Page 149 - Essential Haematology

Chapter 9 White cells: Lymphocytes / 135

that of any other lymphocyte, and consequently will their surface immunoglobulin and although most
bind to only a restricted number of antigens. T and antibody responses require help from antigen -

B cells undergo clonal expansion if they meet an specific T cells, some antigens such as polysaccha-
APC that is presenting an antigen that can trigger rides can lead to T - cell independent antibody
their antigen receptor molecules. At this stage, lym- production. T cells are screened for recognition of

phocytes may develop into effector cells (such as antigen and if a T cell makes an interaction it
plasma cells or cytotoxic T cells) or memory cells. migrates into the follicle. In the follicle, germinal
DC precursors constitutively migrate at low centres arise as a result of continuing response to
levels from blood into tissues but their rate of antigenic stimulation (Fig. 9.10 ). These consist of

migration is increased at the site of infl ammation. follicular dendritic cells (FDCs), which are loaded
Immature DCs are effi cient at macropinocytosis with antigen, B cells and activated T cells which
which allows them to capture antigens from the have migrated up from the T zone. Proliferating B
environment. DCs can be matured by a variety of cells move to the dark zone of the germinal centre

stimuli such as inflammatory cytokines – tumour as centroblasts where they undergo somatic muta-
necrosis factor - α (TNF - α ) and interleukin - 1 (IL - 1) tion of their immunoglobulin variable - region genes.
– and viral and bacterial products such as lipopoly- Their progeny are known as centrocytes and these

saccharide (LPS) or double - stranded (ds) RNA. must be selected by antigen on FDCs otherwise
Mature DCs express high levels of co - stimulatory they will undergo apoptosis. If selected they become

molecules and can efficiently present antigen to memory B cells or plasma cells (Fig. 9.10 ). Plasma
na ï ve antigen - specifi c T cells. cells migrate to the bone marrow and produce high

T cells are unable to bind antigen free in solu- affinity antibody. Although they contain intracel-
tion and require it to be presented on APCs in the lular immunoglobulin they do not express surface
form of peptides held on the surface of HLA mol- immunoglobulin.
ecules (Fig. 9.8 b). T cells therefore recognize not
‘
only the antigen, but also self ’ HLA molecules and Lymphocytosis

are known as HLA - restricted . The CD4 molecule
Lymphocytosis often occurs in infants and young
on helper cells recognizes class II (HLA - DP, - DQ
children in response to infections that produce a
and - DR) molecules, whereas the CD8 molecule
neutrophil reaction in adults. Conditions particu-
recognizes class I (HLA - A, - B and - C) molecules
larly associated with lymphocytosis are listed in
(see Fig. 23.5 ).
Table 9.3 .

The antigen recognition site of the TCR is
Glandular fever is a general term for a disease
joined to several other subunits in the CD3 complex
characterized by fever, sore throat, lymphadenopa-
which together mediate signal transduction. During
thy and atypical lymphocytes in the blood. It may
these structural interactions the cells release
be caused by primary infection with Epstein – Barr
cytokines such as IL - 1, - 2, - 4 and - 10 which act to
virus (EBV), cytomegalovirus (CMV), human
modify expansion of activated cells. Depending on immunodeficiency virus (HIV) or toxoplasma.

+
their cytokine production, CD4 T cells can be

EBV infection, otherwise known as infectious
broadly subdivided into T helper type 1 (Th 1) and
mononucleosis, is the most common cause.
Th2 cells. Th1 cells produce mainly IL - 2, TNF - α

and γ - interferon (IFN - γ ), and are important in
Infectious m ononucleosis
boosting cell - mediated immunity (and granuloma

formation), whereas Th2 cells produce IL - 4 and This is caused by primary infection with EBV and

IL - 10 and are mainly responsible for providing help occurs only in a minority of infected individuals –

for antibody production. in most cases infection is subclinical. The disease is

Antigen - specific immune responses are gener- characterized by a lymphocytosis caused by clonal
ated in secondary lymphoid organs and commence expansions of T cells reacting against B lymphocytes

when antigen is carried into a lymph node (Fig. 9.9 ) infected with EBV. The disease is associated with a
on dendritic cells. B cells recognize antigen through high titre of heterophile ( ‘ reacting with cells of