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Diseases > B cells > Flashcards

B cells Flashcards

1
Q

List the effector functions of B cell antibodies

A

Neutralization of microbes and toxins, opsonization and phagocytosis of microbes, antibody-dependent cellular cytotoxicity, complement activation, inflammation, and lysis of microbes

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2
Q

What are the functions of the Fc receptor?

A

Deliver antibody to inaccessible anatomical sites and link bound antigen to molecules/cells that effect destruction

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3
Q

What region of the antibody does complement And Fc receptors bind to?

A

Fc

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4
Q

T/F: Antigen-bound antibodies can bind to Fc receptors in order to act as opsonins or to activate cells

A

True

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5
Q

Describe the affinity for Ig, cell distribution, and function of the Fc receptor Fc-gamma-RI (CD64)

A

High affinity and can bind IgG1, IgG3, and monomeric IgG; found on macrophages, neutrophils, and eosinophils; function is phagocytosis and activation of phagocytes

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6
Q

Describe the affinity for Ig, cell distribution, and function of the Fc receptor Fc-gamma-RIIA (CD32)

A

Low affinity for Ig; found on macrophages, neutrophils, eosinophils, and platelets; functions in phagocytosis and cell activation (inefficient)

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7
Q

Describe the affinity for Ig, cell distribution, and function of the Fc receptor Fc-gamma-RIIB (CD32)

A

Low affinity for Ig; found on lymphocytes, DCs, mast cells, neutrophils, and macrophages; function is feedback inhibition of B cells and attenuation of inflammation

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8
Q

Describe the affinity for Ig, cell distribution, and function of the Fc receptor Fc-gamma-RIIIA (CD16)

A

Low affinity for Ig; found on NK cells; function is antibody-dependent cellular cytotoxicity (ADCC)

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9
Q

Describe the affinity for Ig, cell distribution, and function of the Fc receptor Fc-epsilon-RI

A

High affinity for monomeric IgE; found on mast cells, basophils, and eosinophils; function is activation (degranulation) of mast cells and basophils

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10
Q

What are some effects of antibody binding to antigens or toxins as it relates to neutralization?

A

Blocks penetration of microbes through epithelial barriers, blocks binding of microbe and infection of cells, and blocks binding of toxins to cellular receptors and thus, the associated pathological effects

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11
Q

Explain the process of opsonization and phagocytosis

A

Microbe is floating around and gets opsonized (bound) by antibodies; the opsonized microbe (immune complex) binds to its Fc receptor; the Fc receptor sends signals that activate the phagocyte; this results in phagocytosis of the immune complex and subsequent killing of the ingested microbe

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12
Q

What is the function of CR1 on erythrocytes?

A

Binds circulating immune complexes with attached C3b and C4b and transports the complexes to the liver and spleen; organ resident phagocytes remove the immune complexes from the erythrocyte surface and the erythrocytes continue to circulate

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13
Q

Describe the process of NK killing of a cell infected with a virus

A

Virus infects a cell and surface antigens are placed on the surface of the infected cell; antibodies bind to the antigens on the cell surface, tagging it as “infected”; NKs with Fc receptors for that antibody bind to the Fc region of the antibody and kill the antibody-coated cell

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14
Q

What is the function of intravenous Ig (IVIG)?

A

For rapid protection after exposure to a disease; also used in autoimmune or inflammatory diseases by engaging the inhibitory FcR on B cells and (maybe DCs?) and suppresses the immune response

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15
Q

What are the natural antibodies and who produces them? What is their function?

A

IgM mainly, but some IgG; produced by B-1 and marginal zone B cells; specific for bacteria in the area and cross react with blood alloantigens

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16
Q

What do IgA and IgM have in common?

