What is the black arrow pointing at and what is this disease and its characteristics?
The black arrow points out where the lymphocytes have gone past the limits of the capsule, which is suspiciously malignant behavior. Often, they form follicle-like structures within fat outside the lymph node, which are called "pseudo-follicles," because they are formed from proliferating malignant B lymphocytes, not normal primary or secondary follicles that would contain polyclonal B cells, T cells, and dendritic cells. Follicular lymphoma.
What is this an image of?
Normal lymph node
In the disease follicular lymphoma what is the object circled in red referred to as?
What is this within the lymph node?
In a benign, reactive lymph node, germinal centers show polarization.
Besides its abbreviation for hockey fans, what is NHL?
Follicular lymphoma is a type of "Non-Hodgkin lymphoma"
What is the most likely cellular origin of follicular lymphoma?
Follicular lymphoma is a lymphoma of follicle center B- cells
Is there a strongly associated chromosomal translocation with follicular lymphoma?
Yes, a translocation of chromosome 14 & 18 results in over expression of the BCL-2 gene. BCL-2 is strongly anti-apoptotic & a proto-oncogene. Its overexpression promotes follicular precursor & memory B cells to be long lived--allowing for the development of 'second hits' to occur & establish follicular lymphoma.
How does follicular lymphoma differ from a reactive lymph node?
The reactive lymph node has numerous follicles & the medullary sinus is very evident. The reactive lymph node's germinal centers have "polarity." This, seen earlier, is visible at higher power and shows a visible distinction between lighter and darker cells.
Conversely, in the follicular lymphoma lymph node, the "pseudo follicles" encroach on the meduallary area of the lymph node. The pseudo follicles are throughout this lymph node and there is little normal tissue visible. You can visualize the follicular lymphoma extending beyond the capsule: this is a neoplastic process.
What is this and what are the defining characteristics?
Celiac In the abnormal specimen, note the increased magnification, and the black arrow which identifies the muscularis propria. Going any deeper with the biopsy would risk perforation of the bowel. Note the marked absence of villi, giving the mucosal surface a ‘blunted’ appearance. Crypts are still present, when compared to normal, but there is a prominent lymphoid infiltrate (which is responsible for the pathology!).
What is one of the defining lymphocyte characteristics associated with celiac disease?
However, in the abnormal slide, there are abnormally high numbers of lymphocytes in the lamina propria. This is evident under high power. If these sections were stained by immunoperoxidase, one would find a high proportion of activated CD4+ T cells, antigen presenting cells, CD8+ killer T cells and plasma cells.
Celiac disease is multi-symptomatic. What are the causative associations between celiac disease and the blistering skin disease Dermatitis herpetiformis?
Circulating IgA antibodies in the blood mistakenly bind to the transglutaminase in the dermal papillae of the epidermis. When the IgA binds, neutrophils are recruited and they start an inflammatory reaction. This creates a rash on the skin.
What is the clinical significance of villous atrophy in celiac disease?
Villi are responsible for absorption in the small intestine. Thus, villous atrophy disrupts the process of absorption. Malabsorption may lead to a number of symptoms, including diarrhea (failure to absorb water), steatorrhea (failure to absorb fat), and anemia (failure to absorb iron and vitamin B12). Patients may also experience weight loss. The treatment for celiac disease is a gluten-free diet. Most symptoms are resolved with this diet. However, some patients may still experience chronic inflammation and immune activation. Over time, this may lead to small bowel cancer and T cell lymphoma.
Celiac disease is often considered an autoimmune disease. Why? What antigen is the primary cause of the pathogenic immune response?
Celiac disease is often considered an autoimmune disease because gluten triggers the immune system to attack the small intestine. The antigen responsible for the pathogenic immune response is gliadin, a 33 amino acid peptide component of gluten.
What is this an image of?
Lymph node andencarcinoma
What is the rationale behind sentinel lymph node biopsy?
Because lymph nodes don't have a basement membrane, it's easier for tumor cells to invade them as opposed to blood vessels. This makes a lymph node the first place where you'll find metastases, so much so that cancer cells in a lymph node aren't always considered metastatic.
The sentinal nodes are the closest to the primary tumor so they are the most likely to house tumor cells. And if they have tumor cells, then further metastasis is highly likely.
What other tests could be performed to confirm the diagnosis of invasive ductal carcinoma?
Some sort of image guided biopsy.
Fine needle aspiration is generally preferred because it is minimally invasive and can be done quickly but it does not distinguish between in situ and invasive cancers.
