Lymph Nodes, Spleen, & Thymus

Lymph

- Interstitial fluid that drains from tissues into lymphatic system → circulates through lymph nodes → drains into subclavian veins

Lymphatic System

- Composed of a network of vessels, ducts, nodes, and organs. Provides defense against infection.

Where does all the lymph in the body eventually drain?

- Into subclavian veins → returned to the venous system of body

What are the types of lymphoid organs?

- Primary

- Secondary

Primary Lymphoid Organs

- Bone marrow and thymus

Thymus is derived from what?

- 3rd pharyngeal pouch

Where is the thymus located?

- Behind the sternum and between the lungs

Thymus: Cortex and Medulla

- Cortex: Peripheral, dark, densely packed with immature T lymphocytes

- Medulla: Central region, light, mature T lymphocytes and hassall corpuscles

What structure is unique to the thymus?

- Hassall Corpuscle

When is the thymus 'large and robust'

- During infancy, as the immune system is still developing and the infant is exposed to a lot of unfamiliar pathogens

What is seen on a chest X ray of an infant?

- Thymic shadow, appears as a sail boat (normal appearance)

Thymic Aplasia

- The thymus fails to develop so T cells don't mature and aren't functional

What happens to the thymus with age?

- Atrophies and is replaced by fat as the T cells previously made there now circulate and protect the body for life

Primary Lymphoid Organs are important for what?

- Sites of lymphocyte formation → creates B/T cells

Secondary Lymphoid Organs

- Spleen

- Lymph nodes

- Peyer's Patches (Small intestines)

- Tonsiles

Why are secondary lymphoid organs important?

- They are areas where B/T cells can proliferate in response to infection

Lymph nodes

- Bean-shaped filters that cluster along the lymphatic vessels of the body. They function as a cleanser of lymph as wells as a site of T and B cell activation

Peyer's Patches

- Large collections of lymphoid tissue found in the submucosa of the small intestine

Tonsils

- Masses of lymphatic tissue in the back of the oropharynx

What are the layers of a lymph node?

1. Cortex

2. Paracortex

3. Medulla

Afferent Lymph Vessel

- Carries lymph toward the lymph node → lymph percolates through the 3 layers of the node

General lymph flow through lymph node

- Cortex → Paracortex → Medulla → Efferent Lymph Vessel

Efferent Lymph Vessel

- Small lymphatic vessels that carry lymphatic fluid away from a lymph node

What surface proteins do dendritic cells express? What is their general role?

- MHC I/II

- B7

APCs who take pieces of bacteria → present them on surface to activate other immune cells

Example: There is a site of infection in the tissues/lungs; what occurs after?

1. Lymph fluid drains from site of infection (containing dendritic cells that have antigens on their surface from site of infection as well as free antigens)

2. Lymph with dendritic APCs enter nodes → there are many B/T cells waiting there for a matching antigen

3. Dendritic cells present antigen to T cells // Dendritic cells already inside lymph nodes can process the free antigen and present it to B cells

4. Adaptive immune response

What is the first layer than lymph encounters in the node?

- Cortex

Where does all the immune action occur within the cortex?

- The follicles

Lymphoid Follicles

- Contain follicular dendritic cells (permanent cells, take up free antigen from lymph) → present it to B cells → activates them

Are able to bind a lot of different antigens (velcro)

What is an important reservoir for HIV? What is seen in early infection?

- Follicular dendritic cells in cortex of node

- Early after infection → large amts of HIV particles in FDCs

What are the types of follicles within the cortex?

- Primary and secondary follicles

Which type of follicle is more prominent during inflammation/infection?

- Secondary follicle

Primary Follicles

- Inactive, containing FDCs and B cells

Secondary Follicles

- An activated cluster of B cells that develops a central germinal center after encountering an antigen

Area of B cell growth/differentiation + class switching

Paracortex

- Contains T cells that are activated by dendritic cells + antigen on their surface

- Contains high endothelial venules

What do the high endothelial venules in the paracortex allow?

