Mar22 M1-Functional Morphology Lymphoid Flashcards
primary or central lymphoid organs
bone marrow and thymus
secondary or peripheral lymphoid organs
lymph nodes, spleen, GI mucosa, MALT (mouth, GIT except stomach, tonsils, etc.)
where are lymphoid cells come from + 3 steps that happen there (4 Ps)
bone marrow: pluripotential stem cells to progenitor (lymphoid) cells (lymphoid, myeloid and erythroid progenitor) to precursor B or T lymphoblasts. 4th P is for pelvis, site of BM bx
what B-lymphoblasts do
in the BM, mature into naive B cells that then go to peripheral lymphoid organs
what T-lymphoblasts do
from BM, go the thymus and mature there. then go to peripheral lymphoid organs
B and T lymphoblasts def
precursors in the marrow and the thymus (T lymphoblasts start in BM then move to thymus)
centroblasts def
mature B cells in the germinal center of lymph nodes
B and T immunoblasts def
cells that, after exposure to Ag, give rise to plasma cells and B memory cells (from B immunoblasts, includes naive B cells?) and T memory cells (from T immunoblasts)
important role of germinal center
in B cell response, important for a lasting Ab production.
charact of cells in the germinal center
very actively proliferating with many mutations (fertile bed for development of malignancy). bc of role of lasting Ab production
acquired immune deficiency examples and one consequence
- HIV
- post transplant immunosuppression
- predisposes to malignancy
important concept in immune and blood malignancies
each malignancy has a normal cell counterpart
what cells give rise to naive (but MATURE) B cells (CD20+)
B-lymphoblasts (precursors) (are hematogones, meaning normal round cells)
naive mature B cells location in the body
- FEW in marrow and blood
- MANY migrate to secondary peripheral lymphoid organs via blood stream
lymphoblasts function (important thing they do)
undergo VDJ rearrangerements to generate a repertoire of Igs
2 functions of the thymus
- maturation and selection of T lymphoblasts (mature naive T cells)
- induction of central tolerance by regulatory T cells to prevent autoimmunity
T-lymphoblasts where they go in the thymus
from BM, go to thymic epithelial space. there, proliferate with the help of thymic epithelial cells
2 spaces of the thymus
- central lymphoid space
- peripheral perivascular space
2 components of the central lymphoid space of the thymus and their cells
- cortex: 1.large cortical epithelial cells 2. macrophages 3. T-lymphoblasts
- medulla: 1. small mature appearing lymphocytes (mature) 2. epithelial cells 3. mature B cells
function of the large cortical epithelial cells in the cortex (thymus)
APCs secreting cytokines. have desmosomes and form cortico-medullary barrier.
function of the macrophages in the cortex (thymus)
APCs. phagocytosis of apoptotic cells
function of T-lymphoblasts in the cortex (thymus) and 2 other names
T-lymphoblast = thymocytes = precursor T-cells
*fct = make mature naive T cells.
(thymocytes are initially double negative then double positive CD4+ CD8+)
function of small mature appearing lymphocytes of the medulla (thymus)
T cell immunophenotype (TdT-, CD3+, CD4 or CD8+)
function of epithelial cells in the medulla (thymus)
small, spindle-shaped, form *Hassall’s corpuscules
function of mature B cells in medulla (thymus)
associated with epithelial cells + may play role in T-cell differentiation.
