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Immunology 2019 > Lecture 14 > Flashcards

Lecture 14 Flashcards

1
Q

Humoral immune responses are initiated by the recognition of Ags by what specific receptor on what specific cell?

A

BCR’s on B lymphocytes

then a single B cell gives rise to thousands of plasma cells that secrete tons of Abs ; 10 to the 12th at it’s maximum

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2
Q

Ag activates naive B cells by binding to which 2 Ab types?

A

membrane IgM and IgD

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3
Q

After an Ag and other stimuli, including helper T cells, stimulates the proliferation and differentiation of a specific B cell clone, state the 3 types of progeny that the B cell clones may become (3 of them)

A
  1. Plasma cells that produce IgM (has lots of Ag binding sites, which make up for their low affinity)
  2. B cells that express other Ig isotypes after undergoing class switching (these usually undergo affinity maturation to make up for the fewer Ag binding sites compared to IgM)
  3. They may persist as memory cells
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4
Q

About how many days does it take for a primary antibody response to an antigen to reach it’s peak levels of antibodies?

A

about 7 days (then contraction occurs)

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5
Q

Compare the type of Ags that can be found in a primary and secondary immune response (Include the Ig types that belong in both of these types of responses as well)

A

Primary immune responses feature mainly “nonprotein Ags” and feature mostly IgM antibodies
(bc they are produced prior to helper cell interactions with B cells)

Secondary immune responses feature mainly “Protein Ags” and feature mostly IgG antibodies
(bc they are produced from memory cells)

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6
Q

True or False:

Primary and secondary Ab responses to PROTEIN Ags differ qualitatively but are very similar quantitatively. explain.

A

FALSE

Primary and secondary Ab responses to PROTEIN Ags differ qualitatively AND quantitatively.

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7
Q

State the 4 characteristics that differentiate a secondary response from a primary response to an antigen.

A

More rapid production of Abs

larger amounts of Abs produced

Isotype switching of the heavy chain

Affinity maturation Ag-Ab binding

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8
Q

B cell responses are divided into 2 categories, T Cell-dependent (TD) and T Cell-Independent (TI) responses. Compare the types of Ags that fit into these categories and what each response is facilitated by.

A

TD responses occur with “Protein Ags and REQUIRE CD4+ T helper cells”
Follicular T helper cells form germinal centers where activated B cells proliferate

TI responses occur with “Multivalent non-protein Ags” with repeating epitopes (polysaccharides, lipids, and nucleic acids)
These responses are elicited by BCR engagement and may be potentiated by other signals

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9
Q

Describe the following subsets of B cells in terms of the types of Ags they respond to and whether they are TD or TI.

Follicular B-2 cells:

Marginal Zone B cells:

B-1 cells: (where are these found?)

A

Follicular B-2 cells: respond to protein Ags and initiate TD Ab responses
(these make up the majority of B cells in circulation)

Marginal Zone B cells: respond to multivalent (non-protein) Ags and are TI
(in the marginal zone in the spleen)

B-1 cells: are found in mucosal sites only, respond to multivalent Ags and are TI

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10
Q

True or False:

Both B-1 and B-2 cells express IgM and IgD on their surface. explain.

A

True

While B-1 cells tend to express IgM > IgD and B-2 cells tend to express IgD > IgM, they both express both types of membrane Abs

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11
Q

Compare B-1 and B-2 cells in terms of the following characteristics.

When they arise:

Location:

Diversity level:

Memory ability:

Usual target:

Isotype switching ability:

TD or TI:

How they are replaced:

A 
B-1
When they arise: Fetal (liver)
Location: mucosal areas (resp and GI tract)
Diversity level: low
Memory ability: little/none
Usual target: Carbohydrates
Isotype switching ability: limited
TD or TI: usually TI
How they are replaced: self-renewing in the periphery
B-2
When they arise: perinatal/postnatal
Location: Widespread
Diversity level: high
Memory ability: yes
Usual target: proteins
Isotype switching ability: yes
TD or TI: usually TD
How they are replaced: continuously replaced from the bone marrow
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12
Q

Which type, B-1 or B-2, creates Abs that are often directed against conserved microbial Ags and bridges between the innate and adaptive immune systems?

