B cell-mediated immunity

Question 1

What is the function of BCR on surface of B cells?

Answer 1

Contains IgM, IgD, Iga, and Igbeta for binding

Question 2

What is the function of Co-BCR on surface of B cells?

Answer 2

The Co-BCR is Cr2 and CD19 which are cytoplasmic tail receptors that recgonize Iga and Igb leading to the transmission of the first signal in B cell activation

Question 3

What is the function of HLA Class II on surface of B cells?

Answer 3

Recognition and presentation of extracellular pathogens

Question 4

What is the function of CD80/86 (B7) on surface of B cells?

Answer 4

Upregulated for Th cells during activation allowing Th to provide the cytokines needed

Question 5

What is the function of CXCR25 in the migration of mature naive B cells in lymphoid tissue?

Answer 5

Facilitates the migration of b cells to the primary follicle if no antigen present

Question 6

What is the response of B-2 (follicular) B cells?

Answer 6

re-circulating B cells

Question 7

What is the response of Marginal zone (MZ) B cells?

Answer 7

Resided in the spleen: blood born polysaccharide Ags

Question 8

What is the response of B1 cells?

Answer 8

Mucosa- limited ag specificity

Question 9

How do mature, naive B lymphocytes migrate in the lymphoid tissue?

Answer 9

Travel to secondary lymphoid tissues from primary lymphoid follicles, enter through HEV
If no antigen then migrate to primary follicle via CXCR5 and exit through efferent lymphatic vessels
Competition for FDCs (survival signals), die within a few weeks in absence of antigen

Question 10

What is the antigen induced first signal in B cells? What ligands interact to contribute to antigen recognition (first signal) leading to activation?

Answer 10

Ag recognition by Migs leading to the cross linking of 2 or more BCRs
- ag bound with C3d recgonized by mIgs and CR2 (CD21) leading to cross linking
Signaling occurs via Iga and Igb cytoplasmic tails and CR2 and CD19= BCR co receptor leading to activation of Syk and B cell phosphorylation
TLR signaling through cytoplasmic domains

Question 11

How does B cell activation lead to change in chemokine receptors?

Answer 11

Cells begin up-regulating CCR7 allowing for migration towards the T cell zone

Question 12

How does B cell activation lead to migration in lymph nodes?

Answer 12

After activation by ag B cells migrate in lymph nodes towards T cell zone due to upregulation of CCR7
Begin secreting low levels of IgM= primary response

Question 13

What is the immune synapse between a B and a T cell?

Answer 13

Co stimulatory signals generated by CD40-CD40L interactinos and adhesion molecules leading to release of cytokines by Th which tells B cells what isotype to switch to and induces AID
Class switching and affinity maturation occur at the same time

Question 14

How does antigen recognition by T cells lead to second activation signal for B cells?

Answer 14

the Cd40/CD40L leads to the release of cytokines by Th cells

Question 15

What are the two functions of cytokines released by Th cells?

Answer 15

Induction of class switching in H chain

Augment B cell differentiation and proliferation

Question 16

What is activation induce deaminase (AID) and what effect does it have?

Answer 16

Key enzyme of affinity maturation, converts Cs to Us allowing ApeI endonuclease to create ds breaks in DNA

Question 17

How do T-independent antigens affect B cell response?

Answer 17

B-1 cells respond to Ag in mucosa

Marginal zone B cells in spleen recognize blood borne polysaccharides

No class switching because no CD40 which means no cytokines

Question 18

What is the mechanism of neutralization of microbes and microbial toxins in the humoral immune response?

Answer 18

Ag binds to antigen so they can enter cell. Any class of Ab works 
Ab neutralizes the infectivity and potential effects of infection

Question 19

What is the mechanism of opsonization and phagocytosis in the humoral immune response?

Answer 19

Opsonization of microbe by IgG
Binding of opsonized microbes to phagocyte Fc receptors
Fc Receptor signals to activate phagocyte
Phagocytosis and killing

Allows clearance of immune complexes (ICs) by CR1 on erythrocytes binding to ICs with attached C3b and C4b and transporting to liver and spleen for phagocytosis

Question 20

What is the mechanism of classical pathway activation of complement activation in the humoral immune response?

