Flashcards in T cells Deck (23):
Stages of T cell Development?
Common lymphoid progenitor
--> T cell linage
--> Migration to Thymus
--> VDJ/TCR rearrangement
--> Negative selection
--> Positive selection
T cell selection process?
- TCR with high affinity for self are deleted OR become regulatory T cells
- T cells with TCR capable of interacting with self-MHC survive
Role of AIRE in T cell development?
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
Chronic mucocutaneous candidiasis
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?
--> 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?
- Down-regulate CD80/86
Secrete inhibitory cytokines - IL-10, TGF-beta, IL-9
Restrict IL-2 access by T cells - CD25
Disease associated with loss of FoxP3?
Immune dysfunction, polyendocrinopathy, enteropathy,
AR X-linked disorder
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 Ig
- Blocks T cell activation
- 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
Absent CD-40-CD40L signal
--> failure of B cell isotype switching and memory B cell generation
- Recurrent bacterial infections - PCP
- 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 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
- 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
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
Anti IL-17 treatments - Secukinumab and brodalimumab
Anti IL-22 treatments - ustekinumab
Disease caused by IL-17 deficiency?
Chronic mucocutaneous candidiasis
--> chronic, recurrent candida infections
Diseases caused by lack of T cells?
Infection with intracellular organisms
What is SCID?
Severe combined immune deficiency
FTT and recurrent opportunistic infections
Risk of autoimmunity and malignancy
- 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