Lecture 12: B-cell activation and antibody production

primary: longer lag phase, less antibody concentration, longer time to achieve peak reponse

secondary: no lag phase from time of exposure, greater antibody concentration, quicker time to achieve response

**compare and contrast the primary and secondary response of the humoral immune response. consider amount of antibodies produced, time to achieve that amount/have a response, and lag phase

primary

**The following describes a __________ humoral response:

- IgM predominates

- long latency period

- short duration

- overall low antibody titer

secondary

**The following describes a __________ humoral response:

- IgG predominates

- short latency period

- much longer duration

- higher antibody titer

- affinity maturation

memory

Secondary response characteristics are due to ________, which is is antigen specific

non-protein antigens (polysaccharides, lipids, etc.)

**what type of antigens produce a humoral response without T helper cell assistance?

Protein

Non-protein

__________ antigens are considered Thymus- dependent antigens, while _________ antigens are considered Thymus-independent antigens

antigens that involved CD4 T cell assistance in order to amount an immune response, are considered thymus dependent (i.e. antigen recognized by B cell (a type of APC) then is further activated (or class switched) when presenting antigen to a helper T-cell

an antigen that just needs to bind to Ig, then to B, and B cell can immediately respond is considered thymus independent

**What is meant by a thymus dependent vs. thymus independent antigen?

independent

**The following describes humoral responses to thymus-___________ antigens (dependent/independent):

- IgM is the predominant (and usually only) isotype

- Lower overall antibody titers

- Low affinity antibody produced

- Little memory cell generation

dependent

**The following describes humoral responses to thymus-___________ antigens (dependent/independent):

- Isotype switching (like to IgA, IgE, IgG)

- Abundant memory cell generation

- Affinity maturation of antibodies produced during IR

thymus dependent antigens produce a more specific response! It involved CD4 T cell help and their cytokines and co-stimulatory molecules

Which type of antigen induces a more specific response, thymus dependent or independent antigens? and how/why?

IgM or IgD in conjunction with IgBeta and Igalpha

What are the components of the B-cell antigen Receptor Complex?

via their ITAMs, helps with kicking off signaling cascade within the B cell

What is the primary function of IgBeta and IgAlpha in the B-cell antigen Receptor Complex?

1) Preparation for proliferation and subsequent differentiation.

2) Up regulation of protein synthesis machinery.

3) Increased surface expression of MHC II

molecules and co-stimulatory molecules

4) Increased membrane expression of receptors for CD4 cell derived cytokines.

What are four early functional responses to B-cell activation stimuli?

1) Recognition of the antigen by CD4 T cells

2) cooperation between the antigen specific B and T cells

Antibody responses to T-dependent (protein) antigens require what two things?

II

Antigen specific B cells bind to the native protein and present it with MHC _____ to antigen specific CD4 cells

B7

Upon activation, B cells up-regulate expression of ______ on their surface

1) CD28 (T cell): B7-1/B7-2 (Bcell)

2) CD40 ligand (CD154 on Tcell) : CD40 (Bcell)

What are two receptor-ligand interactions involved with CD4 T cell "contact mediated" activation of B-cells?

1) stabilization of cell to cell interactions

2) signal transduction! yay

What are two major outcomes of CD4 T-cell "contact mediated" Activation of B cells?

1) they determine the type of antibody isotype to be secreted by promoting heavy chain switching to different isotypes

2) they provide activation/amplification mechanisms by augmenting proliferation and differentiation

What are the two primary functions of cytokines in antibody responses?

IL-2, IL-4, and IL-5

Which 3 cytokines induce proliferation of resting B-cells?

IL-6

Which cytokine induces proliferation of activated B-cells?

IL-1 and IL-10

Which cytokines increase proliferation of B-cells (in vitro only)?

IL-4 and IL-5

Which cytokines potently promote antibody secretion by B cells?

IL-2, IL-6, and IL-10

What three cytokines have demonstrated in vivo, promotion of antibody secretion?

