1st Journal Reading

ADAPTIVE IMMUNITY

Yanne Pradwi Efendi

Alergy-Immunology Subdivision
Medical Faculty of Andalas University/ RSUP DR. M. Djamil Padang
2016
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 Microbial infections are recognized by the innate immune system
both to elicit immediate defense and to generate long-lasting
adaptive immunity.

Multiple mechanisms for the induction of immune responses are

variations on a common design principle wherein the cells that
sense infections produce one set of cytokines to induce lymphocytes
to produce another set of cytokines, which in turn activate effector
responses.

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 Contd
The sensing of microbes by PRRs expressed on antigen-presenting
cells, particularly dendritic cells (DCs), leads to the activation of
adaptive immune responses.
Several classes of PRRs have now been identified and characterized
in some detail.

These include Toll-like receptors (TLRs), nucleotide-binding

oligomerization domain (Nod)-, leucine-rich repeatcontaining
receptors (NLRs), RIG-I-like receptors (RLRs), C-type lectin receptors
(CLRs) and AIM-2 like receptors, as well as a family of enzymes that
function as intracellular sensors of nucleic acids, including OAS
proteins and cGAS.
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 Studies over the past decade have also revealed several important
aspects of immune systems function that require an expanded view
of the innate control of adaptive immunity.

Commensal microorganisms and pathogenic microorganismsexpress

PAMPs and are detectable by PRRs; however, the outcome of their
recognition can depend on additional characteristics, such as
invasiveness and production of toxins.

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 Recognition by the innate immune system

Microbial targets of recognition by PRRs are structurally

diverse and include complex polysaccharides,
glycolipids, lipoproteins, nucleotides and nucleic acids.
Several families of PRRs detect these structures through
the use of distinct ligand-recognition domains, including
leucine-rich repeats, C-type lectin domains and various
nucleic acidbinding domains.

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 Contd

In summary, different modes of recognition by the innate

immune system form distinct layers of sensing by the immune
system that provide requisite information to the adaptive
immune system.

Working in different combinations, the sensing pathways of

the innate immune system instruct the activation of relevant
effector responses of the adaptive immune system.
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Recognition in different compartments

To recognize and respond to

Microbial pathogens enter
the host via mucosal
surfaces, through a breach
in the skin or via bites of
insect vectors.
invasion by vastly different
classes of infectious agents,
innate sensors are strategically
located in distinct anatomical,
tissue, cellular and subcellular
compartments.

The anatomical
compartment in which the
pathogen is recognized
informs the host of the
degree of threat it poses.

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 Microorganisms in the lumen of the gut do not trigger
inflammation, whereas those that have crossed the
epithelial layer induce a local inflammatory response.
Moreover, pathogens in the bloodstream signify a breach
in barrier and are met with a full-blown systemic
response.
This compartment-specific outcome of sensing by the
innate immune system is mediated by distinct sentinel
cells that are strategically located to detect the location
of pathogens.

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 Contd

Although the mechanisms by which multicellular

parasites are detected are not yet known, the defense
strategies used also demonstrate clear compartment-
specific effects.
Thus, the detection of macroparasites in the intestinal
and respiratory tracts promotes their expulsion through
increased production of mucus and peristalsis, whereas
the detection of parasitic eggs in the tissues can promote
their sequestration through granuloma formation.

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 The choice of effector responses

Because DCs have a critical role in the initiation

of T cellmediated responses, it has long been
suspected that different DC populations might be
specialized for the induction of different T cell
effector responses.
Studies of mice with specific deletions of
subpopulations of DCs have revealed an
emerging view of the unique capacity of DC
subpopulations to generate different classes of T
cell responses.
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 Defense by the immune system against
intracellular bacteria and protozoa requires
responses by CD8+ T cells and T helper type 1
cells (TH1 cell), which develop as a consequence
of the engagement of TLRs by PAMPs that leads
to the production of IL-12.

CTL responses to bacterial and protozoan

infection are preferentially induced by Batf3-
dependent CD103+ DCs that produce IL-12.

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 Contd

In summary, different sensing pathways of the innate

immune system are designed to determine the class of
infecting pathogens on the basis of their localization,
viability, replication and virulence.
These parameters are sensed by distinct sensory
pathways, often operating in combination, and are
translated into the signals that initiate the appropriate
types of effector responses.

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NEUTROPHILS: THEIR ROLE IN ADAPTIVE IMMUNITY

Polymorphonuclear neutrophils (PMNs) are

the most abundant leukocytes in the blood
and constitute the first line of host defense
against numerous infectious pathogens,
including bacteria, fungi, and protozoa

Neutrophils are the first leukocytes to migrate

from the blood to injured or infected sites for
killing pathogens and removing cellular debris.
Neutrophils migrate to sites of inflammation
and infection where they recognize and
phagocytose invadingmicroorganisms, in
order to kill them via different cytotoxic
mechanisms
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 Contd
In recent years, it has become evident that
neutrophils not only have a fundamental role in
the acute phase of inflammation when they
actively eliminate pathogens, but also are
capable of modifying the overall immune
response

Neutrophils can do this by exchanging information

with macrophages, dendritic cells, and other cells
of the adaptiveimmune system through either
soluble mediators or direct cell-cell contact.

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When neutrophils cannot kill
microorganisms by the classical
phagocytosis or degranulation
mechanisms, they can also
formneutrophil extracellular
traps (NETs) to kill microbes.
Contd
NETs are fibers composed of
chromatin and neutrophil-
granule proteins and are
induced by several
pathogens and also some
pharmacological stimuli.
Antigen-antibody complexes
can also induceNET
formation.
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 Contd
The paper byO. R. Aleman et al. explores direct
stimulation of individual Fc receptors to induce NET
formation and finds that only FcRIIIb cross-linking
induced NET formation in a NADPH oxidase-, PKC-, and
ERK-dependent.
Phagocytic and oxidative activities of neutrophils of
healthy older women that exercise regularly are higher
than those of sedentary older women.
The physical condition of each individual was a
significant predictor of phagocytosis potential.

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 The paper by M. R. Tardif et al.
describes an alternative secretion
pathway in neutrophils for the
release of the S100A8/A9
(calprotectin) and S100A12,
proinflammatorymediators.

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 Neutrophils seem to have dual roles in promoting
and controlling inflammation. The mechanisms that
control the final outcome are not completely
described, but these opposite functions must be
tightly balanced.

During sepsis, neutrophils are responsible for both

the release of cytokines and the phagocytosis of
pathogens. But, in SIRS (systemic inflammatory
response syndrome), neutrophils contribute to
maintaining of a whole-body inflammatory state.

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 Contd
Moreover, neutrophil derived products can regulate the action of
other immune cells and can contribute to the development and
chronicity of inflammatory diseases.

The two-hit model states that a first injury (i.e., hit) can serve
as a priming event which sequential insults can build on,
culminating in a disproportioned inflammatory response to injury.

On the other hand, the ischemic preconditioning (IPC) model

states that a mild ischemic event, either remote
or local, can be protective and can actually attenuate the
inflammatory response to the following insults.

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THANK YOU

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