Secondary Lymphoid Organs

When does secondary lymphoid tissue develop?

Late in fetal life and will be life-long

What are 3 specific functions of secondary lymphoid tissue?

Support clonal expansion of antigen-specific T and B lymphocytes

Antigen-specific T and B cell effectors move to tissues

Retain antigen specific memory cells

What are the layers of a lymph node going from outside in?

Follicles

Paracortex

Medulla

What cells are in follicles?

B cells

What is the main cell type in the paracortex?

T cells

What is in the medulla?

Cords and sinuses that contain dendritic cells, plasma cells, macrophages

What happens after a T cell in the thymus finds its antigen?

It will undergo clonal expansion

What cell type is in the germinal center?

B cells

Is the follicle in a lymph node CD3 positive or negative?

Negative, no T cells there

Is the paracortex of a lymph node CD3 positive or negative?

Positive lots of T cells

What is the main role of secondary lymphoid tissue?

Facilitate antigen trapping, collect antigen presenting cells and lymphocytes

How do defensive cells get into the lymph node?

Through high endothelial venules (HEV)

What happens after a naive lymphocyte binds to its antigen in a LN?

It leaves the LN via the efferent lymphatic duct and become effector cells and memory cells. It eventually goes to the site of infection

What are the encapsulated secondary lymphoid tissues?

Lymph nodes

Spleen

Hemolymph nodes / hemal nodes

What are the unencapsulated secondary lymphoid tissues?

Mucosal lymphoid tissue (MALT)

• BALT (bronchial associated lymphoid tissue)

• GALT (gut-associated lymphoid tissue

• Tonsil

What is a great antibody to label T cells?

CD3

What does a reactive lymph node look like?

You can see the germinal centers

How does an antigen get to a lymph node to stimulate an immune response

Dendritic cells take up antigens from the skin and move towards to lymph node

What regulates migration to the LN through HEV?

Chemokines and adhesion molecules

What is a CCR and what cells have them?

Chemokine Receptor. Naive T cells always have CCR7

How are T cells and dendritic cells drawn into the LN?

CCR7 binds to CCL21 and CCL19 to tell them to enter

T cells only respond to antigen in the presence of what else?

MHC

Why do effector T cells shed CD62L and CCR7?

They want to leave the LN and go to the tissue affected

What is chemotaxis?

Movement of a cell in response to a chemical stimulus

What is a chemokine?

A family of cytokines with the ability to induce directed chemotaxis

What are integrins?

Transmembrane cell adhesion proteins and signaling receptors

What are HEVs?

High endothelial venules

T/F HEVs are sticky for naive lymphocytes?

True

What do HEVs select for to regulate what can enter the LN?

L-selected (CD62L) they bind to vascular addressins like CD34 on endothelium

What are the 3 general steps for how HEVs let lymphocytes into the LN?

Roll

Stop

Diapedesis

What are the 5 specific steps for lymphocyte entry to a LN through a HEV?

T cell enters HEV

L-selectin binds to CD34 and GlyCAM-1

LFA-1 is activated by chemokines bound to ECM

Activated LFA-1 binds to ICAM-1

Diapedesis

What species has inside out lymph nodes?

Pigs

also elephants, rhinos, hippos, dolphins

What is the path of flow in pigs?

Bloodstream to HEV to LN paracortex to Efferent Vein to Bloodstream

What is the path of flow in canines?

Bloodstream to HEV to LN paracortex to Efferent Lymphatics to Thoracic Duct to Bloodstream

What animals have the most hemalnodes?

Ruminants

What cells are structure are seen in hemal nodes?

B cells in cortex

T cells at center

What do B and T cells form together in the paracortex?

Conjugate pairs (they bind to the same antigen)

Where do B cells go after forming a conjugate pair?

Germinal centers. Proliferation then occurs

What are the 4 phases of B cell activation?

1. B cell activation

   1. Paracortex

2. Somatic hypermutation

   1. Germinal center dark zone

3. Affinity maturation

   1. Germinal center light zone

4. Isotype (class) switching

   1. Germinal center light zone

How does B cell activation happen?

Helper T cells co-stimulate and requires 3 signals

1. Antigen binds to BCR and co-receptor CR2/CD21

   1. Ag processed to peptide and presented to helper T cell on MHC II molecule

2. Co-stimulation of CD40 on B cell by CD154 on T cell

3. IL-4 produced by T cell engages IL-4 receptor on B cell to signal proliferation and differentiation

How does clonal expansion and somatic hypermutation of B cells work?

Helper T cell activated B cells move to the dark zone of the germinal center and proliferate

Somatic hypermutation occurs

• AID facilitates the shuffling of all uracil’s with other nucleotides

What is affinity maturation of B cells?

This happens after somatic hypermutation. B cells encounter antigen presented on follicular dendritic cells. If a B cell binds strongly it will survive.

What is isotype switching?

B cells with high affinity BCRs will swap to a different Ig based on the cytokine signal

What does a IGN-gamma signal induce during isotype switching?

IgM TO IgG

What does a IL-4 signal induce during isotype switching?

IgM TO IgE

What does a TGF-Beta signal induce during isotype switching?

IgM TO IgA

What are the two parts of the spleen?

Red and white pulp

What does the red pulp in the spleen do?

It filters blood and removes old blood cells. It salvages iron and bilirubin

What does the white pulp in the spleen composed of?

Marginal zone: macrophages
Follicles: B lymphocytes

PALS: T cells

NO HEVs

What species can hold additional blood in a sinusoidal type spleen?

Horses, dogs, humans

What are MALTS?

Mucosa-associated lymphoid tissue

Where do memory and plasma cells colonize?

Secondary lymphoid tissue