IgE

IL-4 promotes antibody class switching to ______

IgA

IL-5 promotes antibody class switching to ______

1) Fibrous capsule

2) Afferent

3) Cortex

4) Medulla

Fill in the blank with the tissue architecture of a lymph node:

1) _______ ________: outer covering

2) ________ lymphatics: lymph enters the node at several sites

3) _______: outer region—contains follicles (dense lymphocyte collections & APC's)

4) ________: inner region—less dense lymphocytes and APC's.

5) Primary

6) Secondary

7) efferent

Fill in the blank with the tissue architecture of a lymph node:

5) __________ follicles: (B-cell rich zones): 1°naïve or resting B-cells

6) __________ follicles: (with GC)—FDC's and rapidly expanding B-cells

7) Single _________ lymphatic: all lymph leaves each node by this single vessel.

- Interdigitating DC

- Follicular DC

What specific dendritic cells aid in the establishment of B and T cell zones within the lymph node?

1) FDC's

2) Plasma cells

3) T-cells

4) IDC's

Fill in the blank with the correct cell type:

1) _______: found within Germinal centers—here they are the primary APC for presenting antigen to B-cells for expansion.

2) ________: undergo final differentiation outside of GC and then go throughout peripheral immune system secreting antibody.

3) ______: 1° CD4 T cells—located between follicles and in deep cortex.

4) _______: located at high endothelial venules (HEV's) between follicles: present antigen to CD4 T cells.

in germinal centers of follicles in peripheral lymphoid tissues—frequently in LN.

Where does generation of high affinity antibodies and memory cells in humoral responses occur?

extra-follicular Tcell rich

Interactions between CD4 T-cells and B-cells that initiate humoral responses occur in ___________ ______ _______ zones

germinal center

Follicular Dendritic Cells (FDC) in _____________ _________ present Ag from these initial responses to B-cells inducing proliferation and differentiation to further propagate these responses.

within a secondary follicle with germinal centers - B-cells with high-affinity antigen receptors for the specific antigen being presented by the follicular dendritic cell are selected for survival

What generates affinity maturation?

CD40L

What ligand on follicular dendritic cells are important for affinity maturation of B-cell receptors?

- protein antigen is processed and presented in context of MHC II to CD4 T cells within the T-cell rich zones of the secondary lymphoid tissue

- CD4 T-cells express CD40L and secrete cytokines

- Ag specific B-cells encounter antigen - take it in and process it, present it with MHC II to CD4 T-cells in T-cell rich zones

- Physical contact between B- and T-cells (and cytokine production from CD4 T cells) induces B-cell proliferation, differentiation, and beginning of isotype switching

What humoral responses occur in the extra-follicular pathway of B-cell activation/differentiation?

B-cells migrate to follicles, form germinal centers, and undergo affinity maturation resulting from interaction with and cooperation from FDC.

What humoral responses occur in the follicular pathway of B-cell activation/differentiation?

primary

___________ humeral responses are induced by all immunogens

secondary

___________ humeral responses are induced by only protein antigens

lower

higher

**Primary humeral responses typically have _________ average affinity, but is more variable, whereas secondary humeral responses have __________ average affinity due to affinity maturation

D --> E --> C --> A --> B

Place the following events in chronological order:

A. Isotype Switching

B. Affinity Maturation

C. Antibody Secretion

D. Antigen recognition

E. B-cell Activation [Proliferation (expansion of clone) --> Differentiation (effector + memory cells)]

1) Type of cytokines produced

2) Site of antigen exposure

3) Nature of antigenic stimulus

4) Primary vs. secondary antigen exposure

**What are four general factors that affect or influence humoral responses?

IFN-gamma

IL-4, 5, 6, 10

**______ mediates a cell-mediated immune response (Th1 subtype), whereas _____ mediate humoral responses (Th2 subtype) (fill in with cytokines)

Thymus-dependent antigen!

What antigen, thymus dependent or independent, is able to induce a delayed-type hypersensitivity?

C3d

B-cells express a receptor (CR2) for complement ______. This interaction induces or furthers activation of B-cells.

C3b

FDC possess a receptor (CR1) for _____. When this binds antigen, CR1 promotes the expression of antigen to B-cells in germinal centers.

ensures that there is a B cell response in the presence of microbes!

Why is it beneficial that complement can aid in B-cell activation?