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22 spring: immunology > Test 1: lecture 9 and 10 B cells > Flashcards

Test 1: lecture 9 and 10 B cells Flashcards

1
Q

cell mediated immunity by T cells and NK cells

A
  • Direct elimination or killing of cells bearing foreign antigen
  • Production of immuno-regulatory cytokines
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2
Q

humoral response is by ___

A

B cells and plasma cells

  • Production of antigen-specific soluble molecules (antibodies, also called immunoglobulins) that are secreted into the body “humor”.
  • Antibodies are effector molecules that eliminate pathogens
  • Important for immunological memory
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3
Q

Modulation of immune responses through ___ release

A

cytokine

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4
Q

3 ways B and T cells talk to each other

A
  • Direct binding of T helper cells to B cells
  • T cell cytokines control antibody production by B cells
  • B cell cytokines regulate T cell differentiation induced by antigen
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5
Q

The B cell receptor and the secreted antibodies are comprised of immunoglobulin proteins with the same ___

A

antigen specificity

(react to the same thing)

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6
Q

shape of B cell receptor

A

similar to how antibodies are designed

light and heavy chain, IgA abd IgB

variable and constant region

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7
Q

The primary “job” of B lymphocytes is to specifically ___(microbes, toxins, and other threats) and generate ____against it

A

recognize an antigen

effector molecules (antibodies)

B cells can also acts APCs, produce cytokines and eat things

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8
Q

3 steps of B cell development

A
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9
Q

3 steps of B cell activation

A
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10
Q

3 primary lymphoid organ

A

thymus

bone marrow

burse fabricius (birds)

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11
Q

where do B cells develop

A

humans : bone marrow

birds: Bursa of fabricious

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12
Q

where does proliferation and differentiation of B cells occur

A

in the periphery → secondary lymphoid organs → spleen, lymph nodes ect.

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13
Q

variable area of the C cell receptor is made from ___

A

gene segments (V,C,J)

gene segment for constant (C)

these undergo somatic recombination to create new Bcell

allelic exclusion ensures that each B cell only produces antibodies for one antigen

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14
Q

___ brings together single segments of each type of locus to create unique B cells

A

somatic recombination

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15
Q

___ is used to ensure B cells only produce antibodies for one antigen

A

allelic exclusion

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16
Q

•Through combination of ___ segments and light/heavy chains, an almost limitless diversity of B cells can be achieved

A

V/D/J/C

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17
Q

•The main molecule involved in the recombination process is ___, an enzyme that plays a key role in the rearrangement and recombination of the genes of V(D)J gene segments.

A

RAG (recombination-activating gene)

Two main RAG molecules, RAG 1 and RAG 2

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18
Q

how does negative selection work

A

immature B cells that react to self antigens in bone marrow are killed, only B cells that do not react to self are allowed to survive and move to blood

4 things will happen to B cells that remain in bone marrow:

  1. Clonal deletion (apoptosis)
  2. Anergy (lack of responsiveness, no BCR expressed on B cells)
  3. Receptor editing (changes specificity of the BCR)
  4. Ignorance (leads to potential autoimmunity)
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19
Q

4 things will happen to B cells that remain in bone marrow after negative selection

A
  1. Clonal deletion (apoptosis)
  2. Anergy (lack of responsiveness, no BCR expressed on B cells)
  3. Receptor editing (changes specificity of the BCR)- sequence changed to not react to self any more
  4. Ignorance (leads to potential autoimmunity) → woops makes it out of bone marrow by accident - autoimmune issues
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20
Q

B cells that make it out of the bone marrow after negative selection are considered

A

self tolerant

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21
Q

B cells mature into plasma cells in the ___

A

germinal centers of secondary lymphoid organs such as the lymph nodes and spleen

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22
Q

___ collects antigens from tissues

A

lymph nodes

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23
Q

___ collects antigens from circulation

A

spleen

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24
Q

___ provide the infrastructure for lymphocytes to find cognate antigen & become activated

A

Secondary lymphoid organs

(i.e, lymph nodes, germinal centers)

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25
Q

Secondary lymphoid organs are important for initiating primary (adaptive) response because they bring together ___

A

antigen bearing DCs

B cells and T cells

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26
Q

B cells will mature into ___

A

antibody secreting plasma cells

memory B cells

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27
Q

Antigen binds to BCR - induces ___ and antibody production.

A

proliferation

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28
Q

Costimulation / accessory signals from TH cells that recognize the same antigen enhance Ab production and initiates ___

A

affinity maturation and isotype switching.

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29
Q

how does B cell activation work in lymph nodes?

A

antigens brought in by afferent lymphatic vessels,

B cells will recognize the entire antigen, eat it and present it on its surface

T cells will recognize pieces of antigen and will bind to B cell that matches

T cells will produce co-stimulatory molecules to cause B cells to proliferate and isotype switch

B and T that recognize the same antigen will bind together and form primary focus → primary follicle → germinal center where B cells will proliferate and turn into memory cells (IL-4)or antibody producing plasma cells (IL-10)

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30
Q

how are B cells activated

A

antigen will bind to receptor be eaten, broken up and presented on MHC class II

helper T cell that recognizes that antigen will bind and produce cytokines (co stimulatory molecules) that and activate B cell to induce isotype switch

•T cells upregulate CD40L and produce immunoregulatory cytokines such as IL4.