Core needle biopsy can usually diagnose between invasive and in situ ductal carcinoma. Preferred imaging guidance is stereotactic (prone patient, specific machine) but tomosynthesis can also be used (basically 3-D mammography).
Lymph nodes are the site of initiation of immune reactions, and a primary function of the immune system is tumor surveillance. Would there be an immune response to cancer cells that lodge in a lymph node? Why or why not?
There might be an immune response. Cancer cells replicate very quickly and tend to accrue DNA damage, if that damage results in decreased expression of MHC I or any other deactivating receptors/ligands that regulate NK activity, then the NK cells will react to and kill the tumor cell via perforin. Eliminating MHC I is kind of preferential for tumor cell survival because it prevents T cells from identifying them and mounting an immune response.
What is this an image of? How would you describe it?
The thymus is the site at which T cell progenitors from the bone marrow become “educated”, learning to distinguish self from non-self. It is located in the upper mediastinum anterior to the heart. It is encapsulated and bi-lobed; each lobe is further sub-divided into lobules by connective tissue septa. The thymus is prominent in childhood and, at puberty, involutes.
Why are there no germinal centers in the thymus?
The thymus is the site of T-cell maturation/education, while germinal centers are where the germinal reaction between B and T-cells occurs in order to activate B-cells place. This occurs in peripheral lymphoid organs not the thymus, as such the thymus lacks germinal centers.
What is this an image of?
What is this an image of and structures are delineated by the yellow arrows and encircled in yellow?
Hassall's Corpuscle and adipose tissue
What are T reg cells? What is their function?
T reg cells (regulatory T cells) develop in the thymus or peripheral tissues after recognizing self antigens and suppress the activation of potentially harmful lymphocytes specific for these self antigens . Most T reg cells are CD4 +, have high levels of CD25 (alpha chain of IL-2 receptor), and express transcription factor FoxP3.
What constitutes the blood-thymus-barrier?
The blood thymus barrier consists of capillary endothelium, epithelia reticular cells, and macrophages within the perivascular connective tissue.
Which cells present antigen in the thymus during development?
Thymic epithelial cells (TECs): present self-Ags on MHC to thymocytes; this helps promote self-tolerance
Within the lymph node what is the black and blue arrows pointing to?
Immediately below the sub-capsular sinus (black arrow) is the cortex, which stains more darkly than the deeper and more central medulla. The trabecular sinus branches off the sub-capsular sinus (blue arrow).
What is this an image of?
This benign, hyperplastic lymphnode stained with CD20 (a pan-B cell marker) and CD3 for T cells. On the H&E-stained section, you can appreciate that the number and size of follicles has expanded, to include the medullary area, when compared with the normal Lymph Node. Germinal centers are distinguished by several distinct zones: the mantle zone is a ring of immature B cells (See also Fig. 13-3 and Fig. 13-12, Robbins and Cotran, 9th Edition) the germinal center itself contains actively proliferating and differentiating B cells, which are easily demonstrated here by the pan-B cell CD20 immunostain. Dendritic and T cells are also present within the follicle center, although they are less abundant than the B cells (see below). Once these B cells have fully differentiated, they are then called plasma cells, and begin to secrete copious quantities of antibodies, and assume a position in the paracortex or medulla of the lymph node.
What is circled in this picture?
The limits of this follicle are outlined by a blue line. Notice that CD3+ cells (a pan-T cell marker) stain occasional cells within the follicle center, as mentioned above, but the majority of positively-stained T cells are located in the paracortical (deep cortex) area, surrounding the approximate limits of the follicle.
What are selectins and addressins? What is their role in lymphocyte homing?
Selectins and addressins are adhesion proteins. Addressins are displayed on the endothelial wall of blood vessels and will interact with the selectin . They are important in leukocyte adherence to sites of infection
What are the interactions that allow lymphocytes to exit the bloodstream?
autotaxin- allows lymphocytes to enter secondary lymph nodes from HEV
What are the most common organisms that cause reactive (inflammatory) lymphadenitis?
Group A Streptococcus, EBV, cytomegalovirus (can be viral, bacterial, or fungal)
Which cells would one find in the cortex and medulla of the lymph node?
within the cortex you would find mainly B cells
Within the medulla you would find a mix of cells including plasma cells and macrophages
Where do plasma cells reside? Do they enter the circulation?
they reside within the paracortex (Short lived plasma cells with no affinity maturation or class switching, initial burst of IgM) or the medulla, only the antibodies they produce will enter circulation.
