T-Cell Diversity Flashcards
Define T-cells and where they are formed.
Lymphocytes that express T-cell antigen receptors (TCR’s); formed in the thymus.
What do T-cells secrete and what do these secretions control?
Cytokines: Induce changes in cells, especially the differentiation of B cells into Plasma cells… these secretions control –> Cytotoxins: (Kill [infected] cells via the adaptive immune response.)
What antibody is associated with B-cells, and with Plasma Cells?
B cell = IgM ; Plasma cell = IgG
What is the Immunologic Synapse? What secretion is it associated with?
Space that allows for communication between T-cell and Target cell; associated with cytotoxins.
Define DiGeorge Syndrome.
Lack of a thymus due to a mutation in the transcription factor causing T-cell deficiency. (Susceptible to viral/bacterial/fungal/parasitic infections.)
Why would the lack of T-cells cause susceptibility to viruses?
Because Cytotoxic T-cells kill virus infected cells and Helper T cells provide cytokines to B-cells that allow them to make neutralizing antibodies against viruses.
Why does lack of T-Cells cause susceptibility to Pygogenic (pus inducing) Bacteria? Intracellular Bacteria?
T-cells are essential for B-cell responses (to eliminate bacteria);
T-cells make cytokines (interferon-gamma) that activate macrophages to kill intracellular bacteria.
About how many different T-cells are there in Humans? TCR’s?
10^12 ; 10^10
Where does V(D)J recombination generating T cell diversity occur? How does this contrast to B cell diversity?
In the thymus only; B cells diversify in Bone Marrow and the Periphery in a process called Affinity Maturation.
Irreversible genomic rearrangement occurs where?
At the alpha & beta loci (each lymph gets a unique Ab receptor).
What exactly are the alpha and beta loci?
They are each arm of the dimer receptor.
When does diversity of T-cell receptors occur, before or after encountering antigens?
Before, so your body is ready.
List the mechanisms for generating TCR diversity.
Each TCR has 2 chains (products of V(D)J). Multiple variable domain exons. Multiple diversity/joining segments. Imprecision in the joining process (nucleotides added/deleted– N region diversity).
Which molecule transmits T-cell receptor signals?
CD3 - once TCR binds to Ag, this molecules signals cell to react
What antigens do T-cells see?
MHC molecules loaded with peptides.
What are MHC molecules?
Cell surface proteins encoded by a genomic locus known as the Major Histocompatibility Complex
What is another name for MHC molecules in humans?
Human Leukocyte Antigens (HLA molecules)
Which MHC class has only 1 membrane penetrating chain and is slightly smaller?
MHC class 1.
What peptides are presented by MHC molecules?
Short (8-17 AA) peptides that come from the degradation of self or foreign proteins.
Where are these peptides generated?
Either the cytosol or in the endocytic compartments that retrieve proteins from outside cells.
What is the only way a T-cell receptor recognizes anything?
When it encounters a MHC – Peptide complex (not individually).
MHC Class, CD4/CD8?
CD4 T-Cell: Class II
CD8 T-Cell: Class I
Type of T-Cell, CD4/CD8?
CD4 T-Cell: Helper T-Cell
CD8 T-Cell: Cytotoxic T-Cell
On which type of cells, CD4/CD8?
CD4 T-Cell: Dendritic/B/Macrophage
CD8 T-Cell: All nucleated cells
Peptides from, CD4/CD8?
CD4 T-Cell: Outside cells (serum)
CD8 T-Cell: Inside cells (cytosol)
Helper T cells secrete? Cytotoxic T cells kill?
Cytokines; Kill virus infected cells
What is the difference between B and T cells regarding Antigen receptors and recognition?
T-cell: Receptor is T-cell receptor (TCR)-only found on cell surface
B-cell: Receptor is Antibody molecule - can be on cell surface or cell free in the serum
T-cell: Recognizes only cell bound antigens (MHC-peptide complexes)
B-cell: Recognizes cell bound or cell free (serum) antigens.
Which cell does not undergo Affinity maturation/hypermutation?
T-cells
What happens in Bare Lymphocyte syndrome?
Patients are unable to express MHC class II molecules and thus CD4 T cells fail to develop and antigens can’t be recognized.
How is Clonal Expansion critical for the immune response?
The production of daughter cells (arising from one cell) with specific antigen receptors can eliminate the pathogen quickly.
List the 3 key steps in an immune response.
- Antigen recognition and T cell activation (signaling by CD3)
- Proliferation of antigen-specific T cells (TCR signaling induces rapid expansion of T-cells specific for new pathogen)
- Differentiation of antigen-specific T cells into Effector cells:
a. Proliferating T cells can make Cytokines/Cytotoxins
b. Some T-cells become Memory cells for future pathogen encounters
What do CD4 T cells differentiate into?
A) TH1 effector cells-Macrophage/B cell activation, production of opsonizing antibodies such as IgG
B) TH2 effector cells-General activation of B cells to make Ab’s
What does Th1 secrete? What is it essential for?
Interferon y – activates macrophages
IL-2 – promotes T cell growth, other cytokines
*Essential for resistance against intracellular bacteria.
What does Th2 secrete? What is it essential for?
IL-4 – causes B cell growth and differentiation (for IgE production)
IL-5 – causes B cell/eosinophil differentiation, other Cytokines (IL-13)
*Essential for resistance against worms and other parasites.
What do CD8 T-cells differentiate into?
Cytotoxic T cells (with lytic granules).