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Molecules and Cells II > Development of Cells in the Adaptive Immune Response > Flashcards

Development of Cells in the Adaptive Immune Response Flashcards

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Organic Chemistry 101 flashcards
1
Q

B-2 Cells

A

Develop after birth

Do not express CD5 glycoprotein

Replaced from bone marrow

Primary location is lymphoid organs

Produces only highly specific antibodies

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2
Q

Naive Cell Populations and their genotype

A

gamma delta T cells: CD3+gammadelta TCR+CD4-CD8- T cells

Helper T Cells: CD3+alphabeta TCR+CD4+CD8- T cells

Cytotoxic T Cells: CD3+alphabeta TCR+CD4-CD8+ T cells

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3
Q

What happens in Positive Selection?

A
  1. The Double positive cells bind to MHC I or MHC II on epithelial cells. Successful binding renders the cell MHC-restricted to self
  2. Binding to either MHC I or MHC II causes the other MHC molecule (CD4 OR CD8) to be eleminated and cells become single positive
  3. Self MHC-restricted cells move on to the medulla
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4
Q

T- Cell Maturation (Phase 1)

A
  1. T Cell precursors from the bone marrow enter the thymus
  2. T Cell lacks TCRs, CD3, CD4, CD8 surface and express early developmental antigens
  3. Beta chain rearranged by DN3 and pre-TCR expressed
  4. DN4 caused alpha chain rearrangement, with allows expression of a Double Positive aB TCR
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5
Q

MHC II pathway

A
  1. The antigen enters the macrophage
  2. It is ingested by lysosomes and then spit out
  3. Antigen then binds to the MHCII molecule
  4. The MHCII molecules goes to the surface of the cell, wheere it binds to the T- cell receptor of the Helper T cell
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6
Q

What components make up the surrogate light chain?

A

VpreB and gamma5

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7
Q

DN2 (Genotype, Location, Description)

A

Genotype: c-kit (CD117)++, CD44+, CD25+

Location: Subcapsular Cortex

Description: TCR gamma, delta, and Beta chain rearrangment; T- cell lineage commitment

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8
Q

Failure of light chain to rearrange leads to _________ or ____________

A

Apoptosis; light chain editing

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9
Q

Signals sent once Pre-TCR is formed by Beta chain rearrangement

A

Cell becomes permissive for TCR alpha-chain locus arrangement

Stimulates expression of CD4 and CD8 coreceptors

Stimulates proliferation

Stops additional TCR Beta-chain locus rearrangement

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10
Q

Other cells arising from Double Positive thymocytes

A

Natural Killer T cells- Innate Immunity, expresses TCR with invariant alpha chain. Binds to CD1, not classical MHC

Tregs- CD4 CD25

IELs (intraepithelial)- innate immunity, CD8, mucousal surfaces

TH17- Inflammation; protects againts fungal and bacterial infections

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11
Q

DiGeorge Syndrome results from delection in chromosome __________

A

22

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12
Q

Bruton’s Hypogammaglobulinemia

A

X-linked agammaglobulinemia (XLA)

Extremely low IgG levels and absence of other Ig classes

Babies are born with very few peripheral B cells and suffer recurrent bacterial infections

Defect in Bruton’s Tyrosine Kinase which is required for signal transduction through the pre-B/ B cells receptor; without functional Btk in developing B cells, cell development is arrested at pre-B stage

Heavy chain rearranged but light chains reamin in germline configuration

Disease manageable with antibiotics and passively administerd antibodies

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13
Q

What are the 10 Warning Signes of Primary Immunodeficiency

A
  1. Four or more new ear infections within 1 year
  2. Two or more serious sinus infections within 1 year
  3. Two or more months on antibiotics with little effect
  4. Two or more pneumonias within 1 year
  5. Failure of an infant to gain weight or grow normally
  6. Recurrent, deep skin or organ absesses
  7. Persistent thrush in mouth or fungal infection or skin
  8. Need for intravenous anitbiotics to clear infection
  9. Two or more deep-seated infections including septicemia
  10. A family history of Primary Immunodeficiency
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14
Q

The CD3 complex is composed of 4 distinct chains: __________,_________,____________, and ________

A

2 Episilon, delta, gamma,

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15
Q

Hyper IgE Syndrome (Job’s Syndrome)

A

Autosomal dominant mutation in the STAT3 gene

STAT3 gene is involved in intracellular signaling induced by IL-6 and TGF-Beta

Important in TH17 cell differentation

TH17 protects against fungal and bacterial infections; role in inflammation

Characterized by: Skin abscesses, recurrent pneumonia, eczema, elevated IgE, facial abnormalities, and bone fragility

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16
Q

What are the subsets of B cells?

A

B-1 cells (minor subset)

B-2 Cells (major subset)

Marginal Zone B cells

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17
Q

Which cells rearrange the Beta chain gene?

A

DN3

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18
Q

Functions of gamma- delta T cell

A

Lysis of infected or stressed cells

Cytokine and chemokine production

B cell help and IgE production

Priming of alphaBeta T cells via antigen presentation

Dendritc cell maturation

Regulation of stromal cell function via growth factor production

19
Q

In the ________ stage, Double positive cells express a mature _______________

A

DN4; alphaBeta TCR

20
Q

What happens in negative selection?

