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96 Cards in this Set

  • Front
  • Back
What are the two major intracellular compartments separated by membranes?
the cytosol & the vesicular system
What comprises the vesicular system?
1. Endoplasmic reticulum
2. Golgi apparatus
3. Endosomes
4. Lysosomes
Where are cytosolic pathogens degraded?
in the cytosol
Where are intravesicular pathogens degraded?
in endocytic vesicles (low pH)
Where are extracellular pathogens and toxins degraded?
in endocytic vesicles (low pH)
Peptides from degraded cytosolic pathogens are bound to what molecule?
MHC class I
Peptides from degraded intravesicular pathogens are bound to what molecule?
MHC class II
Peptides from degraded extracellular pathogens and toxins are bound to what molecule?
MHC class II
Peptides bound to MHC class I molecules are presented to what type of cell?
CD8 T cells
Peptides bound to MHC class II molecules are presented to what type of cell?
CD4 T cells
TAP
Transporters associated with antigen processing
What are TAP-1 and TAP-2?
(transporters associated with antigen processing) TAP are ATP-binding cassette proteins involved in transporting short peptides from the cytosol into the lumen of the endoplasmic reticulum, where they associate with MHC class I molecules
li
invariant chain
What does the invariant chain (li) do?
The invariant chain assembles as part of a MHC class II protein in the ER and shields the MHC molecule from binding peptides there. When the MHC molecule reaches an endosome, li is degraded, leaving the MHC class II molecule able to bind Ag'ic peptides
HLA
Human Leukocyte Antigen
HLA-DM
The invariant HLA-DM protein in humans is involved in loading peptides onto MHC class II molecules. It is encoded in the MHC within a set of genes resembling MHC class II genes.
HVGD
Host-Versus-Graft-Disease
What is the major function of the MHC?
The major function of the MHC is to bind and display peptide fragments from pathogens.
Human MHC genes are...
highly polymorphic
What is special about MHC class 1B?
It's where NK cells bind
Expression of MHC alleles is...
codominant
What does codominant mean?
Codominant means that there is expression from both alleles.
In MHC molecules, polymorphism is restricted to...
the amino terminal end of the MHC molecule
MHC class II beta chains have...
lots of variation
Different alleles of an MHC molecule bind...
different peptides
How do MHC class I molecules bind peptides?
molecules bind at the ends of the MHC class I molecules
How do MHC class II molecules bind peptides?
molecules bind throughout the whole peptide
Allogeneic
Two individuals or two mouse strains that differ at the MHC are said to be allogeneic.
Rejection of grafted tissues from unrelated donors usually results from...
T cell responses to allogeneic MHC molecules (alloantigens) expressed by the grafted tissues
What are cytokines?
A cytokine is any small protein made by a cell that affects the behavior of other cells. Cytokines act via specific cytokine receptors on the cells that they affect.
What are cytokines made by lymphocytes often called?
Lymphokines or interleukins (IL)
What are endotoxins?
Endotoxins are bacterial toxins that are released only when the bacterial cell is damaged, as opposed to exotoxins, which are secreted.
What is the most important endotoxin medically?
LPS of Gram negative bacteria; LPS is a potent inducer of cytokine synthesis; when present in large amounts in the blood it can cause a systemic shock reaction called endotoxin shock
T cell-mediated immunity involves (4):
1. Production of armed effector T cells
2. Properties of armed effector T cells
3. T cell-mediated cytotoxicity
4. Macrophage activation by TH1 cells
Naive T cells are...
Naive T cells are mature T cells that haven't yet seen Ag
Primary immune response...
activation of naive T cells by Ag and differentiation and proliferation into effector cells
Armed effector T cells...
rapidly respond to Ag
Target cells are...
Target cells are cells on which armed effector cells act
Cytotoxic T cells
CD8+ cells kill infected target cells displaying peptides in MHC class I
Costimulatory molecules
surface molecules that synergize with Ag to activate T cell
TH1 cells
subset of CD4+ cells that activate macrophages
TH2 cells
subset of CD4+ cells that stimulate B cells to produce Ab
High Endothelial Venules (HEV)
specialized venules in lymphoid tissue; lymphocytes migrate from blood to LT by attaching to cells in HEV and going between them
T cells must recognize peptides...
presented on MHC molecules
All effector T cells act on...
host cells, not the pathogen
Host cells on which effector cells act are...
target cells
T cells are exposed to Ag in...
secondary/peripheral lymphoid organs (lymph node, spleen, MALT, GALT, BALT)
For the production of armed effector T cells, Ag is phagocytised in the....
tissue by dendritic cells
APCs are distributed differently in the lymph nodes; dendritic cells found mainly in...
cortex
APCs are distributed differently in the lymph nodes; macrophages found mainly in...
the marginal sinus
APCs are distributed differently in the lymph nodes; B cells found mainly in...
germinal centers
The Ag presented by dendritic cells (typically)...
1. Peptides
2. Viral Ags
3. Allergens
The Ag presented by macrophages (typically)...
1. Particulate Ags
2. Intracellular and extracellular pathogens
The Ag presented by B cells (typically)...