A

Both have J chains

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17
Q

Explain the exchange of IgG between a mother and a fetus

A

IgG can leave the circulation and enter extracellular spaces within tissues via transcytosis via FcRn (natal FcR); this transports IgG from the maternal circulation across the placental barrier as well as the transfer of maternal IgG across the intestine; FcRn takes bound IgG and recycles it to the cell surface and releases it at neutral pH, returning the IgG to the circulation

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18
Q

Where is the FcRn found?

A

Surface of endothelial cells, macrophages, and other cell types

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19
Q

What antibodies are produced at the time of birth and what antibodies are produced 6-12 months post-birth?

A

IgM and then IgG and IgA come later

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20
Q

Define immunization

A

Antigenic stimulus that elicits a specific adaptive immune response(s) that can be recalled during subsequent infections

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21
Q

What is a passive immunization? Give examples

A

Introduction of antibody or antiserum into a naive recipient; immediate immunity but transient; uses preformed antibodies

Ex: snake bite venom, passive transfer of Ig from mother to child

22
Q

What is an active immunization? Give examples

A

Introduction of an antigen that provokes an adaptive immune response; delayed immunity but more permanent; produces memory

Ex: natural exposure to pathogens and vaccines

23
Q

Define vaccination

A

Intentional delivery of an antigenic stimulus

24
Q

Explain how immunizations work

A

A normal immune response is invoked to destroy and clear the components of the vaccine; the primary immune response results in immunological memory (priming); each subsequent immunization results in increased intensity and magnitude of response

25
Q

What is hyper-immunization?

A

Occurs when repetitive challenge with antigen achieves a heightened state of immunity

26
Q

What is the function of a combined passive-active immunization? Give examples

A

Designed to give both immediate, transient protection as well as slowly developing durable protection

Ex: tetanus and rabies

27
Q

What are the criteria for an effective vaccine?

A

Needs to be safe, protective, give sustained protection, induce neutralizing antibodies, induce protective T cells, and it needs to be practical (inexpensive and easily distributable)

28
Q

What are some potential problems with vaccines?

A

Clinically important epitomes may not be intact in vaccine; individual genetics may effect efficacy; some individuals may be genetically predisposed to adverse events (allergies); often work poorly in very young infants or the elderly; many do NOT induce CMI and antibody may not be sufficient

29
Q

What do mature naive B cells express?

A 
BCR expresses IgM, IgG, IgA and IgB 
CoBCR elements: CD19, CD81, CR2 (CD21) 
HLA class II 
CD40 
CD20
30
Q

What are the two categories of B-2 cells?

A

Follicular: recirculating B cells, make up the majority of the B cells

Marginal: in the spleen; blood borne polysaccharide

31
Q

What are B1 cells?

A

mucosa; specific Ag specificity

32
Q

Describe the migration of naive B cells

A

The B cells enter the lymph nodes through the lymphatics and the spleen through the blood

Enter through the HEV. If there is no antigen present, then they migrate into the primary follicle and express CXCR5 which helps them to respond to the chemokine that are being made in the B cell zone

FDCs give them signals to survive, if there are too many B cells, then some will die if there is no antigen present

33
Q

What are the two signals that are involved in B cell activation?

A
  1. Ag recognition by the membrane bound Igs
    (must crosslink with at least 2 BCRs)
  2. costimulation via the connection to the T cell
34
Q

Given that the steps of the B cell signaling is basically identical to that of the T cell signaling, describe the subtle differences that are present in B cell signaling

A

B cell signaling utilizes Syk for phosphorylation of the ITAMS (with the help of Fyn, Lyn, Blk) and also stimulates a response in PLCgamma and ras/rac

Myc is an additional transcription factor that is at the end

35
Q

Describe the mechanism and the results of the first signal

  1. process of Ag binding
  2. what happens
A

Ag binds via C3d and is recognized by miss and CR2 (CD21) and signaling commences through the ITAMS that are present on IgA and IgB, CD21, and CD19 tails

TLR signaling can also be used

Both result in proliferation and differentiation of the B cell

36
Q

What are the various changes that can occur following the Ag binding to the B cell and what do these changes result in?

