5 The Organization and Structure of Lymphoid Tissues Flashcards
Site for development of thymic-derived lymphocytes, or T cells
Thymus
The thymus is located in the __________ mediastinum, overlying, in order, the left brachiocephalic (or innominate) vein, the innominate artery, the left common carotid artery, and the trachea.
Superior mediastinum
The thymus receives its blood supply from the
Internal thoracic arteries
Arising from the_____________as an epithelial organ populated by lymphoid cells and endoderm-derived thymic epithelial cells, the thymus develops at about the _________week of gestation.
Third and fourth brachial pouches
Eighth week of gestation
The thymus increases in size through fetal and postnatal life and remains ample into puberty, when it weighs approximately
40 g
Content of thymus:
Cortex:
Medulla:
Corticomedullary junction:
- Cortex: thymocytes (developing immature T cells)
- Medulla: mature thymocytes; tightly packed whorls of squamous-appearing epithelial cells, called thymic or Hassall corpuscles
- Corticomedullary junction: antigen-presenting cells, mostly interdigitating dendritic cells and macrophages
Often have a stellate shape, display desmosomal intercellular connections, and likely function as support cells to developing thymocytes, providing important growth factors such as interleukin-7 (IL-7)
Epithelial cells in the cortex and medulla
After puberty, thymic involution begins within the
Cortex
Glucocorticoids also may induce atrophy of the cortex secondary to glucocorticoid-induced apoptosis of cortical thymocyte
Patients who lack the genes required for thymic development
Patients do not develop T cells and hence have profound immune deficiency
DiGeorge syndrome, or chromosome 22q11.2 deletion syndrome
Found in prothymocytes and immature thymocytes but is absent in mature T cells
Terminal deoxynucleotidyl transferase (TdT)
Positive or Negative
Marrow-derived CD34+ pre-T cells enter the cortex via small blood vessels and are double ___________ for CD4 and CD8 antigens
Double negative for CD4 and CD8 antigens
One of the earliest identifiable T-cell membrane antigens
CD2
Chemokine receptor that directs thymocyte migration to CCL19- and CCL21-producing cells in the thymic medulla, where they undergo further maturation
CCR7
Double-positive (CD4+ and CD8+) thymocytes undergo an initial _________ selection step that is mediated exclusively by thymic _________ epithelium
Positive selection step: thymic cortical epithelium
***Negative selection step: thymic medullary epithelium
These thymic medullary epithelial cells uniquely express this gene
Autoimmune regulatory gene (AIRE)
Disease characterized by chronic mucocutaneous candidiasis, hypoparathyroidism, and adrenal insufficiency
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) or polyglandular autoimmune (PGA) syndrome type I (PGA I)
Have genetic defects in AIRE
WHITE OR RED PULP OF THE SPLEEN
Consists of secondary lymphoid tissue that provides an environment in which the cells of the immune system can interact with one another to mount adaptive immune responses to bloodborne antigens
White pulp
WHITE OR RED PULP OF THE SPLEEN
Contains macrophages that are responsible for clearing the blood of unwanted foreign substances and senescent erythrocytes, even in the absence of specific immunity. Thus, it acts as a filter for the blood
Red pulp
Approximately ______% of individuals have one or more accessory spleens
10%
The commonest location of accessory spleens
Near the hilus of the spleen
The average weight of the spleen in the adult human
135 g (range, 100–250 g)
When emptied of blood it weighs only approximately 80 g
Can be used to estimate splenic volume
Computed tomography (CT) of the abdomen
Sonography
The splenic volume also can be estimated by sonography, which provides good correlation with volumes measured by helical abdominal CT or actual volume displaced by the excised organ.
The stroma is composed of branched, fibroblast-like cells called ________
Reticular cells
Three major types of filtration beds of the spleen
- White pulp
- Marginal zone
- Red pulp
Is composed of cuff of lymphocytes of mostly of T lymphocytes, about two-thirds of which are CD4+ T cells
Periarteriolar lymphoid sheath (PALS)
On gross inspection of the surface of a freshly cut spleen, these follicles appear as white dots referred to as
Malpighian corpuscles
Physiologic substance that can induce fluid extravasation from the splenic circulation into lymphatic reservoirs
Atrial natriuretic peptide, nitric oxide, and adrenomedullin
TRUE OR FALSE
The spleen is the major site of immune responses to bloodborne antigens, but lymph nodes are involved in responses to antigens in the lymph
TRUE
The spleen is the major site of immune responses to bloodborne antigens, but lymph nodes are involved in responses to antigens in the lymph
Chemokines responsible for migration of T and B cells to PALS
T Cells: CCR7 in response to CCL19 and CCL21
B Cells: CXCR5 in response to CXCL13
Are secondary lymphoid tissues (SLT)
The primary sites of immune response to tissue antigens
Lymph nodes
The lymph nodes are round or kidney-shaped clusters of mononuclear cells that normally are less than_______ cm in diameter
1 cm
A collagenous capsule surrounds a typical lymph node and has an indentation called the_________ where blood vessels enter and leave.
