Huma immunity Flashcards by BLACK H

What are the types of light chain in an antibody?

→κ or λ chain

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How many types of heavy chains?

→5

→μ,δ,γ,α or ε chain

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What is the hinge region made from?

→disulphide bonds

→between the cystine groups

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What Bcells have antibodies?

→activate Bcells- membrane bound

→plasma

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Which regions make the antigen binding domain?

→variable region of H and L

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What do all chains have at the beginning and end and why?

→NH3 at the beginning
→COO3 at the end

→chains are a string of amino acids

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Where is the hinge region and why?

→between CH1 and CH2 for flexibility

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What group is added to the antibody to allow interaction of immune cells?

→CHO glycosylation on CH2

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Which fragments make the Fc fragment?

→CH2 and CH3 domain

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Which fragments make the Fab fragment?

→variable and 1st constant domain

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What is the function of Fab fragment?

→binds to antigens

→antigen-binding site

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What is the function of the Fc region?

→interacts with Fc receptors on macrophages and some proteins of the complement system

→bear a highly conserved N-glycosylation site

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What is the Fv region?

→the smallest fragment that maintains the full binding capacity of the intact antibody

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What are hypervariable regions?

→3 of them

→on heavy and light chains

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What are the functions of antibodies?

→Virus & toxin
neutralization- prevents pathogen-host binding
→Opsonization+ ADCP
→Complement fixing/+ 
MAC formation (CDC)-Phagocytosis
or lysis
→Opsonization
\+ ADCC leads to NK-induced apoptosis

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What is ADCC and ADCP?

→ADCC: an excess of engaged CD16A induces the release of cytotoxic granules which kill the target

→ADCP: an excess of engaged CD32A induces the phagocytosis of the microbe or target cell

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What gene region fixes light chain?

→VD-J

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Describe IgM

→3rd most common 
→heaviest
→fixes complement
→does not cross placenta
→pentameric

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What is the function of IgM?

→Main Ab of primary response
→ best at forming immune complexes fixing complement;

→monomer serves as BCR

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What are the functions of IgD?

→BCR;

→indicates mature B cells

→only Ab not secreted

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What are the functions of IgG?

→Main Ab of secondary responses

→neutralize toxins;

→opsonization

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What are the functions of IgA?

→Secreted into mucous, tears, saliva, colostrum

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What are the functions of IgE?

→allergy

→parasite

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Which Igs can cross the placenta?

→IgG

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Which Igs fixes complement?

→IgM | →IgG

Which Igs is heaviest?

→IgM

How many types of IgG?

→1-4

How many types of IgA?

→2

Which Igs is involved in primary response?

→IgM

What joins the two IgA monomers?

→J chain

What is another structure found in IgA?

→secretory component

What is the only Ab not secreted?

→IgD

What are the major changes in heavy chain class switching?

→DNA recombination →IgM to IgG, IgA, IgE →IgG to IgA, IgE

What are the minor heavy chain changes in class switching?

→: Differential splicing (mRNA level) →IgM and IgD →Does not affect the DNA of Bcell itself

What does clas switching recombination require?

→Cytokine signal →Switch regions- infront of constant gene segments constant →AID and DSB repair proteins

What happens to the gene code after class switching occurs?

→other regions are removed

Before recombination what does the Bcell express?

→expresses gene in two forms: IgM and IgD

Compare secreted and membrane-bound Abs

secreted →has cytoplasmic tail →has a tail piece membrane bound →hydrophobic transmembrane region →cytoplasmic tail

Which gene regions codes for transmembrane region of membrane bound Ab?

→M1 and M2 heavy chain

What is unique about transcription of membrane bound Ab?

→whole gene region is transcribed

What is involved in somatic recombination of Ab?

→V(D)J recombination →Tdt nucleotide addition →Somatic hypermutation →Class switching

What molecules are involved in class switching recombination?

→AID | →DSB repair proteins

Which Ab do immature Bcells express?

