T cells Flashcards
(23 cards)
Stages of T cell Development?
Common lymphoid progenitor
- -> IL-17
- -> T cell linage
- -> Migration to Thymus
- -> VDJ/TCR rearrangement
- -> Negative selection
- -> AIRE
- -> Positive selection
T cell selection process?
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
Role of AIRE in T cell development?
Autoimmune regulator
AIRE controls expression of tissue specific antigens in the thymus
T cells who react with high affinity to self antigen are deleted
What is the disease associated with dysfunctional AIRE?
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
Role of peripheral T-cell tolerance?
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
Role of T-reg cells?
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
Subsets of T-reg cells
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
Mechanisms for suppression by T-reg cells?
CTLA-4
- Down-regulate CD80/86
Secrete inhibitory cytokines - IL-10, TGF-beta, IL-9
Restrict IL-2 access by T cells - CD25
Cytolysis
Disease associated with loss of FoxP3?
Immune dysfunction, polyendocrinopathy, enteropathy,
AR X-linked disorder
Frequently fatal
DM, Thyroiditis Enteropathy AIHA ITP Atopy - eczema, food allergies, eosinophillia
What is required to activate T-cells?
MHC + peptide + costimulation signals
CD80/86 on T cells bind:
- CD28 = activation
- CTLA-4 = deactivation
- PD-1 = inhibitory
CTLA-4 therapies?
Abatacept:
- CTLA-4 Ig
- Blocks T cell activation
Ipilumumab:
- CTLA-4 Ab
- Stimulates immune response
Stimulation of B-cells
CD-40 from T-cell bind CD-40 ligand on B cell
–> activation and proliferation
Hyper-IgM syndrome
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
Role of Th-1 cells?
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
Th-1 cells and mycobacterial immunity
Mendelian susceptibility to mycobacterial disease
Genetic deficiency of Th1 pathway components
- -> susceptible to:
- Non TB mycobacteria
- TB
- BCG vaccine
- Invasive salmonellosis
Role of Th-2 Cells?
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
Role of Th-17 Cells?
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
Role of IL-17 in psoriasis?
IL-17 has a critical role in psoriasis pathogenesis
Stimulates keratinocytes
Anti IL-17 treatments - Secukinumab and brodalimumab
Anti IL-22 treatments - ustekinumab
Disease caused by IL-17 deficiency?
Chronic mucocutaneous candidiasis
Th-17 deficiency
–> chronic, recurrent candida infections
Diseases caused by lack of T cells?
Infection with intracellular organisms
Fungi CMV EBV VZV HSV PCP Listeria MAC TB
What is SCID?
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
What is idiopathic CD-4 T cell Lymphopenia?
Low CD-4 count without evidence of HIV
Recurrent opportunistic infections
CD-4 count <300
Treat with prophylaxis for infections
Role of follicular helper cells and ICOS?
Help B cells
• class switching
• affinity maturation
