Lecture 8 - Immunity & B cells and AB's Flashcards

(75 cards)

1
Q

B cell activation requires what two signals?

A
  1. Antigen binding to the B cell receptor
  2. Th2 cell CD40L binding to the CD40 receptor on a B cell
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2
Q

What is the “third” signal that a B cell receives during activation?

A

Comes via cytokines, and determines whether the cell differentiates into a memory cell or a plasma cell

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3
Q

In order for antigens to signal B cell activation, what has to happen to the B cell receptors?

A

They must cross-link (with the antigens)

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4
Q

What is the purpose of having the Ig-alpha and Ig-beta coreceptors?

What is the next couple of steps?

A

They contain a longer cytoplasmic domain (ITAM) that gets phosphorylated (by Blk, Fyn, or Lyn)

Syk then binds to the ITAMS and is continues signal cascade

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5
Q

In addition to the IgM/Ig-alpha/Ig-beta of the B cell receptor, what other molecules are part of the B cell receptor complex?

A

Cr2

CD19

CD81

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6
Q

The CR2 molecule of the BCR complex binds to…

A

C3d o the bacterial cell

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7
Q

What happens after CR2 binds to C3d?

A

The CD19 molecule’s intracelular domain gets phosphorylated and a signal cascade occurs

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8
Q

Where do we find C3d?

A

On bacterial surface or bound to immune complexes (Ag/Ab complexes)

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9
Q

What type of B cells are BCR complexes expressed on?

A

All of them!

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10
Q

Which area of the lymph node has a high amount of proliferation?

A

The Dark zone of the germinal center

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11
Q

What makes up the mantle zone of the lymph node?

A

Non activated (naive) B cells

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12
Q

Antigens enter the lymph node via ____. B cells enter via _____.

A

Antigens = Afferent lymphatics

B cells = HEV’s

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13
Q

Antigen pathway once it gets to the lymph node

A

Afferent – subcapsular sinus – transport to follicle – binds to Follicular Dendritic Cells

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14
Q

The CR2 domain (yes, the same one that is part of the BCR complex) is also found on which cells?

A

Macrophages and Follicular Dendritic Cells

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15
Q

B cells are activated in the ______

By what?

A

paracortex

By a specific antigen that is presented by FDC’s in the T cell area

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16
Q

Antigen activated T cells __________

Antigen activated B cells move to _________

A

T cells proliferate and differentiate

B cells move to the boundary region and present antigen to effector TFH cells

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17
Q

What is formed when B cells present antigen to effector TFH cells?

A

Cognate interactions / Cognate pairs

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18
Q

The primary focus for expansion f antigen activated B cells is in the _________

The secondary focus for these cells is in the _________

A

Medullary cords

Primary follicle

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19
Q

Clonal expansion of the antigen-activated B cells occurs in ______, which creates _______

A

Primary follicle

Germinal center

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20
Q

Two surface molecules on FDC’s that bind and deal with virus/bacteria. Whats the main function of these?

A

CR1 and CR2

  • CR1 binds to C3b
  • CR2 binds to C3d

These bind to intact viruses and hold them at the surface.

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21
Q

Immature B cells (leaving) get what signal from FDR’s?

A

BFF

(induces maturation)

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22
Q

Somatic hypermutation occurs in the _____

It comes before _____, and that comes before ______

A

rapidly proliferating germinal center cells

SH -> Selection -> Affinity maturation

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23
Q

Affinity of the antibody will increase over time due to…

A

affinity maturation

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24
Q

If a B cell contains low affinity surface molecule in the germinal center, it doesn’t receive

