Basic Immunology 4

dr. Tegar Adriansyah Putra Siregar, M. Biomed., Ph.D.

Department of Microbiology
Faculty of Medicine
Universitas Muhammadiyah Sumatera Utara
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1 Complement system

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2 Mediator of immune response
 Complement system

• Part of innate immunity  NOT adaptable, does NOT change over the course of
a person’s lifetime  however, can be recruited/activated by the adaptive
immune system

• Plasma proteins produced by the liver that work together to support immune
system

• Circulating in blood serum and within tissues

• Named “complements” because it complements the cells of the immune system

in destroying microbes
 Complement system

• Complement proteins are usually designated by an uppercase letter C and are

inactive until they are split into fragments (products).

• The proteins are numbered C1 through C9, named for the order in which they
were discovered

• Complement proteins act in a cascade; that is, one reaction triggers another,
which in turn triggers another, and so on

• Has 3 activation pathway: Alternative, Classical, Lectin

1. Alternative
pathway
• named “alternative” because
it was discovered after the
classical pathway
• is triggered when some
complement proteins are
activated on microbial
surfaces and cannot be
controlled, because
complement regulatory
proteins are not present on
microbes (but are present on
host cells).
• The alternative pathway is a
component of innate
immunity
2. classical
pathway
• is most often triggered
by antibodies that bind
to microbes or other
antigens and is thus

• a component of the
humoral arm of
adaptive immunity
3. Lectin pathway
• is activated when a
carbohydrate-binding plasma
protein, mannose-binding
lectin (MBL), binds to
terminal mannose residues on
the surface glycoproteins of
microbes.

• This lectin activates proteins

of the classical pathway, but
because it is initiated by a
microbial product in the
absence of antibody, it is a
component of innate
immunity.
Outcomes of
complement activation:
What’s next?
 Mediator of immune response

• In response to microbes, dendritic cells,

macrophages, mast cells, and other cells
secrete cytokines that mediate many of the
cellular reactions of innate immunity

• Cytokines are a large group of secreted

proteins with diverse structures and functions,
which regulate and coordinate many activities
of the cells of innate and adaptive immunity.

• The nomenclature for cytokines is

inconsistent (with some named Interleukin
followed by a number, and others named for a
biological activity first attributed to them,
such as tumor necrosis factor (TNF) or
interferon)
 Mediator of immune response
IFN
Based on receptor
specificity, classified into
three major types: (types I,
II, and III).
Receptor binding results in
the initiation of
downstream signaling
cascades, the result of
which is the activation of
transcription factors and
the induction of hundreds
of IFN-stimulated genes.
These genes encode
protein products with
antiviral, antiproliferative,
or immunomodulatory
properties.  therapeutic
use of IFNs.
IL
In contrast to the IFNs, the
interleukins are a diverse
family of immune system
regulators that function
primarily in immune cell
differentiation and
activation. They may be
either pro- or anti-
inflammatory.
chemokines
The largest family of
cytokines is the
chemokines, with 44
members (and increasing)
that bind to one or more of
21 G-protein-coupled
receptors
These small secreted
proteins are classified into
four types (CXC, CC, C,
and CX3C)
Chemokines function as
chemoattractants to
control the migration of
cells, particularly those of
the immune system
 Mediator of immune response
IL
Interleukins are a diverse
family of immune system
regulators that function
primarily in immune cell
differentiation and activation
either pro- or anti-
inflammatory.
chemokines
The largest family of cytokines is the chemokines,
with 44 members (and increasing) that bind to one
or more of 21 G-protein-coupled receptors
These small secreted proteins are classified into
four types (CXC, CC, C, and CX3C)
Chemokines function as chemoattractants to
control the migration of cells, particularly those of
the immune system
Mediator of immune response

chemokines

The largest family of cytokines is the chemokines, with

44 members (and increasing) that bind to one or more of
21 G-protein-coupled receptors.
Classified into four types (CXC, CC, C, and CX3C).
Chemokines function as chemoattractants to control the
migration of cells, particularly those of the immune
system
CSF
Colony-stimulating factors (CSFs), such as
granulocytemacrophage colony-stimulating factor (GM-CSF),
macrophage colony-stimulating factor (M-CSF), and
granulocyte colony-stimulating factor (G-CSF), stimulate
hematopoietic progenitor cell proliferation and differentiation

The name of this cytokine derives from its original

TNF identification as a serum substance (factor) that caused

necrosis of tumors, now known to be the result of
inflammation and thrombosis of tumor blood vessels.

TNF is expressed by a variety of immune cells, and its primary

receptor, TNFR1, appears to be expressed by all cell types,
ensuring widespread effects of this cytokine
• Dendritic cells, macrophages, and other cells respond to microbes by
producing cytokines that stimulate inflammation (leukocyte
recruitment) and activate natural killer (NK) cells to produce the
macrophage-activating cytokine interferon-γ (IFN-γ)
Antiviral State

• Defense against viruses is a special

type of host response that involves
interferons, NK cells, and other
mechanisms.
• Type I interferons inhibit viral
replication, and induce an antiviral
state, in which cells become resistant
to infection.
• Type I IFNs, which include several
forms of IFN-α and one of IFN-β, are
secreted by many cell types infected
by viruses.
• A major source of these cytokines is a
type of dendritic cell called the
plasmacytoid dendritic cell
 Thank You
References:
• Jawetz, Melnick & Adelberg. Medical Microbiology, 28th edition.
• Abbas. Basic Immunology, 5th edition.