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78 Cards in this Set

  • Front
  • Back
what is special about splenic marginal zone B cells?
they have a repertoire of BCR that is heavily biased toward bacterial cell wall components
what B cells are particularly important for T independent responses?
marginal zone b cells (for encapsulated bacteria)

B-1 B cells (create no memory cells, located at peritoneum and
what is the B cell response to low and high concentrations of type 1 T-independent antigen (i.e. LPS)
at low concnetrations a small amount of MONOCLONAL Ab is produced.

at high concentrations, your innate TLR4 induces secretion of polyclonal B cell antibodies to various Ag of the bacteria
how do B cells get a robust response to type 2 T-independent antigens?
repeated polysaccharides structures are able to cross link multiple BCRs
why are young kids susceptible to infection by encapsulated bacteria?
for whatever reason, they can't mount effects T independent responses to type 2 antigens
what cells secrete the majority of interleukins?
CD4 helper T cells
CD4 T cells only respond to antigen bound to...
MHC class II
what are the MHC gene loci like?
they are polygenic and polymorphic
what cells express MHC I and what cells express MHC II?
MHC I expressed by all cells (any cell is a potential target of a CD8)

MHC II is only expressed by professional Ag-presenting cells (dendritic cells, B cells, macrophages)
which MHC class is important in Tissue transplantation?
MHC class I
(MHC II also helps)
what 2 signals are ABSOLUTELY required for T-cell activation?
1. TCR and peptide:MHC II interaction

2. CD 28 (on T) and CD80/86 (on APC)
what is the concept of linked recognition
the BCR and the TCR must be able to recognize different parts of the same antigen
how does linked recognition happen?
clonally expanded B-cell presents antigen to CD4 T cells on MHC II
what is the germinal center?
a region in 2nd lymphoid organs where B cells are undergoing somatic hypermutation (most die, but a couple are extra sensitive. Those have undergone "affinity maturation")
what are centrocytes?
B cells that have received T cell help and are in the germinal center undergoing somatic hypermutation
what Ab isotype is produced by B cells that have undergone affinity maturation?
IgG
what is the cause of immunodeficiency in nu/nu "nude" mice?
no "whn" gene results in no epithelial differentiation => no thymus develops
what is the cause of immunodeficiency in scid/scid mice?
defect in Ag receptor gene rearrangement. No T or B cells develop in bone marrow
how can you combine nu and scid mice to get normal immune system?
bone marrow from nude mice to scid mice
or
give thymus of scid mice to nude mice
what is teh path of T cells through teh thymus as they mature?
they go from the cortex (immature) and some die as they move inward toward the medulla, where they exit to peripheral lymphoid organs
what are the two regions of the TCR?
2 chains, each with a V-region and a c-region
what is the mature TCR complex?
the TCR associates with CD3 (the signaller)
What formula is good for distention and pain in the epigastrium, due to excess with tidal fever?
Da Chai Hu Tang

Shao Yang and Tai Yang
how does positive selection work/
MHC I and MHC II positive cells in the cortex express all self proteins and present them, those with some affinity mature further
what is the caused of APECED autoimmune disease?
loss of "aire" gene which allows thymic cells to express all self proteins
why is the negative selection pattern reversed in the periphery?
because now you want very high affinity binding to lead to lots of cell signalling, not apoptosis
what happens in the event of low affinity binding of the TCR in the periphery?
it is ignored because you can't count on the T-cell getting exposed to all self antigen in the thymus
what is the main determining factor of the TCR repertoire?
the MHC (because only those TCR that can bind MHC are selected)
what is unique about professional APCs that makes them able to present well to T-cells?
they express MHC I, MHC II, AND costimulatory molecules (CD80,86)
what are the most potent APCs?
dendritic cells
what is the difference between mature dendritic cells and immature dendritic cells?
immature: high phagocytic, low MHC and low co-stim (low CD80 and CD86)

mature: low phagocytic, high MHC and high co-stim (CD80 and CD86
how are endogenous and exogenous antigen different? and how are they presented differently?
endogenous proteins are viral, made by self machinery, expressed on MHC I (to CD8 killler)

exogenous proteins are from phagocytosed microbes, expressed on MHC II (to CD4 helper)
what is the functional difference between Th1 and Th2 CD4 cells?
Th1 promote cellular immunity
Th2 promote humoral immunity
what is the most likely result if your T cells get "signal 1" without "signal 2"
anergy
what are the possibilities for "signal 2" for T cell activation?
B7, CD80 or CD86 can be expressed on teh APC

CD28 is constituitively expressed on T cell
CTLA-4 is very high affinity for B7, is only expressed AFTER activation leading to inactivation
what is the functional difference between B7 (on APC) binding to CD28 (on T cell) versus B7 binding to CTLA-4?
B7:CD28 leads to T cell activation

B7: CTLA-4 inactivates the T cells after the job is done (by reducing IL-2 production)
what cytokine is most important for clonal expansion of activated T-cells?
IL-2 (induces mitosis, and is produced by activated T cells leading to more mitosis)
how is the activation of memory T cells different than naive T cells?
for CD8 memory T cells, signal 2 is NOT required
what cytokines do Th1 CD4 T cells release?
IFN-gamma
TNF
what cytokines do TH2 CD4 T cells release?
IL-4, IL-5, IL-10
what cytokines drive CD4 cells toward Th1 and Th2, respectively
IL-12, IFN-gamma toward Th1

