Lymphocyte Activation Flashcards
Which T cell receptors transduce signals
CD3 and zeta-zeta (TcR cannot transduce signals)
Which part of B cell receptor serve as signaling molecules once cell engages antigen?
Igα and Igβ
Initiate early stages of lymphocyte activation by phosphorylation
ITAM (immunorecetpro tyrosine based activation motifs)
Where are ITAMs located?
Cytoplasmic portion of CD3/zeta zeta (T cells) and Igα/ Igβ (B cells)
Location of B and T cell interaction
lymph node
Lymph node is (secondary/primary) lymphatic tissue
secondary
B-cells in lymph node are found in
follicles
T cells in lymph node are found in
parafollicular zone (outside of follicles)
For B-cell initiation, how are antigen brought into lymph nodes?
By lymphatic drain
This cell binds native antigen on its membrane surface for B-cell to bind
Follicular-dendritic cell
How do appropriate T-cells and B-cells interact?
MHCII presentation on B cell; T cell activated by presence of antigen on MHC II
IL-2 receptor
receptor made by T cells in naive state
low affinity IL-2 receptor
Beta and common gamma chain
IL-2
IL-2 synthesized BY T CELL after early stages of interaction will induce creation of alpha chain on receptor. Higher affinity leads to cell division and activation
inducible factors during APC - Tcell interaction
B7 (on APC/Bcell) and CD40L (Th)
CD40L: Where found? Interacts with what?
upregulated on activate T-helper cells, interacts with CD40 on B cells and APCs
CD40L fundamental for induction of
AID (for somatic hypermutation of B cells)
membrane immunoglobins cross-link through presence of
antigen and ITAMs of BCR (phosphorylated to recruit signaling molecules)
How are membrane IgM and IgD assembled with the B cell receptor complex?
non-covalently
CD40
expressed by B-cells and APCs, interact with induced CD40L on T helper cell
CTLA-4
blocks CD28 and interacts with B7 on B cell. Has higher affinity than CD28, inhibits cell from further activation
Used in autoimmune diseases and auto sensitivity designed to block interaction of B7 to T cells
CTLA-4
What are examples of T independent responses regarding B cell activation?
Polysaccharides, lipids, and non protein antigens tend to be T-independent
Upon receiving B cell growth factors and differentiation factors from T cells, B cells can undergo
expansion and differentiation (antibody producing cells)
What initiate interactions of T cells and APCs?
Cell adhesion molecules (Selectins, vascular addressins, integrins, and immunoglobulin superfamily members)
what begins T cell activation?
T-cell receptor engages a specific MHC-peptide complex
T regulatory cell’s key cyotkine
TGF-B
function of T regulatory cell
inhibit immune response
A major co-stimulation signal
CD28 (on surface of naive T cell) and B7 (on professional APC)
Activation of IL-2 gene uses signals delivered from which two things?
TcR and CD28 molecules
Following activation, T cells udnergo a rapid phase of cell division under control of which cytokine?
IL-2; self synthesized and created by T cell, thus controlling their own proliferation
IL-5
can be made by Th2 for eosinophil activation
How does B cell take in a little antigen?
Pinocytosis
Migration is crucial for B cell response. Where do B cells migrate to?
margine of the follicle, can communicate directly with T helper cell that will also migrate to that area from otuside
ITIMS
inhibiting step (I=inhibitory). If already have antibody against an antigen, soluble antibody bound to antigen can bind to Fc gamma RII. Inhibitory, because don’t want to continue activating B cells.
= feedback inhibition to shut off B cells
Primary lymphoid tissues
Bone marrow and thymus
Diagnostic feature of child’s thymus; granule cells surrounded by epithelial cells
Hassall’s corpuscle
A transcription factor that allows expression of tissue specific self-peptides
AIRE (auto immune regulator)
Site in thymus for T-cell positive selection
Cortex (immature thymocytes bind MHC)
Site in thymus for T-cell negative selection
Medulla
What are secondary lymphoid tissue sites and what are some examples
Collection, more organized point for circulating lymphocytes. Spleen (systemic infection), encapsulated lymph nodes (local infection, Peyer’s patches (sm intestine)
Tertiary lymphoid tissues
MALT (mucous associated lymphoid tissue)-inducible; GALT (large intestine); NALT (nasal); BALT (bronchus)
specialized post-capillary venous swellings "bag shaped vessel" function is to control selective entry into the lymph nodes( i.e. Naive T cells)
High endothelial evnule
Which secondary lymphoid tissue lacks HEVs and afferent lypmhatics?
Spleen
Red pulp as diagnostic feature
large numbers of CD8 T cells and plasma cells
Where do stem cells enter the thymus?
Cortico-medullary junction
During involution of the thymus, what replace the functional parenchyma tissue?
CT fibers and fat cells; degenerative process
cortical thymic epithelial cells (cTEC) express what in the thymus?
MHC molecules
Survivors of positive selection in the thymic cortex move where? (Survivors=TcR bind to MHC molecules, prevent cell-death)
Medulla
What do mTEC express? (medullary thymic epithelial cells)
AIRE
List four subsets of T cells produced in thymus
1) CD8+ cytotoxic T cells
2) CD4+ helper T cells
3) Regulator T cells (express FOXP3)
4) gamma delta T cells (just know they exist)
Mature lymphocytes intearct with other immune cells in primary/secondary/tertiary lymphoid tissues
Secondary
B cells and T cells collect in distinct regions of lymph nodes and spleen. What are they?
Within cortex:
T cell area = paracortex
B cell area = primary follicles (homeostasis), germinal centers (infection)
Lymph enters lymph nodes via
Afferent lymphatics (which drain into the capsule)
Lymph leaves the peripheral lymph nodes via
Efferent lymphatics (empty into blood at thoracic duct)
Dendritic cells pick up antigens in
subapical dome
What do peyer’s patches lack?
Do not have afferent lymphatics (also are nonencapsulated)
3 zones of spleen
Red pulp, white pulp (B and T cell compartments), and perifolliculor zone (surrounds B and T cell zones)
What is the marginal zone?
Area in spleen that surrounds the B cell follicles but not the T cell zone
Non-selective entry
spleen, due to lack of HEV
All lymphocytes enter the spleen via
Marginal zone and red pulp
Systemic infection
spleen
local infection
peripheral lymph nodes
Germinal centers are not present in
thymus (present in spleen, lymph node, and malt)
What is the only tissue that contains afferent lymphatics?
Lymph node (not present in thymus, spleen, or MALT)