→IgM

What are the gene changes that occur between pro-Bcell and mature Bcell?

→D to J, heavy chain variable region →V to DJ →V to J, light chain variable and constant

Where in the antibody does affinity chain maturation occur?

→heavy chain constant region

What is IgD considered as?

→quality control

How many Abs genes are inherited?

→none | →only gene segments

Compare the gene segments of light and heavy chain

→heavy chain has D region but light chain doesn't

What do J or D/J region code for?

→Codes for CDR3 | →Most variable region of Ab

What are the genetic loci encoding Ig?

→Two for light chain: kappa (κ)- chromosome 2 →lambda (λ) locus- chromosome 22 →One for heavy chain- chromosome 14

How many variable region segments does the kappa light have on chromosome 2?

→40

How many joining segments does kappa light chain have?

→5

Describe the proximity of V and J and C regions in germline DNA

→J segments far from V segment | →J segments closer to C segment than V segment

How many variable segments present on gamma heavy chain genes?

→51

How many D segments on gamma heavy chain?

→27

How many J segments on gamma heavy chain genes?

→6

What are RSS?

→recombination signal sequences | →conserved sequences upstream or downstream of gene segments

What is the function of RSSs?

→Turns’ consisting heptamer and nonamer with a 12 or 23 bp spacer →Recombination only occurs between a segment with a 12bp spacer and a 23bp spacer →One turn two turn rule prevents V fragments and V/J fragments from combining

What factors are involved in the generation of antibody diversity?

→Multiple germline V, D and J gene segments →Combination V-J and V-D-J joining →Junctional flexibility → P-nucleotide addition → N-nucleotide addition → Combinatorial association of heavy and light chains → Somatic hypermutation during affinity maturation

What is a disadvantage of junctional diversity?

→incorrect reading frame – | wasteful process eg loss of stop codon

What is the difference between minor and major hairpin?

→Major hairpin=hole DNA folded in half →Minor hairpin=between two strands of DNA

What is Artemis?

→endonuclease | →resolution of hairpin coding ends

Describe the junctional diversity process

→Once hairpin is formed, the Artemis enzyme nicks on end of the dsDNA →Nicked ends linearise →Repair enzymes adds nucleotides P nucleotides →Tdt adds N nucleotides before the ends are ligated →P and N nucleotides shifts reading frame

Which chain does Tdt mostly work on?

→heavy chain

How is Ab allele expression different from normal expression?

→Two copies of each Ig gene – one from mother and one from father → In other cells, both genes are expressed →Only one heavy chain allele and one light chain allele is expressed

State the order of rearrangement in antibody rearrangement

→Heavy>kappa>lambda; 1st allele then 2nd →Ensure each B cell makes one type of antibody

Where does class switching occur?

→spleen →lymph node →light zone

What are the two types of Bcell activation?

→Tcell independent | →Tcell independent

Describe Tcell independent Bcell activation

→production of IgM by plasma cells and →does not produce memory B cells →clonal expansion

Describe Tcell dependent activation

→BCR recognise antigen →Th cell MHC: TCR and CD40 interaction →cytokines

What does SyK do?

→phosphorylates signal molecule for Bcell activation

Describe affinity maturation

→Initially, the antibody binds weakly- low affinity so antigen takes longer to bind to antigen or quickly falls away →When Bcell is activated, there is mutations in variable region genes and selects for antibodies with best affinity →occurs in germline centre

Which is the only cell that can enter germline centres?

→T follicular helper cells (Tfh)

Which cells present antigens in the germline centre?

→Follicular Dendritic Cells (FDC)

Where do activated Bcells go to make clones?

→germline centre

What changes occur before Bcells turn into plasma or Bcells?

→class switching

What is the role of AID?

→generate point mutation in variable region- somatic hypermutation in dark zones

What do Bcells compete for in the light zone?

→compete to bind on the FDC and present it to Tfh cells →Bcells then return to dark zones until affinity is high enough. →Cells that don’t survive undergo apoptosis