Aula TE4

Punt • Stranford • Jones • Owen
Kuby Immunology
EIGHTH EDITION
Lecture PowerPoint
CHAPTER 4
Innate Immunity
Copyright © 2019 by W. H. Freeman and Company

Barriers are just one difference between
innate and adaptive immune responses
Anatomical
Barriers to
Infection
• Several barriers, both physical and chemical, exist
to prevent pathogens from gaining access to deep
Anatomical tissues
Barriers to • Should those barriers be breached, innate immune
system receptors recognize the threat
Infection • Conserved pathogen-associated molecular patterns
(PAMPs) found on microbes
• Aging, dead, or damaged self-structures can also be
recognized
• Conserved Damage-associated molecular patterns
(DAMPs)
• Pattern recognition receptors (PRRs) recognize
these structures and target them for clearance
Epithelial barriers prevent pathogen entry into the body’s interior
Anatomical
Barriers to
Infection
Antimicrobial Proteins and Peptides Kill Potential Invaders
Families of PRRs recognize a wide
Cellular variety of PAMP ligands
Innate Toll-like C-type lectin NOD-like RIG-I-like
Response receptors
(TLR)
receptors
(CLR)
receptors
(NLR)
receptors
(RLR)
Receptors
& Signaling
Signaling pathways are activated,

contributing to innate/inflammatory
responses
TLR recognize conserved
molecular patters
present in a variety of
molecules
• Some are expressed in
the plasma membrane
• Some are expressed in

endosomes
• Location helps determine

what each TLR will bind
TLR binding to
PAMP/DAMP activates
signaling pathways that
induce:
• Activation of transcription
factors NF-κB and AP-1
• Activation of interferon
regulatory factors IRFs
• Induction of antimicrobials
and inflammatory cytokines:
TNF-⍺, IL-1β, IL-6, IFN-⍺, IFN-β
CLR recognize carbohydrates, are
present in the plasma membrane,
and binding of PAMP/DAMP to CLR
results in:
1. Activation of signaling pathways (NF-κB ,
AP-1 and IRFs)
2. Production of inflammatory cytokines
(TNF-⍺ / IL-1β / IL6 / IFN-⍺ / IFN-β)
3. Phagocytosis
• NLR are expressed intracellularly,
namely in endosomes.
• Binding of intracellular PAMP/DAMP
induces:
1. Expression of genes encoding for:
• Inflammatory cytokines
• Antimicrobial peptides
2. Autophagy: formation of
autophagosomes that fuse with
lysosomes and kill bacteria
3. Some NLR (and other PRR) form
large complexes with caspases called
INFLAMMASOMES (secretion of IL-1)
Production of
Innate Immunity
Proteins
Induced by PRR
Signaling
• Derived from common lymphoid progenitor
cells
Innate • Include NK cells and six other ILC populations

Lymphoid
• NK cells found in lymphoid tissue and
Cells (ILC) recirculate, other ILC mainly found in
epithelium
• Each group of ILC based on cytokines

produced
• ILCs lack PRRs and thus are not activated

directly by pathogens
• NK cells are lymphocytes with innate immune
functions
Natural
• Express a limited set of receptors for self-proteins
Killer (NK) induced by:
Cells • Infections
• Malignant transformations
• Other stresses
• Activated NK cells perform one of two functions:

• Kill the altered self-cell by releasing perforin
and granzymes inducing apoptosis
• Produce cytokines that induce adaptive
responses against the altered self-cell
Lymphoid Tissue inducer
Effector
Mechanisms
of Innate
Immunity
PRR signaling pathways activate
expression of a large variety of
Cellular genes:
Innate • Antimicrobial peptides
Responses • Type I interferons (potent antiviral activity)
• Inflammatory cytokines (IL-1, TNF-α)
• Chemokines (IL-8)
• Enzymes: iNOS and COX2
Phagocytosis is an Important Mechanism to
Eliminate Microorganisms
1) Destruction by O2-independent
mechanisms (e.g., enzymes)
2) Autophagy
3) Destruction by O2-dependent
mechanisms (ROS and RNS)
4) Clearance of Dead Cells
Destruction by O2-dependent mechanisms
Clearance of Dead Cells – DAMP (Damage or Danger)
Apoptosis (e.g.,
Necrosis Netosis Pyroptosis
TNF-⍺)
• Programmed • Uncontrolled cell • Release of • Induced by
(regulated) cell dead neutrophil inflammasome
dead • Inflammation extracellular traps • Regulated cell dead
• No inflammation (NETs) • Eliminates infected
• Scavenger • Requires NADPH macrophages
Receptors, oxidase and • Allows release of
Phosphatidylserine generation of ROS IL-1β and IL-18
Receptors,
Calreticulin
Receptor
Eat-Me
Signals
NETosis
Inflammation is Triggered by Innate Immune Responses
These events cause:

• Redness
• Swelling
• Heat
• Pain
four characteristics of
local inflammation
The Innate
Immune
System
Activates
Adaptive
Immune
Responses
A constant interplay between

the two systems exists, and
dendritic cells are a key
bridge
Basic barrier mechanisms and simple
biochemical defenses are the frontline of
immunity
Summary Innate immune responses depend on recognition

of “general” pathogen molecules
• Responses are varied, but include:
• Phagocytosis
• Triggering of inflammatory responses
• Direct destruction by natural killer cells
• Initiation of adaptive immune responses
Learning the first defense strategies of immunity

helps to better understand the later adaptive
methods

Aula TE4

Uploaded by

Copyright:

Available Formats

Aula TE4

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Aula TE4

Uploaded by

Copyright:

Available Formats

Punt • Stranford • Jones • Owen

Copyright © 2019 by W. H. Freeman and Company

Signaling pathways are activated,

• Some are expressed in

• Location helps determine

Innate • Include NK cells and six other ILC populations

• Each group of ILC based on cytokines

• ILCs lack PRRs and thus are not activated

• Activated NK cells perform one of two functions:

These events cause:

A constant interplay between

Summary Innate immune responses depend on recognition

Learning the first defense strategies of immunity

You might also like