1. Soluble Ags
2. Toxins
3. Viruses
Lymphocyte entry into a lymph node from the blood occurs in distinct stages involving the activity of...
adhesion molecules, chemokines, and chemokine receptors
Lymphocytes in the blood enter lymphoid tissue by...
crossing the walls of high endothelial venules (HEV)
Briefly describe the process whereby lymphocytes in the blood enter lymphoid tissue (5)
1. Circulating lymphocyte enters HEV in lymph node
2. L-selectin binding to GlyCAM-1 and CD34 allows rolling interaction
3. LFA-1 is activated by chemokines bound to extracellular matrix
4. Activated LFA-1 binds tightly to ICAM-1
5. Lymphocyte migrates into the lymph node by diapedesis
Lymphocyte migration, activation, and effector function depend on...
cell-cell interactions
Integrins are...
heterodimeric molecules (alpha, beta)
Cell adhesion plays a huge role in...
lymphocyte activation and effector function
Briefly describe the process whereby T cells enter the lymph node and become activated.
1. T cells enter lymph node cortex from the blood via HEV
2. T cells not activated by Ag presented by dendritic cells exit the lymph node via the cortical sinuses
3. T cells activated by Ag presented by dendritic cells start to proliferate and lose the ability to exit the lymph node
4. Activated T cells differentiate to effector cells and exit the lymph node
Cell adhesion molecules are also needed for...
T cell/APC interactions
The initial interaction between T cells and APCs...
may be transient
For clonal expansion of naive T cells, one needs both...
specific Ag and co-stimulatory signals
B7...
CD28
CD28...
B7
What is the difference between a resting T cell and an activated T cell?
Resting T cell:
1. condensed nucleus
2. scant cytoplasm
3. live for many years w/o dividing
Activated T cell (blast cell)
1. expanded nucleus
2. lots of cytoplasm
3. proliferates rapidly
Besides activation by Ag and co-stimulators, T cells need what to divide?
T cells need IL-2 to divide
High affinity IL-2 receptors are...
High affinity IL-2 receptors are 3-chain structures that are present only on activated T cells
An activated T cell will generate a complete IL-2R and also make and use...
IL-2 that it makes
Which parts of the IL-2R are present on resting (naive) T cells?
gamma and beta
Activated T cells secrete and respond to...
IL-2
The attribute that distinguishes Ag recognition by most T cells from recognition by B cells is...
MHC restriction
The potential antigenic diversity of the T cell population is reduced during maturation by a selection process that allows...
only MHC-restricted and nonself-reactive T cells to mature
Activation of mature peripheral T cells begins with...
the interaction of the TCR with an Agic peptide displayed in the groove of an MHC molecule
Activation of mature peripheral T cells leads to...
the proliferation and differentiation of T cells into various types of effector cells and memory T cells
Positive selection
A process that permits the survival of only those T cells whose TCRs recognize self MHC
Negative selection
The induction of death in lymphocytes bearing receptors that react too strongly with self Ags
Which type of selection is an extremely important factor in generating a primary T cell repertoire that is self tolerant?
Negative selection
Thymocytes in early development lack...
CD4 and CD8
Thymocytes that lack CD4 and CD8 are referred to as...
double negative (DN) cells
The most distinctive property of mature T cells is that they...
recognize only foreign Ag combined with self-MHC molecules
What are the two selection processes that thymocytes undergo in the thymus?
Positive and Negative selection;
Positive selection for thymocytes bearing receptors capable of binding self-MHC molecules, which results in MHC restriction. Cells that fail positive selection are eliminated within the thymus by apoptosis.
Negative selection that eliminates thymocytes bearing high-affinity receptors for self-MHC molecules alone or self-Ag presented by self-MHC, which results in self-tolerance.
Approximately what percentage of thymocytes die by apoptosis within the thymus?
~98%
Thymic stromal cells, including epithelial cells, macrophages, and dendritic cells, play essential roles in...
positive and negative selection.
What types of cells play essential roles in positive and negative selection?
1. Thymic stromal cells (including epithelial cells)
2. macrophages
3. dendritic cells
Positive selection ensures...
MHC restriction
Where does positive selection take place?
Positive selection takes place in the cortical region of the thymus and involves the interaction of immature thymocytes with cortical epithelial cells.
During positive selection, only those cells whose.... are selected for survival
During positive selection, only those cells whose ALPHA BETA TCR HETERODIMER RECOGNIZES A SELF-MHC MOLECULE are selected for survival
The absence of class I or II MHC molecules prevents...
positive selection of CD8+ or CD4+ T cells, respectively.
The central event in the generation of both humoral and cell-mediated immune responses is...
the activation and clonal expansion of T cells
T cell activation is initiated by...
interaction of the TCR-CD3 complex with a processed antigenic peptide bound to wither a class I (CD8+ cells) or class II (CD4+ cells) MHC molecule on the surface of an Ag-presenting cell
Signal transduction begins with...
the interaction between a signal and its receptor
Superantigens induce T cell activation by...
binding the TCR and MHC II simultaneously
Activated T cells generate...
effector and memory T cells
Functional TCR genes are produced by rearrangements of... in the alpha chain and gamma chain families and ... in the beta chain and delta chain families.
V and J segments in alpha, gamma
V, D, and J segments in beta, delta