B Cells and Humoral Immunity

Question 1

(blank) is a state of severe hypertension and spasticity in which an individual’s head, neck and spinal column take a complete “bridging” or “arching” position. This posture is caused by spasm of the axial muscles along the spinal column.

Answer 1

opisthotonus

Question 2

(blank) is a highly fatal disease of humans. Mortality rates reported vary from 40% to 78%. The disease stems from a potent neurotoxin produced when spores germinate and vegetative cells grow after gaining access to wounds. The organism multiplies locally but symptoms appear remote from the infection site.

Answer 2

Tetanus

Question 3

What is the causative agent of tetans?

Answer 3

clostridium tetani (found in heavily manured soil and GI of animals)

Question 4

Why is tetanus vaccination so important?

Answer 4

because natural recovery from this disease is unlikely because it doesnt ellicit an immune response, you just die

Question 5

In humoral immunity, what are the effectors of protection?

Answer 5

antibodies

Question 6

How can you distinguish between humoral vs. cellular immunity?

Answer 6

adoptive transfer tests

Question 7

(blank) is transferred by serum containing antibodies or by antibodies aone ( rattle snake venum, tetanus toxoid)

Answer 7

humoral immunity

Question 8

(blank) is transferred only by cells (usually done in completely inbred mice or rats)

Answer 8

cellular immunity

Question 9

How is humoral immunity transferred?

Answer 9

by serum containing antibodies by antibodies alone.

Question 10

If you are transfering humoral immunity wthin a species, what happens?

Answer 10

they are accepted as self and are considered effective

Question 11

What happens if you transfer antibodies across species?

Answer 11

antibodies last 5-7 days because they are immunogenic (elicit an immune response)

Question 12

Is the transfer of antibodies awesome? why?

Answer 12

yes because it is practical and safe. Antibodies are human “self” and Ig can be irradiated to prevent viral infection

Question 13

What is this:

an immune response that is not elicited by antibodies but rather antigen sepcific T cells and is tranferred only cells.

Answer 13

Cellular immunity

Question 14

Why cant you really transfer T cell immunity?

Answer 14

because its hard to match MHC I and MHC II antigens and if they are not matching those cells will be killed

Question 15

What three things influence humoral immunity?

Answer 15

amount of antigen, route of natural or prophylactic immunization, use of adjuvants

Question 16

How long do specific antibodies live?

Answer 16

maintained for life, although concentrations drop slowly.

Question 17

The affinity and concentration of an antibody is sometimes critical. Explain this as a priniciple for tetanus toxin/

Answer 17

antibodies for tetanus toxin nee to have an extremely high affinity and concentration in order to out-compete the toxin, this is why the tetanus vaccine is repeated.

Question 18

What are immunogens?

Answer 18

molecules that elicit an antibody response

Question 19

What are some common immunogens?

Answer 19

proteins > 25 micrograms (toxoids), killed pathogens, live attenuated viruses, conjugate and DNA vaccines.

Question 20

What are adjuvants?

Answer 20

something that is added to improve immunizations but it itelf is not immunogenic.

Question 21

What can adjuvants activate?

Answer 21

they can activate macrophages to secrete IL-1 and TNF alpha to activate helper T and B cells AND they keep immunogens localized

Question 22

Routes of administration of vaccine or immunization affects the types of antibody made.
intramuscular?
Oral or intranasal?
IV?

Answer 22

IgG
IgA
poor route of immunization

Question 23

If you repeatedly expose someone to a antigen what will happen?

Answer 23

you will increase the quantity and affinity of IgG and IgA

Question 24

(blank) is a measurement of the binding strength of Fab antigen-biding site for its single antigenic epitope.

Answer 24

affinity
expressed as Ka=1/Kd
(ka= affinity, Kd= concentration to fill half the binding sites)

Question 25

(blank) is a measurement of the total combined binding strength of a complete immunoglobulin molecule for a complex antigen that contains repeating epitopes.

Answer 25

avidity. (think of this like velcro, one tooth of velcro wont have any strength, but numerous teeth of velcro create a very strong connection)

Question 26

Explain how you can have low affinity but high avidity

Answer 26

an IgM antiody molecule with low affinity for a particular antigen (but that has 10 antigen binding sites) will bind with high avidity to a complex antigen that contains repeats of the epitope

Question 27

(blank) becomes medically important for IgM and IgA because bacteria and viruses have repeating epitopes and proteins in the membranes, flagella, and capsules

Answer 27

avidity

Question 28

WHy is antibody super important for botulin toxin, ebola virus, and tetanus?

Answer 28

Because these are very lethal in small concentrations so you must have high affinity to be able to bind even the smallest dose. (need to outcompete toxin for binding site)

Question 29

How do you classify an immunoglobulin?

Answer 29

5 classes denoted by english letter (A-E) Greek letters to describe heavy chains AND Numbers for the isotypes 2 for IgA 4 for IgG 2 types of light chains called Kappa and Lambda

Question 30

How many J chains are there for every polymeric unit (i.e immunoglobulin)

Answer 30

1 (think of it like a clasp of a necklace)

Question 31

How do you determine the molecular weight of a immunoglobulin?