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31
Q

Certain ___ can activate B cells in the absence of T cell help allowing rapid antibody production against many bacterial pathogens. In the absence of T cell help, the antibodies do not undergo affinity maturation or isotype switching.

A

microbial antigens

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32
Q

Out of the many different mature B cells, only the ones that are activated (___) start proliferating (____) and differentiate into plasma cells, which produces the specific Ab, and memory B cells

A

clonal selection

clonal expansion

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33
Q

___ produce antibodies

A

plasma cells

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34
Q

how are plasma cells different from B cells

A
  • They do not express surface immunoglobulin or MHC II and cannot present Ag to T cells.
  • Plasma cells migrate to specific sites in lymphoid organs (e.g. red pulp in the spleen) and the bone marrow
  • Most plasma cells are short-lived (weeks to months) but a few long-lived plasma cells survive in the bone marrow and produce Ab

have a high-rate Ig secretion

are not inducible

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35
Q

isotype switching

A

T cells will cause B cells to switch from IgM to other immunoglobulins by changing the genetic recombination of the C segment → changes the constant region. variable and light chains stay the same

36
Q

how does a immature B cell change the type of Ig it produces?

A

T cells will cause isotype switching

T cells will cause B cells to switch from IgM to other immunoglobulins by changing the genetic recombination of the C segment → changes the constant region. variable and light chains stay the same

37
Q

affinity maturation

A

somatic hypermutation

random change in sequence of the antibody (amino acids change)

AID (activation-induced (cytidine) deaminase) → enzyme that causes the change

this will create B cells with all different levels of binding, any that bind worse are removed creating a class of very specific antibody responses

38
Q

somatic hypermutation is caused by ___

A

(Enzyme responsible is the Activation- Induced (Cytidine) Deaminase, or AID)

random change in DNA sequence that creates different levels of affinity of B cells for antigen → affinity maturation

39
Q

Gene recombination during development, clonal expansion, isotype switching and affinity maturation ensure huge ___yet high ___ of the antibody response

A

diversity

specifity

40
Q
A

B cells that recognize antigen will multiply(clonal expansion), while these cells multiply some genetic recombination occurs (somatic hypermutation) , those that have improved affinity survive and bind to antigen coated DC cells that cause B cells to produce different type of Ig (class switching) and mature into plasma cells or memory cells (differentiation)

41
Q

___ do not secrete antibodies but can turn into plasma cells upon activation

A

memory B cells

(can live for many years)

usually come from cells that have undergone affinity maturation and isotype switch

secondary response to re-exposure

42
Q

primary vs secondary immune response

A

will have bigger response the second exposure (more IgG B cells→ more antibodies)

43
Q

regulatory B cells

A

type of B cell that creates cytokines

responds to CD4 T cells and produce IL10 to create different type of t cells

IL10 → will decrease immune response

44
Q

antibodies or ___

A

Ig immunglobulins

45
Q

make up of antibodies

A
  • They are built of 2 heavy chains and 2 light chains linked through disulfide bridges
  • The N-terminal domain of each chain has a variable structure and determines antigen specificity

The other domains form the constant region defining isotype and effector function

46
Q

light chain and heavy chain are held together by

A

disulfide bones

(antibodies /Ig)

47
Q

variable region of the antibodies ___

A

antigen recognition specificity

48
Q

constant region of the antibody will ___

A

effector function

neutralization, complement activation, sensitization, phagocytosis, opsonization

49
Q

antigen binds to antibody by __

A

non covalent binding such as H bonding and electrostatic

C3 and C4 will bind covalently

50
Q

antibody affinity

A

better fit will bind better

constant K if many antigens binded to antibodies vs free floating antigens and antibodies

51
Q

variable region + antigen =

A

Fab region

52
Q

affinity vs avidity

A

1 Fab = 1 antigen and 1 variable area = affinity→ intrinsic affinity

2 or more Fab = avidity → functional affinity

53
Q

valance

A

repeated or not? in same molecule

54
Q

interactions between the Ag and Ab depends on :

A
  • The nature of the antigen (Valence(repeated or not) of the antigen)
  • Specificity and affinity of the antibody
  • Ab type and class (Monoclonal, polyclonal, IgG, IgM)
55
Q

determinant

A

also called epitope

region of the antigen recognized by the Fab region of an antibody

56
Q

true or false a univalent and unideterminant antigen can agglutinate?