Answer 20

IgG x2 or IgM binds causing conformational changes allowing C1 to bind to Fx of antibody/antigen complex initiating classical pathway

Question 21

What is the mechanism of IgE and eosinophil/mast cell meidated reactions in the humoral immune response?

Answer 21

IgE binds to Fce receptors on mast cells resulting in degranulation of cell

Question 22

What is the function of IgA antibodies at mucosal surfaces?

Answer 22

IgA and IgM have J chains so can secreted into the lumen

Question 23

What is the role of antibodies in neonatal immunity?

Answer 23

IgG only Ab that can cross the placenta, binds to FcRn and endocytosis via macrophages and other endothelial cells, able to be recycled
IgM produced around birth
Additional protection gained from IgA in breast milked
6-12 months immunocompetent because moms iG G levels drop as you begin to synthesize your own

Question 24

What is the mechanisms of resistance of pathogens and microbes to humoral immunity?

Answer 24

Change of surface Ags

Outer capsule or coat that prevents complement activation, binding of Abs, and phagocytosis

Question 25

What is Immunization? What is the difference between active and passive immunization?

Answer 25

Antigenic stimulus that elicits specific adaptive immune responses that can be recalled during subsequent infections Passive= intro of antibody or antiserum, immediate immunity but transient Active= intro of on antigen that provokes an adaptive immune response, more permanent creates immunological memory "priming" process

Question 26

What is switch recombination?

Answer 26

``` CD40:CD40L and cytokines trigger isotype switching by increasing the accesibility of DNA at a specific C region and inducing the expression of AID Once switched cant go back because cut out that class In T dependent Ags only ```

Question 27

What is affinity maturation?

Answer 27

Introductions of point mutations in the switch regions of the variable areas (a lot of times in hypervariable) of Ig resulting in expansion of antibody repertoire to generate high affinity Have to recheck to make sure works

Question 28

What is the role of T follicular helpers

Answer 28

Cd4+/low levels of CD25, provide help via CD40 CD40L interaction ICOS ICOSL essential for germinal center reaction inducible costimulator of B7 --> selective survival of B cells Secrete IL-21 facilitating differentiation to plasma blasts Provides IFN-gamma and IL-4 for cytokine switching

Question 29

What are plasma cells?

Answer 29

Terminally differentiated effector B cells Cell marker= CD27 wth decreased CD19,20 and HLA class II Secrete Abs super quickly so have extensive ER

Question 30

What is antibody feedback?

Answer 30

Control mechanism triggered by secreted Ab that blocks further Ab production, IgG only If excess Ab binds to FcgammaRIIB blocking B cell receptor signaling so no activation

Question 31

What is the cell distribution, function, and affinity for Ig of FcgammaRI (CD64)?

Answer 31

macrophages, neutrophils, eosinophils Phagocytosis High, binds IgG1 and IgG3

Question 32

What is the cell distribution, function, and affinity for Ig of FcgammaRIIA (CD32)?

Answer 32

macrophages, neutrophils, eosinophils, platelets phagocytosis; cell activation (inefficient) low

Question 33

What is the cell distribution, function, and affinity for Ig of FcgammaRIIB (CD32)?

Answer 33

B lymphocytes, DCs, mast cells, neutrophils, macrophages Feedback inhibition of B cells, attenuation of inflammation low

Question 34

What is the cell distribution, function, and affinity for Ig for FcgammaRIIIA (CD16)?

Answer 34

NK cells Antibody dependent cellular cytotoxicity Low

Question 35

What is the cell distribution, function, and affinity for Ig for FcepsilonRI?

Answer 35

Mast cells, basophils, eosinophils Activation (degranulation of mast cells and basophils) High

Question 36

What are natural antibodies?

Answer 36

IgM but some IgG, produced naturally in reaction to go flora by B-1 and MZ B cells Cross react with blood alloantigens which is why we have to type before transplant

Question 37

What are the outcomes of the first signal in B cell activation?

Answer 37

Expression of proteins that promote survival and cell cycling antigen presentation, increased B7 allowing for interactions with helper T increased expression of cytokine receptors increased expression of CCR7 leading to migration from follicle to T cell area