Answer 31

multiply each repeate by 150,000. (important because determines whether it can get out of the blood into tissues. greater than 50,000 cant get out of the kidneys, things that are smaller can.

Question 32

How many antigen bining sites are on a pentameric Ig?

Answer 32

10, times each unit by 2

Question 33

What is the first antibody made in immune responses and appears right after antigen is introduced?

Answer 33

IgM

Question 34

Does IgM have a low or high affinity for antigens?

Answer 34

low affinity, but potential for high avidity

Question 35

What is the serum concentration of IgM?

Answer 35

1.2 mg/ml

Question 36

What is the serum half life of IgM?

Answer 36

about 5 days

Question 37

What is the function of IgM?

Answer 37

fixes complement extremely well. Just 1 IgM antiboy on a bacterium can start complement killing

Question 38

Is IgM made for life?

Answer 38

nope, it is termporary and tells you if you have had a recent infection or not

Question 39

Where can you find IgM?

Answer 39

in secretions :)

Question 40

What size is an IgG?

Answer 40

150Kd

Question 41

How many binding sites does IgG have?

Answer 41

2

Question 42

What are the differences among the 4 classes of IgG?

Answer 42

AA seq of the IgGs differ in constant regions, hinges

Question 43

What is the second antibody made in the immune response and how long does it last? What is its struture

Answer 43

IgG persists for life monomer so only has 2 binding sites

Question 44

Does IgG have a high or low affinity for antigen

Answer 44

high affinity

Question 45

What is the serum concentration for IgG?

Answer 45

7-12 mg/ml

Question 46

Which kinds of IgG have long half lives (21-24 days)?

Answer 46

IgG1, IgG2, IgG4

Question 47

Which kind of IgG has a short half life (7-8 days)?

Answer 47

IgG3

Question 48

What does IgG1 and IgG3 do?

Answer 48

fix complement

Question 49

HOw can you start a complement cascade with IgGs?

Answer 49

you need 2 of them close together

Question 50

What does IgG1 and IgG3 support?

Answer 50

antibody-dependent cell mediated cytotoxicity (ADCC)

Question 51

(blank) crosses the placenta to provide neonatal protection

Answer 51

IgG

Question 52

Whydo babies start getting sick around 6 months of age?

Answer 52

because the half lives of the immunoglobulins has pretty much depleted the IgG (passive immunity) that was given to the baby by its mother

Question 53

What is the structure of IgA?

Answer 53

it can be a dimer or trimer

Question 54

What is the weight of IgA?

Answer 54

dimer-300 | trimer-450 Kd

Question 55

What are the 2 subclasses of IgA?

Answer 55

IgA1 and IgA2

Question 56

What is the number of antigen binding sites?

Answer 56

4 or 6

Question 57

Where do you find IgA?

Answer 57

in plasma and in secretions including breast milk, gut, tears, saliva, vagina

Question 58

Since IgA is passed through breast milk, how does this help the baby?

Answer 58

it doesnt because IgA just remains in the babys gut and does not enter the babys circulation

Question 59

What is the serum concentration and half life of IgA?

Answer 59

around 2 mg/ml | about 6 days

Question 60

What is the function of IgA?

Answer 60

to block pathogens at mucosal sites, their adhesion, their attachment to the gut wal

Question 61

How is IgA transported?

Answer 61

through eptihelial cells into mucosal secretions via secretory component

Question 62

What is the secretory component?

Answer 62

it is the tranport receptor for IgA

Question 63

What do Igs have secretory component?

Answer 63

IgA and IgM nly in secretions :)

Question 64

How big is IgD and what is its structure?

Answer 64

180kD, it is a monomer with 2 binding sites

Question 65

What is the serum concentration of IgD?

Answer 65

less than 30 microg/ml

Question 66

Where do you find IgD?

Answer 66

on virgin B cells that have never seen an antigen

Question 67

What is the structure of IgE, concentration and half life?

Answer 67

180 kD, monomeric with 2 binding sites, less than 100 nanograms (super small amounts). half life of 1-2 days (very short lived) used for allergic reactions

Question 68

resting mast cells are full of granules and proteases, kinases, and tryptases and lots of specificities of IgEs. How do you get the mast cell to become activated and release its granules?

Answer 68

by having a multivalent antigen that is cross linked bind to the IgE antibody (has to close together)

Question 69

What are 2 ways to diagnosis IgE allergic responses?

Answer 69

via in vivo skin tests ([prick-puncture) and intradermal AND In vitro IgE tests of serum

Question 70

What are the 2 in vitro IgE tests of serum?

Answer 70

ImmunoCAP Immunolite HY Tec

Question 71

What are the 5 mechanisms of protection by antibodies?

