Lymphoid System - Functional Morphology Flashcards
Primary (central) lymphoid organs (2)
Thymus
Bone marrow
Secondary (peripheral) lymphoid organs
Lymph nodes
Spleen
MALT
What is MALT?
Mucosa-associated lymphoid tissue: diffuse system of lymphoid tissue found in the mucosa
- Waldeyer ring (tonsils, adenoids)
- Peyer’s patches (ileum)
- Appendix
The pluripotent stem cell (in bone marrow) undergoes asymmetric division to give rise to…
lymphoid progenitor cells
myeloid progenitor cells
Lymphoid progenitor cells divide into…
precursor B cells (B-lymphoblasts)
precursor T cell (T-lymphoblasts)
Main site of bone marrow biopsy
pelvis
Where is most bone marrow found in adults (site of hemtopoiesis)
Axial skeleton:
- proximal femur
- vertebrae
- pelvis
- skull
- ribs
- sternum
Where do B-lymphoblasts mature?
bone marrow
Main marker expressed by immature B-lymphocytes
CD19
What are naive B cells?
Mature B cells that have not yet been exposed to antigens
Where do most mature B-cells go?
Lymphoid organs (secondary/peripheral)
Where do T-lymphocytes mature?
Thymus (primary/central)
How does the thymus change with age
Children: very large, very active (lots of T cell maturation)
Puberty: Gradual involution, largely replaced by adipose tissue, but still somewhat active
2 regions of the thymus
cortex (outer)
medulla (inner)
3 types of cells in the cortex of the thymus
- cortical epithelial cells
- t-lymphoblasts (TdT+)
- macrophages
functions of cortical epithelial cells (thymus)
- Secrete cytokines
- Act as APCs
- Create a blood-thymus barrier and cortico-medullary barrier
- Cytoreticulum (structural support)
Main marker expressed by immature T-lymphocytes
TdT
4 types of cells in the medulla of the thymus
- More mature T-lymphocytes (TdT-)
- Epithelial cells (form Hassal’s corpuscle, cytoreticulum, cortico-medullary barrier)
- Mature B cells (small population)
Role of Hassal’s corpuscle in the medulla of the thymus
Important for developing regulatory T cells (peripheral tolerance)
Positive selection of T cells (what and where)
Process by which only T cells with functional T-cell receptors (TCRs) that recognize MHC class I or II can survive.
Occurs in the cortex of the thymus
Negative selection of T cells (what and where)
Process that allows survival only of those T cells that do NOT bind self-antigens (central tolerance)
Occurs in the medulla of the thymus
How does expression of CD4 and CD8 change over the maturation process of T cells?
Initially, T-lymphocytes are double negative for CD4 and CD8.
In the cortex (thymus), become double positive for CD4 and CD8.
After positive selection, become single positive either for CD4 or CD8 (still in cortex).
What protein regulates negative selection of T cells?
Aire protein (thymic epithelial cells): expresses tissue-specific proteins to eliminate T cells that bind them as though they were antigens
Where does VDj rearrangement occur for T and B cells?
B cells: bone marrow
T cells: thymus (cortex)
Describe chronologically the sequence of VDJ rearrangements and positive/negative selection (T cell maturation)
- Beta chain VDJ rearrangement
- Positive selection
- Alpha chain VJ rearrangement
- Negative selection
How do naive B and T cells enter the lymph nodes (after leaving the bone marrow/thymus)?
Circulate through bloodstream and enter via high endothelial venules
Lymph nodes are an important source of…
Antibodies (mostly IgM and IgG) produced by plasma cells in the medulla
Afferent vs efferent vessels of lymph nodes - key difference
Afferent: multiple vessels
Efferent: single vessel
What lymphocyte is primarily present in the lymph node cortex?
B cells (naive; await antigens in primary B-follicles)
When stimulated by antigens, B-follicles form…
germinal centers
What lymphocyte is primarily present in the lymph node paracortex?
T cells (enlarges with antigen stimulation, but no follicles or germinal centers)
What part of the lymph node is the site of entry for high endothelial venules (HEVs)?
Paracortex
2 components of lymph node medulla
- Medullary cords: mature B and T cells, plasma cells (post-antigen exposure)
- Medullary sinuses: discontinuous endothelial cells allowing free lymph filtration; contain many macrophages
Journey of lymph in lymph nodes
- Afferent lymphatics bring in the antigens/microbes/tumour cells
- Subcapsular sinuses
- Cortical sinuses expose B and T cells to antigens
- Medullary sinuses are where antibodies are added to the drainage system
- Efferent lymphatics: drain lymph to other more central nodes, then blood
Describe the early primary immune response
Occurs outside the germinal centre, in the paracortex.
* B cell activation in the primary response is independent of T-cells
* Naive B cells are activated to become proliferating B-immunoblasts
* B-immunoblasts are short-lived IgM-secreting plasma cells
* IgM antibodies have a lower affinity for the antigen than the antibodies produced in the secondary response
* Some IgM+ B-immunoblasts migrate to primary B follicles, where they initiate the secondary response
* No memory cells are produced
Describe the secondary immune response
Occurs inside the germinal centres (3-7 days after the antigen is introduced).
* B cell activation is dependent of T cells
* Naive B cells are activated to ultimately become plasma cells and memory cells
* Plasma cells are secrete IgG and are long-lived
* Antibodies produced through this response have a high affinity for the antigen
What cytokines are required for the secondary immune response in germinal centres? (2)
BCL6
CD10
(both GC markers)
What protein is down-regulated in germinal centres during the secondary immune response?
BCL2, an anti-apoptotic protein (down-regulated to facilitate apoptosis)
What are centroblasts? Where are they located?
Centroblasts are rapidly proliferating B lymphocytes in the germinal centres of lymph nodes (light zone of GC)
Centroblasts mature into…
centrocytes
Centrocytes become…
B-immunoblasts that differentiate into memory B cells and plasma cells
Plasma cells of the primary and secondary response
Primary response: IgM short-lived plasma cells
Secondary response: IgA or IgG long-lived plasma cells
Each plasma cell secretes…
- Either kappa OR lambda light chains
- Only one heavy chain (IgA, IgG)
Plasma cells in a lymph node are polyclonal. Explain.
Every lymph node has a mix of kappa and lambda plasma cells.
Functions of the spleen (3)
- Filters blood
- Destroys old RBCs
- Produces antibodies and effector T cells
Describe the structure of the spleen
- Covered by fibrous capsule
- Trabecular carry arteries, veins and nerves entering at the hilum
- On efferent lymphatics exit at the hilum
Unlike lymph nodes, the spleen receives antibodies from blood, not from the lymph
2 regions of splenic parenchyma
- White pulp
- Lymphoid nodules (B cells)
- PALS (T cells) - Red pulp
- Blood-filled sinusoids
- Splenic cords
Describe splenic blood flow
- Trabecular arteries
- Central arterioles
- Penicillar arterioles
- Sheathed capillaries
From there, blood can either enter a closed circulation (splenic sinuses) or open circulation (splenic cords).
What is Waldeyer’s ring?
Ringed arrangement formed by tonsils (lymphatic tissue).
Waldeyer’s ring is a component of MALT.
Where can we find MALT?
- Waldeyer ring (mouth)
- Appendix and Peyer’s patches (intestine)
- “Acquired” MALT in stomach (due to inflammation from H. pylori)
- Tracheo-bronchial tree of respiratory tract
Function of MALT
Defense of internal passages (tracts) against foreign invaders
In addition to being a lymphoid organ, the appendix may….
serve as a reservoir of beneficial bacteria to replenish the depletion that follows diarrheal diseases.
