4. Effector Mechanisms Of Humoral Immunity

Question 1

What are the four main effector functions of Abs?

Answer 1

1. Neutralize microbial toxins
2. Opsonize them for phagocytosis
3. Sensitize them for Ab-dependent cellular cytotoxicity (ADCC)
4. Activate the compliment system

Question 2

Polio- Vaccine: Oral atenuated poliovirus Mechanism?

Answer 2

Neutralization of virus by mucosal IgA Ab

Question 3

Tetanus, Diptheria- Vaccine: Toxoids, Mechanism?

Answer 3

Neutralization of toxin by systemic IgG Ab

Question 4

Hepatitis A/B- Vaccine: Recombinant viral envelope proteins, Mechanism?

Answer 4

Neutralization of virus by mucosal IgA or systemic IgG Ab

Question 5

Pneumococcal, Pneumonia, Haemophilus- Conjugate vaccines: composed of bacterial capsular polysacchride attached to a carrier protein. Mechanism?

Answer 5

Opsonization/phagocytosis mediated by IgM and IgG Abs, directly or secondary to complement activation

Question 6

How is affinity maturation induced?

Answer 6

Repeated stimulation with protein Ags

Question 7

The increase in Ab affinity with repeated stimulation of B cels is one reason for the recommended practice of giving multiple rounds of immunizations with the same Ag fo?

Answer 7

generating protective immunity

Question 8

IgG Abs have a half life of 3 weeks, contains a neonatal Fc receptor (FcRn) transports Abs from the mother circulation to the fetus. FcRn can be found where and what is its function?

Answer 8

Can be found in endothelial cells and phagocytes, inside an endosome where it binds to IgG that has been phagocytosed. FcRn PROTECTS IgG Abs from intracellular catabolism, take Ag which die by lyosomal enzymes and transport back to cell surface

Question 9

Abs prevent infections by binding to microbial structures by steric hindrance and prevent the interaction between microbe and cell surface receptors. What happens if there are no antibodies?

Answer 9

Microbes will attach to cell receptors and infect the tissue beneath. EX: influenza virus use envelope protein hemagglutinin to infect resp. epithelial cells/ Gram - bacterai use pili to attach to and infect cell hosts

Question 10

Virulence factors refers to properties of bacterial gene products that enable microorganisms to cause disease. They include bacterial toxins and cell surface proteins that mediate bacterial attachment and hydrolytic enzymes that may contribute to?

Answer 10

the pathogenicity of the bacterium… (ANTIBODIES BLOCK THESE VIRULENCE FACTORS)

Question 11

How do Antibodies of the IgG isotype coat/opsonize microbes and promote their phagocytosis?

Answer 11

By binding to Fc receptors on phagocytes

Question 12

FcyRI (CD64): high affinity for Fc, found on Mø, neut, Eosin, Function?

Answer 12

Phagocytosis cell activation

Question 13

FcyRIIb (CD32): low affinity for Fc, found on Mø, N, DCs, B/NK cells, Function?

Answer 13

Phagoctosis cell activation and feedback inhibition

Question 14

FcyRIII (CD16): low affinity for Fc, found on NK cells, Function?

Answer 14

Ab-dependent cell-mediate cytotoxicity (ADCC)

Question 15

FcERI: High affinity for Fc (binds IgE), Found on mast, basophils, eosinophils, function?

Answer 15

Cell activation (degranulation)

Question 16

Phagocyte FcyRI (CD64) binds Fc receptors of opsonized Ab-Ag complexes. Signals from binding activate the phagocyte it bound to and destroys the microbes. What are the most efficient opsonins for promoting phagocytosis via FcyRI?

Answer 16

IgG3 and IgG1

Question 17

When an Ag-Ab complex binds BCR and FcyRIIb (see last note card deck) instead of activating, it inhibits BCR signaling to active B cell by doing what?

Answer 17

SHIP (phosphatase) converts PIP3 into PIP2 in B cell receptor complex, Blocking downstream signaling (REMEMBER: PIP3 is need to signal and continue cascage)

Question 18

Since worms are too large to be engulfed by phagocytes, Mø and N cannot do anything. IgE, Mast, and eosinophils work together to mediate the killing of parasites. What is the mechanism?