Answer 71

- neutralize toxins (tetanus, diptheria, snake) - Block adhesion to prevent bacterial and viral entry into cells - initiate complement (to opsonize bacteria and yeast) - Support neutrophils' killing of yeast and bacteria - ADCC of infected host cells and parasites

Question 72

(blank) can block the binding chain of dimeric toxins (diptheria, tetanus)

Answer 72

antibodies

Question 73

Toxins are effective at 10 to the negative 9 M so what does this mean for antibodies?

Answer 73

they must have an affinity higher than this to be effective

Question 74

Amounts of antibody must be high enough to reach sites of infection.

Answer 74

FACT

Question 75

(blank) block bacterial adhesion to prevent bacterial entry into cells and to prevent bacterial and viral pathogens from crossing into the body from the gut

Answer 75

Antibodies

Question 76

Antibodies can initiate (blank) to opsonize bacteria and yeast.

Answer 76

complement

Question 77

C3b, iC3b, C3dg and C3d are (blank) attached (through special thioester of C3), to tag yeast or bacteria for opsonization

Answer 77

covalently

Question 78

Usually, complement (blank) products are coupled to pathogens

Answer 78

C3

Question 79

How does ADCC of infected host cels work?

Answer 79

targe cell has membrane antigen (cannot be yeast or bacteria)-> antibody is specific for that antigen-> NK cell kills the target cell

Question 80

What antibodies support ADCC?

Answer 80

IgG1 and IgG3

Question 81

How do you measure if your ADCC is working

Answer 81

You radio label with chromium 51 (which enters cells and radiolabels them) you wash the cell and only intact cels have the radiolabel. The NK cell should recognize the bound antibodies of the infected cell and then should lyse the cell which will spill radioactive into the supernate and you can measure that to make sure that your cells are getting killed properly.

Question 82

For an ADCC assay What is this: the counts per min (cpm) released by targets alone, without killer cells and without antibody.

Answer 82

spontaneous release (SR)

Question 83

For an ADCC assay What is this: the counts per min (cpm) released by targets with detergent

Answer 83

Maximum release

Question 84

For an ADCC assay What is this: the counts per min (cpm) released by targets with killer cells and/or with antibody

Answer 84

experimental release

Question 85

For an ADCC assay | WHat does a plus sign mean when dealing with an assay? a negative sign?

Answer 85

something was added | something was taken away

Question 86

How does Rho gam work?

Answer 86

it is an antibody feedback inhibition medicine that will block B cell signaling and make the anti-RHD B cells unresponsive so an RhD negative mommy can not attack her RhD positive baby :)

Question 87

What does neutrophil mediating killing require?

Answer 87

oxidative and nonoxidative steps

Question 88

What is the oxidative step in neutrophil mediated killing? Why is this important?

Answer 88

oxidative inchreases pH, and potassium enteres the phagosome. It increases the potentcy of the nonoxidative step (the oxidative step would probably mediate no damage by itself)

Question 89

WHat is the nonoxidative step in neutrophil mediated killing?

Answer 89

toxic proteins from primary granules enter phagolysosomes | p91 an p21

Question 90

Neutrophil klling involves superoxide anion in the phagosome (before/after) formation of the oxidative enzyme complex. This is step 1

Answer 90

after

Question 91

How does a neutrophil assemble the oxidative enzyme compled?

Answer 91

via cytochrome p558 oxidase

Question 92

In chronic granulomatous disease (CGD) what is disrupted ?

Answer 92

step one (the oxidative step) of neutrophil killing

Question 93

(blank) is activated by neutrophil receptors to assemble the oxidase complex

Answer 93

Rac2

Question 94

Neutrophil nonoxidative step 2, proteins are added to kill the bacteria. These toxic proteins come from primary granules (modified lysosomes). The toxic proteins of the primary granules include.....?

Answer 94

``` defensins bactericidal permeability increasing factor (BPI) phosphoplipase A Cathepsin G, elastase ```

Question 95

What is this: | 4000 m.wt.; 30% of granule protein; pI = 10; poison ion pumps of bacteria

Answer 95

defensin

Question 96

What is this: | kills gram negative bacteria in seconds

Answer 96

BPI

Question 97

What is this: | generates lysolecithin, a detergent that solubilizes microbial membranes

Answer 97

phospholipase A

Question 98

Where does the oxidative burst occur and why is it needed?

Answer 98

in the phagosome to raise salt and pH so non-oxidative killing can happen

Question 99

Pyogenic bacteria and yest require (Blank) to be killed

Answer 99

oxidative step

Question 100

Patients with hereditary Chronic Granulomatous Disease (CGD) lack the (blank) pathway and usually die from bacterial infections.

Answer 100

oxidative

Question 101

(blank) p’ts lack nonoxidative killing, have large granules in neutrophils, NK cells & hair

Answer 101

Chediak Higashi Syndrome | ...sady this means their neutrophils will not kill bacteria

Question 102

What disease is this: The mutation alters both lysosomal loading with proteins and lysosomal trafficking. The disease has neurological defects, too, which persist even after stem cell transplantation.

Answer 102

Chediak Higashi Syndrome