Lymphocytes : Structure & immunological Function
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Transcript of Lymphocytes : Structure & immunological Function
CD4 T-HELPER CELL
EFFECTOR FUNCTIONS
CD8 CYTOLYTIC T
LYMPHOCYTES (CTL)
antigen recognition does not occur at site of entry, but usually in lymph nodes/spleen
activated T cells then migrate to target
tissues
IL2R – complex of αβγ that associate non-covalently, essential for immune function, as its chains are involved in MANY ILR’s
IL2 is not absolutely
necessary b/c other
cytokines can replace function
ag:MHC complex binding to TCR triggers IL2R assembly/synthesis
ensures that IL2 only activates
clonal expansion of ag-specific
cells
ag:MHC complex binding to TCR can also stimulate IL2 SYNTHESIS
some cells can make IL2 autocrine/endogenous
can be used
can’t make IL2 paracrine/exogenous IL2
necessary
TH1 – synthesize IL2/3, TNFα, γ-INTERFERON
activates macrophages and enhances their
ability to kill ingested microbes (bacteria,
fungi, protozoa)
TH2 – synthesize and release IL4//5/6/10
activate B-cell growth/differentiation
CD4
TH1
1) γ-inteferon is released in response to macrophage MHC II antigen presentation
• these combined enhance macrophage lysosome-phagosomefusion
• DTH – delayed type hypersensitivity can be used to determine immune status (Tb skin test- PPD)
2) CD40 (macrophage) binds CD40L(T cell) and/or TNF (T cell)
interacts with TNF-R (macrophage)
• - occurs in response to antigen-activation of TH1 cells that are already sensitized to the specific antigen
• - positive test indicates presence of sensitized T cells indicates past infection
- inflammation results from local accumulation
of macrophages
TH2
synthesize and release IL4//5/6/10 activate B-cell growth/differentiation
B cell antigen receptors (Ig) can take up antigen very efficiently
presents antigen on MHCII in high quantities
TH2 cells recognize this on B cells CD40/CD40L interaction
IL4/5/6 is produced and released to activate B cell class switching
CD4 T cells do not differentiate into TH1 or TH2 until antigen is encountered
NK cells secrete IL12 induces T-BET TH1 pathway
IL12 is secreted as
part of response to
infection
IL10 is secreted by TH2 cells
INHIBITS TH1 differentiation
IL4 induces GATA-3 TH2
IL4 is secreted by a small subset of NK cells early in infection
also secreted by other TH2 cellsinhibited by interferon-γ made by
TH1 cells
CD8 CYTOLYTIC T LYMPHOCYTES (CTL):
Function
virally infected cells
(MAJOR)
bacterial infected cells
tumor cells
graft rejection
important that their activity is confined only to target cells
some CD4 and some NK cells also have cytolytic activity
PROTECTION AGAINST VIRAL INFECTION
antigenic viral proteins can be cytosolic or nuclear-localized
viral escape mechanisms –
latent infection
privileged site
replication (cells
lacking MHC I)
inhibit class I MHC
expression
inhibit TAP1/2 activity
(peptides cannot enter
ER)
mutation in antigenic peptide
sequence
PROTECTION AGAINST BACTERIAL
INFECTION
• while this might elicit MHCII/CD4 response in some cells, certain cell types
several types of bacteria can reside
and replicate WITHIN host cells
Salmonella, Listeria, Myobacteria
LACK these proteins and the MHCI/CD8
route is the only alternative
ACTIVATION OF CTL
• initial stages are CD4 independent, but CD4 is required eventually
• mechanism is unclear but maybe…
• CD40/CD40L binding
• CD4 effect on APC’
• “Cross Priming” – if APC’s are not directly infected
• due to protein fragments that are released from cytolysed infected non-APC’s
• fragments are taken up and presented by APC’s on MHCI to CD8+ cells
after activation, clonal
expansion and expression of cytokines also expression of
cytolyticproteins (perforin,
granzymes)
MECHANISM OF CYTOLYSIS
initial contact is antigen-independent (ICAM on target, LFA1 on T cell)if TCR encounters antigen:MHCI, then CD8 will bind MHCI also signal cascade is initiated
effect – ICAM/LFA interaction strengthens unidirectional cytolysis
perforin – self-polymerizes and makes a
pore for granzymes
granzymes – serine proteases that activate
CAPSASES
granulysin – saposin like protein; highly cytolytic
Specificity
directional release of cytotoxins from T cell towards target cell
perforins cannot diffuse through extracellular fluid
OTHER MECHANISMS OF CYTOLYSIS
expression of FAS-L on some activated CD8+ cells (and CD4+)activates apoptotic pathway
accounts for some cytolysis in perforin-deficient mice
activated T-cells express Fas may help reduce T-cell response by affecting T cell death
in some cases, one of the pathways will kill bacteria and the other will SPREAD it