5 Adaptive Immunity and Autoimmunity Flashcards
TCRs vs BCRs: Recognize peptide fragments bound to MHC molecules
TCRs
TCRs vs BCRs: Recognize intact proteins, carbohydrates, or other macromolecules
BCRs
Elimination of T cells or B cells with antigen receptors that recognize self during development
Central tolerance, (thymus or bone marrow)
Inhibition of mature lymphocyte function
Peripheral tolerance
Central vs peripheral tolerance: Induction of anergy
Peripheral
Central vs peripheral tolerance: Deletion of autoreactive cells
Peripheral
Central vs peripheral tolerance: Development of antigen-specific regulatory T and B cells
Peripheral
FOXP3+ T cell subset
Regulatory T cell
T cell subset function: B cell activation
CD4+ helper T cell
T cell subset function: Macrophage activation
CD4+ helper T cell
T cell subset function: Killing of cells infected with intracellular microbes
CD8+ cytotoxic T cell
T cell subset function: Killing of tumor cells
CD8+ cytotoxic T cell
T cell subset function: Suppress function of other T cells
Treg
T cell subset function: Maintenance of self-tolerance
Treg
T cell subset function: Helper and cytotoxic functions in the gut
MAIT cells
T cell subset phenotype: CD3+, CD4+, CD25+, FOXP3+
Treg
T cell subset phenotype: CD56+, CD16+, CD3+
NK cell
T cell subset phenotype: CD3+, CD8 ( majority
MAIT cells
Effector T cells
CD4+ and CD8+ T cells
Treg cells directly derived from the thymus
Natural Treg cells
Treg cells induced in the periphery
Adaptive Treg cells
Mutations in FOXP3 leads to this syndrome, a fatal autoimmune disease with onset early in life
IPEX syndrome
T/F Quantitative deficiency of Treg cells is seen in most autoimmune diseases
F
Signal 1 for T cell activation
TCR recognition of peptide/MHC complex on APC
Signal 2 for T cell activation
Costimulatory signals via cell surface molecules
Signal 3 for T cell activation
Soluble factors along the T cell: APC immune synapse
Site where naïve T cells are primarily activated
Peripheral/secondary lymphoid tissues
Costimulatory receptor CD28 binds with costimulatory molecules ___ expressed on dendritic cell surface
1) B7-1 (CD80)
2) B7-2 (CD86)
T/F Effector and memory T cells do not need much costimulation for activation
T
Treg cells depend on ___-mediated costimulation for their generation and maintenance
CD28
3 major subsets of CD4+ effector cells and the 4th subset
Th1, Th2, Th17; 4th subset T follicular helper cells
Signature cytokines of CD4+ T effector subsets
Th1: IFN-γ
Th2: IL-4,5,13
Th17: GM-CSF
CD4+ T effector subset that expresses high levels of ligands for E-selectin and P-selectin
Th1
CD4+ T effector subset that expresses CCR3, CCR4 and CCR8, which recognize chemokines that are highly expressed at sites of helminthic infection or allergic reactions, particularly in mucosal tissues
Th2
CD4+ T effector subset that expresses CCR6 which binds the chemokine CCL20 in certain viral and fungal infections
Th17
Th1 differentiation is driven mainly by ___ produced primarily by dendritic cells and macrophages in the lymphoid organ where the response is initiated
IL-12 and IFN-γ
Inhibits development of Th2 and Th17, thus reinforcing Th1 polarization
IFN-γ
The primary cytokine that initiates Th2 development
IL-4
IL produced by both mast cells and Th2 cells that functions as both an inducer and an effector cytokine of the Th2 cell subset
IL-4
Stimulates B cells to produce IgE, which are involved in many Th2-mediated defense reactions and allregic responses
IL-4
Promotes the development of proinflammatory Th17 cells when other mediators of inflammation like IL-6 or IL-1, are present
TGF-β
Th17 development is stimulated by
IL-6, IL-1, IL-23
Th17 differentiation is inhibited by ___ therefore strong Th1 and Th2 responses tend to suppress Th17 development
IFN-γ and IL-4
T cell subset especially abundant in mucosal tissues, particularly of the GIT
Th17
T cell subsets that appear to contribute to detrimental immune responses in JIA and RA and other autoimmune diseases, including IBD, psoriasis, and multiple sclerosis
Treg and Th17
B cell undergoes central tolerance by one of 3 processes
1) Receptor editing
2) Clonal anergy
3) Clonal deletion
In which immature B cells that react with self-antigens with low to high avidity undergo secondary rearrangement at the Igχ allele
Receptor editing
In which immature B cells that react with low-avidity self antigen can migrate into the spleen as anergic B cells
Clonal anergy
Occurs for those cells that fail receptor editing
Clonal deletion (slow rate)
Signals that induce antigen production by B cells
CD4+ T-cell/B-cell interaction:
1) TCR-MHCII
2) CD154-CD40
3) ICOS-ICOSL
4) CD28/CTLA-4-CD80/CD86
Primary sites of antibody diversification and maturation
Germinal centers
Histologically, mature germinal centers consist of a dark zone containing (1 )___ and a light zone containing (2) ___
(1) Densely packed proliferating B cells (centroblasts)
(2) FDCs, Tfh cells, macrophages, and nonproliferating B cells known as centrocytes
Antibody class: Activates phagocytosis and neutralizes antigen
IgG
Antibody class: Usually found on B cell surface; activation is an important B cell survival signal
IgD
Antibody class: Destroys parasitic worms
IgE
Antibody class: Contributes to allergic diseases
IgE
Antibody class: First Ab produced during an immune response
IgM
Antibody class: Protects mucosal surfaces
IgA
Breg cells are identified by their production of ___
IL-10
