immu3102 Flashcards

1
Q

What is humoral immunity mediated by?

A

Antibodies

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2
Q

What is the difference between naive and activated B cells

A

Naive B cells recognise antigens but do not secrete antibodies

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3
Q

What surface antibodies do naive B cells have?

A

IgM and IgD

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4
Q

Draw out the antibody structure

A

4 polypeptide chains assembled into a Y shaped molecule
2 L chains
2 heavy chains
check

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5
Q

How many light chain types are there?

A

kappa and lambda

C domain is different, no functional differences

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6
Q

How many types of heavy chains are there?

A

5 different classes of heavy domains. They differ in their C domain and function.

This is what determines what classes antibodies can be divided into

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7
Q

Why is T independent antibody responses important?

A

It means pathogens with polysaccharides, lipids and other non-protein antigens could stimulate antibody production without T cell help

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8
Q

What antibodies are released in T independent Ab response?

A

IgM
almost no heavy chain isotype switching
no affinity maturation
no memory

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9
Q

What are properties of T dependent Ab responses

A

heavy chain isotype switching, affinity maturation, memory B cells and long-lived plasma cells

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10
Q

How are B cells activated in Thymus dependent activation of B cells?

A

Proliferation is induced by

1) antigen binding to the BCR-proteins (antigen specific)
2) Interaction between B cells and CD4+ T helper cell-co-stimulation (CD40-CD40L)
3) cytokines released by T helper cells

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11
Q

where do naive B cells move

A

naive B cells recirculate and enter follicles in secondary lymphoid tissues

In the secondary lymphoid tissues, they migrate into the B cell zones

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12
Q

How are Naive B cells attracted to specific places in the secondary lymphoid organ

A

Naive B cells are attracted to follicles via CXCL13 secreted by FDCs

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13
Q

how are antigens delivered into the lymph nodes?

A

Small antigens are delivered to the lymph nodes by afferent lymphatic vessels that drain the subscapular sinus

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14
Q

How are antigens delivered to follicles?

A

Subscapsular sinus macrophages capture large microbes and antigen antibody complexes and deliver these to follicles

Some large antigens are captured in the medullary region by resident Dendritic cells and are transported into follicles

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15
Q

How do immune complexes bind onto B cells or follicular dendritic cells?

A

They might bind on CR2 on B cells.

They bind to complement receptors.

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16
Q

Are antigens presented to B cells intact?

A

Yes, they are intact (native form), meaning they are not processed by APCs

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17
Q

How does the BCR activate the B cell

A

2 identical epitopes on aggregated protein antigen/repeated identical epitopes bind to adjacent immunoglobulin receptors to trigger B cell activation.
Receptor cross activation

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18
Q

How does signal transduction in B cells work?

A

Cross linking IgM and IgD receptors by antigen triggers signals that they are relayed across the cell membrane by Igalpha and Igbeta signal transducers

This causes the phosphorylation of ITAMS which initiates phosphorylation cascades.

These signal cascades activate enzymes and transcription factors for initiating gene expression and synthesis of proteins needed for B cell proliferation and differentiation

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19
Q

What are the characteristics of activated B cells

A

Proliferation
expansion of antigen specific clone
Increased expression of B7 co-stimulators

Express cytokine receptors

Increased expression of chemokine receptors

Low level of IgM secretion

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20
Q

Function of IgM

A

binds easily on polysaccharides, and could effectively cross link many B cell antigen receptors

Is an excellent activator of complement

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21
Q

How do antigen specific T helper cells and B cells get together?

A

They meet at the very edges of the follicles

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22
Q

Are BCRs apcs?

A

Yes, proteins could bind antigens via BCR and they could be processed and displayed on MHC class II in B cell membrane

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23
Q

What is T cell help

A

When CD40 L newly expressed on activated T cells binds to CD40 molecules expressed on B cells

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24
Q

What does the engagement of CD40L and CD40 do?

A

They help induce B cell proliferation
Antibody synthesis and secretion

They also initiate heavy chain isotype class switching and affinity maturation

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25
Q

What are innate like T cells

A

They have T cell receptors

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26
Q

How are the TCR on Innate like T cells different

A

their TCR are invariant meaning that they have limited diversity and restricted repertoire of TCR compared to ab T cells

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27
Q

What do innate like T cells recognise

A

They recognise non-peptide antigens

Non polymorphic antigen presenting molecules (not MHC classes)

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28
Q

How fast do innate like T cells respond?

A

Very quickly

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29
Q

What is a semi invariant TCR

A

V regions are expressed, and there is little to no junctional diversity

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30
Q

What does the limited diversity of unconventional T cells mean?

