somatic hypermutation, at the DNA level

what are the heavy and light chain functions?

Heavy chain determines function and the light chain helps structure

Why does order matter on the locus of the Ig types?

Once a segment is taken out, it loops out the DNA for the Ig. For example ABCD, if you cut out BC, you can only switch to D

why can a b cell have IgM and IgD on the surface?

governed by mRNA splicing and not a change at the DNA level, so in the bone marrow they express IgM and as they travel to the spleen they switch to IgD

what helps BCRs get to the surface of the cell to signal?

Two chaperons, Immunoglobulin domains alpha and beta

where and when does a b cell make the change from surface bound to secreted antibodies?

In the lymph node and later by alternative splicing the C terminus

what does VDJ form?

V region of the heavy chain

what does VJ form?

V region of the L chain

name the mechanisms of diversity

VDJ recombination, P and N insertion at DJ and J, allelic exclusion combo of H and L, somatic hypermutaton

what B cells do not class switch?

Plasma IgM cells

How does class switching work?

AID binds to switch region once transcription opens the DNA, leads to both nicks in DNA and stimulates recombination

what happens when someone has no AID

No high affinity antibodies

IgA

forms a dimer when J chain which manages commensal load and distrubutuon, monomeric is produced in plasma cells and circulates

IgE

on mast cells, promote allergic reaction due to being “loaded gun” since cells bind IgE that have not captured any antigen. so once the pollen is introduced can create a quick allergiv reaction. also promotes cross linking

IgD

upper respiratory tract - tonsils, basophils also bind IgD that have not captured

IgG

most abundant, promotes phagocytosis, crosses placenta and super flexible, allowing for binding of pathogens but also is more suseptible to degredation by proteases

IgG4

Anti-inflammatory and can hook up with another type once pamps decrease; called Fab-arm exchange, which creates functionally monovalent cannot efficiently cross-link antigens or trigger inflammatory cascades

what are some similairites between BCRs and TCRs?

Disulfide bonds

what are some key differences between BCR and TCR?

TCRs are not soluble, monovalent Ag binding, and no post pathogen changes

what are the professional antigen presenting cells?

BCR, macrophages, Dendritic cells

What is the function of T lymphocytes?

interact with cells to help make them more effective or to kill them

How do T lymphocytes make cells more effective?

Secrete cytokines such as IfnY to activate macrophages

Can TCRs change after they move from the thymus to the periphery?

Nope

Where does diversity in TCRs happen

Thymus pre-antigen

What are some different mechansims of diversiry of TCRs?

VDJ recombinaition, junctional diversity (more than BCRs) and Beta/alpha diffferent combos between daughter cells

Why is there more diversity in TCRs?

more opprotiunity for recombination

Describe the mechansims of VDJ recomb. In TCRs

In the alpha chain, a random V gene segment and J gene segment will be joined to make the V exon region. In the beta chain, a random D gene segment and J gene segment will be joined to make the DJ segment. then a second recombination will combine a V gene segment to the DJ gene segment.

what is the source of the most diversity in TCRs?

non templated nucleotides in P and N insertion

What does the alpha chain contain in TCRs?

V and J gene segments

what does the beta chain contain in TCRs?

V D and J regions

what do TCRs require to get to the surface and signal

CD3 complex

What would happen in an LOF of these CD3 cherperon complex?

TCRs would not be able to signal as effectivly and the adaptive immune system would be diminished, although the innate immunity would still be intact.

what are the two kinds of TCRs?

alpha/beta and gamma/delta

can a t cell express both alpha/beta and gamma/delta?

No, because during genetic rearrangement the alpha locus will delete the delta locus as they are on the same chromosome

what does the gamma/delta receptor recognize?

CD1 - lipids and fatty acids, epithelial tissue, recognize non-peptide AGs

Where is the peptide recognized on TCRs?

H3 in MHC

what does MCH1 load?

Cytosolic peptides?

what does MCH1 need to be functional?

b2-microglobulin, derived from the cytoplasm

what does MCHII load

vesticular peptides, dereived from outside of the cell

what MHC does CD8 interact with?

MHC1. all cells express; kill infected cells

what MHC does CD4 interact with?

MCH2; secrete cytokines to activate macrophages and increase their phagocytosis of extracellular pathogens (IL-12)

Why is AIDS so deadly?

CD4 cells decline and unable to activate macrophages and B cells, letting opprotunistic infections ensue

how does peptide binding occur?

anchor residues, only a few needed to be intact so the receptor can recognize a lot of peptides

what must happen before the MHC receptors go to the surface?

They must bind the peptide

What is a pathway that MHC2 gets peptides?

Macrophages/dendritic cells binds to PAMPS and phagocytose and then loads onto MHC2

what activates the immunoproteasome?

A macrophage can secrete IL-12 activating NK cells, which secrete IFN-y that will induce proteosome subunits that replace the cap to PA28Cap. This changes what the proteosome recognizes. TAP will transport the degraded product from the cytosol to the ER - MCH1

where is the immunoproteosome activated

cytosol

what MHC class uses the immunoproteosome

MHC1 loads peptides derived from this

what happens if TAP cannot work correctly?

Peptides cannot be bound to MHC1 which then compromises the function of CD8 cells since they cannot recognize intracelllular threats

Tapasin binds empty MCH1 to TAP

yay

what mediates the effector function of the antibody

FC region

Which hypervariable regions contribute to the antigen-binding specificity of an antibody? 

VH and VL

structure of immunoglobulin V domains

Framework regions are primarily comprised of beta strands. 

.Hypervariable regions are the primary determinant of antigen specificity in immunoglobulins. 

CDR1 and CDR2 are shaped by

germline V gene differences

N nucleotides are added independently by

TdT

Hairpins are opened to produce

palindromic (P) nucleotides

what do Naive B cells express?

IGM and IGD

what access the switch regions?

AID

briefly explain how switch regions induce class switching

AID will change C to U which APE1 will then create single stranded nicks at these sites one at Cmew and another at the switch region activated by cytokines. DNA damage machinery will join these two regions together. Now these VDJ region is upstream of a new constant region.

Why does IgE contribute to allergies?

Mast cells bind IgE that has not yet captured any antigen so they are loaded once pollen hits. This triggers R-cross linking