Antibody molecules

Question 1

Linus Pauling

Answer 1

Model proposed that a pre-formed, undifferentiated “immunoprotein”. Single immunoprotein react to all antigens. WRONG

Question 2

Sir Frank MacFarlane Burnet

Answer 2

1959. Clonal Selection Theory. Somatic mutation during embryonic life - random specific antibodies. eliminate self-reactive antibodies

Question 3

Antigens

Answer 3

Any molecule or part of a molecule that is recognised by a variable antigen-receptor on an immunoglobulin

Question 4

Paratope

Answer 4

antigen-binding region of the natibody

Question 5

epitope

Answer 5

specific region of antigen that binds to immunoglobulin

Question 6

Heavy chain

Answer 6

55kDa. gamma, mu, alpha, delta, epislon.

Question 7

Light chain

Answer 7

22kDa. kappa or lambda.

Question 8

IgG

Answer 8

gamma heavy chain. monomer. valency of 2. circulating - greatest conc found in circulation

Question 9

IgM

Answer 9

mu heavy chain. circulating. pentamer (with J chain). first response. low affinity. valency of 10.

Question 10

IgA

Answer 10

alpha heavy chain. mucosal membranes. monomer, dimer or trimer (J chain). secretory component.

Question 11

IgE

Answer 11

allergic reactions. epsilon heavy chain. monomer.

Question 12

IgD

Answer 12

delta heavy chain. monomer.

Question 13

Porter and Edelman

Answer 13

1972. Porter used papain (protease) to show that immunoglobulin has 3 fractions. Fraction 1 and 2 bound antigens - Fab. Fraction 3 crystallised - Fc. Edelman used pepsin (protease) to show IgG consisted of 4 chains (2x heavy and 2x light).

Question 14

Vh and Vl

Answer 14

hyper-variability within four conserved framework regions (FR1, FR2, FR3, FR4). form loops that combine toghether to form antigen binding surfaces. complementary determining regions (CDR1, CDR2, CDR3) are important for engineering antibodies.

Question 15

Trans-epithelial transport of IgA

Answer 15

IgA dimer with J chain binds to the polymeric Ig receptor (pIgR) - transmembrane protein expressed at basal surface of epithelial cells of gut and airways. Binding of IgA induces transcytosis of pIgR. Complex delivered into the lumen.

Question 16

IgA secretory component

Answer 16

protects against proteases within mucus and anchors IgA at the desired location

Question 17

Opsinisation and Phagocytosis

Answer 17

opsonise with IgA, Fca/uR binds to IgA (or IgM) to mediate uptake by macrophage and DC. FcaRI mediates uptake by neutrophil.

Question 18

ITAM

Answer 18

immunoreceptor tyrosin-based activation motif. Contains precisely spaced tyrosines. always have leucine or isoleucine in amino acid repeat. When phosphorylated, the tyrosine residues provide a binding site for intracellular tyrosine kinases (Syk in most immune cells or ZAP-70 in T cells). These have SH2domain –> singal transduction

Question 19

ADCC

Answer 19

anitbody-dependent cell-mediated cytotoxicity. antibody attracts cytotoxic cells by means of their Fc receptor to the opsonized pathogen to kill cell

Question 20

complement-mediated cytotoxicity

Answer 20

antibody binding results in the fixation of complement to target cell

Question 21

Fc-gamma-RI (CD64)

Answer 21

expressed by macro, DC, neut, eosin.

Question 22

Fc-gamma-RII A (CD32)

Answer 22

expressed by macro, neut, Langerhans cells

Question 23

Fc-gamma-RII B1 (CD32)

Answer 23

expressed by MC and B cells

Question 24

Fc-gamma-RII B2 (CD32)

Answer 24

expressed by macro, neut, eosin

Question 25

Fc-gamma-RIII A (CD16)

Answer 25

expressed by NK

Question 26

Fc-gamma-RIII B (CD16)

Answer 26

expressed by eosino, macro, neut, MC

Question 27

Fc-epsilon-RI

Answer 27

expressed by MC , baso, eosino. Degranulation.

Question 28

Fc-alpha-RI (CD89)

Answer 28

expressed by monocytes, neut, eosino

Question 29

Fc-epsilon-RII (CD23)

Answer 29

expressed by B cells, macro, eosin

Question 30

lectin pathway

Answer 30

recognition of carbohydrate moieties

Question 31

classical pathway

Answer 31

antibody binding to antigen in immune complexes or pentraxins

Question 32

alternative

Answer 32

directly at microbial cell surfaces

Question 33

a fragment

Answer 33

inflammatory mediator

Question 34

b fragment

Answer 34

goes onto become a subunit of next protease in cascade

Question 35

pentraxins

Answer 35

pentameric serum proteins that participate in innate immuniuty and can activate classical pathway of complement

Question 36

Cqrs complex

Answer 36

antibody binds antigen on the outside of the cell --> complex forms and activates classical

Question 37

classical complement

Answer 37

Ab-Ag complex binds C1 complex (C1qrs). C1q activates C1r, which cleaves C1s. C1s cleaves C4 into C4a and C4b. C1 also cleaves C2 into C2a and C2b. C4b and C2b bind to form C2bC4b complex aka C3 CONVERTASE. C3 convertase cleaves C3 into C3a and C3b. C3b binds C2bC4b to form C5 CONVERTASE. C5 convertase cleaves C5 into C5a and C5b. C5a attracts inflammatory cells. C5b binds C6, C7, C8, C9 to form MEMBRANE ATTACK COMPLEX.

Question 38

LECTIN pathway

Answer 38

activated by MASPs. Mannose binding lectin associated serine proteases. MASP-2 cleaves C4. Found within Mannose-binding lectin or ficolin molecules that recognise carbohydrate on microbial surface,.

Question 39

surfactants

Answer 39

layer of phospholipids and proteins that line the epithelium of the respiratory tract

Question 40

Collectin family

Answer 40

function as opsonin. Surfactant protein A and surfactant protein D. Mannose-binding lectin.

Question 41

Ficolins

Answer 41

Bind to N-acetylglucosamines.

Question 42

Collectin molecule structure

Answer 42

Cystein rich region, followed by a collagen-like domain and an alpha-helical neck region. Then a carbohydrate recognition domain (CRD)

Question 43

C1q deficiency

Answer 43

More susceptible to sepsis, meningitis and pneumonia (Neisseriameningitidis, Streptococcus pneumoniae)

Question 44

C3 deficiency

Answer 44

Increases susceptibility to respiraotry tract infections and meningitis caused by Neisseriameningitidis, Streptococcus pneumoniae, Haemophilus influenzae, Streptococcus pyogenes, Staphylococcus aureus

Question 45

C5 deficiency

Answer 45

meningitis and sepsis caused by Neisseria

Question 46

C9 deficiency

Answer 46

meningitis and sepsis caused by Neisseria

Question 47

Collectins

Answer 47

Function as opsonins. PRR that recognise carbohydrates (have a C-type lectin). e.g. Surfactant A and Surfactant D (found in respiratory tract), Mannose-Binding Lectin