Transcript Innate Immunity To Intracellular Bacteria

Department of Immunology
IMMU 7070-Introductory Immunology 2010-2011
Immune Response against Infectious
Diseases
Oct 20, 2011
Dr. Nyla Dil
437 Apotex Centre
272-3149
Objectives
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To understand how the immune system
performs its major physiologic function.
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To illustrate the physiologic relevance of
various aspects of immune system function to
different types of pathogenic microorganisms
and how microbes try to resist the mechanisms
of host defence.
Outline
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General Features of Immune Response to
pathogenic microorganisms
Immune response to:
-Viruses
-Extracellular Bacteria
-Intracellular Bacteria
Immune System
The principal function of the immune
system is to protect the host against
pathogenic microbes.
 Immunity may be innate or specific.
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Pathogens & Disease
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Pathogens are defined as microbes
capable of causing host damage.
When host damage reaches a certain
threshold, it can manifest itself as a
disease.
Pathogenesis of Infectious Diseases
Development of an infectious disease in an
individual involves complex interactions
between the microbe and the host.
Key events during infection include:
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Entry of the microbe
Invasion and colonization of host tissues
Evasion of host immunity
Tissue injury or functional impairment
Important General Features of Immunity to
Pathogens
• Defense against pathogens is mediated by both
innate and specific immunity.
• The innate immune response to pathogens plays
an important role in determining the nature of
the specific immune response.
• The immune response is capable of responding in
distinct and specialized ways to different
pathogens in order to combat these infectious
agents most effectively
Important General Features of Immunity to
Pathogens
• The survival and pathogenicity of pathogens in a
host are critically influenced by their ability to
evade or resist effector mechanisms of
protective immunity.
• Tissue injury and disease consequent to
infections may be caused by the host response to
the pathogen and its products rather than the
pathogen itself.
Agents That Cause Infectious
Disease
Pathogens
Viruses
Bacteria
Parasites
Fungi
Immunity To Viruses
Immunity To Viruses
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Obligatory intercellular pathogens that
replicate within cells.
Use the nucleic acid and protein synthesis
machineries of the host cell.
Infect a variety of cell populations by
utilizing normal cell surface molecules as
receptors to enter cell.
Innate Immunity To Viruses
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The principal mechanisms of
innate immunity against viruses
are :
-Inhibition of infection by
type I IFNs
-NK cell-mediated killing of
infected cells.
Innate Immunity To Viruses
Adaptive Immunity To Viruses
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Adaptive immunity against viral infections is
mediated by:
- Antibodies: block virus binding and entry into
host cells
- CTLs: eliminate the infection by killing
infected cells
Adaptive Immunity To Viruses
Mechanism of Immune Evasion by Viruses
Mechansim of Immune Evasion Examples
Antigenic variation
Influenza, rhinovirus, HIV
Inhibition of antigen processing
Blockade of TAP transporter
Herpes Simplex
Removal of class I molecules
from ER
Cytomegalovirus
Production of cytokine
Receptor
homologs
Vaccinia, Poxviruses
Production of
Immunosuppressive cytokines
Epstein-Barr virus
Infection of Immunocompetent HIV
cells
Immunity To
Extracellular Bacteria
Immunity To Extracellular Bacteria
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Extracellular bacteria are capable of replicating
outside host cells.
They cause disease by two principal mechanisms:
 They induce inflammation, which results in tissue
destruction at the site of infection.
 Many of these bacteria produce toxins:
- Endotoxins
- Exotoxins
The immune responses against extracellular
bacteria are aimed at eliminating the bacteria and
at neutralizing the effects of their toxins.
Innate Immunity To Extracellular Bacteria
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The principal mechanisms of innate immunity to
extracellular bacteria are:
-Complement activation
-Phagocytosis
-Inflammatory response
Innate Immunity To Extracellular Bacteria
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Complement activation leads to opsonization and
enhanced phagocytosis of bacteria
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Complement by-products stimulate inflammatory
response by recruiting and activating leukocytes
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Phagocytes use surface receptors (mannose
receptors,scavenger receptors), to recognize
extracellular bacteria.
Phagocytes use Fc receptors and complement
receptors to recognize opsonized bacteria.
Innate Immunity To Extracellular Bacteria
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TLRs participate in the activation of the
phagocytes as a result of encounter with microbes.
These various receptors promote the phagocytosis
of the microbes and stimulate the microbicidal
activities of the phagocytes.
Activated phagocytes secrete cytokines, which
induce leukocyte infiltration into sites of infection
(inflammation).
Injury to normal tissue is a pathologic effect of
inflammation.
Adaptive Immunity To Extracellular Bacteria
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Humoral immunity is the principal protective
immune response against extracellular bacteria:
Functions to block infection, eliminate the
microbes, neutralize toxins
Adaptive immune responses to EC microbes
consists of :
-Antibody production
-Activation of CD4+ helper T cells
Adaptive Immunity To Extracellular Bacteria
Adaptive Immunity To Extracellular Bacteria
Mechanism of Immune Evasion by Extracellular
Bacteria
Immunity To Intracellular
Bacteria
Immunity To Intracellular Bacteria
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Intracellular bacteria survive and even replicate
within phagocytes.
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These microbes are able to find a niche where they
are inaccessible to circulating antibodies.
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Their elimination requires the mechanisms of cellmediated immunity
Innate Immunity To Intracellular Bacteria
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The innate immune response to intracellular
bacteria is mainly mediated by:
-Phagocytes
-Natural Killer (NK) cells
Innate Immunity To Intracellular Bacteria
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Mice with severe combined immuno deficiency,
which lack T and B cells, are able to transiently
control infection with the intracellular bacterium
Listeria monocytogenes by NK cell-derived IFN-γ
production. However, innate immunity usually fails
to eradicate these infections, and eradication
requires adaptive cell-mediated immunity.
Adaptive Immunity To Intracellular Bacteria
The major protective immune response against
intracellular bacteria is T cell-mediated
immunity.
Adaptive Immunity To Intracellular Bacteria
Mechanism of Immune Evasion by Intracellular
Bacteria
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Group Activities
Summary