Lymph

Question 0

Hierarchy of lymphatic drainage structures:

Answer 0

tissues -> lym. capillaries -> lym. vessels -> rt. lym. duct (upper right quadrant of body) or thoracic duct (rest of body) -> subclavian veins

Question 1

What are the encapsulated organs of the lymphatic system?

Answer 1

lymph nodes, thymus, spleen

Question 2

What are some morphological differences between lymphatics and blood vessels?

Answer 2

lymphatics: thinner walls, more valves, never fenestrated

Question 3

What is lymphedema (elephantitis)? Primary vs. secondary? When is it most commonly seen?

Answer 3

Lymph flow blockage causing a buildup of lymph. Inherited (1º) or caused by injury/disease (2º). Most commonly seen in people who received cancer treatments that damage the lymphatic system – lymph node dissection, surgery, radiation therapy

Question 4

Filariasis:
Cellulitis:

Answer 4

Filariasis: tropical parasitic infection, common cause of secondary lymphedema. nematodes colonize the lymphatic system, blocking flow
Cellulitis: inflammation/infection of the lymphatic system, lower skin layers

Question 5

Acute lymphangitis:

Answer 5

Lymph vessel inflammation. Bacteria enter lymphatic system, multiply, travel through lymphatic vessels -> vessel inflammation (red streaks visible below the skin surface). Rampant bacterial growth too much for immune system -> local and systemic tissue destruction -> abscess formation, cellulitis, septicemia

Question 6

Innate immune system cells:

Adaptive immune system cells:

Answer 6

Innate: Neutrophils, macrophages, natural killer (NK) cells
Adaptive: T cells, B cells, antigen-presenting cells (APC)

Question 7

Where are T cells and B cells generated? Where do they mature? What do they do?

Answer 7

B cells: generated and mature in bone marrow (bursa), produce antibodies, humoral immune response. -Plasma cells, Memory B cells
T cells: generated in marrow, mature in thymus, cell-mediated immune response. -Cytotoxic (Killer), Helper, Suppressor, Memory T cells

Question 8

Which part of the immune system is nonspecific? What is it composed of?

Answer 8

Innate.

1. Complement: group of proteins that combine with an antigen-antibody complex and cause lysis of foreign cells
2. Macrophages and neutrophils: phagocytose invaders
3. Natural killer (NK) cells: kill tumor cells and virally-infected cells, bacteria, and parasites

Question 9

The ____ immune system eliminates threats from specific invaders.
What distinctive properties does it exhibit?

Answer 9

adaptive: reacts against one specific part of a pathogen (an antigen) and improves over time
1. specificity
2. diversity
3. memory
4. self/non-self recognition

Question 10

How do the cells of the adaptive immune response communicate with each other?

Answer 10

cytokines (signaling molecules released in response to encounters with antigens)

Question 11

What are the primary and secondary lymphatic organs and what do they do?

Answer 11

Primary: thymus, bone marrow, fetal liver - Lymphocyte development and maturation into mature immunocompetent cells

Secondary (distributions of mature lymphoid cells): lymph nodes, spleen, mucosa-associated lymphoid tissues (MALT), postnatal bone marrow - Create the environment for immunocompetent cells to interact with each other, with antigens, and with other cells to mount an immune response against invading pathogens

Question 12

What are the main responsibilities of the thymus?

Answer 12

1. Immunological competence of T cells

2. Elimination of self-reactive T cells (i.e. establishing and maintaining self-tolerance)

Question 13

Pathway taken by thymocytes to become immunocompetent:

Answer 13

bone marrow » circulating blood » corticomedullary junction of thymus » cortex (progressively deeper with maturation) » medulla (become immunocompetent) » venules/efferent lymphatic vessels » secondary lymphatic organs

Question 14

Hassall’s corpuscles are characteristic of what structure?

Answer 14

thymic medulla

Question 15

Steps involved in thymic instruction of T cells:

Answer 15

1. Maturation: stimulated by hormones produced by epithelial reticular cells
2. Testing their ability to recognize HLA I/II molecules AND self epitopes: mediated by type II/III epithelial reticular cells and bone marrow dendritic APCs.

Question 16

What is the purpose of the blood-thymus barrier and where is it located? How is T-cell instruction accomplished?

Answer 16

Shields thymocytes from foreign antigens and blood-borne macromolecules – in the cortex of the thymus.
Blood vessels enter trabeculae in the corticomedullary junction and create capillary beds that penetrate the cortex, allowing self-macromolecules to cross and participate in T-cell education and self-tolerance

Question 17

Encountering ____ in the thymus is necessary for T cell education and is required for rescue from ___/___ (this is known as “______ selection”). BUT, if rescued T cells have receptors with too ___ an affinity for ____ antigens, this is bad and they need to be removed (“_____ selection”).

Answer 17

self-HLA, apoptosis/anergy, positive; high, self, negative

Question 18

What is the relationship between diabetes and thymic instruction?

Answer 18

there is a lack of positive selection of regulatory T cells, and a lack of negative selection of autoreactive CD4+ T cells

Question 19

What is thymic involution and how is it clinically relevant?

Answer 19

shrinking of the thymus with age, (not linked with senescence, as it starts happening from birth – why it happens is still a mystery), possible explanation for the reduction in immunosurveillance seen in the elderly.

Question 20

Which cells undergo V(D)J recombination? What purpose does it serve? Where does this take place?