A

B-1

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13
Q

Describe which area of the lymph node is the T cell zone and which is the B cell zone? what is another name for the B cell zone of a LN?

A

T cell zone: central part of LN

B cell zone: peripheral part of LN
“Follicles” are another name for the B cell zone of a LN

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14
Q

What chemokine is secreted by FDCs (follicular DCs, which are NOT the DCs coming from the tissues) in order to guide the movement of naive B cells into follicles? is this an attractant or repulsive chemokine?

A

CXCL13 is and attractant chemokine that is secreted by FDCs into the follicle of LNs to guide naive B cells to the periphery

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15
Q

Describe the function of the macrophages in the subscapular sinus of the LN and how this can be important for secondary infections from an Ag.

A

They pick up antigens that are too large to enter the follicle via the “conduit”, glue them to their surface without breaking them down, and bring them to the follicle to be presented

This presents the Ag in it’s intact, native conformation (which will allow the Abs to respond to the native conformation of the Ag incase of a secondary infection. Does not need to take the time to respond to the digested version of the Ag if it recognizes its native conformation)

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16
Q

For the following Ag types, explain how they are handled in the LN.

Most Ags: (how to they enter and where do they go

Soluble Ags:

Large Ags:

Microbes and Ag-Ab complexes:

A

Most Ags: transported to the LN via afferent lymphatic vessels and drain into the Subcapsular sinus

Soluble Ags: reach the B cell zone and interact DIRECTLY with B cells

Large Ags: captured by FDCs and transported to the follicle intact so they may interact with B cells

Microbes and Ag-Ab complexes: captured by subcapsular sinus resident macrophages and are delivered to the follicles (intact, not processed)

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17
Q

True or False:

FDCs are not professional APC’s, despite regular DC’s being professional APC’s. explain.

A

True.

FDCs do not express MHC class II molecules, they do not phagocytose, and they do not process exogenous Ags.

Since FDCs only “glue” Ag’s to their surface, they are not considered professional APC’s like regular DCs are.

18
Q

When an FDC binds an Ag to it’s surface, it forms what is called an Ag-Ab immune complex. State the 3 possible receptors that retain this complex on the surface of FDC’s and state how long they can retain this complex on their surface.

A

Ags retention on the surface of FDCs is mediated by:
FcgammaRIIb (Fc receptors
CR1 or CR2 (CD21) complement receptors

these complexes can be retained for long periods of time (weeks to months)

19
Q

Immune complexes on FDCs play a key role in germinal center reactions by providing an antigenic substrate that drives ____ _____ ______.

A

antibody affinity maturation.

20
Q

Follicular B cell survival depends on signals from the BCR as well as signals from which cytokine? what signals does this cytokine provide for the follicular B cell, and what cells secrete it (also where does this secretion happen?)?

A

BAFF (B cell Activating Factor of the TNF family)

BAFF provides “maturation and survival signals” through the BAFF receptor on follicular B cells

BAFF is produced by Myeloid cells in lymphoid follicles and in the bone marrow

21
Q

What initiates the process of B cell activation? what occurs directly after this?

A

BCR signaling initiates B cell activation

At the same time, the BCR internalizes the bound Ag into endosomal vesicles
If the Ag is a protein, it is processed and presented (via MHC class II molecules) on the B cell surface to be recognized by T helper cells
22
Q

State and describe the 2 complementary receptors on the surface of a B cell (these occur simultaneously alongside BCR recognition of the Ag) that can potentiate B cell activation.

