Uic Com Immuno

Front 1

What is the function of the J chain of immunoglobulin? What is the result for IgM vs IgA?

Back 1

Multimerization - IgM can form a pentamer while IgA dimerizes

Front 2

which immunoglobulins pass across the placenta?

Back 2

IgG (mostly 1 and 3)

Front 3

Which IG is moslty in gut mucosa?

Back 3

IgA

Front 4

Which IG is most prevalent in serum?

Back 4

IgG1 (more than all others combined)

Front 5

describe the function of AID in IG development

Back 5

deaminates C's in switch regions, (C->U) U excised by UNG -> DSBs allow for deletion of loop -> class switching recombination

Front 6

Do Ig isotypes arise from C or V region diversity?

Back 6

C region

Front 7

is the shift of IgM to IgD in mature B cells a DNA or RNA rearrangement?

Back 7

RNA

Front 8

Which IG is involved in allergic reactions?

Back 8

IgE

Front 9

describe the oder of VDJ joining. Is this process involved in a heavy or light chain locus?

Back 9

D joins with J, followed by V joining DJ

Front 10

describe the timing and role of the pre-B receptor in B cell development

Back 10

After VDJ rearrangement, a surrogate light chain joins with the mature heavy chain to test functionality of H chain. Positive signal allows cell to progress to L chain rearrangement stage

Front 11

what is the primary site of receptor editing? why?

Back 11

mostly on L kappa locus.

this is because the order or its V and J components in two separate blocks allows for repeated recombination. Also somewhat on L lambda locus, but very little on H chain.

Front 12

describe the role of T helper 1 cells

Back 12

CD4+ cells recognize MHC II -> activate infected macrophage to help it kill internal pathogen

Front 13

describe the role of T helper 2 cells

Back 13

CD4+ cells recognize MHC II on B cells, activates B cell to proliferate and differentiate -> increase AB production relevant to presented antigen

Front 14

With what do CD8+ T cells interact

Back 14

Cytotoxic T cells

interact with MHC I -> kill these cells by releasing granzymes etc

Front 15

describe the function of tapasin

Back 15

stabilizes the binding groove of MHC I, speeding peptide exchange, and competing with peptides to ensure only those with high affinity replace it

Front 16

what lymphocyte is involved in innate immunity? describe their functions

Back 16

NK cells

act like cytotoxic T cells, but instead of recognizing antigen breakdown products they are inhibited by the presence of MHC class I -> infected cells that stop expressing MHC I are killed - cytotoxicity is mediated by granzyme/porforin or FasL

-also has antibody mediated cytotoxicity

also activate macrophages -> release INF-1 in response to IL-12 from macrophages

Front 17

describe the differences in peptides presented by MHC I vs MHC II

Back 17

MHC I
Smaller peptides, with specific peptide binding motifs at positions 2 and 9, and occasionally soft anchors at other sites

MHC II
Longer (up to about 15 AA) peptides with variable anchor sites

Front 18

Which increases more in response to secondary immunization, IgG or IgM

Back 18

IgG, remember IgM spikes after primary immunization, but is decreases and is mostly static to subsequent exposures

Front 19

Which portion of an Ig has effector functions? Is this part of the light or heavy chains?

Back 19

Fc, part of the heavy chain

Front 20

what is an immunogen? Antigen?

Back 20

an immunogen is a substance that binds to a BCR or TCR AND elicits a response

an antigen is any substance that is bound by an antigen receptor (BCR/TCR)

Front 21

What is a hapten? a carrier?

Back 21

A hapten is a substance that can interact with an antibody or TCR but does NOT elicit an immune response

a carrier is a protein that when coupled with a hapten forms an immunogenic molecule

Front 22

give three effector functions of secreted antibodies

Back 22

neutralization - physically disrupting epithelial interactions
opsonization - ie making delicious, promoting phagocytosis
Complement activation - antibodies provides binding site for C1q to begin complement cascade

Front 23

describe the structural role of hypervariable regions in antibodies

Back 23

3 hypervariable regions (complementarity determining regions) on both the light and heavy chains form loops that are exposed to the antigen binding site

Front 24

which light chain locus is expressed first? is this expressed before or after the heavy chain?