A

survival signals from the FDC’s

…undergoes apoptosis

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25
Isotype switching begins with what signal?
CD40L (from TH2 cell)
26
Isotype switching from IFN gamma?
IgG2a, IgG3
27
Isotype switching from TGFb and IL-5?
IgA IgG2b
28
Isotype switching from IL-4?
IgE IgG1
29
What cytokine makes B cells differentiate into: * plasma cells * memory cells
* IL10 -\> plasma cell * IL-4 -\> memory B cell
30
Why didn't patient 2 have trouble expressing both IgM and IgD, despite his problems?
M + D are formed at the level of mRNA splicing \*not\* recombination at the DNA level
31
Why did the patient make antibodies against the blood group antigens but not against tetanus toxoid?
Blood group antigens are IgM-mediated antibodies to Tetanus toxoid would be IgG, which this patient can not form.
32
What did Patient 2 have that kept his Ig's from class switching?
Hyper IgM syndrome
33
Hyper IgM syndrome is a ____ mutation of _____ molecule What do these patients lack?
X linked mutation of **CD40L** No germinal centers!
34
T independent antigen 1 (TI-1) function and example
_Polyclonal_ activation of B cells via a different receptor than Immunoglobulin ex: bacterial _LPS_
35
What does LPS, a T-independent antigen, bind to to activate the B cell?
TLR-4
36
TI-2's... What's their structure and function?
Repetitive epitopes in the **capsule** of bacteria, made of polysaccharides or proteins. They **activate B-1 or B-2 cells** by binding to the B cell co-receptor
37
TI-2 can't activate B cells when?
In patients under 5 years old.
38
Athymic people can only form antibodies by what mechanism?
_T-independent antigens_ T-dependent response will NOT work because no thymus for T cell maturation
39
TI-1 and TI-2 do not result in...
* Isotype switching * Formation of memory cells
40
How do you make a vaccine that will create a response to a bacterial polysaccharide (a TI-2), if it normally doesn't elicit a B cell response in kids under 5?
Use polysaccharide-toxoid conjugate 1. B cell receptor binds to the polysaccharide 2. Conjugate is internalized, degraded 3. Toxoid peptides are presented to Tcell, which then activates the B cell \*\*effectively turns it into a *T cell dependent repsonse*\*\*
41
Examples of conjugate polysaccharide vaccines
* H. influenzae * Use tetanus toxoid * Strep Pneumo * Uses diphtheria protein * Neisseria M. * Use diphtheria toxoid/protein
42
Strep pneumo cell type, clinical presentations, number of serotypes, and vaccines
* Gram+ coccobacillus * URT infection, Otitis Media, PNA, Meningitis * \>90 serotypes * Polysaccharide vax (23), Conjugate vaccine in kids
43
Serotypes of Strep pneumo have...
limited cross reactivity
44
What are the two Ig's that cross barriers, and what do they cross?
_IgA_ crosses **epithelial** cell into mucosal secretions _IgG_ crosses **endothelial** cells into extravascular space, OR across the **placenta** to fetus
45
IgG active transport is mediated by what?
The Brambell receptor \*FcRB
46
Steps in IgA active transport
1. bids basolateral **poly-Ig receptor** 2. Endocytosed 3. Transported to apical surface 4. Receptor is cleaved and IgA is bound to **secretory component** \*The secretory component is a remnant of the poly-Ig receptor that was left behind after cleavage
47
What happens to the secretory component during IgA deficiency disease? What else do we see happen?
It increases in the lumen IgM is also increased because the Poly-Ig receptor can bind to it also
48
Difference in structure of IgA1 and IgA2
IgA1 has a hinge region that is twice as long \*Both can be monomeric OR dimeric
49
Function of the secretory component?
It _protects IgA from cleavage_ by proteases in respiratory tract
50
Difference in IgA1/2 distribution
IgA1 = URT IgA2 = GI system (A2 is better suited to deal with bacterial enzymes due to shorter hinge region)
51
Active transport of IgG across placenta from mom-baby begins and ends when?
Begins months before birth The passively transferred maternal IgG is done by 6-9 months postpartum
52
What's the deal with maternal IgA?
IgA from the milk remains in the GI, and doesn't circulate in the system
53
Effector functions of AB
Neutralization Opsonization Complement activation
54
Neutralization by AB is useful for preventing... What specific ones?
Bacterial toxin poisoning of the cell Toxins from: Diphtheria, Tetanus, Cholera, Staphylococcus
55
Bacterial toxins comonly have what two domains
A+B B binds the cell A is released into cell after endocytosis -- poison
56
Two types of Fc receptors
Gamma and epsilon
57
Fc gamma receptors are on what cells? What do they cause?
* PMN * MQ * B cells * FDC * NK _Opsonization_ in PMN and MQ _ADCC_ in NK cells
58
What cells have FcE receptors? Function?
Mast cells and Basophils (the degranulators) \*have a role in Allergy response
59
The Fcgamma receptor on PMN and MQ What does it bind? What happens next?
**Fcγ-RI** _High affinity for IgG1+3_ (binds to the hinge region) The bound IgG3 molecule then binds **antigen** with its variable domain that is sticking out, and causes signaling of **phagocytosis**
60
Opsonization: 4 steps
1. Antibody binds to bacterium 2. antibodies on bacteria bind to Fc receptors 3. cell engulfs it into the **phagosome** 4. fuse with lysososome and is degraded
61
Other names for FcγRI, FcγRII, and FcγRIII
I = CD64 II = CD32 III = CD16
62
Which Fcγ receptor has highest binding to IgG1
Fcγ-RI (CD64)
63
What are the two inhibitory Fcγ receptors?
(Fcγ) **R2B2** + **R2B1**
64
What are the two most effective classes of IgG for binding to the Fcγ receptors
IgG3 + IgG1
65
ADCC (NK cells) is initiated by the interaction of what molecule/receptor What is the second step
**CD20** (on tumor or virus infected cell) + **Anti-CD20** (free) ---\> The NK cell will bind the Anti-CD20 and **cross-link its Fc receptors** (FcγRIII)
66
What are the 2 phases of mast cell degranulation?
_Resting_ = IgE is bound to FcERI receptor _Activated_ = multivalent antigen crosslinks the IgE antibodies -----\> Degranulate \*\*\*This is why first formation of IgE isn't as big of a problem, its the *second exposure* that causes the crosslinking and degranulation in serious allergic reactions.
67
IgG4 has more of a ______ function
anti-inflammatory
68
IgG3 is a strong complement activator because... but.......
It has a long hinge region (flexibility) but it is more susceptible to cleavage
69
Strongest immunoglobulin molecules in activation of complement
IgM, IgG1, IgG3
70
The ratio of ______ is important for an alergic response
**IgG4 : IgE**
71
Formation of immature B cells is an ______ and _______ process
Ag-independent, Constant
72
Mature, naive B cell can circulate for
3-8 weeks \*will die if they done contact an antigen with their Ag-specific receptors
73
Activation takes place in the \_\_\_\_\_\_\_\_\_\_ Isotype switching takes place in \_\_\_\_\_\_\_
Paracortex Germinal Center
74
Primary and secondary immune response... initial AB response takes about \_\_\_\_\_\_\_ The secondary response (re-exposure) is ____ and \_\_\_\_\_
A week _Rapid_ and _Stronger_ \*higher affinity AB made
75
Better quality antibodies of the secondary exposure are a result of what process? What does this mean in a cellular context?
_Affinity maturation_ B cells with low affinity Ig receptors will be given an **inhibitory** signal (*FcγR2B1*) that _prevents_ production of low-affinity IgM antibodies --\> only produce high affinity IgG, IgA, IgE