Answer 18

Parasite sends allergens to DC, presents to T cell. Effector T cell sends IL4/6 to B cell to produce IgE, IL4/13 to mast cell, binds IgE, releases granules, T cell sends IL4/5 to Eosinophil, binds IgE. Then Killed by major basic protein (cationic) released by granules of eosinophils

Question 19

Ab-dependent cellular cytotoxicity (ADCC) d/t low affinity. Abs bind Ags on surface of target cell, FcyRIII(CD16) receptors on NK cell recognize bound antibody, and what happens?

Answer 19

Crosslinking of Fc receptors signals the NK cell to kill target cell, TARGET CELL DIES BY APOPTOSIS

Question 20

Classical pathway is activated by C1 binds to Ag-Ab complexes, How are alternative and lectin pathways activated?

Answer 20

Alternative: (spontaneously) C3 to C3a C3b
Lectin: mannose binding lectin, activates MASP1/2, cleaves C4/C2

Question 21

C1 in the classical pathway is made up of C1q which binds to Ab, C1r and C1s which are proteases. C1q has 6 subunits, The head regions contact the Igs. What is important of C1r/s?

Answer 21

They form a tetramer composed of 2 C1s and 2 C1r, the ends of them contain catalytic domains of the proteins

Question 22

C1 must bind to two or more Fc regions of antibodies. Soluble (free floating) IgG or IgM will not bind to C1, what do the Abs need to be doing in order for C1 to bind?

Answer 22

Need to bind to antigens!

Question 23

once bound, activated C1s cleaves C4 to generate C4band binds to microbe surface via thioester bonds.C1s then cleaves?

Answer 23

C2 to form C2a and C2b, C2a binds to C4b on the microbe forming C3 convertase

Question 24

For lectin pathway, microbial polysacchrides bind to lectin such as MBL, which activates serine proteases-MASP1,2,3 which are structurally homologous to what and do what?

Answer 24

C1r C1s proteases which will cleave C4 and C2

Question 25

MBL functions in agglutinin, opsonin, and complement fixing. MASP1 formx complex with MASP2 and collectins/ficolins and activates MASP3. What do MASp 2& 3 do?

Answer 25

MASP2: forms complex with lectins (ficolin-3) MASP3: associated with collectin or ficolins and MASP1 to cleave C4

Question 26

When C5 convertase cleaves into C5a and C5b, C5b is on the microbe surface and binds C6. When C7 is bound, what occurs?

Answer 26

C7 is hydrophobic! so the C5bC6C7 complex inserts into the lipid bilayer of the membrane where it becomes a high affinity receptor for C8, C8 binds!

Question 27

CR1 (CD35) is a high affinity receptor for C3b,C4b. CR1 promotes phagocytosis of C3b and C4b coated particles and clearance of immune complexes from circulation. CR1 also transduces signals that activates killing mechanisms on what?

Answer 27

On phagocytes such as neutrophils, B/Tcells, eosinophils, FDCs, which use CR1 to bind and internalize microbes and debris

Question 28

How does C3b for C3d? C3b by Factor I forms iC3b, by CR1 forms C3dg, and then by what step does it form C3d?

Answer 28

plasma proteases form C3dg into C3d

Question 29

CR2(CD21) on B cells and FDCs, binds cleavage products of C3b (C3d,C3dg,iC3b), which enhances the response of B cells to Ags. FDCs CR2 binds iC3b in germinal centers. What does epstein-barr virus do? (EBV)

Answer 29

EBV enters B cells via CR, infectes the cells and can remain latent in infected cells for LIFE

Question 30

CR3 (complement receptor), known as Mac-1 or CD11bCD18, is an integrin that acts as a receptor for iC3b. It also recruits leukocytes to sites of infection by binding ICAM1 on endothelial cells (phagocytes, N, NK cells) What about CR4 (CD11cCD18)?

Answer 30

CR4 on phagocytes, neturophils, and NK cells bind iC3b and function like CR3, leading to phagcosytosis and possibly cell adhesion

Question 31

C1 INH, a complement regulator, displaces C1r2C1s2 from C1q (c1q activates the serine proteases for degredation) which lead to what?

Answer 31

Terminates classical activation!

Question 32

DAF, decay accelerating factor, dissociates what to regulate complement pathway?

Answer 32

C3 convertase on both classical (C4bC2a) and alternative (C3bBb). Classical binds C4b and cleaves C2a, Alternative binds C3b and cleaves Bb

Question 33

MCP/C1, membrane bound cofactors, act in the same way as complement regulator DAF. When present, MCPandCR1 will bind C3b or C3b and bring in Factor I, which does what?