A
  1. B cells can express proteins that will promote survival and cell cycling which leads to increased survival and proliferation
  2. B cells can express the Ag with an increased B7 expression which will lead to the interaction with T cells
  3. B cells can have increased cytokine receptors which will lead to increased responsiveness to the cytokines
  4. B cells can have increased expression of CCR7 which will allow for migration in to the T cell areas from the follicle
  5. B cells can secrete IgM
37
Q

Describe how B cells change their signals in order to migrate to the T cell zone

A

They increase the expression of CCR7 and decrease the expression of CXCR5 so that they are able to go into the T cell region at the edge of the follicle and interact with the T cells

38
Q

Describe the two ways in which the second signal can be received by the B cell

A

Through a TI-1 antigen (T cell independent)

or through a TD antigen (T cell dependent) and an interaction with CD40/CD40L which leads to proliferation of B cells

39
Q

Describe what kind of effect the T cell has on the B cell during binding

A

Whatever cytokines the T cell is giving off the cytokines that will lead to class switching on the B cell

increases the expression of the AID enzyme

affinity maturation of the secreted Abs from the B cell (class switching and affinity maturation can happen at the same time)

40
Q

Where does class switching occur and briefly describe that process

A

After the B cell receives T cell help, it migrates back to the follicle where it creates germinal centers, which is where class switching occurs. The T cells continue to provide help from an extracellular focus

41
Q

What is the function of the cytokines that are released by the Th cells?

A
  1. induce H chain class switching

2. augment B cell differentiation and proliferation

42
Q

how is the CD40:CD40L able to trigger isotope switching and the affinity maturation?

A
  • modulation of switch regions
  • increasing the accessibility of DNA at the C regions
  • expression of AID (activation induced deaminase)
43
Q

Describe the mechanisms behind class recombination

A

The VDJ region that is in the DNA of the B cells is combined with a c region that is stimulated by the cytokines that is released by the T cells, that allows for class switching to occur

44
Q

Describe the process of affinity maturation

A

Point mutations are introduced in the switch regions of the variable regions in the Igs that will expand the antibody repertoire.

Done with the help of AID, which allows Ape endonuclease to create double stranded breaks in the DNA

45
Q

Describe the number of point mutations that are seen in the antibodies in primary, secondary, and tertiary reactions

A

INCREASE LIKE CRAZY

46
Q

Describe how T follicular helper cells (Tfh) are able to help the B cells with class switching and affinity maturation

A
  • CD4+ low levels of CD25
  • ICOS/ICOSL is essential for germinal center reactions co-stimulator with B7
  • secrete IL21 which facilitates differentiation to plasmablases
  • provide cytokines for class switching
47
Q

Describe the selection checkpoint

A

The B cells with the highest affinity Abs are selected to survive and receive the interactions with the FDCs and Tfh which help them to survive

48
Q

Describe the role of plasma cells and what they are made of

A

plasma cells are terminally differentiated effector B cells; they have a decrease in CD19, CD20, and HLA class 2 but and INCREASE in CD27, are Ig independent

plasma cells can secrete a crap ton of Abs per second and help out with the humoral immunity

49
Q

Describe T cell independent B cell activation

A

B1 cells respond to the Ags that are in the mucosa and B2 cells respond to the blood bourne pathogens

50
Q

Describe memory B cells

A

can survive for a long time without additional Ag stimulation

High levels of anti-apoptotic Bcl-2

Ig class independent

can create a rapid response with subsequent exposures

51
Q

Define humoral immunity

A

Branch of adaptive immunity that consists of B cells and Abs that is key in defending against extracellular pathogens

52
Q

Where are the effector functions of the Abs mediated?

A

The Fc region but ALL FUNCTIONS ARE TRIGGERED BY THE BINDING OF AG TO THE Fab (V) REGION

Diseases (8 decks)

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