steps of T cells selection
- CORTEX: POSITIVE selection: only T cells with functional TCRs that see MHC 1 and 2 are kept
- MEDULLA: NEGATIVE selection: only T cells that DON’T bind tightly to self-Ags are kept
peripheral perivascular space of the thymus: cells there
mature naive T lymphocytes that travel to lymph nodes and other peripheral lymphoid sites and blood
compartments of the lymph node (4)
- cortex: contains many B follicles (inner germinal center and outer mantle zone) separated by interfollicular areas
- paracortex (between cortex and medulla)
- medulla = where lymph flows
- subcapsular sinus (around the cortex) = 1st place of metastasis in metastatic CA
other name for mantle zones (outer B follicle)
B zone
2 lymph node stages and how it relates to B follicles
quiescent node = no Ag stim
with Ag stim, mantle zone (naive B cells) forms the germinal center (naive B cells)
cells in follicles, germinal centers
- B-lymphocytes in various stages of activation (centrocytes, centroblasts). naive B cells is if didn’t see Ag
- helper CD4+ T cells
- follicular dendritic cells (APCs)
- macrophages (tangible body macrophages) (phagocytosis of B cells with low Ag affinity)
cells in the lymph node paracortex
- T cells in various stages of activation MOSTLY
2. interdigitating dendritic cells (APCs)
high endothelial venules of the lymph node: location and fct
- specialized entry points for blood lymphocytes coming from BM and thymus
- venules entering lymph node at level of the T cell zone which is in the middle of the lymph node
cells in high endothelial venules
lot of endothelial cells
compartments (and their cells) of the lymph node medulla
- medullary cords (B and T cells + plasma cells)
- medullary sinuses (many macrophages for filtration + lined by endoth cells)
2 compartments of the germinal center and their cell types
- dark zone (centroblasts: B cells rapidly proliferating and mutating their Ig. Bc immune resp started, lymph node stopped being quiescent, germinal center being made)
- light zone (centrocytes: centroblasts that STOPPED proliferating and that are subject to selection by follicular helper T cells with help of follicular dendritic cells)
marginal zone of the lymph node (near germinal center): cells in there
immunoblasts (large cells giving rise to plasma and memory c) + plasma + memory B cells
PRIMARY immune response location in lymph node + cells
- paracortex (OUTSIDE GC)
- T cells activate naive B cells, form proliferating B-immunoblasts, short lived IgM plasma cells + NO memory cells
- Some IgM+ immunoblasts go to PRIMARY B follicle to initiate 2ndary resp
SECONDARY immune response location in lymph node + cells
- GC
- T cell activ of naive B cells, make proliferating centroblasts, then centrocytes then immunoblasts then these make long-lived IgG plasma cells + memory cells
4 steps of GC reaction to Ag
- proliferation
- somatic hypermutation of Ig V region genes to increase affinity of Ab for Ag
- Selection
4 Differentiation
proliferation step of GC reaction to Ag
B centroblasts proliferate a lot. dark zone.
- apoptosis by macrophages
- BCL2 (anti-apoptotic gene) inactivated
selection step (3) step of GC reaction to Ag
centroblasts to centrocytes in light zone of GC. class switch to IgA or IgG. apoptosis of low affinity ones. (GC T cells check that)
differentiation step (4) of GC reaction to Ag
immunoblasts (from centrocytes) form plasma and memory cells
location of B-immunoblasts, plasma cells and memory cells after differentiation step
in marginal zone, OUTSIDE of GC
origin of plasma cells
primary immune response = from naive B cells, in paracortex (short-lived, IgM)
secondary response = from immunoblasts, in light zone of GC
locations of plasma cells
- paracortex and GC light zone
- move to lymph node medulla, BONE MARROW and other sites
function of plasma cells
secrete one specific Ab with one light chain (kappa or lambda) and one heavy chain type
IHC profile of plasma cells
POSITIVE: CD27++ (also, memory cells are +), CD138+, CD78, IL-6 R
NEGATIVE: CD19, CD20***
IHC profile of plasma cells
POSITIVE: CD27++ (also, memory cells are +), CD138+, CD78, IL-6 R
NEGATIVE: CD19, CD20***
2 main compartments of the spleen
white pulp (20%) and red pulp (80%)
structure of the white pulp
- lymphoid nodules
- periarteriolar lymphoid sheaths (PALS)
structure of the red pulp
- blood filled sinusoids
- splenic cords
lymphoid nodules of the white pulp description
mantle zone + margina zone (plasma + memory) around. if active bc exposed to Ag, GC in middle of mantle zone
splenic blood flow (red pulp function)
- to feed areas of immune cells
- central arteriole to penicillar arteriole to sheathed capillaries
2 circulations in splenic red pulp, blood flow
- closed circulation via splenic sinuses
- open circulation through splenic cords and reenter via walls of the sinuses
goal of open circulation in spleen red pulp
circulation in reticular fibers and splenic cords = trap red cells that can’t get through or that aren’t in good shape
tissues that form or contain MALT
- Waldeyer ring in the whole pharyngeum (naso and oropharynx, tonsils, adenoids)
- GIT (SI and colon. appendix. Peyer patches in ileum)
- tracheobronchial tree
- acquired MALT in stomach or site of chronic inflam
MALT (Peyer’s patches for example) structure
marginal zone, mantle zone and ALWAYS HAVE A GERMINAL CENTER (bc always see Ags and always activated)
MALT function
- defense of internal passages against foreign Ags
- mainly IgA
- secondary immune response to microbes in oral cavity, gut, etc.
- appendix = lymphoid + may serve as reservoir of beneficial bacteria for replenishing after diarrhea