A

It means that unconventional T cells won’t need to clonally expand and are ready for a rapid response

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31
Q

Natural Killer T cell properties

A

They have MHC Class I like molecule: CD1d

They recognise lipid antigens

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32
Q

How are NKT cells different to conventional T cells

A

They respond to lipid based antigen presented by CD1d
They exit the thymus with an antigen experienced phenotype= functionally mature
They respond rapidly to TCR and/or cytokine signals causing immediate production of cytokines
They are non-circulating

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33
Q

How are NKT cells similar to conventional T cells

A

Their subsets resemble CD4 T cell subsets
They differentiate in thymus and periphery

Can kill cells via perforin and granzyme B

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34
Q

What are 2 subsets of NKT cells

A

tissue homing and tissue resident

Functional not clear
one is homeostasis of gut
One is homeostasis of adipose tissue

35
Q

what are MAIT cells activated by?

A

activated by vitamin B intermediates

Vitamin B intermediates like riboflavin are importantly found in some bacteria

36
Q

How are MAIT cells unique in how they detect an infection?

A

They detect infection based on a metabolic signature of a pathogen, and not a pathogen structure-whatever that means

37
Q

Are mait cells functionally mature

A

yes, they exit the thymus with an antigen experienced phenotype

38
Q

What are MAIT cell response to TCR signally?

A

immediate production of cytokines

39
Q

What is thymic development of MAIT cells dependent on?

A

remote production of Vit B2 metabolites by commensal bacteria

40
Q

gdT cells

A

unknowwn
they apparently have an immune surveillance role and can respond rapidly by directly killing target cells or cytokine production.

41
Q

what are some ligands of gdT cells

A

stress induced, empty or non-presenting MHC like molecules

Surface associated and soluble structures.

42
Q

The Germinal Centre

A

Site of affinity maturation, isotype switching, generation of long lasting plasma cells and memory B cells

43
Q

Where and how are germinal centers created?

A

They are created within lymphoid follicles during T dependent immune responses

44
Q

What kind of cells are found in Germinal center

A

Each Germinal center contains B cells derived from one or a few antigen specific clones

45
Q

In the dark zone of a GC, how many progeny could 1 lymphocyte give rise to?

A

5000 progeny. Progeny are small cells that undergo further differentiation and selection in the C light zone

46
Q

Outline the germinal centre reaction

A

activated B cells migrate into follicle, proliferate and form the dark zone

Once in the darkzone, B cells undergo extensive isotype switching and somatic hypermutation of IG V genes and migrate into the light zone

In the light zone, they encounter follicular dendritic cells and T follicular helper cells

B cells with the highest affinity receptors selected to survive
finally they differentiate

47
Q

What are the benefits of isotype class switching?

A

Different microbes are eliminated most efficiently by different immune responses.

48
Q

What is the mechanism of heavy chain class switch

A
The CD40 engagement induces the enzyme AID-activation induced deaminase.
AID is the pivotal enzyme for isotype class siwtching
49
Q

where are gd T cells found?

A

They are present at the epithelial and mucosal barriers

50
Q

What are ligands of gdT cells

A

phosphoantigens
butyrophilins
surface associated and soluble structures

stress-induced empty or non-presenting MHC like molecules

51
Q

phosphoantigens

A

small phosphorylated metabolites
microbial phosphoantigen produced by bacteria.

Some phosphoantigens are common in both prokaryotes and eukaryotes which may be upregulated in tumour cells and endogenous danger siganlls

52
Q

Butyrophilins

A

Unclear, but apparent it is not a p-Ag antigen presenting molecule; it could be a co-factor

pAg bind intracellular region of BTN3A1=> which may cause conformational change. A danger signal presented on the surface of infected or stressed cells in the presence of phosphoantigens

53
Q

What are innate lymphoid cells?

A

These are lymphocytes which do not express diversified antigen receptors like T and B cells

They are mostly tissue resident and respond to signals from tissue resident cells
Fast-acting, but also around later for cross-talk with T cells

54
Q

What are the functions of ILCs

A

They conduct the early defense against pathogens
They recognise stressed and damaged host cells-help to clear, repair and rebuild
They maintain tissue integrity and homeostasis

55
Q

Give examples of what ILC 2 could do in tissue modelling, growth and repair

A

ILC2 could secrete IL13, which drives epithelial cells towards secretory lineages
They secrete AREG which controls epithelial cell proliferation and differentiation needed for repair after pathogen expulsion

56
Q

What does ILC3 do in tissue modelling, growth and repair

A

produce IL22 which could protect the epithelial barrier: promote proliferation and protect from apoptosis,
instructs epithelial cells to make anti bacterial peptides

57
Q

what could ILC2 do in tissue homeostasis

A

IL13 helps polarise M2 macrophages, regulate insulin resistance

IL4 and IL13 beiges pre adipocytes

58
Q

How do you activate naive CD8+ T cells

A

They mature and develop TCR in the thymus

then naive but functionally inactive CTL (known as pre CTL) migrate from thymus to peripheral lymphoid tissue

The activation and generation of effector CTLs requires signal 1 and signal 2
Signal 1 TCR recognising antigenic peptides in association with MHC class 1
59
Q

How does T cells help activate naive CD8+ T cells

unknown check

A

They could secrete cytokines that stimulate CD8+ T cell differentiation

The antigen stimulated helper T cells express CD40 L which binds to CD40 on APCs

60
Q

Does this mean CD8 T cells could be independently activated and if so, what is the difference?