A

false

there is only 1 place for an antibody to bind = unideterminant→ uni-epitope

anti- bodies can not cross link (agglutinate)

57
Q

precipitation of antibody and antigen

A

antigens with many spots for Ab to bind (multi-determinant) will allow for Ab to cross link and bind to each other → creating a large heavy structure that agglutinates and sinks

58
Q

specificity and cross reactivity of antibody

A

specificity → all of the Ab react to the different epitope (binding sites) on the antigen

cross reaction → only one type of antibody react to the antigen (light binding)

59
Q

neutralization by antibodies

A

toxins = bind to antibody and make inactive

viruses → bind and prevent virus from binding to human cell

bacteria → prevent bacteria from binding to self

60
Q

opsonization

A

antibodies will tag an antigen to prepare it to be eaten by other immune cells

61
Q

___ describes the tagging of antigens by immune effectors such as antibodies or complement

A

opsonization

62
Q

___ describes the tagging of antigens by immune effectors such as antibodies or complement

A

opsonization

63
Q

antibody binding to antigen can lead to activation of complement system which leads to ___

A

innate immunity

lysis, release of inflammatory mediators, and facilitate phagocytosis

64
Q

____ - different individuals may have allelic differences in antibody genes. Typically a few amino acids in heavy chain.

A

antibody allotype

65
Q

IgM

A
  • Monomeric membrane-bound form expressed during B cell development
  • First antibody produced after immunization

.•Elevated IgM indicates recent infection

  • Secreted as large pentameric macroglobulin
  • Does not pass through human placenta.
  • Only isotype synthesized in appreciable amounts by a fetus.
  • IgM include isohemagglutinins, naturally occurring antibodies against ABO blood groups.
  • Activates/fixes complement, does not neutralize toxins or viruses.
66
Q

___ is the first antibody produced after immunization

A

IgM

67
Q

___ antibody does not pass through the human placenta

A

IgM → large amounts are made in a fetus

68
Q

___ activates or fixes complement system and does not neutralize toxins or viruses

A

IgM

69
Q

IgG

A
  • Predominant antibody in blood, lymph, CSF,
  • Four subclasses (IgG1-4) with distinct effector profiles
  • longest lasting Ig
  • Only isotype to pass placenta, also in colostrum.
  • Ab-dependent cell-mediated cytotoxicity. Binds target and Fc receptors on NK cells focusing the killer cell to its target.
  • Activates the complement system.
  • Opsonizes – binds Fc receptors of phagocytic cells- tags to be eaten
  • Neutralizes toxins (passive immunization), viruses (blocks attachment sites) and immobilizes bacteria
70
Q

___ is the only isotype of Ig that can pass through the placenta

A

IgG

71
Q

___ trigger the complement system, opsonize and neutralize toxins, viruses and bacteria

A

IgG

72
Q

___ is important in secondary immune response

A

IgG

73
Q

___ cause ab-dependent cell-mediated cytotoxicity. Binds target and Fc receptors on NK cells focusing the killer cell to its target.

A

IgG

74
Q

IgD

A
  • Rare (0.25% of all immunoglobulins).
  • IgD is coexpressed on the surface of mature B cells with IgM. Starts to being expressed when the B cells migrate from the bone marrow to peripheral lymphoid tissue.
  • Immunological function still not fully understood; possible role in respiratory immune defense, negative selection of autoreactive B cells. Potentially also involved in allergic reactions.

Binds to and activates basophils and mast cells

help with microbiome in GI tract?

75
Q

__ might help with the microbiome of the GI tract

A

IgD

76
Q

IgA

A
  • Two subclasses: IgA1 and IgA2 (in humans)
  • Major isotype of external secretions (saliva, tears, mucus, sweat, gastric fluid, colostrum).
  • IgA-secreting plasma cells are found in the lymphoid tissues underlying mucosal surfaces.
  • Poly-Ig-receptor transfers IgA through epithelial cells and into extracellular fluids.
  • Defense against local infections, prevents attachment and penetration by microbes.
  • Does not strongly fix or activate complement
  • Secretory IgA is antiviral, prevents virus attachment and agglutinates.
  • Monomeric form remains systemic
77
Q

___ helps maintain the microbiome of the gut inside the gut

A

IgA

IgA transferred to lumen of the GI and binds to antigens in the GI and promote growth (colonization) or breakdown of some pathogens

78
Q

___ receptor transfer IgA into the gut lumen

A

pIgR

79
Q

___is actively transported across epithelial cells, neutralizes pathogens, keeps commensal flora in check, and exports toxins

A

•Dimeric IgA

80
Q

IgE

A

allergies

  • Role in parasitic (helminths) infections, hypersensitivity and allergic reactions.
  • IgE can attach to mast cells and eosinophils that have a high affinity Fc receptors for the CH chain of IgE, thereby thereby inducing degranulation of these cells, which release histamine and other pro-inflammatory and toxic factors (involved also in allergy).
  • No complement fixing.

binds to parasites

81
Q

___ binds to parasites and cause inflammatory response

A

IgE

82
Q

___ antibodies activate complement system

A

IgM, IgG

83
Q

polyclonal antibodies

A

antigen will be reacted to by many different types of antibodies because antigen has many different spots for recognition (multiple epitopes)

84
Q

___ are uniform, only contain one antibody type against a single antigen/epitope

A

monoclonal antibodies

85
Q

FACS

A

fluorescence activated cell sorter

detects: granularity, size and fluorescence

stain with antibodies bound to a specific color, can sort by that color to find specific type of cell

22 spring: immunology (23 decks)

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