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Immunology > T cells > Flashcards

T cells Flashcards

1
Q

Stages of T cell Development?

A

Common lymphoid progenitor

  • -> IL-17
  • -> T cell linage
  • -> Migration to Thymus
  • -> VDJ/TCR rearrangement
  • -> Negative selection
  • -> AIRE
  • -> Positive selection
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2
Q

T cell selection process?

A

Negative selection:
- TCR with high affinity for self are deleted OR become regulatory T cells

Positive selection:
- T cells with TCR capable of interacting with self-MHC survive

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3
Q

Role of AIRE in T cell development?

A

Autoimmune regulator

AIRE controls expression of tissue specific antigens in the thymus

T cells who react with high affinity to self antigen are deleted

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4
Q

What is the disease associated with dysfunctional AIRE?

A

Autoimmune polyendocrinopathy with candidiasis and ectodermal dystrophy - APECED

Autosomal recessive disorder –> mutated AIRE gene

  • -> failure to express tissue specific antigens
  • -> Failure to delete autoreactive T cells
  • -> Autoimmunity

Results in:
Chronic mucocutaneous candidiasis
Autoimmune hypoparathyroidism
Autoimmune Addisons disease

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5
Q

Role of peripheral T-cell tolerance?

A

Chronic and recurrent presentation of self antigens in the periphery without co-stimulatory signals –> apoptosis

  • CD80/86 only expressed in response to Ags which engage innate PRRs *

Clonal ignorance in immunological privileged sites

Suppression by T-reg cells

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6
Q

Role of T-reg cells?

A

Express foxP3

  • -> reinforces regulatory phenotype - CTLA-4 and IL-10
  • -> blocks transcription of IL-2 gene

Results in reduction in immune response
Suppress auto-immunity and atopy

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7
Q

Subsets of T-reg cells

A

Thymic T-reg cells:

  • Apoptosis of autoreactive T cells
  • Formation of new T reg cells

Peripheral T-reg cells
- form in response to food antigens, commensal bacteria and allergens

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8
Q

Mechanisms for suppression by T-reg cells?

A

CTLA-4
- Down-regulate CD80/86

Secrete inhibitory cytokines - IL-10, TGF-beta, IL-9
Restrict IL-2 access by T cells - CD25
Cytolysis

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9
Q

Disease associated with loss of FoxP3?

A

Immune dysfunction, polyendocrinopathy, enteropathy,

AR X-linked disorder
Frequently fatal

DM, Thyroiditis
Enteropathy
AIHA
ITP
Atopy - eczema, food allergies, eosinophillia
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10
Q

What is required to activate T-cells?

A

MHC + peptide + costimulation signals

CD80/86 on T cells bind:

  • CD28 = activation
  • CTLA-4 = deactivation
  • PD-1 = inhibitory
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11
Q

CTLA-4 therapies?

A

Abatacept:

  • CTLA-4 Ig
  • Blocks T cell activation

Ipilumumab:

  • CTLA-4 Ab
  • Stimulates immune response
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12
Q

Stimulation of B-cells

A

CD-40 from T-cell bind CD-40 ligand on B cell

–> activation and proliferation

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13
Q

Hyper-IgM syndrome

A

Absent CD-40-CD40L signal
–> failure of B cell isotype switching and memory B cell generation

Results in:

  • Recurrent bacterial infections - PCP
  • Diarrhoea
  • Cancer
  • Autoimmune diseases

High IgM and Low IgG, IgE, IgA
Normal B cells

Treat with IVIG, bactrim, G-CSF

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14
Q

Role of Th-1 cells?

A

Differentiate in response to IL-12 and IFN-alpha

Secrete IFN-alpha, TNF anf lymphotoxin

Activates macrophages
Activates NK cells
Acts on B cells to isotype switch and form antibodies

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15
Q

Th-1 cells and mycobacterial immunity

A

Mendelian susceptibility to mycobacterial disease

Genetic deficiency of Th1 pathway components

  • -> susceptible to:
  • Non TB mycobacteria
  • TB
  • BCG vaccine
  • Invasive salmonellosis
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16
Q

Role of Th-2 Cells?

A

Differentiate in response to IL-4

Secrete IL-4, IL-5, IL-6, IL-10, IL-13

B cell isotype switching to IgE
Activate eosinophils

Atopic response and helminth defense

17
Q

Role of Th-17 Cells?

A

Differentiate in response to IL-1, IL-6 and IL-23

Secrete IL-17 and IL-22

Stimulates the release of chemokines and cytokines to attract neutrophils
Defensin secretion –> increased barrier function

Defense against candida and staph

18
Q

Role of IL-17 in psoriasis?

A

IL-17 has a critical role in psoriasis pathogenesis
Stimulates keratinocytes

Anti IL-17 treatments - Secukinumab and brodalimumab

Anti IL-22 treatments - ustekinumab

19
Q

Disease caused by IL-17 deficiency?

A

Chronic mucocutaneous candidiasis

Th-17 deficiency

–> chronic, recurrent candida infections

20
Q

Diseases caused by lack of T cells?

A

Infection with intracellular organisms

Fungi
CMV
EBV
VZV
HSV
PCP
Listeria
MAC
TB
21
Q

What is SCID?

A

Severe combined immune deficiency

FTT and recurrent opportunistic infections
Risk of autoimmunity and malignancy

Genetics:

  • IL-7 receptor deficiency
  • RAG1 or 2 deficiency
  • Gamma common chain deficiency
22
Q

What is idiopathic CD-4 T cell Lymphopenia?

A

Low CD-4 count without evidence of HIV

Recurrent opportunistic infections
CD-4 count <300

Treat with prophylaxis for infections

23
Q

Role of follicular helper cells and ICOS?

A

Help B cells
• class switching
• affinity maturation

Immunology (4 decks)

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