A

CR2(CD21) coreceptors that recognize complement-coated Ags via the C3d bound to the Ag surface

TLR’s that recognize PAMPs

(Both of these occur simultaneously alongside BCR signaling from the Ag)

23
Q

Explain how a B cell presents an antigen to T cells and be sure to address how the Ag receptors on the B cell and T cell are usually different yet they can both respond to the same Ag.

A

Membrane Ig on the B cell recognizes a conformational epitome of an antigen, bind to the Ag, endocytose it, and present a “linear peptide” from the Ag on the surface of the B cell via a “class II MHC-peptide complex”

Helper T cells then recognize the linear peptide from the Ag in the Class II MHC-peptide complex and stimulate B cells responses

(the B cell finds the Ag, prepares it in a linear peptide form that the T cell can recognize, and then is stimulated by the T cell after it is activated)

24
Q

After a B cell has presented a linear peptide version of the Ag to the T cell, explain how a T cell then activates the B cell (2 mechanisms)

A

After being activated by recognizing an Ag, the T cell expresses CD40L which then interacts with the CD40 molecules on the B cell to stimulate proliferation and differentiation

The T cell also produces cytokines to help activate the B cell

25
Q

When an immune response is initiated by the recognition of Ags by B cells and CD4+ T cells, the activated lymphocytes move towards one another and interact. If this is occurring outside of a germinal center of a LN, what does this cause? What 3 things occurs after this initial interaction when B cells migrate into the germinal center?

A

B and T cell interactions outside of a germinal center cause MINIMAL isotype switching to produce “short-lived plasma cells” that mainly produce IgM (bc isotype switching has not yet occured)

  1. somatic mutation
  2. affinity maturation
  3. Isotype switching (generation of memory and plasma cells that produce either IgG, IgA, IgM, or IgE)
26
Q

What type of tissue is a diffuse system of small concentrations of lymphoid tissue found in various submucosal membrane sites of the body such as the GI tract, oral passage, nasopharyngeal tract, or lungs?

A

MALT (mucosa-associated lymphoid tissue)

27
Q

Compare Extrafollicular and Germinal B cell responses in terms of the following categories.

Localization:
CD40 Signals:
Specialized T cell help:
Class Switching:
Somatic Hypermutation:
Antibody Affinity:
Terminally differentiated B cells:
A

Extrafollicular B cell responses
Localization: medullary cords of LNs/junctions between T cell zone and the red pulp of the spleen
CD40 Signals: Required
Specialized T cell help: Extrafollicular Helper T cells
Class Switching: Yes, limited
Somatic Hypermutation: Low Rate
Antibody Affinity: Low
Terminally differentiated B cells: Short-lived plasma cells (live for 3 days)

Germinal Center B cell responses
Localization: Secondary follicles
CD40 Signals: Required
Specialized T cell help: Tfh cells in germinal center of LN
Class Switching: Yes, extensive
Somatic Hypermutation: High Rate
Antibody Affinity: High
Terminally differentiated B cells: Long-lived plasma cells which migrate to bone marrow or MALT and memory cells
28
Q

State the sequential activation of cells that much occur in order to generate a Tfh cell from a Naive CD4+ T cell. (really 2 steps here)

A

The naive T cell must first be activated by a DC (this gives it a CXCR5 receptor for CXCL13)

Then it must be activated by an activated B cell (via an interaction between the ICOS-L on the activated B cell and the ICOS receptor on the T cell)

Then the Tfh cell migrates to the GCs where it can activate B cells

29
Q

Which cytokine is produced by Tfh cells and is required for GC development and the generation of plasma cells? Which cytokines (3 of them) do Tfh cells produce in order to control isotype switching?

A

IL-21 (required for GC development and generation of plasma cells)

IFN-gamma, IL-4, and TGF-beta (all 3 control isotype switching)

30
Q

How many days does it take after Ag exposure for activated B cells to induce some previously activated T cells to differentiate into Tfh cells? How are these Tfh cells then draw into lymphoid follicles so that they may create GC’s?