IL-4, IL-10 toward Th2
do CD8 (CTLs) need 2 signals in order to mediate effector function?
no, they only need their antigen on MHC I
what cytosolic proteins are released by CTLs to induce apoptosis?
perforin, granzymes, and Fas ligand
what are SMACs (Supramolecular Adhesion Complex)
the organelles of CTLs line up in the CTL cytoplasm right next to the target cell in order to release and kill it
how do Th1 cells mediate their function?
they express CD40L and bind CD40 on the macrophage to induce killing of phagocytosed microbes
what is the main antinflammatory cytokine?
IL-10
how are Th2 cells partly responsible for some allergic reactions
Th2 cells induce expression of IgE and promote produciton of eosinophils
how are Th1 cells responsible for delayed type hypersensitivity reactions?
they overactivate in response to antigen, not just to macrophages
what are the 4 steps of CTL effector function?
adhesion (via integrins)
granule release (perforin, granzymes)
apoptosis
CTL leaves and roams for other cells to kill
what is the key issue for recognition of tumor cells by CD8 T cells?
if they recognize the altered self proteins and
if they receive signal 2 (B7-CD28)
what is Activation Induced Cell Death (ACID)?
Fas and Fas ligand are upregulated with activation, but the T cell only has a 4-5 day window during which it is resistant to apoptosis
what allows T cells to be resistant to their own Fas and Fas ligand during activation?
the expression of FLIP (fas ligand signal blocker)
what are the cell markers on Regulatory T cells
CD4, CD25, FOXP3
what are the key marker's on NK cells?
CD16 (an Fc receptor), CD56
how do NK cells decide whether or not to kill a cell?
if it doesn't have MHC class I, it kills the cell
what cells have low levels of MHC class I?
virally infected cells, tumor cells
what are the effector mechanisms of NK cells?
perforin and granzymes (just like CD8 T cells)

induction of apoptosis

Antibody dependent cellular cytotoxicity (CD16, an Fc receptor, recognizes IgG Ab)
what are lymphokine activated killer cells?
a type of NK cell that kills with or without MHC class I
what is diapedesis?
movement of leukocytes across blood vessel wall into tissue through an endothelial monolayer
what are the structural similarities of chemokines?
a 4-cysteine motiff, 60-140 motif
what is the main function of induced chemokines vs. constituitive chemokines?
induced: mediating local inflammatory response

constituitive: development, maturation, adaptive immune responses
what type of receptors are chemokine receptors?
they are GPCRs
what are the major classes of chemokines?
CC and CXC (C: cysteine, X: some AA)
what is the function of CCR7 and when is it expressed?
it guides T and B cells to the secondary lymphoid tissue, it is expressed on naive T/B, downregulates after activation
what is the function of CXCR3 and when is it expressed?
guides Th1 cells to sites of inflammation and is expressed after T cell activation
what Selectin:Addressin binding leads to rolling of WBCs on endothelium?
L-selectin on neutrophils binds CD34 on endothelium
what selectin:ligand binding leads to diapedesis in secondary lymphoid tissue of naive lymphocytes
L-selectin binds GlyCAM-1 on HEV
what integrin interaction allows leukocytes to integrate at endothelium
LFA-1 on leukocytes binds ICAMs on endothelium
what interactions result in leukocyte rolling and arrest?
rolling: selectin:addressin
arrest: LFA:ICAM
what is the role of IL-8 in neutrophil diapedesis?
IL-8 secreted by inflamed tissue binds the IL-8R on neutrophils.
binding of IL-8R changes conformation of LFA-1 so it binds ICAM-1 better
what interaction mediates rolling at the HEV?
L-Selectin (lymphocyte)
binds
GlyCAM-1 on HEV
what interactions medate arreset at the HEV?
CCL21 (constituitively expressed chemokine at HEV) is bound by CCR7 on lymphocyte
that induces change in LFA-1
increased affinity for ICAM-1
how is the spleen unique as a lymphoid organ
it is the only lymphoid organ (it is 2ndary) which has no lymphatic ducts. lymphocytes enter and leave directly from blood stream
what triggers an immature dendritic cell to mature?
a danger signal (TLR4) so that the antigen it has taken up is broken down and loaded onto MHC I and II
what changes in mature dendritic cells favor activation of naive CD4 T cells?
increased MHC
increased co-stim
secrete CCL18 (attracts naive T cells)
how do TCR:Ag and BCR:Ag interactions facilitate linked recognition between B and T cells?
binding of each downregulates CCR7 and upregulates CXCR5 which move them toward each other, at the intersection between the B cell follicle and the T cell area
what cells express CD40L and when do they express it?
CD40L is expressed only on CD4 T cells. It is only expressed when activated, otherwise you would have hyperactive macrophages causing lots of tissue damage with their ROS and such
what does IL-8 do?
it acts on NEUTROPHILS increases the affinity of LFA-1 for ICAM