A
  1. Cells again bind to self MHC
  2. Medullary epithelial cells express AIRE transcription factor which facilitates the expression of tissue specific proteins to which thymocytes bind
  3. If those cells binds to avidly to MHC, self-peptide will undergo apoptosis and die
21
Q

Checkpoints for B -Cell Receptor Development

A
  1. The early pro-B Cell commitss to the B-cell lineage
  2. Heavy chain rearrangement: Generates heavy chain gene diversity in pro- B cell population
  3. First checkpoint: Selects for functional heavy chain
  4. Light chain gene rearrangement: Generates light chain gene diversity in pre- B cell population
  5. Second check point: Selects for functional light chains
  6. Immature B cell: Makes functional IgM
22
Q

Stages of B cell Development

A
  1. Lymphoid stem cell
  2. Pro B cell
  3. Pre B cell
  4. immature B cell
  5. Naive B cell
  6. Mature B cell
23
Q

Positive selection occurs in the ___________

A

Cortex

24
Q

Which immunoglobulins are present of Mature B cells?

A

IgM and IgD

25
Q

Marginal Zone B cells

A

Located in the outer cones of white pulp of the spleen

First B cells encountered by blood-borne antigens which enter the spleen

Broadly cross reactive antibodies (IgM)

Do not require T cell help

26
Q

DN1 (Genotype, Location, Description)

A

Genotype: c-kit (CD117)++, CD44+, CD25-

Location: Bone Marrow to Thymus

Description: Migration to thymus

27
Q

Failure of heavy chain to rearrange leads to __________

A

apoptosis

28
Q

Which DN stage expresses a double positive, mature alphaBeta TCR?

A

DN4

29
Q

B cell Maturation

A
  1. VCAM 1 binds VLA-4 on pro-B cells
  2. SCF binds c-kit on pro-B cells
  3. IL-7 binds IL-7 receptor
  4. Pre- B Cells Formed
  5. Immature B cells formed
30
Q

Negative selection occurs in the ____________

A

Medulla

31
Q

DN3 (Genotype, Location, Description)

A

Genotype: c-kit (CD117)+, CD44-, CD25+

Location: Subcapsular cortex

Description: Expression of pre-TCR; Beta selection

32
Q

MHCI pathway

A
  1. Antigen is intracelluar and cell is infected
  2. The viral DNA leaves nucleus and is transcibed to viral mRNA
  3. The viral mRNA is translated to viral peptides.
  4. The viral peptides bind to the MHC I
  5. The MHCI goes to the serve of the cell
  6. The T cell receptor binds the the peptide, which is still attached to the MHCI

7.

33
Q

DiGeorge Syndrome

A

Results from delections in chromosome 22

T box transciption factor delection most significant

Occurs during embryonic development when facial structures, heart, parathyroid, and thymus are forming

Patients present with symptoms not only of immunodeficiency, but hypothyroidism and congenital heart anomalies, cleft palate, delayed development; behavioral and emotional problems

Degrees of DiGeorge syndrome vary widely

Severe DiGeorge syndrome leaves patient no T cell function and therefore poor antibody response

Patients susceptible to all kinds of opportunistic pathogens, bacterial, viral, fungal

34
Q

What is the role of CD4+?

A

It lines up the receptor and the MHCII molecule

35
Q

Bone marrow _________cells support B cell development by stabilizing them in the bone marrow long enough to receive signals for differentation.

A

Stromal

36
Q

What effect does notch have on T cell?

A

Notch signaling regulates cell fate decisions during development.Notch signaling is essential for initial commitment to the T cell lineage and may function together with signals from the pre-TCR and the TCR to regulate subsequent steps of T cell development.

37
Q

Thymocytes that successfuly rearrange gamma and delta genes will express __________. Once this component is expressed what happens?

A

CD3. Gamma, delta T cell is ready to leave the thymus

38
Q

DN3 cells will bind a pre alpha chain, forming a _________and express __________. Cells are then committed to a ____________ lineage.

A

Pre-TCR; CD3; alphaBeta TCR

39
Q

Reticular Dysgenesis

A

Disruption in hematopoietic cell development

All downstream development impaired

Condition called De Vaal’s Syndrome

Symptoms include: Severe opportunistic infections (bacterial, viral, and fungal), severly impaired development, underdeveloped thymus, reduced lymphocytes, and severe leukemia)

40
Q

B-1 Cells

A

Develop early in embryonic life

Express CD5

Self renewing

Primary location is body cavities

Produce polyspecific antibodies

Source of natural antibodies (IgM)

Part of the first line defense against invasion by a variety of bacterial organism

Do not require T cell help

41
Q

What differentiates the Pre-B cell receptor from the B-Cell receptor?

A

The presence of the surrogate light chain (VpreB and gamma5)

42
Q

Treatment for DiGeorge Syndrome

A

Limited Thymus Function- Infections recurrent but may not be severe; treatment same as with normal childhood infection

Severe Thymic Dysfunction- Susceptible to all types of infections; thymic transplant

43
Q

DN4 (Genotype, Location, Description)

A

Genotype: c-kit (CD117) lowf-, CD44-, CD25-

Location: Subcapsular cortex to the cortex

Description: Proliferation, allelic exclusion of B chain locus; alpha- chain locus rearrangement begins; becomes double positive thymocyte

44
Q

Final step of lineage determination

A

DN2

Molecules and Cells II (14 decks)

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