Answer 33

Factor I, with the help of Factor H cofactor for C3b, will cleave C3b or C4b into an inactive form- iC3b. Stopping complement activation (CANT FORM C3 CONVERTASE)

Question 34

MAC is formed on cell surfaces (C7 and C8 or inside membrane) as a result of complement activation. Membrane protein CD59 and plasma S protein can dowhat?

Answer 34

CD59 binds to C5b where it binds to C9, inhibiting poly-C9 assembly, NO PORE TO ENTER CELL Plasma S protein inhibits membrane insertion of C7, so does not bind to C8 = NO MAC!!

Question 35

C3b binds to microbe cause opsonization and phagocytosis, recognize by phagocyte receptor and kills. C3a*** and C5a (C4a) do what?

Answer 35

Recruit and activate leukocytes, inflammation, leukocytes kill this way.

Question 36

When MAC forms, it kills the bacteria/microbe by?

Answer 36

Formation of membrane attack complex which causes osmotic lysis of bacteria

Question 37

C1q,C2 (MOST COMMON DEFICIENCY), and C4 deficiencies are associated with systemic lupus erthematosus. The defects in complement activation lead to?

Answer 37

Failure to clear immune complexes (Ab-Ag), which are then deposited in blood vessel walls/tissues where they produce local inflammation!

Question 38

C3 deficiency is associated with pyogenic bacterial infections that can be fatal! (not commonly C2/C4 because alternative pathway can still work around that) Why does C3 lead to fatal infections?

Answer 38

Because C3 is need for all complement pathways, and without, humoral immunity is compromised!

Question 39

Deficiencies in properdin and Factor D result in increased susceptability to infection with pyogenic bacteria, while C5,C6,C7,C8 and C9 deficiencies may lead to?

Answer 39

Disseminated infections by NEISSERIA BACTERIA

Question 40

Complement system can cause tissue damage, is associated with intravascular thrombosis and cal lead to ischemic tissue injury. In an autoantibody mediated kidney disorder, what can happen caused by complement pathway?

Answer 40

Membranous nephropathy, damage to glomerular epithelia cells can be mediated by the MAC that is generated after Ab binds to a glomerular auto-Ag

Question 41

Newborns are protected agains infection by maternal Abs that are transported across the placental into fetal circulation. The transport of IgG from mom to kid is mediated how?

Answer 41

Mediated by an IgG-specific Fc receptor called the neonatal Fc receptor (FcRn)

Question 42

Along with IgG, ingested IgA by breast milk can neutralize pathogenic organisms that attempt to colonize in the childs gut. How is IgA from milk transported inside the bb?

Answer 42

It is transported across the gut epithelium of newborns by a process know as TRANSCYTOSIS

Question 43

During fetal months, maternal IgG is increased around 2months until birth and then decreases. IgM is made by fetus starting around month 5. What is the total percentages of Abs at 12 months.

Answer 43

IgG is main component at 60% IgM next main compenent IgA is last main component at 20% At around months 2-3 after being born if when there is the lowest amount of antibodies which means highest chance of getting sick!

Question 44

What are the three ways extracellular bacteria can evade innate immune?

Answer 44

1. inhibition of complement activation (many do this) 2. Resistance to phagocytosis (Pneumococcus/Neisseria meningitidis) 3. Scavenging of reactive oxygen species (catalase positive staphylococci (cationic positive) )

Question 45

What are the three ways bacteria and viruses can evade humoral immunity?

Answer 45

1. Antigenic variation-cant be recognized by Abs produced (flu virus, HIV, E coli, Rhinovirus, trpanosome parasite) 2. Inhibition of complement activation (many bacteria) 3. Blocking by hyaluronic acid capsule-resisting opsonization and phagocytosis (streptococcus)

Question 46

Conjugate vaccines are composed of microbial polysacchride antigens coupled to carrier protein. What are Subunit vaccines?

Answer 46

Vaccines composed of microbial proteins and polysacchrides

Question 47

the main focus of vaccines are how they can stimulate CMI againt intracellular microbes. Injected/orally administered vaccines/Ags are extracellular and induce mainly Ab responses. What are two new approaches that are being tested?

Answer 47

1. Microbial Ags are incorporated into viral vectors, which will infect host cells and produce Ags inside the cell 2. DNA encoding a microbial Ag in bacterial plasmid can be ingested by host APCs, and Ag is produced inside the cell