Hilus
Lymph nodes originate from a subset of innate lymphoid cells (ILCs) known as
Lymphoid tissue inducer cells (LTis)
**In combination with mesenchymal lymphoid tissue organizer (LTo) cells
The lymph nodes that receive lymph that drains from the skin
Somatic nodes
The lymph nodes that receive their lymph from the mucosal surface of the respiratory, digestive, or genitourinary tract
Visceral nodes
Parts of LN cortical follicle
- B-cell area (cortex)
- T-cell rich area (paracortex)
- Central medulla
Are the specialized sites for the generation of memory B cells and antibody affinity maturation via the process of immunoglobulin variable-region somatic hypermutation
Germinal centers
Follicles without germinal centers
Primary follicles
Consist predominantly of small, mature, recirculating B lymphocytes.
Follicles with germinal centers
Secondary follicles
Contains proliferating B cells and macrophages
The ______________ zones are formed mostly of T cells.
The ratio of T cells to B cells in these zones is approximately_______________
Paracortical zones
Three is to one
Contains scattered B cells, dendritic cells, macrophages, rare NK cells, and, during an immune response, plasma cells
Medulla
Particularly enriched with T cells, forming an area that sometimes is referred to as the thymic-dependent area
Deep cortex
The major T-cell population found within the lymph node consists of _______ T cells.
CD4+ T cells
The T cell–rich paracortex is also relatively enriched with a heterogeneous family of specialized ILCs which are separated into three groups:
- Group 1 : NK cells and ILC1s that are cytolytic and interferon (IFN)-γ–producing cells
- Group 2 : ILC2s that produce IL-5 and IL-13
- Group 3: ILC3s and lymphoid tissue inducer cells that produce IL-17 and IL-22
Lymphocytes primarily enter lymphatic tissues from the blood by migrating across the tall, active endothelium of specialized postcapillary venules called
High endothelial venules
Comprise the largest numbers of cells in the early germinal center
Centroblasts
- B cells undergo affinity maturation within the germinal center.
- Subsequently, centroblasts give rise to smaller B cells, the centrocytes.
- During this process, the genes encoding the surface immunoglobulin of B cells undergo high rates of mutation, called somatic hypermutation
- B cells that express immunoglobulin with little or no affinity for antigen undergo apoptosis. The resulting cellular debris is tingible, or capable of being stained, and is found prominently within macrophages specifically designated tingible body macrophages.
After the release of specific antibody, antigen–antibody complexes may form and become sequestered on the surface of follicular dendritic cells within the germinal centers.
The antigen–antibody complexes produce a coating of small, beadlike, immune complex–coated bodies called
Iccosomes
Are diffusely organized aggregates of lymphocytes that protect the respiratory and gastrointestinal (GI) epithelium
Mucosa-associated lymphoid tissues (MALTs)
The lymphoid aggregates associated with the respiratory epithelium
Bronchial-associated lymphoid tissue
The lymphoid aggregates associated with the intestinal epithelium
Gut-associated lymphoid tissue (GALT)
Lymphocytes in the GALT are located in three main regions:
- Within the epithelial layer
- Scattered through the lamina propria, and
- Clustered in organized collections in the lamina propria
CD4 or CD8
Most intraepithelial lymphocytes in MALT are
CD8+ T cells
The majority of plasma cells in the mucosa of the bronchi and gut contain
IgA
The most important and highly organized lymphoid tissue of the GALT
Peyer patches
Peyer patches are found in the
Lamina propria of the ileum (near the ileocolonic junction)
Antigens from the intestinal epithelium are collected by specialized epithelial cells called
M cells
The tonsils are the major component of the Waldeyer ring of pharyngeal lymphoid tissues.
They are covered by variable epithelial surfaces that have deep, branching depressions called________________.
Crypts