Back 24

kappa locus, light chain development occurs after the heavy chain

Front 25

what does the 12/23 rule describe?

Back 25

in V(D)J joining, gene segments join via RSS's which have either a 23 or a 12 base pair spacer between homologous heptamer and nonamer segments. Gene segments will join only when a 12 RSS matches with a 23 RSS. Note that one full turn of DNA is about 12 base pairs

Front 26

what is the function of RAG enzymes?

Back 26

binds to RSS's catalyzing cleavage which leaves signal ends (removed DNA) and hairpin loops at coding ends of immunoglobin gene segments

Front 27

what enzyme opens DNA hairpins on coding ends?

Back 27

artemis (in complex with DNA-PK) opens hairpins to leave palindromic segments of P nucleotides

Front 28

which enzyme adds N nucleotides to opened hairpins on coding ends?

Back 28

TdT adds N nucleotides randomly

Front 29

why is CDR3 an exceptionally diverse region of the variable chain?

Back 29

it is generated by the joining of the DJ segments, and is the center of the Ag binding site

Front 30

How is a TCR different than an antibody?

Back 30

Has alpha/beta or gamma/delta chains rather than heavy/light chains

Front 31

what feature is characteristic of B cell maturity?

Back 31

co-expression of IgM and IgD on the plasma membrane

Front 32

is the IgM -> IgD transition in mature B cells an RNA or DNA rearrangement?

Back 32

RNA, mu and delta constant segments are transcribed together and adjacent, alternative splicing results in either IgM or IgD

Front 33

describe the mechanism determining secretion or membrane binding of IgM

Back 33

alternative RNA polyA and splicing. If mb exon is present, it will be membrane bound (BCR), if the secretion exon is exposed it will be secreted

Front 34

Give three types of IG isotype switching

Back 34

RNA level: IgM->IgD and membrane -> secretion, both through alternative splicing
DNA level: class switch recombination

Front 35

what portion of the Ig determines its isotype?

Back 35

the C terminus, ie Fc

Front 36

give the order of C region gene segments

Back 36

M D G E A

Front 37

how do Ig isotypes respond to appropriate stimuli?

Back 37

cytokines act as triggers to turn on germline transcripts which act to stabilize the DNA loops to class switch to appropriate isotypes.

EG IL4 from T helper cells -> IgG1
LPS -> IgG3

Front 38

what complement protein binds to Fc domains to initiate the complement cascade? What is the effect of this binding?

Back 38

C1q -> conformation change which activates C1r -> activates C1s

Front 39

What is the function of C1r?

Back 39

cleaves (activates) C1s

Front 40

What is the function of C1s?

Back 40

cleaves C4 -> C4a + C4b
exposes catalytic (thioester site) on C4a, C4b floats away\

Also cleaves C2 when bound to C4b -> active C4b/C2a complex

Front 41

what is the function of C4a?

Back 41

none, lost after being cleaved off of C4

Front 42

what acts as the classical C3 convertase?

Back 42

C4b/C2a complex

Front 43

What is the function of DAF?

Back 43

decay accelerating factor - inhibits association and speeds dissocation of C2 (and C2a) with C4b

Front 44

which component protein is most abundant in serum?

Back 44

C3

Front 45

What is the function of C3a?

Back 45

acts as a stimulator of the inflammatory response (anaphlyatoxin)

also upregulates cleavage of C5 by C4b/C2a -> C5a an even more potent anaphlyatoxin

Front 46

what is the activation site for MAC proteins?

Back 46

C5b (remember this doesnt bind to membrane) activates C6->C9

Front 47

what is the function of MBL?

Back 47

MB lectin (mannose binding lectin) is analogous to C1q - binds specific carbohydrate patterns of patterns - ANTIBODY INDEPENDENT

Front 48

what acts as the alternate C3 convertase?

Back 48

C3(H20)Bb

Front 49

describe the antibody independent amplification loop

Back 49

in the AB independent loop, C3b is a component of the C3 convertase, generates more C3b -> convertase

Front 50

which component of MHC I is not an HLA locus gene product?

Back 50

beta-2-microglobulin

Front 51

which domains of MHC I are most polymorphic?

