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Lymphocyte Maturation (1.18.5.11) - Coggle Diagram
Lymphocyte Maturation (1.18.5.11)
Lymphoid tissues
Primary: These are locations of lymphocyte development and maturation
Bone marrow
Thymus
Other - species variation in B- cell maturation
Secondary: These are the hub for the adaptive immune response
Spleen
Lymph nodes
Mucosal - associated lymphoid tissues
B and T cell development
Yolk sac
Foetal liver
Most T and B cells produced in bone marrow
Lymphoid Progenitor cells
progenitor b- cell
mature b - cell
Migrates to lymph node and differentiates
Peyer's patches (intestine) or cloacal bursa in birds
Migrates to lymph node and differentiates
Progenitor t- cell
Migrates to thymus
Migrates to lymph node and differentiates
T- cell education and central tolerance
Locations of B- cell maturation species variation
Bursa of Fabricius
birds
Ileal Peyer's Patch
dogs
pigs
Ruminants
horses
Bone marrow
primates
rodents
humans
birds
Appendix
rabbits
Lymph Tissues
Spleen
Function
Specialised lymph node for blood borne antigens
very well vascularised
part of vascular blood system
only efferent to lymphatics
bleeds a lot if injured
Red and White Pulp
Red Pulp
removes defective erythrocytes and platelets
stores erythrocytes and platelets
Filters blood for foreign pathogens
White Pulp
many cell types including:
macrophages for phagocytosis
ageing erythrocytes
antigen presenting cells
T and B lymphocytes
immune response to foreign pathogens
capsule allows for rapid contraction of spleen so lots of blood can be put into circulation very quickly if body under stress
Lymph Nodes
Function
Presentation of antigen to lymphocytes and mount an immune response if necessary
Lymph enters node though afferent lymphatics
lymph leaves node via efferent lymphatics
Densely packed with
T and B lymphocytes
antigen presenting cells
monocytes
Thymus
Function
Thymic education or central tolerance of T- cells
prevents T- cells from reacting to 'self' antigen
begins during foetal life and continues for the first few months of life
after first few months of life the thymus shrinks
lymphoid tissues replaced with adipose and connective tissue
irreversible and loses most of its function
'Self' vs 'non-self' cells
'Self'
in healthy cells, MHC groove filled by peptide generated from the cell
'Non- Self'
In infected cells, (intracellular virus/bacterium) MHC groove filled with peptide derived from pathogen' proteins
Major Histocompatibility Complex (MHC)
Controls how immune system detects + responds to specific antigens
display peptide fragments for recognition by appropriate T- cells
MHC relates to role in transplantation- determines if tissues are self or non- self
2 classes of MHC molecule have similar functions
MHC class I
on every nucleated cell
presents endogenous ('self') peptides
MHC class II
on antigen presenting cells
dendritic cells
B- cells
macrophages
presents exogenous ('non-self') peptides if infected
Expressed on cell surface
delivery of short peptides to the cell surface for recognition by CD8+ and CD4+ T cells respectively
Thymic education of T- lymphocytes
Positive Selection
T- cells which recognise the body's own MHC (I or II) are retained
Negative Selection
T- cells which respond to 'self peptides' in the MHC are eliminated
T- cells which ignore self peptides are retained
Outcome
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 antigen presenting cell
Maturation of T- cells
t- helper cells
t- cytotoxic cells
Central Tolerance
T- cells that do not react to body's own antigens are selected
if not educated, they could attack own body cells, causing an autoimmune reaction
Important T- cell surface molecules
T cell receptor
+ive T cells
CD4
65% +ve (T helper)
MHC class II (dendritic cells, macrophages, B- cells)
T- cells mediated activation of other immune cells
CD3
+ive T cells
CD8
35% +ve
MHC class I (most nucleated cells)
T- cell mediated cytotoxicity
Primary lymphoid tissues- T-cells
Thymus
maturation
education
Bone marrow
B-cells
Primary Lymphoid Tissues
Bone marrow
self antigen presented on stromal cells
If B- cells respond to self antigen through their b- cell receptor:
Interaction leads to cell death by apoptosis
Receptor editing (rearrange BCR genes to avoid recognition of self antigens)- unique to b-cells
educated naive b-cell expresses both IgD and IgM on cell membrane
Other- species variation in maturation
Peyer's Patches in ruminants
bursa of fabricius in birds
Thymus
B- cell diversity
While still in progenitor stage in bone marrow, B- cells randomly rearrange their Variable (V), diversity (D) and joining (J) genes
Diversity comes from there being multiple copies of V, D and J which join in different combinations
junctional diversity- addition of random extra nucleotides between V, D and J regions
changes structure of variable regions that will be produced
specificity of a particular antibody is determined by the shape of its variable region
T-Cell Diversity
Diversity comes from there being multiple copies of the V, D and J genes
joined in different combinations
junctional diversity
addition of extra nucleotides between V, D and J regions
While at the progenitor stage in thymus they randomly rearrange their V, D and J genes
Recombination processes for BCR and TCR variation unique to lymphocytes
Specificity determined by the shape of its variable region