Antibody-Mediated Immune Response Flashcards by Sarah Gillen

What all is expressed on a mature naive B cell (6 things)

BCR (IgM, IgD, Ig-alpha and Ig-beta)

Co-BCR: CD19, CD81, and CR2 (CD21)

HLA class II

CD40

CD45R(A)

CD20

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B-2 cells can be divided into what 2 major subsets and which one makes up the majority?

Follicular B cells (majority)

Marginal B cells

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Which class of B-2 cells are the re-circulating B cells?

Follicular

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What is the purpose of marginal B cells?

Reside in the spleen and recognize blood-borne polysaccharide Ags

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How do naive B cells enter primary lymphoid follicles in the spleen?

Via the blood

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How do naive B cells enter primary lymphoid follicles in lymph nodes?

Via lymphatics

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Describe the passage of naive B cells through secondary lymphoid tissue

Enter through HEV

If no antigen, migrate to primary follicle

Receive signal to survive from follicular DCs

Exit through efferent lymphatics

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How do follicular dendritic cells differ from other antigen presenting cells?

They hold the antigen without processing it

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The B cell activation process begins when a response is initiated by recognition of antigen (________) by B cell specific for that antigen (_________)

Epitope; idiotope

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What are the 2 mechanisms for naive B cell activation?

T-dependent

T-independent

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Complete activation of naive B cells requires how many signals?

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What are the 2 signals involved in B cell activation?

Antigen recognition by mIgs

2. Th cell help via CD40/CD40L

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What is the requirement for Ag recognition by naive B cells for activation?

Ag must crosslink 2 or more BCRs

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B cell signaling occurs through Ig-alpha and Ig-beta cytoplasmic tails. The intracellular signaling steps in B-cell activation are identical to those of T cells.

What is the only difference?

Only difference lie in the Src-family kinases involved in initial intracellular signaling steps

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True or false: Effective cross-linking of the BCR by Ag generates a signal that is necessary and sufficient to activate naive B cells

False, it is necessary but NOT sufficient, need second signal

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One mechanism of BCR crosslinking involves Ag with bound _____, which is recognized by mIgs and CR2

C3d

[if C3d is attached to protein Ag, Ag is 1000x more immunogenic!]

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The following changes occur in activated B cells:

Expression of proteins that promote ______ and cell cycling.

Antigen presentation and increased ____ expression

Increased expression of _______ receptors

Increased expression of chemokine receptor ______

Secretion of _____

Survival

Cytokine

CCR7

IgM

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What is the functional consequence of increased B7 expression after naive B cell activation?

Interaction with helper T cells (this is second signal)

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What is the functional consequence of increased CCR7 expression after initial activation of naive B cells?

Migration from follicle to T cell areas

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What 2 important B-cell related immunological processes require a T-dependent response?

Class-switching

Generation of memory B cells

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Are CD40 and B7 constitutive or inducible on B cells?

CD40 is constitutive

B7 is inducible

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What effect does the B7-CD28 interaction have on T cells?

Causes upregulation of CD40L which binds CD40 on B cell, providing the second signal for activation

Leads to proliferation and expansion

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Where and when do germinal centers form?

After receiving T cell help, B cells change their chemokine receptor expression again and migrate back to follicular area where GCs are established

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What modulates BCR class switching?

Th cytokines

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Class switching requires what enzyme?

Activation-induced deaminase (AID)

When does class switching occur relative to affinity maturation during B cell activation?

They often occur at the same time

Successful arrangements of B cell receptors (based on class switching and affinity maturation) are selected/supported by what 2 cell types?

T follicular helper cells Follicular dendritic cells

What are the 2 general functions promoted by the cytokines released by Th cells?

1. Induce H chain class switching | 2. Augment B cell differentiation and proliferation

Primary functions of IgM class

Classical complement activation

Primary functions of IgG class

Neutralization Opsonization and phagocytosis Classical complement activation ADCC mediated by NK cells Neonatal immunity (placental) Feedback inhibition of B cell activation

Primary functions of IgE

Eosinophil and mast cell-mediated defense against helminths

Primary functions of IgA

Mucosal immunity

CD40:CD40L ligation and cytokines trigger isotype switching and affinity maturation by: Modulation of _____ regions Increasing accessibility of the _____ at specific ___ region ____-dependent Ag Expression of _____ enzyme

Switch DNA; C T AID

Class switching occurs when the previously rearranged ______ gene segment recombines with downstream _____ region gene, and the intervening DNA is ___________

VDJ C Deleted

Affinity maturation involves introduction of ______ mutations in the switch regions of the ________ areas of the Ig genes, resulting in an expansion of the Ab repertoire to generate high-affinity antigen-specific Abs

Point; variable

Generation of __________ _________ allows for 10^3 to 10^4 times higher than normal spontaneous mutation rates

Somatic hypermutation

What is the key enzyme in affinity maturation?

AID

How does AID contribute to affinity maturation?

Converts Cs to Us, allowing Ape I endonuclease to create double-stranded breaks in the DNA

Affinity maturation generated by AID can be very useful, but when would it not be useful?

Possible to randomly generate a B cell that will not respond to Ag, or there may be introduction of stop codons B cell will be checked for functionality before being released into periphery

Where exactly does somatic hypermutation occur in the BCR?

In the 3 hypervariable regions of the heavy and light chains

After undergoing class switching and affinity maturation, the B cell must be checked for efficacy. Where does this occur?

In the germinal centers, they are checked by FDCs and Tfh's [FDCs provide intact antigen in form of complexes called immune complexes]

What is the end result of T-independent B cell activation?