Answer 20

T and B cells, but not natural killer cells; diversified T and B cell receptors (TCR, BCR) capable of recognising a wide range of pathogen epitopes.

B cells: bone marrow.
T cells: thymus (thymocytes migrate from bone marrow)

Question 21

Which lymphatic organs are completely surrounded by a connective tissue capsule?

Answer 21

lymph nodes, thymus, spleen (the “encapsulated” lymphatic organs)

Question 22

What are parenchymal cells of lymph nodes?

Answer 22

T cells, B cells, APCs, macrophages

Question 23

Elaborate on the two major functions of lymph nodes.

Answer 23

1) Lymph filtration
•Resident macrophages in the sinuses remove bacteria and foreign substances

2) Antigen presentation and recognition
•APCs that contact antigens migrate to the nearest lymph node and present their epitope-MHC complex to lymphocytes

Question 24

The lymph node capsule and trabeculae suspend the _______ that forms the architectural framework of the node.

Answer 24

reticular fiber network

Question 25

Details of B cell and T cell migration pathway in lymph nodes:

Answer 25

-Both enter paracortex of lymph node from high endothelial venules B cells: migrate to cortex (1° lymphoid nodules) •When presented with MHC-epitope complex, they proliferate and form 2° lymphoid nodules •New memory/plasma B cells exit 2° lymphoid nodules •The majority of B cells migrate to the medulla and form the medullary cords •Then they migrate to the medullary sinuses and exit via efferent lymphatic vessels •Plasma cells » bone marrow, make antibodies •Memory B cells » other 2° lymphatic organs T cells: stay in the paracortex •When Th cells are activated they proliferate and expand the paracortex depth (swollen lymph nodes in infection) •New Th cells exit the paracortex •Then they migrate to the medullary sinuses and exit via efferent lymphatic vessels

Question 26

What are the two morphologically distinct areas of secondary lymphoid nodules? What is occuring in each of them?

Answer 26

Mantle zone (corona): dense accumulation of B cells migrating out of the germinal center ``` Germinal center: B cells (centroblasts) proliferate, migrate, express secretory immunoglobulins (sIgs), switch Ig class, and are exposed to antigen-bearing follicular dendritic cells. B cells (centrocytes) that do not synthesize the proper sIgs » apoptosis/phagocytosis. Surviving cells exit the 2° nodule as memory B cells or plasma cells (and migrate to the medullary sinuses) *Expansion and mutation = dark zone of the germinal center *Selection, class switching, and differentiation = light zone ```

Question 27

What are the functions of the spleen?

Answer 27

* Filter blood * Form lymphoid cells (T and B cell proliferation) * Eliminate blood-borne antigens * Destroy aged platelets and erythrocytes * Fetal hematopoiesis * Can resume hematopoietic function in the adult

Question 28

Pathway of lymph node circulation:

Answer 28

``` *afferent lymphatic vessel subcapsular sinus cortical (trabecular) sinus medullary sinus *efferent lymphatic vessel (at Hilum) ``` *both have valves to prevent backflow

Question 29

In the spleen, blood travels through the ___ then ___ and then ___, which are located in the middle of the ____, together making up the ___ pulp. Blood then travels through ____, which are made up of ____ and ____, and constitute the ___ pulp. From the terminal arterial capillaries, blood can be in closed circulation ( » ___, ____, ____, ____) or in open circulation (_____).

Answer 29

splenic artery, trabecular arteries, central arteries, periarterial lymphatic sheath (PALS), white pulp pencillar arteries, terminal arterial capillaries, macrophage-sheathed arterioles, red pulp splenic sinuses » pulp veins » trabecular veins » splenic vein (through hilum); open-ended vessels in splenic cords of bilroth

Question 30

What does the red pulp do? White pulp?

Answer 30

macrophages in red pulp filter blood (so does marginal zone/marginal sinuses of white pulp). White pulp produces lymphocytes and antibodies (B cells » lymphoid nodules enclosed within the PALS, T cells stay in the PALS, both leave via marginal sinuses)

Question 31

What are the splenic parenchymal cells and where do they first come into contact with blood-borne antigens?

Answer 31

T cells, B cells, macrophages, dendritic APCs; marginal sinuses of marginal zone

Question 32

What is unencapsulated lymphatic tissue otherwise known as? What are the 3 principal examples? What is its function?

Answer 32

MALT (Mucosal-Associated Lymphoid Tissue) •GALT (Gut-Associated Lymphoid Tissue) •BALT (Bronchus-Associated Lymphoid Tissue) •Tonsils Respond to airborne/ingested antigens

Question 33

The most prominent accumulation of GALT is in the ____, where it forms _____. What is different about lymphatic circulation here? What special cells are located in this area and how do they contribute to GALT function?

Answer 33

ileum, Peyer's patches; efferent lymph drainage occurs but afferent lymph vessels are absent; Microfold cells (M cells) in the epithelium just deep to the GALT are thought to capture antigens and transfer them to macrophages in the Peyer's patches

Question 34

A dense fibrous capsule separates the deep aspect of the ____ from the surrounding connective tissue (therefore, it is considered "_______ encapsulated"). Superficial epithelial invaginations create 10-12 ____. Its parenchyma is composed of lymphoid nodules, many of which display ________ (indicative of B cell activation by antigen and proliferation).

Answer 34

tonsil, incompletely; crypts; germinal centers