Lymphoid Tissues Flashcards
1
Q
Lymphoid tissues and organs
A
Primary: where lymphocytes develop (bone marrow and thymus)
Secondary: where adaptive immune responses initiated and lymphocytes maintained (lymph nodes, spleen, mucosa associated lymphoid tissue)
2
Q
Primary lymphoid organs
A
- main site of haematopoiesis
- haematopoietic stem cells are precursors of immune cells
- B and T cells are major components of lymphoid tissues and organs
- B cells mature in bone marrow and are released to circulation
- T cells mature in the thymus
3
Q
T cell maturation
A
- occurs in thymus
- T cell precursors travel from the bone marrow to develop in the thymus
- mature T cells travel to secondary lymphoid tissues
4
Q
Cellular Organisation of Thymus
A
- lots of positive deselection as some T cells don’t have functional intact receptors
- bi-lobed organ
- lobules separated by connective tissue
- each lobe has a inner Medulla and outer Cortex
- Cortex: immature thymocytes, epithelial cells, macrophages
- Medulla: mature thymocytes, epithelial cells, dendritic cells, macrophages
- epithelial cells produce IL-7 (survival cytokine)
- Hassall’s corpuscles thought to be sites of cell destruction
5
Q
T cell production
A
- in thymus is maximal at birth and decreases with age
- establishes reservoir of T cells that are long living early in life
- with age T cell producing tissue is replaced by fatty tissue
- T cell immunity not greatly impaired with age though
- Thymus is therefore important in establishing a repertoire of functional T cells in the body that are long-lived and self-renewing
6
Q
Cluster of Differentiation
A
- different cells express cell surface molecules specific to that cell
- cell surface molecules given a cluster of differentiation number
- antibodies to these cell surface markers can be used to phenotype cells and to purify them
7
Q
Examples of CD
A
- leukocytes express CD45 (tyrosine phosphatase)
- T cells express CD3 (signalling complex)
- helper T cells generally express the CD4 accessory molecule as well
- cytotoxic T cells express the CD8 accessory molecule and CD3
8
Q
Mature T cells
A
- cells arrive in the thymus as uncommitted progenitors with SC characteristics
- interact with stromal cells and commit to T cell lineage
- express surface markers characteristic of T cell lineage
- rearrange T cell receptor genes
- no expression of either CD4/CD8
- need IL7 and Notch1 signals for development
- mature T cells express either aB or y-gamma T cell receptors
- if cells fail to rearrange their genes to express a T cell receptor they die by apoptosis
- during development thymocytes change from CD4-CD8- to CD4+CD8+ (double positive)
- T cells become either helper or cytotoxic cells and leave the thymus
9
Q
Positive and Negative Selection
A
Outer Cortex
- tightly packed with cells
- immature proliferating thymic lymphocytes
- site of positive selection of cells that have rearranged a functional T cell receptor
Inner Medulla
- loosely packed with cells
- mature thymocytes
- site of negative selection
- key for thymic education whereby thymocytes learn to interact correctly with self-MHC molecules (ie. bind correctly)
- most fail to do and die via apoptosis
10
Q
Positive Selection
A
- thymocytes with TCR binding to a self MHC molecule on cortical epithelial cells or macrophages are signaled to survive
- those not binding to MHC molecules die
- CD8 interacts with class 1 MHC (universal) and CD4 with class 2 MHC (made by APC in immune system)
- interaction of the TCR with either class1/2 MHC leads to a single positive thymocyte expressing either CD8/CD4
11
Q
Negative Selection
A
- removes T cells which bind too strongly to MHC+ self peptides
- prevent an auto-immune response
- MHC presents fragments of inside cells constantly that usually are self but sometimes can be pathogenic
- antigen presentation by several cell types takes place in medulla
- removes autoreactive T cells which otherwise cause tissue damage and autoimmune disease
- this is central tolerance
12
Q
T cell development Steps
A
- double negative CD3- thymocytes in the subcapsular zone
