Secondary Lymphoid Organs

When do secondary lymphoid tissues develop?

Late in fetal life

How long do secondary lymphoid tissues persist?

Life-long

What is the function of secondary lymphoid tissue?

Facilitate antigen trapping, collects antigen presenting cells and lymphocytes

Supports colonal expansion of lymphocytes

What is retained in secondary lymphoid tissue?

Antigen specific memory cells

What are the two types of secondary lymphoid tissue?

Encapsulated and unencapsulated

What are the encapsulated secondary lymphoid tissues?

Lymph nodes

Spleen

Hemolymph/ hemal nodes

What are the unencapsulated lymphoid tissues?

Mucosal lymphoid tissue (MALT) which includes GALT, BALT, etc. and the tonsils

Where do naive lymphocytes enter a lymph node?

Through high endothelial venules into the paracortex

Where does B cell clonal proliferation occur in a lymph node?

In the follicles in the cortex

Where does T cell clonal proliferation occur in a lymph node?

Paracortex

What is located in the medulla of a lymph node?

Dendritic cells

What is found in the paracortex of a lymph node?

T cells

The paracortex is positive for what?

CD3 antibody

What does the CD3 antibody in the paracortex do?

Labels T cells

Germinal centers in a follicle in a lymph node are negative for what?

CD3 antibody

What is found in the germinal centers in a lymph node follicle?

B cells

How does an antigen get to the lymph nodes?

A dendritic cell takes up the antigen and enters a draining lymphatic vessel that takes it to the draining lymph node

Where do antigen bearing dendritic cells settle in a lymph node?

In T-cell areas (paracortex)

What is the pathway through the lymph node for a lymphocyte?

Enters through high endotheleal venules to seek an antigen in the paracortex

If activated, goes through colonal expansion

Leaves through efferent lymphatics

What leaves through the efferent lymphatics in a lymph node?

T and B effector cells

Antibodies

Where do B cells migrate for colonal expansion and affinity maturation?

Germinal centers

What regulates lymphocyte migration to the lymph node?

Chemokines and adhesion molecules

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

Molecules that tell cells where to go

What is an integrin?

A transmembrance cell adhesion protein and signaling receptor

High endothelial venules only allow what to enter the lymph node?

Naive lymphocytes

What do high endothelial venules express to make lymphocytes initially stick?

CD34

What is expressed on lymphocytes that makes them initially stick to endothelium?

CD62L

What are the two molecules necessary for lymphocyte to initially stick to the high endothelial venules?

CD62L from the lymphocytes

CD34 from the endothelium

For loose adhesion, what two molecules are needed?

CD62L (L-selectin) from lymphocytes

CD34 (GlyCAM-1) from the endothelium

What molecules are necessary for tight adhesion and diapedesis?

LFA-1 on the lymphocyte

ICAM-1 on the endothelium

What is expressed in the paracortex to attract T cells and dendritic cells?

CCL19 and CCL21

What is expressed on T cells and dendritic cells so they can respond to CCL19 and CCL21?

CCR7 receptor

What receptor on dendritic cells homes to CXCL12?

CXCR4

What is expressed in the paracortex that reacts with the CXCR4 receptor?

CXCL12

Why do effector T cells shed CD62L (L-selectin) and CCR7?

They are no longer needed since the T cell has matured and won't return to the lymph node

How often do T cells recirculate?

Every 12-24 hours

What receptor expressed on B cells responds to CCL19 and CCL21 from the paracortex?

CCR7

What receptor expressed on B cells responds to CXCL13 in the lymph node follicle?

CXCR5

What cytokine is release from the lymph node follicle to attract naive B cells?

CXCL13

How long to naive B cells survive in the lymphoid system?

Up to 100 days

What happens to B cells that encounter their specific antigen in the lymph node?

They stay in the T cell zone and process the antigen to present to T cells

How do B cells present antiens to the T cells in the lymph node?

Via MHC II

What happens to naive T cells after encountering a specific antigen in the paracortex?

Proliferate and differentiate to a helper T cell subtype

What is cognate interaction?

When B and T cells recognize different epitopes on the same antigen

When do B and T cells form conjugate pairs?

When they both have specific antigens for the same pathogen

What are the phases of B cell activation and differentiation?

B cell activation in the paracortex

Somatic hypermutation

Affinity maturation

Isotype (class) switch

Where does somatic hypermutation occur?

In the dark zone of the germinal center

Where does affinity maturation and isotype switching occur?

Light zone of the germinal center

What part of B cell activation happens in the dark zone of the germinal center?

Somatic hypermutation and proliferation

What part of B cell activation happens in the light zone of the germinal center?

Affinity maturation and isotype switching

What is required for complete B cell activation?

Multiple signals from other sources (Helper T cell)

What are the three signals helper T cells use to activate B cells?

Antigen specific

Co-stimulation

Cytokines

What is the first step in B cell activation?

Antigen binding to the B cell receptor (BCR) and co-receptor CR2/CD21

What happens during antigen binding to the BCR?

Antigen is processed into a peptide and presented to helper T cells on the MHC II molecule

What is the second signal required to activate a B cell?

Co stimulation of CD40 on the b cell by CD154/CD40L on a T cell

What is the third signal required to activate a B cell?

T cell produces IL-4 which engages on the IL-4 receptor on the B cell to signal proliferation and differentiation

What is required for B cell somatic hypermutation?

Activation-induced cytidine deaminase (AID)

What makes AID?

Only B cells

What does AID do?

Allow for randomization in nucleotide replacement during cell division which alters antigen affinity

Where do B cells migrate after somatic hypermutation?

Light zone of the germinal follicle

What happens to B cells during affinity maturation?

They encounter an antigen presented by a follicular dendritic cell

High affinity b cells survive while low affinity b cells undergo apoptosis

What happens to B cells with high affinity?

They move to the margin of the germinal center and interact with T follicular helper cells

What do the T follicular helper cells do to help B cell activation/maturation?

Provides cytokine signaling to cause class switching

What cytokine results in IgG production?

IFN-gamma

What cytokine results in IgE production?

IL-4

What cytokine results in IgA production?

TGF-beta

What do the antibodies start off as?

IgM

What cytokine is essential for T follicular helper cells and plasma cell differentiation?

IL-21

What is IL-21 important for?

T follicular helper cells and plasma cell differentiation

What do hemal nodes do?

Filter blood and substances in circulation

Contain B cells in the cortex and T cells at the center

What are the two types of pulp in the spleen?

Red pulp and white pulp

What does the red pulp do?

Filters blood

Removes aged blood cells and immune complex coated cells

Salvages iron and bilirubin from RBC

What is in the white pulp?

Marginal zone

Follicles

Periarteriolar sheath

What is in the marginal zone of white pulp?

Macrophages (APC)

What is in the follicles in the white pulp?

B lymphocytes

What surrounds the periarteriolar sheath (PALS)?

T cells

What are the two types of spleen?

Sinusoidal and nonsinusoidal