CD4 T cells recognize antigen presented on MHC class II and differentiate into either TH1 or TH2 effector cells. TH1 cells activate macrophages and release cytokines like IFNγ to kill intracellular pathogens. TH2 cells activate B cells to secrete antibodies through cytokines like IL4. CD8 cytotoxic T lymphocytes recognize antigen on MHC class I and kill infected cells through release of perforin and granzymes or Fas-Fas ligand interaction. T cell activation involves cytokine signaling and interaction with antigen presenting cells to mount an adaptive immune response against pathogens.

1. CD4 T-HELPER
CELL
EFFECTOR
FUNCTIONS
CD8
CYTOLYTIC T
LYMPHOCYTES
(CTL)

2. antigen recognition
does not occur at site
of entry, but usually in
lymph nodes/spleen
activated T cells then
migrate to target
tissues

3. 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

4. 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

5. TH1
1) γ-inteferon is released in response to
macrophage MHC II antigen presentation
• these combined enhance macrophage lysosome-phagosome
fusion
• 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

6. 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

7. 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 cells
inhibited by interferon-γ made by
TH1 cells

8. 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

9. 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

10. 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

11. 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
cytolytic
proteins
(perforin,
granzymes)

12. 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

13. 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