Back 51

alpha 1 and 2

Front 52

describe the gene segments of the alpha/beta TCR loci

Back 52

the beta chain (remember this rearranges 1st) has VDJ segments

the alpha chain has VJ, but also contains all of the delta genes, which are lost during the first rearrangement

Front 53

what are superantigens?

Back 53

antigens which produce non-specific T-lymphocyte activation. act by binding both MHC and TCR but not necessarily as part of normal peptide/MHC complex.

Implicated in anaphlyaxis, TSS etc

Front 54

what is the funciton of CD3

Back 54

associates with the preTalpha/Beta complex -> signals successful B chain rearrangement

complexes with TCR in mature T cells

Front 55

what is the function of TAP?

Back 55

transports cytosolic peptides after degradation by the proteasome into the ER, where they are bound by MHC I

Front 56

what is the function of Li?

Back 56

complexes with MHC II, stabilizing it in the vessicle. cleaved by the acidifying endosome -> CLIP remains in binding cleft, removed by HLA DM

Front 57

what is the function of granzyme?

Back 57

released by CD8+ cytotoxic T cells, granzyme enters target cell and signals apoptosis via activation of caspase protease cascade

perforin also involved -> opens cells membrane for granzyme uptake

Front 58

what is the function of INF-gamma? what cells secrete it?

Back 58

secreted by Th1 cells

activates macrophages and induces many cell types to express more MHC

Front 59

what cell type secretes IL-2? what is its function?

Back 59

Th1 cells, causes growth of T cells

Front 60

what cell type secretes IL-4? what is its function?

Back 60

Th2 Cells, B cell maturation factor -> signals class switching (IgG1 and IgE)

Front 61

what is the function of CD178?

Back 61

same as CD95 - late expression death receptor to reduce response

Front 62

What is the function of CD28?

Back 62

co stimulator receptor on T cells, provides required 2nd signal for initial activation

activated by CD86 or CD60, mostly on denditic cells

Front 63

What is the function of CD28?

Back 63

co stimulator receptor on T cells, provides required 2nd signal for initial activation

activated by CD86 or CD60, mostly on denditic cells

Front 64

what is the function of CTLA-4?

Back 64

expressed very late in T cell activation cycle

binds CD60 and CD86 with high affinity and delivers inhibitory signal to T cell

Front 65

what is the function of M cells?

Back 65

antigen processing, transport across epithelium to dendritic cells

Front 66

how does mucosal humoral immunity work?

Back 66

IgA is secreted, binds toxins on mucosa - can be internalized in endosomes, or secreted from lamina propria

Front 67

what is unique about gamma/delta TCR's?

Back 67

able to recognize phosphoantigens as in tuberculosis infection

Front 68

what is the function of Treg cells?

Back 68

inhibit other immune cells to prevent over reactive immune responses

note these are CD25+ Foxp3+ T cells

Front 69

what is the function of Th17 cells?

Back 69

activate fibroblasts, epithelial cells (TGF-B) and neutrophils (IL-10)

Front 70

describe the expression of TdT

Back 70

only expressed in adults in thymus heavy chains

fetal repertoire is different, doesnt have TdT variety

Front 71

how is aid involved in somatic hypermutation?

Back 71

deaminates C->U. this is usually involved in generating double stranded breaks -> CSR. However, if the gaps are instead filled in by an error prone polymerase, leads to mutation -> affinity maturation by ensuing selection

Front 72

describe somatic hypermutation

Back 72

DNA level mutations of V regions, mechanism involves AID to generate high mutation rate

Causes increasing antigen affinity as mutated products with higher affinity are selected for

Front 73

what do primary follicles contain in lymph nodes?

Back 73

mostly B cells

Front 74

what is the function of CD59>

Back 74

inhibition of the MAC

Front 75

where are T cells predominantly found in lymph nodes? in the spleen?

Back 75

node: paracortical area

spleen: periarteriol lymphoid sheath

Front 76

what is the function of UNG?

Back 76

removes U residues after AID deaminates C's -> generates double sided breaks

Front 77

what cells do the common lymphoid progenitor give rise to?

Back 77

B, T, and NK cells

Front 78

what cells do common myeloid progenitors give rise to?

Back 78

granulocytes, mast cells, macrophages