- Special vascular structures that allow B/T cells to enter the nodes

- Different from normal vessels → has spaces that B/T cells can squeeze through

When is the paracortex engorged?

- During immune response (swollen lymph nodes)

What is underdeveloped in the setting of DiGeorge Syndrome?

- The paracortex of lymph nodes (T cell deficiency disorders)

What is the innermost section of the lymph node?

- Medulla

What are the components of the medulla?

- Medullary cords and sinuses

Medullary Sinuses

- Cavities lined with macrophages → filters lymph → phagocytosis (of bacteria, viruses, or other antigens that get into sinus)

Medullary Cords

- Tissue between the sinuses/cavities that contain plasma cells that secrete antibodies

Spleen

- An organ that is part of the lymphatic system; it produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells

LUQ

Filters BLOOD, NOT lymph

Order of Blood Flow in the Spleen

- Enters via splenic artery → white pulp → red pulp → splenic vein to drain from the organ

What are the important structures within the white pulp of the spleen?

- Follicles

- Pariarteriolar Lymphocyte sheaths (PALS)

- Marginal Zone

What are the important structures within the red pulp of the spleen?

- Sinusouds

White Pulp vs Red Pulp of Spleen

- White: Acts as part of the immune system to fight infections; blood is exposed to B/T cells & Macrophages

- Red: Filters the blood through sinusoids and removes old or damaged blood cells; area of platelet storage

Marginal Zone

Contains:

- Macrophages to remove debris from blood

- Dendritic cells to process antigens from blood

What do the follicles of the spleen contain?

- B cells

What does the PALS of the spleen contain?

- T cells

Sinusoids of spleen

- Lines the red pulp

- Open endothelium → cells can pass in/out

What is the order of blood flow to the sinusoids?

- Capillaries → cords → sinusoids ( → then to venous system)

Cords contain macrophages for filtering/removal of dying RBCs from circulation

Splenic Dysfunction causes an increased risk of what?

- Spleen uses macrophages → when lost in splenic dysfunction, cannot process/phagocytes encapsulated organisms → ↑ risk of infection

Encapsulated organisms

- Microbes shielded by an outer protective layer, usually a polysaccharide capsule, that helps them hide from the host immune system

Ex: Pneumoniae, Influenza, Meningitides, Cryptococcus etc

Sepsis

- Dangerous infection of the blood

What is the predominant pathogen that causes sepsis

- Strep Pneumonia (death in >50% of pts with splenic dysfunction)

What are the most common reasons for splenic dysfunction?

- Splenectomy: d/t trauma, can also elective when wanting to ↓ phagocytosis of platelets and to ↓ anemia

- Functional asplenia (sickle cell)

Howell Jolly Bodies

- Some RBCs leave marrow w/ nuclear remnants; this is normally cleared by the spleen but their presence can be seen in peripheral blood and can indicate splenic dysfunction

Target Cells

- Appear on a blood smear when red blood cells have an excess membrane relative to their internal volume

What happens to platelets in a patient with splenic dysfunction?

- Thrombocytosis bc/ spleen fails to remove them

SCID

- Severe combined immunodeficiency disease

- Both T/B cells affected

SCID Symptoms

- Failure to thrive

- Chronic diarrhea

- Recurrent viral/bacterial/fungal infection

Direction of Lymph Flow

- Afferent lymphatic vessel → subcapsular sinus → Trabecular sinus → Medulla → efferent lymphatic vessel

Functions of the Lymphatic System

- Immune surveillance

- Transport large molecules (hormones, lipids)

- Fluid Balance (returns fluid → heart)

Flow of lymph to drainage

- Lymph capillaries → vessels → trunks → ducts → subclavian vein

Right lymphatic duct vs thoracic duct

Right lymphatic duct drains much smaller area (right upper quarter).

Thoracic duct drains entire left side and both LEs.

Lymphedema

- Swelling due to an abnormal accumulation of lymph fluid within the tissues (drainage obstruction)

How can we improve lymphatic drainage?

- Compression garments

- Exercise

- Manual lymphatic drainage