Primary Lymphoid Organs

What are the functions of primary lymphoid organs?

Develop and educate T and B lymphocytes

Provide T and B lymphocytes with receptors specific for diverse antigens for secondary lymphoid tissues

Make T and B cell tolerant to self antigens

What is central tolerance?

Lymphocytes that are tolerant to self antigens

What are the primary lymphoid organs?

Bone marrow

Thymus

Ileal Peyer's patches in ruminants and horses

Where are T and B lymphocytes developed?

Primary lymphoid organs

What is the pathway of lymphocytes from creation to maturity?

Bone marrow (stem cells) -> primary lymphoid organ -> secondary lymphoid organ

What are the primary lymphoid organs for B-cell development?

Bone marrow, ileal Peyer's patches, bursa

What are the two options for lymphocyte progenitor cells?

Develop into B cells in the bone marrow or migrate to the thymus to develop into T cells

What is the last step in B cell development before its mature?

Negative selection

What is the most important event in the development of a lymphocyte?

Generation of the antigen receptor

What is a B cell receptor?

Membrane bound immunoglobulin

What is the structure of an immunoglobulin?

Two heavy chains and two light chains linked by a disulfide bond

What is the CD79 marker?

B-cell identifier

What marker is the B-cell identifier?

CD79

What is the hallmark of humoral immunity?

Specificity of the immune response due to gene rearrangement and somatic hypermutation

What is gene rearrangement?

Random selection of gene segments resulting in genetic diversity of T and B cell receptors

When does gene rearrangement occur?

During lymphocyte development in primary lymphoid organs

What causes the genetic diversity of B and T cells?

Gene rearrangement

What is somatic hypermutation?

High frequency mutations in variable region of immunoglobulin genes after B cell activation resulting in increased affinity for antigens

When does somatic hypermutation occur?

In mature lymphocytes in lymph node germinal centers

What is it called when activated B cells have mutations that result in increased affinity for an antigen?

Somatic hypermutation

What are the two types of Peyer's patches?

Continuous and discontinuous

Where are continuous Peyer's patches located?

Ileum

In what species are continuous Peyer's patches a primary lymphoid organ?

Ruminants and horses

What happens to continuous Peyer's patches?

Involutes by 15 months

What is the primary cell types in continuous Peyer's patches?

B cells

Where are discontinuous Peyer's patches found?

Jejunum

What is the classification of discontinuous Peyer's patches?

Secondary lymphoid tissue

How long do discontinuous Peyer's patches last and what's the primary cell type?

Life long, T-cells

When do continuous Peyer's patches reach maximal size and maturity?

Before birth

What are continuous Peyer's patches the site of?

Rapid B cell proliferation

Where are bursa of Fabricius found?

Only in birds

Round sac located just above the cloaca

What happens to the bursa of Fabricius after hatching?

Shrinks

What is a bursa of Fabricius?

Hollow sac with folds of epithelium containing lymphoid follicles

What is the function of bursa?

Generate BCR diversity

What happens in the cortex of a bursa?

B-cells proliferate and gene rearrangement occurs

What happens in the medulla of a bursa?

Negative selection of self-reactive B cells

What is the average percentage of B cells in the blood?

20%

What happens when ileal/continuous Peyer's patches are removed?

Total circulating lymphocytes slightly decreases

Antibody concentration markedly decreases

What type of immunity is damaged by continuous Peyer's patches removal?

Humoral immunity (antibodies decrease)

What are thymocytes?

Immature T cells in the thymus

How do T cells mature in the thymus?

Develop T cell receptor

Become class restricted

Become tolerant to self through negative selection

What is a T cell receptor?

Heterodimer of 2 chains

What are the chains present in a T cell receptor?

Gamma and delta for ruminants

Alpha and beta are the most numerous

What is CD3?

A T cell receptor co-receptor required for signal transduction

What generates T cell receptors?

Somatic recombination (gene rearrangement)

Why is somatic recombination/gene rearrangement important?

It increases diversity

What is required during somatic recombination?

Removal of genes by recombinase enzymes

What is the consequence of a defect in VDJ recombination?

No longer able to develop B or T cells resulting in severe combined immunodeficiency (SCID)

What are the first two steps in T cell development?

Proliferation and rearrangement of TCR genes

What happens if gamma delta TCRs are expressed?

T cell leaves the thymus

Acts more like an innate cell due to lower specificity

What happens if alpha beta TCRs are expressed?

CD3 and CD4 or CD8 surface molecules are expressed

What are CD3, CD4, and CD8?

Co-receptors

What happens to T cells during positive selection?

Become class restricted by recognizing antigens presented by thymic epithelial cells on either MHC class I or MHC class II molecules

How are T cells positively selected?

They have to bind to MHC plus an antibody

What happens when a T cell binds to MHC class I?

Matures to a CD8+ T cell (cytotoxic)

What happens when a T cell binds to MHC class II?

Matures to CD4+ T cell (helper)

What is class restriction in T cell maturation?

Binding of MHC classes to determine if the T cell is CD4+ or CD8+

What is T cell negative selection?

Checking for binding to self MHC

If binds, undergoes apoptosis

What is the AIRE gene?

Autoimmune regulator gene

Present in the thymic medullary epithelial cells

Why is the AIRE gene important?

Important for developing self-tolerance

What happens if the AIRE gene is missing?

Autoimmune polyendocrinopathy

Polyglandular autoimmune syndrome

T cells respond to self-antigens

T cells are what at the beginning of maturation?

Double positive, have both MCH class I and II

What is the average percentage of T cells in the blood of adult animals?

50-65%

What happens to the thymus as an animal matures?

Shrinks and is replaced by fat

Small amounts of functional lymphoid tissue remains

What happens when an animal doesn't have a thymus?

Increased susceptibility to infection

No T cells in circulation or in secondary lymphoid tissues

Decreased IgG and IgA due inability to activate B cells