Lymphocyte Maturation Flashcards
Describe where T and B lymphocytes develop in mammals
Primary Lymphoid tissues
Locations of lymphocyte development & maturation
-Bone marrow
-Thymus
-Other - species variation in B-cell maturation
Describe the location of B cell maturation in humans, primates, rodents and birds
Bone marrow
Describe the location of B cell maturation in birds
Bursa of Fabricius
Describe the location of B cell maturation in ruminants (cows, sheep), dogs, pigs, horses
Ileal Peyer’s patch
May be secondary to bone marrow in some species
Describe the location of B cell maturation in rabbits
Appendix
Outline the process of lymphocytes maturation
Initial lymphocyte development occurs in the yolk sac of the embryo, then the fetal liver and then the bone marrow.
Stem cells within the bone marrow give rise to many cells of the immune system, including lymphocytes.
Immature T lymphocytes are exported from the bone marrow into the thymus, where they mature and become “educated”
B lymphocyte maturation often occurs in the bone marrow, but also in Ileal Peyers patches of some species, but at other locations in many species.
What does primary lymphoid tissue consist of?
Bone marrow
Thymus
What does secondary lymphoid tissue consist of?
Spleen
Lymph nodes
Mucosal–associated lymphoid tissues (eg gut, respiratory tract)
Describe the basic function of the thymus gland in the development of immune responses
Thymic education or central tolerance of T-cells
T-cells must be prevented from reacting to “self” antigen.
Thymic education of T-cells begins during foetal life and continues for the first few months of life.
Thereafter the thymus involutes (shrinks) - The lymphoid tissues become replaced by adipose and connective tissue.
Describe the basic function of the spleen in the development of immune responses
‘Specialized lymph node for blood borne antigens’
Very well vascularised, but only efferent (going away from) lymphatics, so part of vascular blood system.
Consists of red and white pulp areas
Red pulp: Filters blood for foreign pathogens, removes defective erythrocytes & platelets; stores erythrocytes & platelets
Many cell types, including macrophages (phagocytosis) and antigen presenting cells and aging erythrocytes. T- and B-lymphocytes within this area
immune response to foreign pathogens
Explain the two types of thymic education for t-lymphocytes
Positive Selection
T cells which recognise the body’s own MHC (I or II) are retained.
(CD4+ CD8- recognise MHCII & CD4-&CD8 recognise MHC I)
Negative Selection
T cells which respond to “self peptides” in the MHC are eliminated T cells which ignore self peptides are retained.
Outline the outcomes of thymic education
Central tolerance
T cells which do not react to their body’s own peptide antigens (ie tolerant) are
selected (negative selection).
If T cells were not educated, they could potentially attack the body’s own cells,
causing autoimmune reactions.
Huge T cell diversity in peptide recognition
T cells will recognise any non-self peptide, provided it is presented by their own
MHC molecule on an APC.
Maturation of T cells
Eg T helper cells, cytotoxic T cells.
Explain bone marrow education of lymphocytes
In the bone marrow, self antigen is presented on stromal cells*.
If B-cells responds to this self antigen through their B-cell receptor
interaction leads to cell death by apoptosis
Receptor editing (re-arrange BCR genes to avoid recognition of “self” antigens) – unique to B-cells!
Educated naïve B-cell express both, IgD and IgM on their cell membrane
Outline how T lymphocytes recognise a huge diversity of antigens
Similar to BCR/antibody variation:
The specificity of a particular T-cell receptor is determined by the shape of its variable region.
While still at the T-cell progenitor stage in the thymus, T cells randomly rearrange their variable (V), diversity (D), and joining (J) genes.
Diversity comes from the fact that there are multiple copies of the V, D and J genes that can be joined together in different combinations.
Addition of random nucleotides between the V, D and J regions junctional diversity.
Recombination processes for BCR and TCR variation unique to lymphocytes.
Outline how B lymphocytes recognise a huge diversity of antigens
The specificity of a particular antibody is determined by the shape of its variable region.
While still at the B-cell progenitor stage in the bone marrow, B cells randomly rearrange their variable (V), diversity (D), and joining (J) genes.
Diversity comes from the fact that there are multiple copies of the V, D and J genes that can be joined together in different combinations.
Addition of random extra nucleotides between the V, D and J regions, changing the structure of the variable regions that will be produced Junctional diversity.