A

4 to 7 days

CXCL13 (interacts with the CXCR5 receptor on Tfh cells to draw them into lymphoid follicles and form GCs)

31
Q

What sets Tfh cells apart from Th1, Th2, Treg, and IL-17 subsets of T cells?

A

they have a unique phenotype

32
Q

State the 3 processes directly involved in the development of B cells that IL-21 induces

A
  1. isotype switching
  2. Affinity Maturation
  3. Antibody production
33
Q

Compare what occurs in the dark zone and light zone of a germinal center

A

Dark zone: activated B cells migrate to this zone initially to proliferate.
EXTENSIVE isotype switching and somatic hypermutation of IgV genes occurs here

Light zone: Where B cells encounter follicular DC’s (displaying Ags) and Tfh cells
Here, B cells with the highest affinity Ig receptors receive the “tonic signal” to survive and move on to positive/negative selection and BCR editing

34
Q

Say a group of B cells makes it through the dark and light zones of a GC, where do the long-lived plasma cells go and where do the memory cells go?

A

Plasma cells go reside in the bone marrow and secrete-Abs

Memory cells enter the re-circulating lymphocyte pool

35
Q

Explain the spatial organization of the dark, light, and mantle zones in a LN GC. Include what types of cells can be found in each layer.

A

The dark zone, which contains proliferating B cells is in the center, clustering around the FDC’s in the light zone

The light zone, which contains FDC’s, forms a crescent shape around the dark zone

The mantle, which contains tightly packed small B cells of the primary follicles, sits on the periphery bc it is being pushed aside by the GCs

(remember the dog mom picture ; weak ones in mantle, strong ones in dark zone)

36
Q

Ag-induced cross-linking of the BCRs and signaling induces what 3 processes to occur in Naive B cells? (hint: one of these involves a GPCR that you need to know specifically)

A
  1. production of proteins that promote survival and proliferation
  2. responsiveness to helper T cells and cytokines
  3. The expression of CCR7 which is a GPCR that senses chemokines to allow the B cell to migrate from the follicle to the T cell zone
37
Q

Define Centroblast

A

Centroblast: an activated B cell that is enlarged and proliferating in the GC of a secondary lymphoid follicle (in the dark zone)

38
Q

Describe the marginal zone in the spleen

A

it is a framework of reticular fibroblasts that is known for housing MZ (marginal zone macrophages) and Marginal B cells

39
Q

Which cells serve as “sentinels” at the interface between circulation and lymphoid tissue by adopting a “crossover-defense” strategy somewhere between innate and adaptive immunity? describe their repertoire of Abs.

A

MZ (marginal zone) B cells

They have a ready to use pre-immune Ab repertoire that can provide a rapid (almost innate-like) response to pathogens and commensal bacteria that breach the mucosal barrier

40
Q

MZ B cells what type of threshold for activation when compared to follicular B cells? Also describe the way they conduct class switching. Is this method TI or TD?

A

MZ B cells have a low activation threshold

Their CSR (class switching recombination) method requires both BCR and TCR engagement alongside costimulatory molecules

This is a TI pathway

41
Q

Explain the type of Ags that are presented to MZ B cells and which complement receptor these Ags in immune complexes can interact with on a MZ B cell.

A

Ags are presented to MZ B cells in their native conformation (not processed by APCs)

They can interact with CR2 complement receptors on MZ B cells

42
Q

Explain how a blood-borne pathogen and a polysaccharide Ag will be presented to a MZ B cell (include the presenting cells and where this occurs)

A

Blood-borne pathogens are captures by plasmacytoid DCs in the blood and transported to the spleen to be presented to MZ B cells
(blood borne is more work for the DC)

Polysaccharide Ags are captured by MZ Macrophages (in the spleen) which then present them to MZ B cells
(MZ macrophages are lazy ; never leave the spleen)

Immunology 2019 (22 decks)

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