Mainly IgM, low-affinity Abs, short-lived plasma cells

What is the end result of T-dependent B cell activation?

Isotype-switched, high-affinity Abs Memory B cells Long-lived plasma cells

What terminology is applied to terminally differentiated effector B cells that secrete Abs?

Plasma cells

What are the cell markers that are decreased in plasma cells?

CD19 and 20, HLA class II

What cell markers are increased on plasma cells?

CD27 CD38 CD138

What type of B cells survive for long periods of time without additional Ag stimulation?

Memory B cells

What allows memory B cells to survive for long periods of time without additional Ag stimulation?

They express high levels of Bcl-2, which is anti-apoptotic

What are the primary surface markers of memory B cells?

CD27 CD45R(O) As well as sIg class (IgE, IgA, etc.)

_________ ________ is a control mechanism triggered by secreted Ab that blocks further Ab production This can only be done by _____ Abs

Antibody feedback IgG

How does Ab feedback occur?

Secreted IgG forms complex with Ag, this complex then binds B cell Ig and Fc receptor (has ITIM) which blocks the BCR signaling

The effector functions of Abs are mediated by the ____ region. Different isotypes serve different effector functions

Fc'

Although the effector functions are mediated through the Fc' region, all functions are triggered by what?

Binding of Ag to the Fab'(V) region

What are the 2 primary effector functions of secreted Ab (on their own)

Neutralization of microbes and toxins Complement activation (opsonization, inflammation, lysis of microbes)

What is the primary effector function of Ab bound to Fcy receptor of a phagocyte?

Opsonization and phagocytosis of microbe

What is the primary effector function of Ab bound to NK cell Fcy receptor?

ADCC

What are the 2 distinct functions served by the Fc region of Ab?

Deliver Ab to inaccessible anatomical sites Link bound Ag to molecules/cells that effect destruction

Antigen-bound Abs will bind to Fc receptors (FcR) in order to act as _______ or to activate cells

Opsonins

What is the cellular distribution of the FcyRI receptor and its affinity for Ig?

Macrophages Neutrophils Eosinophils High affinity

What is the function of the FcyRI (CD64) receptor?

Phagocytosis; activation of phagocytes

What is the cellular distribution of the FcyRIIA (CD32) receptor and its affinity for Ig?

Macrophages Neutrophils Eosinophils Platelets Low affinity

What is the cellular distribution of the FcyRIIB (CD32) receptor and its affinity for Ig?

``` B lymphocytes Dendritic cells Mast cells Neutrophils Macrophages ``` Low affinity

What is the cellular distribution of the FcyRIIIA (CD16) receptor and its affinity for Ig?

NK cells Low affinity

What is the cellular distribution of the FceRI receptor and its affinity for Ig?

Mast cells Basophils Eosinophils High affinity

What is the function of the FcyRIIA (CD32) receptor?

Phagocytosis; cell activation (inefficient)

What is the function of the FcyRIIB (CD32) receptor?

Feedback inhibition of B cells, attenuation of inflammation

What is the function of the FcyRIIIA (CD16) receptor?

ADCC

What is the function of the FceRI receptor?

Activation (degranulation) of mast cells and basophils

Many microbes bind to surfaces of cells to gain entry. What Ab function works to prevent this?

Neutralization - may occur through steric hindrance or simply block binding

True or false: Neutralization only requires binding of Ag, and any class of Ab will work

True

With neutralization, the higher the ________, the better

Affinity

What Ab function works to allow clearance of immune complexes?

Opsonization - CR1 on erythrocytes binds circulating immune complexes with attached C3b and C4b and transports them to the liver and spleen Organ resident phagocytes remove the immune complexes from the erythrocyte surface, and the erythrocytes continuously circulate

How does ADCC work in the anti-viral state?

NK bind to IgG antibody-coated cells by FcyRIII (CD16) receptors and destroy infected cells

What Ab is the most effective "fixer" of classical complement?

IgM (because 5 exposed FcCr bind one C1q) IgG can activate classical by cross-linking of two or more Ag bound IgG to bind one C1q

Some autoimmune/inflammatory diseases are treated with IVIG, how might this suppres the immune response?

Engages the inhibitory FcR on B cells and possible dendritic cells

In maternal to fetal transfer: IgG can leave the circulation and enter extracellular spaces within tissues via transcytosis via ______, which transports IgG from the maternal circulation across the placental barrier as well as the transfer of maternal IgG across the intestine

FcRn (FcRb)

FcRn is required for transcytosis of IgG in maternal to fetal transfer, where is this receptor found?

On surfaces of endothelial cells, macrophages, and other cell types

FcRn does not target bound IgG to lysosomes, but recycles to the cell surface and releases it at _______ pH, returning the IgG to circulation

Neutral

What effect does acidic pH of the endocytic vesicle have on IgG's interaction with FcRn during maternal IgG transfer?

Causes association of IgG with FcRn, protecting it from proteolysis

On reaching the basolateral face of the endothelial cell, the ______ pH of the ECF dissociates IgG from FcRn [maternal IgG transfer]

Basic

during the first year of life, IgM production begins right away. IgG and IgA lag for _____ months, leaving a vulnerable period where baby is not _________

6-12 Immunocompetent

What are 3 general mechanisms of humoral immune evasion used by pathogens?

Antigenic variation Inhibition of complement activation Blocking by hyaluronic acid capsule

Antibody-Mediated Immune Response Flashcards

(82 cards)