- positive selection: double positive CD3+ in thymic cortex
- negative selection: double positive CD3+ thymocytes throughout cortex
- entry to circulation of mature, self-restricted, self tolerant, single positive CD4 or CD8 T cells leave the thymus in blood venules
13
Q
Secondary lymphoid organs
A
- peripheral
- once B/T cells have developed they enter bloodstream and migrate to peripheral lymphoid organs
- site of lymphocyte activation by antigen
- provide signals to sustain re-circulating lymphocytes
- lymphocytes re-circulate between blood and peripheral lymphoid organs until meet specific antigen
1. naive lymphocytes enter lymph nodes from blood
2. node is site of activation: antigen reach nodes via lymphatics (if recognition then lymphocytes recognise antigen)
3. lymphocytes and lymph return to blood via thoracic duct
14
Q
Lymph Nodes
A
- encapsulated bean structure
- clustered at junctions of lymphatic vessels
- filter and trap antigen from lymph
- nodes consist of cortex (B cell area) and paracortex (T cell area) and the medulla
15
Q
Dendritic Cells
A
- take antigens at site of infection and wounding and carry them to draining lymph nodes for T cell presentation
- dendritic cells bearing antigen entering draining lymph node where they settle in T cell areas
16
Q
Naive lymphocytes rolling
A
- circulating T cell enters the high endothelial venule in the lymph node
- binding of L-selectin to GlyCAM-1 and CD34 allows rolling interaction
- LFA-1 is activated by chemokines bound to extracellular matrix
- activated LFA-1 binds tightly to ICAM-1 and stops rolling (selectins allow lymphocyte rolling to slow them down)
- diapedesis - lymphocyte leaves blood and enter lymph node
17
Q
Naive Lymphocytes Activation
A
- naive lymphocytes enter lymph nodes from bloodstream at HEV
- T and B cell zones for activation and development
- T cells meet dendritic cells and macrophages which present antigen
- if the T cell does not recognise antigen, leaves node by efferent lymphatic and recirculates
- if it recognises antigen, activated to proliferate and differentiate
- leaves as effector T cells
18
Q
Lymphoid Follicles
A
- sites of B cell activation by specialised follicular dendritic cells
- all secondary lymphoid organs contain lymphoid follicles (loose network of follicular dendritic cells in region rich in B cell)
- FDCs are not conventional DCs - FDCs display antigen to B cells
- pathogens opsonised by Abs and complement are delivered to secondary lymphoid organs where they are captured by FDCs which have receptors for complement and Abs
- FDCs display antigen on the surface in a stable long lived manner
- B cells with receptors cross linked by antigen coating the FDCs proliferate to form germinal centers
- some B cells differentiate immediately into plasma cells which secrete Ab and leave node
- others stay in germinal center and differentiate further into memory B cells
19
Q
Spleen
A
- largest secondary lymphoid organ
- filters the blood with 2 major functions
- major site of lymphocyte activation
Red: removes old red blood cells and recycles iron
White: defends against blood-borne pathogens ‘systematic lymph nodes’ - T cell areas (periarteriolar lymphoid sheath) and B cell areas (primary lymphoid follicles and germinal centers)
20
Q
Spleen Lymphocyte Structure
A
- similar to lymph nodes
- specific aggregations of T and B cell activation
T cells in the PALS and B cells in the corona/germinal center
21
Q
Mucosal Tissue
A
- most secondary lymphoid tissue associated with mucosal tissue
- most infection occurs through respiratory, gastrointestinal and urogenital tracts
- mucosal associated lymphoid tissue protects these mucosal surfaces (such as Peyers patches in intestinal lining)
22
Q
Peyer’s Patche
A
- gut associated lymphoid tissue
- gut lined with Peyer’s patches (specialised lymph nodes)
- specialised epithelial M cells transport antigens into the lymphoid tissue
- lymphocytes enter via capillaries and leave via efferent lymphatic vessels
- dendritic cells in the Peyer’s patch take up the antigen from M cells and present to the B cells in the germinal center