A

unknown

61
Q

what does the differentiation of CD8+ T cells into effector cells result in?

A

molecular events in CTL differentiation
Transcription factors: T bet and eomesodermin

Transcription factors contribute to high level expression of cytoplasmic granules and cytokines such as interferon gamma
development of membrane bound cytoplasmic granules

cytokine secreting capability

62
Q

How does activated T cells know where to migrate/recognise sites of infection

A

Activation of CD8+ T cells lead to an upregulation of integrins, selectin ligands and chemokine receptors

Endothelial cells at the site of infection are induced by cytokines such as TNF and IL-1 to express selectins and ligands for integrins

63
Q

What are granzymes?

A

They are serine proteases that enter target cells
Granzyme B is the most important of these enzymes, and they cause proteolytic cleavage after aspartate residues.

Granzyme B’s proteolytic cleavage activates caspases and helps induce apoptosis

64
Q

What does fas ligand do?

A

unknown

65
Q

What are NK cells

A

They are a subtype of type 1 innate lymphoid cell. They are large granular lymphocytes that do not express diverse, clonal antigen receptors

66
Q

How are NK cells activated and proliferated

A

IL12 and IL15 cause proliferation of NK cells

67
Q

What is the activating receptor of an NK cell

A

unknown check the lecture

68
Q

What is the inhibiting ligand of the NK cell

A
An MHC class I
it binds to receptors such as KIR, CD94/NKG2
69
Q

Function of IgM

A

They neutralise microbes/toxins
activate classical pathway of complement
about 6% in serum

70
Q

FUnction of IgG

A

neutralisation of microbes and toxins
opsinization of Ag for phagocytosis by macrophages and neutrophils
antibody dependent cellular cytotoxicity by NK cells
Feedback inhibition of B cell activation
neonatal immunity
activation of complement

71
Q

function of IgA

A

Mucosal immunity

neutralisation of microbes/toxins in mucosal organs

72
Q

IgE

A

mast cell degranulation
eosinophil mediated defense against helminths
Antigen receptor on naive B cells

73
Q

FcgammaR (CD64) mediated effector functions

A

Opsonisation of antigen for phagocytosis
Antibody dependent cellular cytotoxicity by NK cells
feedback inhibition of B cell activation
neonatal immunity

By phagocyte FC receptors
causes them to produce ROS, nitric oxide and hydrolytic enzymes

74
Q

CD64 has the highest affinity for

A

IgG FC receptor for phagocytes

75
Q

CD16

A

binds to IgG on cell surface

causes NK cells to release cytotoxic granules

76
Q

What happens to simultaneous cross linking of inhibitory Fc gamma RII b and BCR

A

leads to phosphorylation of ITIM and blocks downstream signalling and proliferation.
It is the checkpoint for activation and proliferation of autoreactive B cells or modulation of an immune response

I think it is basically the same for isolated cross linking \

77
Q

How are newborns protected against infection?

A

Maternal IgG transported across the placenta during pregnancy and some suggest IgE could also cross the placenta

Maternal IgG and IgA is transported across the gut epithelium from breastmilk

78
Q

How does IgG cross these barriers

A

actively transferred by the neonatal Fc receptor which is an MHC class 1 like molecule

79
Q

How does FcRn mediate directional transport?

A

so, it’s pH dependent
The direction is from maternal blood to placenta to fetal blood.

Physiological pH (maternal IgG is taken up to endosomes)
then the acidic pH causes high affinity binding of Fc region of IgG to FcRn as endosomes are acidified

then the physiological pH in fetal circulation promotes dissociation

80
Q

FcRn functions

A

helps transfer of breast milk derived IgG from intestinal lumen to neonatal blood

In adults, they have a role in transporting IgG across polarised barriers in adult tissues

In the gut, IgG transported into the lumen and then IgG immune complexes transported back

IgG immune complexes taken up by FcgammaR on DC to create tolerance against food antigen and immune response to pathogen

This recycles Igg through endosomes of epithelial cells or monocytes to keep IgG in serum for longer

81
Q

outline IgA structures

A

IgA dimers are held together by the J chain

and the dimer is transported across epithelium into the lumen by the poly Ig receptor made by mucosal epithelial cells
Also called transcytosis

it neutralises toxins and viruses, blocks colonization and entry of pathogens and commensals

the FcAR are expressed on cells of myeloid lineage, including kupffer cells in the liver

cross linking of FcARI by IgA immune complexes or IgA opsinized pathogens induces phagocytosis and activation of FcaRI bearing cells

82
Q

What are monoclonal antibody therapy used for

A

1) triggering target cell death
2) agonist: stimulate signalling
3) antagonist: block receptors or ligands

83
Q

Antibody engineering

A

enhance or minimize Fc mediated functions
add effector functions
extend half-life
optimise antigen binding