Primary Lymphoid organs: B and T cell development

Where does adaptive immunity occur

lymphocytes are generated in the primary lymphoid organs

naive when leave primary lymphoid organ: have not yet encountered specific antigen

mature naive lymphocytes—encounter antigen and are activated and develop into an effector lymphocyte

T and B lymphocyte development and education

development: generate a functional B cell receptor (BCR) or T cell receptor (TCR)

education: tolerant to self antigens

create a collection of T and B lymphocytes with receptors specific for diverse antigens (gene arrangement)

primary lymph organs

bone marrow

thymus

intestine—ruminants and horses

secondary lymphoid organs

bone marrow

spleen

lymph nodes

salivary glands

resp. tract

mammary glands

intestine

urogenital system

hematopoietic cells are produced in

bone marrow

lymphocyte progenitor cells from bone marrow either

develop into B cells in bone marrow

migrate to the thymus to develop into T cells

site of B cell development is species specific

bone marrow—most species

ileal peyers patches—ruminants, horses

bursa—birds

continuous peyers patches

illeum

involutes by 15 months of age

primary lymphoid tissue for B cell development in ruminants, horses

continuous peyers patches

discontinuous peyers patches

jejunum

life-long

secondary lymphoid tissue

discontinuous peyers patches

thymus

epithelial outgrowth of third pharyngeal pouch

lymphoid progenitors from bone marrow migrate to thymus and become thymocytes

thymocytes mature to naive T lymphocytes

develop T cell receptor (TCR)

become MHC class restricted

educated (tolerized) to self antigen

most important step in life of a lymphocyte

development of the BCR or TCR

BCR/immunoglobulin structure

Fab=antigen binding regions consisting of variable regions (V) of amino acid (aa) structure

Fc region=constant (C) aa structure, determines isotype and primary function of immunoglobulin

membrane bound BCR are IgM isotype

T cell receptor

alpha and beta (Most numerous)

gamma and delta prevalent in ruminants

the hallmark of adaptive immunity is the

specificity of the immune response due to a diverse repertoire of unique BCR and TCR

gene arrangement—random selection of gene segments resulting in genetic diversity of BCR and TCR

occurs during lymphocyte development in primary lymphoid tissues

gene rearrangement occurs in each lymphocyte during development

it is random process like shuffling cards

segments of gene arrangement

v=variable gene segment

D=diversity gene

J=joining gene segment

V-D-J recombinase

enzymes need to recombine

RAG1 and RAG2 genes found only in lymphocytes—cleave DNA and protect dsDNA breaks from DNA repair mechanisms

central tolerance

process by which self-reactive lymphocytes are deleted or programmed to become unresponsive to self-antigen

immature B cells that bind self antigens with high affinity undergo

apoptosis and negative selection or

receptor editing of variable region genes

MHC I

CD8+ t cell

receptor binds

cytotoxic

MHC II

CD4+ T cell

receptor binds

helper

autoimmune regulator gene (AIRE)

controls expression of >400 tissue specific proteins

expressed by thymic medullary epithelial cells with MHC molecules

important for developing T cells to become self-tolerant

without bursa or ileal peyers patches

B cells constitute approximately 20% of circulating lymphocytes

total circulating lymphocyte pool slightly decrease

humoral immunity (antibody concentration) markedly decreased

absent or deteriorated thymus

no T cells in secondary lymphoid tissue

No T cells in circulation (60-70% circulating lymphocytes)

defective T-cell mediated immunity

SCID

severe combined immunodeficiency

cannot develop B or T cells