CELL-MEDIATED

IMMUNITY
DR. DEDY SUTRIYATNO
• EFFECTOR CELLSthe cells that perform effector functions during an
immune response, such as secreting cytokines (e.g helper T cells), killing
microbes (macrophages, neutrophiles, eosinophiles), killing microge-infected
host cells (CTLs), secreting antibody (Plasma cells)
• CYTOKINESsecreted proteins that function as mediators of immune &
inflammatory reactions.
• INTERLEUKINanother name for a cytokine that acts on leukocytes,
originally used to describe a cytkine made by leukocytes.
 • whose role is to combat infections by intracellular microbes.
• Mediated by T lymphocytes.
• 2 types of infection may lead to microbes finding a haven insde cells

Microbes are ingested by phagocytes as part of the early defense mechanism

of innate immunity, but some of these microbes have evolved to resist the
microbicidal activities

Viruses may bind to receptors on a wide variety of cells & are able to infect &
replicate in the cytoplasm of these cells
Antigen Recognition & Costimulation
The initiation of T cell responses requires multiple
receptors on T cells recognizing ligands on APCs

• TCR  MHC-associated peptide antigens

• CD4 or CD8 co receptors recognize MHC molecules
ACCESORY
• Adhesion molecules strengten MOLECULES
SIGNALLING &
• Receptors for costimulatros recognizes second signals ADHESION
• At the time when th TCR is recognizing the peptide-MHC complex, CD4 or
CD8 recognizes the class II or class I MHC molecule respectively, at a site
separate from the peptide-binding cleft.
• Two or more TCRs and coreceptors need to be engaged simultaneously to
initiate the cell respone
• Each T cell needs to engage antigen for a long period at least several minutes or
multipel times to generate enough biocheimcal signal to initiate a response.
 Role of adhesion molecules in T cell response

• Recognize their ligands on APCs & stabilize the binding of the T cells to the
APCs
• Integrins (leukocyte function-associated antigen-1{LFA-1}) – ICAM-1
(intercellular adhesion molecule-1)
 • Adhesion molecules on T cells recognize their ligands on APCs & stabilize the
binding of the T cells to the APCs

Naive T chemokine Naive T T cell + APC bind each

cells+low- cells+high- another strongly at site
affinitiy LFA-1 affinitiy LFA-1 infection
& cluster within
minute

• Adhesion molecules on T cells recognize their ligands on APCs & stabilize the
binding of the T cells to the APCs
ROLE OF COSTIMULATION IN T CELL
ACTIVATION
• The full activation of T cells is dependent on the recognition of
costimulators on APCs.
• Ligand B7 (B7-1/CD80 & B7-2/cd86) incresed when APCs encounter
microbes CD28. in the absence of CD28-B7 interactions, engagement of
TCR alone is unable to activate Tcells
• CD40CD40L (T cells), activates APCs to express more B7 & secrete IL-12
(enhace T cell differentiation), INDIRECTLY
STIMULI FOR THE ACTIVATION OF CD8
T CELLS
HAS UNUSUAL FEATURE CELL ACTIVATION:
1. Require that cytoplasmic antigen from one cell hast to be cross-presented
by dendritic cells
2. Their diffrentiation into CTLs may require the concomitant activation of
CD4 helper T cells. (CTL responses to some viruses do not appear to
require help from CD4m for reasons that are not known.
Functional responses of T lympocytes to
Antigen & costimulation
SECRETION OF CYTOKINES &
EXPRESSION OF CyTOKINE
RECEPTORS
• In response to antigen & costimulators, T lympocytes, especially CD4 T cell,
rapidly secrete several different cytokines that have diverse activities.
• The first cytokine to be produced by CD4 T cell, within 1-2 hours after
activation, is IL-2.
• Enhance the increasing the expression of IL-2 receptor.
• Functions IL-2survival & proliferation of T cells (↑ antigen-specific T
cells), regulatory
• CD8 do not appear to secrete large amounts of IL-2.
CLONAL EXPANSION
• 1-2 days after activation, T lympocytes begin to proliferate, resuling in
expanxion of antigen-specific clones
• Expansion of CD8>CD4
• CD8 1 in 105-106 10-20% of all lympocytes. 100.000 fold, double in 6
hours
• CD4100-1000-fold
 DIFFERENTIATION OF NAIVE T CELLS
INTO EFFECTOR CELLS
• Differetiated effector cells appear within 3-4 days after exposure to microbes..
These cells leave peripheral lymphoid organs & migrate to the site of infection.
• CD4 helper T cells differentiate into effector cells that respond to antigen by
producing surface molecules & cytokines that function to activate phagocytes & B
cells
• CD40 L most important cell surface protein in effector function