Some memory plasma cells will migrate to the bone marrow. Exit the LN via efferent lymphatics
What are the yellow arrows and what are they in?
These are high endothelial venules of tonsil
What is the function of HEVs?
HEVs enable lymphocytes to enter lymph nodes directly from the blood. They are found in secondary lymphoid tissues.
What is this?
The epithelial edge of the pharyngeal tonsil
What is the distinguishing feature of pharyngeal versus palatine tonsils?
The distinguishing feature is the type of epithelium lining the surface of the tonsil's crypt. The palatine tonsil is associated with alimentary epithelium, and therefore will have stratified squamous epithelium. The pharyngeal tonsil is associated with respiratory epithelium, and therefore will have ciliated pseudostratified columnar epithelium.
Are there afferent lymphatics in the tonsils?
There are no afferent lymphatics in the tonsils. Instead, the crypts function in delivery of the antigen to lymphoid tissue.
Where are the lingual tonsils located?
Lingual tonsils are located within the base of the tongue.
Stratified squamous epithelium is on what tonsil?
ciliated pseudostratified columnar epithelium is on what tonsil?
What is this an image of?
What are the function of the tonsillar crypts?
function in delivery of antigen to the lymphoid tissue
What are SALT, BALT, MALT, GALT?
MALT: Mucosa-associated lymphatic tissue, populated by lymphocytes (B and T cells, plasma cells, and macrophages), regulates mucosal immunity.
SALT: skin-associated lymphoid tissue, associated with the dermis and epidermis. Includes Langerhans cells and resident phagocytes, keratinocytes.
BALT: bronchus-associated lymphoid tissue, aggregations of B and T lymphocytes in the lower respiratory tract.
GALT: gut-associated lymphoid tissue, aggregations of mucosal-associated lymphoid tissue in the GI tract, including adenoids, tonsils, Peyer's patches, and lamina propria of the intestine. Responsible for a local immune response to antigens.
What is this an image of and what is important about it?
The spleen is distinguished by two types of tissue: red pulp and white pulp, both of which are located throughout the spleen. White pulp is the lymphoid component, and consists of the central artery with its surrounding peri-arteriolar lymphoid sheath (PALS), which contains T cells, and lymphoid follicles, many of which contain germinal centers. Follicles contain an outermost marginal zone, consisting of T cell-independent B cells (these cells are activated directly by antigen), a mantle zone, consisting of T cell-dependent resting B cells (these cells, like those in the lymph nodes, require T cell help for differentiation), and a germinal center, which consists of marginal zone-derived B cells that have been activated and are proliferating and differentiating into antibody-secreting plasma cells.
What is PALS? Why is it significant?
PALS: peri-arteriolar lymphoid sheath; Part of the white pulp in the spleen that surrounds the central artery
It's a T-dependent region (site where T cells seed after educated in thymus)
What is labeled with the R, the chiefs arrowhead, and the yellow arrow?
R - Red pulp
KC Chiefs - Trabeculae
Arrow - PALS
What is the significance of an open circulation?
Open circulation gives macrophages access to RBCs
Macrophages can then destroy old or damaged RBCs --> heme recycling
Macrophages can also remove particulates in circulation and screen for macromolecular antigens
How is the spleen affected in sickle cell disease?
Many patients with sickle cell disease can be considered to be functionally asplenic beginning in early childhood, owing to the repetitive RBC sickling and subsequent infarctions within the spleen because of its activity in filtering blood. This is caused by sickled RBCs blocking capillaries in the spleen due to slow blood flow and low oxygen tension in the spleen
What is an autosplenectomy?
An autosplenectomy occurs when a disease damages the spleen to such an extent that it is non-functioning and so equivalent to the spleen having been surgically removed.
May occur in sickle-cell disease and spherocytosis when abnormal RBCs repeatedly block off small blood vessels, causing infarction of parts of the spleen.
Why are encapsulated bacterial infections prevalent in individuals with sickle cell disease?
Lack of the spleen caused by autosplenectomy observed in sickle cell sufferers does not allow for the clearing of encapsulated bacteria.
If the spleen is non functional as a result of sickle cell, the marginal zone, which is unique to the spleen and an area rich in macrophages is rendered ineffective. Marginal B-cells are important against pathogens that enter the blood, especially against blood borne encapsulated bacteria, because these bacteria are not able to be presented by MHCII. This requires the T-independent activation of marginal b-cells found in the spleen and their subsequent IgM and IgG2 production against antigens.
What is this?