Flashcards in Immunoregulation Deck (67):
What are the cell surface markers of T-regs?
CD4+, FoxP3+, and CD25
What is CD 25?
The alpha chain of IL-2 receptor
What is IL-2's role in Treg cells?
Growth factor for Treg cells
What is IPEX syndrome?
An absence of T reg cells, causing autoimmunity d/t overstimulation of immune system
What is the function of CTLA-4?
Inhibits the activation of T cells by blocking the B7 receptor found on antigen presenting cells
What is TGF-β's role in Treg development?
Induces the expression of FoxP3
What are the two general functions of Treg cells?
1. prevent excessive immune responses to foreign antigens
2. prevent immune responses to self-antigens missed by tolerization
What cytokines do Treg cells express?
IL-10 and TGF-β
What is the function of IL-10 expressed from Treg cells? (2)
inhibits IL-12 production by dendritic cells and macrophages and downregulates expression of costimulatory molecules and class II MHC by these cells
What is the function of TGF-β expressed by Treg cells? (2)
suppresses the activation of macrophages and T cells and promotes the development of Treg cells
What role does IL-2 play in Treg cells mechanism of action?
Treg cells consume it, inhibiting development of other cells
What is an idiotype?
an antibody's antigen-binding site made up of the hypervariable regions of the heavy and light chains
What is an anti-idiotope? What is the function of anti-idiotopes?
an antibody to another antibody's idiotope
bind to and inhibit the B lymphocytes that express the original idiotope
How do anti-idiotypes work?
Produced a few days after antibody to antigen are produced. Not understood how
What are the two ways in which antibodies produced by B cells can inhibit B cells?
1. Bind up/eliminate all antigen
2. Complexes of Antibodies bind to Fc receptors and membrane antibody
What is tolerance in immunology?
is a block in the growth and differentiation of lymphocytes brought about by antigen
Loss of tolerance leads to what?
Is tolerance antigen specific?
Is tolerance aquired or inborn?
Do all individuals have the ability to develop antibodies to self antigens?
Is it easier to tolerize immature lymphocytes or mature ones?
What are the two mechanisms of tolerance?
1. Clonal Deletion
2. Functional inactivation (clonal anergy)
Can mature lymphocytes be tolerized to antigen?
Why are T lymphocytes a better target of regulation than B cells?
They are more central to activation of immune response
What is central tolerance?
Deletion of reactive self T cells in the thymus
What is peripheral tolerance?
the clonal anergy of mature T lymphocytes in the periphery
What is clonal anergy?
Inactivation (not death) of T cells due to the absence of costimulatory molecules
Expression of self-antigens, in the absence of co-stimulator-producing inflammation (which would be seen during infection and injury), normally produces what?
True or false: T lymphocyte tolerance is relatively long lasting
True or false: B lymphocyte tolerance is relatively short-lived
We have tolerance to lipids, polysaccharides etc, but T cells only recognize proteins. Explain this.
Tolerance of B lymphocytes
When can reaction to self antigens occur in B lymphocyte maturation?
When only IgM is expressed at the surface of B cells, and they are exposed to antigen (immature stage)
B cells get a "second chance" when they are found to express antibodies to self proteins. How?
Through receptor editing of light chain
What is the effect of corticosteroids on Thymocytes?
Kills them =immunodeficiency
What are the four populations of thymocytes in the thymus?
1. CD4-CD8- ("double negative")
2. CD4+CD8+ ("double positive"
Double positive thymocytes turn into what?
Mature thymocytes, with only one CD4/8 expressed
What is positive selection?
Getting rid of T cells that cannot bind to self MHC proteins, or bind foreign ones.
What is negative selection?
The process of getting rid of thymocytes that bind to self antigen
What are the thymocytes that you want, and the body maintains after positive and negative selection?
thymocytes that recognize foreign protein and self MHC proteins
What cells/where is negative selection carried out?
by dendritic cells at the cortico-medullary junction
What is the AIRE gene, and what does it do?
Thymic gene the is responsible for the expression of tissue specific proteins (e.g. insulin), that allows for proper development of T lymphocytes
Mutations in the AIRE gene lead to what?
widespread autoimmune disease
The thymus atrophies with age. If there are remnants of it left, can it/they produce T lymphocytes?
What are monokines? What produces it, what does it do?
Cytokine produced by mononuclear phagocytes to regulate the effector functions of phagocytic cells
What are lymphokines? Functions (2)?
Cytokines produced by activated T lymphocytes to aid in the activation and differentiation of lymphocyte subsets as well as control the activity of macrophages, neutrophils, and eosinophils
What are colony stimulating factors (CSF)?
Cytokine produced by lymphocytes and mononuclear phagocytes to stimulate the production of granulocytes and monocytes in the bone marrow
What are the three mechanisms of action for cytokines?
How many cytokines are needed to regulate the production of other cytokines?
How do cytokines initiate their action?
By binding to cellular receptors on target cells
What is type I interferon composed of? What does it do? (3)
Composed of alpha and beta IFN
1. Inhibits viral replication
2. Enhance NK cell action
3. Increase cellular expansion of class I MHC molecules
What is Tumor necrosis factor (TNF)-α produced by?
Produced by mononuclear phagocytes and T lymphocytes in response to bacterial lipopolysaccharide (LPS or endotoxin).
Very high concentrations of (TNF)-α produce what?
What are the two chains that compose IFN?
alpha and beta
What are the biological actions of IFN? (3)
1. Inhibit viral replication via paracrine action
2. Enhance cytolytic capabilities of NK cells
3. Increase expression of class I MHC
What produces tumor necrosis factor (TNF)-α?
Mononuclear phagocytes in response to bacterial LPS
What are the five biological actions of (TNF)-α? (last one is extreme concentrations).
1. Activates mononuclear phagocytes and PMNs
2. Increases adhesiveness of vascular epithelium
3. Generates fever
4. Induction of neutrophilia
5. Shock/DIC at high levels
What produces IL-1?
Activated mononuclear phagocytes
What is the biological action of IL-1? What about at high concentrations?
Induces the production of IL6
High conc = fever and wasting
What produces IL-6? (3)
mononuclear phagocytes, endothelial cells, activated T cells?
What are the biological actions of IL-6?
1. Aids in differentiation of B cells to plasma cells
2. induces hepatocytes to synthesize plasma proteins, such as fibrinogen
What produces IL-2?
CD4+ T cells in response to antigenic stimulation
What are the biological effects of IL-2?
1. Autocrine/paracrine growth factor for T cells
2. Induces NK cells to become LAKs
What produces IL-4? What is its biological activity?
produced by CD4+ T cells and mast cells/basophils and induces B cell isotype switching to IgE production
What produces Transforming growth factor-beta (TGF-beta)? (2)
1. produced by activated T cells and activated mononuclear phagocytes
2. Stromal cells
What are the biological effects of TGF-beta? (3)
1. inhibits T cell proliferation and differentiation into CTL's as well as inhibits macrophage activation.
2. induces B cells to produce IgA antibody
3. Initiates wound healing
What cells produce Interferon-γ? (3)
mainly produced by CD4+ and CD8+ T cells, but NK cells can also produce it