T cells-PART III

FUNCTIONS OF EFFECTOR CD4+ T CELLS

Intracellular bacteriaListeria monocytogenes,

Mycobacterium leprae,
Mycobacterium tuberculosis
These microbes use evasion
mechanisms to prevent their
destruction by macrophages

Cooperation of CD4+ and CD8+ T cells in defense against intracellular microbes. Intracellular bacteria
such as L. monocytogenes are phagocytosed by macrophages and may survive in phagosomes and escape
into the cytoplasm. CD4+ T cells respond to class II MHC-associated peptide antigens derived from the
intravesicular bacteria. These T cells produce IFN-gamma;, which activates macrophages to destroy the
microbes in phagosomes. CD8+ T cells respond to class I-associated peptides derived from cytosolic
antigens and kill the infected cells.

Adaptive immune responses to extracellular microbes.

Adaptive immune responses to extracellular microbes, such as bacteria, and

their toxins consist of antibody production and the activation of CD4+ helper T
cells. Antibodies neutralize and eliminate microbes and toxins by several
mechanisms. Helper T cells produce cytokines that stimulate B cell responses,
macrophage activation, and inflammation. (Abbas).

(Abbas AK., Lichtamn AH, Pillai ,S.)

Functions of human Ig classes and subclasses

IgG1 and IgG3 -IFN--Th1 (signature cytokine)

IgE, IgA-IL-4 and IL-5-Th2 (signature cytokine)

Effector Functions of Th1 cells-Defense against intracellular

pathogens (Macrophage activation, antiviral responses) but also
extracellular pathogens (antibodies)

Effector functions of TH1 cells. CD4+ T cells that differentiate into TH1 cells secrete IFN-gamma;,
lymphotoxin (LT) and TNF, and IL-2. IFN-gamma; acts on macrophages to increase phagocytosis and killing
of microbes in phagolysosomes and on B lymphocytes to stimulate production of IgG antibodies that
opsonize microbes for phagocytosis. LT and TNF activate neutrophils and stimulate inflammation. IL-2 is
the autocrine growth factor made by this subset of T cells (not shown). APC, antigen-presenting cell
(Abbas)

Th1 cells

Activation and functions of macrophages in cell-mediated immunity. In cell-mediated immunity,

macrophages are activated by CD40L-CD40 interactions and by IFN-gamma; and perform several functions
that kill microbes, stimulate inflammation, and enhance the antigen-presenting capacity of the cells.
(Abbas)

Following T-B cell interactions cytokines are released by

activated T cell-Determines class of antibody that is produced

Th1 cytokine

Selected examples of switched isotypes in humans are shown

IgG1 and IgG3 can opsonise microbe for phagocytosis

(Abbas) Antibody-mediated opsonization and phagocytosis of microbes.

Antibodies of certain IgG subclasses bind to microbes and are then
recognized by Fc receptors on phagocytes. Signals from the Fc
receptors promote the phagocytosis of the opsonized microbes and
activate the phagocytes to destroy these microbes.

IgG1 and IgG3 can opsonise cells for killing by NK cells

(Abbas) Antibody-dependent cell-mediated cytotoxicity. Antibodies of

certain IgG subclasses bind to cells (e.g., infected cells), and the Fc
regions of the bound antibodies are recognized by an Fcgamma
receptor on NK cells. The NK cells are activated and kill the antibodycoated cells.

Th2 response predominates in Helminth infections-2 billion people infected

most parasites in intestine, some invade epithelial barrier and others found
in tissues such as liver, lung.
Th2 cytokines lead to high IgE production and recruitment of mast cells & eosinophils

(Abbas) Effector functions of TH2 cells. CD4+ T cells that differentiate into TH2 cells
secrete IL-4 and IL-5. IL-4 acts on B cells to stimulate production of antibodies that
bind to mast cells, such as IgE. IL-4 is also an autocrine growth and differentiation
cytokine for TH2 cells. IL-5 activates eosinophils, a response that is important for
defense against helminthic infections.

Parasitic Infections
Eosinophils attacking a schistosome larva

Parasites such as worms cannot be ingested by phagocytes, instead

antibodies coat the parasite and eosinophils can attack the parasite
through their binding to FcRs. Eosinophils express FcR, FcRs, FcRs
bind to IgE, IgG and IgA coated parasites. Eosinophils-major basic
protein and eosinophil cationic protein-highly toxic to helminths

Parasitic Infections-IgE causes Mast cell Degranulation

IgE binds to high affinity FcRI

on tissue mast cells

Crosslinkage of receptor-bound
IgE molecules by antigen induces
degranulation of mast cells

Mast cells located in high numbers

in GIT

Histamine, lipid mediators lead to

gut peristalsis

Vasodilation and increase in

vascular permeability, increase in
neutrophils/eosinophils to the site
of infection (chemokines),
important in defense against
parasitic infections, eosinophil
binds to antibody coated parasite

Th17 cells
Named Th17 as secrete IL-17
Important in defense against certain bacteria and fungi
Early Response-leads to recruitment of neutrophils and
macrophages to infected tissues.
Induces expression of proinflammatory cytokines (TNF and IL-6),
chemokines (neutrophil chemotaxis), matrix metalloproteinases
Associated with autoimmune diseases (eg rheumatoid arthritis,
Multiple Sclerosis)

Mechanisms of CTL-mediated lysis of target cells. CTLs kill target cells by two main
mechanisms. A. Complexes of perforin and granzymes are released from the CTL by granule
exocytosis and enter target cells. The granzymes are delivered into the cytoplasm of the
target cells by a perforin-dependent mechanism, and they induce apoptosis. B. FasL is
expressed on activated CTLs, engages Fas on the surface of target cells, and induces
apoptosis (Abbas).

Immune synapse between CTLs and a target cell (Abbas)

Learning Outcomes
CD8+ cytotoxic T cells together with which CD4+ effector T
cells are concerned with the elimination of intracellular
pathogens?
IFN- leads to the differentiation of IgX (?) secreting B cells
Th1 cells lead to the activation of macrophages, what are the
other effector functions of the Th1 cells? What type of
pathogens do Th1 cells eliminate? (intracellular/extracellular?)
IL-4 is the signature cytokine of Th2 cells. What are the key
roles of Th2 cells in the immune response to pathogens?
Describe how CTL kill their target cells?

Fill in this table

Effector
CD4+ T cell
Indicate the
Effector
Functions

Th1

Th2

Th17

Reading Material
Parts of Chapters 8 & 9 (Janeway)
Or
Parts of Chapters 10 & 13 (Abbas, Lichtman, Pillai Cellular and
Molecular Immunology)
Or
Alternative Textbook (Humoral and Cell-Mediated Immunity)