Download Immunity to Viruses

Immunity to Pathogens
Pin Ling (凌 斌), Ph.D.
ext 5632; [email protected]
References:
1. Abbas, A, K. et.al, Cellular and Molecular
Immunology, 7th ed., 2012. Chapter 15
2. I. Roitt et al., Immunology (8th ed., 2013),
Chapters 13 ~ 15
Question
What are the extra mechanisms to
generate Ab diversity in lymph nodes ?
Ans: 1. VDJ gene recombination 2. Somatic hypermutation -
=> V regions => Ag binding
3. Isotype switching => Fc portion => Effector function
Overview of immune responses
Outline
• Overview of infectious diseases
• Immunity to Viruses
• Immunity to Bacteria & Fungi
• Immunity to Parasites
• Summary & Question
Plagues & Infectious Diseases:
Threats from Pathogens
Smallpox epidemic in the Americas & Europe
The first vaccination against smallpox
Exudate from a
cowpox pustule on
the hand of
milkmaid Sarah
Nelmes was
inserted into
scratches on the
arms of James
Phipps, May 14,
1796.
Adopted from www.ebinrushed.com/history/images/history_7.jpg
More pathogens are emerging from zoonotic infection
or climate changes, e.g., IAV (H5N1 & H7N9);
SARS…etc.
Different pathogens interact our human body
differently => Tropism, Pathogenesis…etc.
Outline
• Overview of infectious diseases
• Immunity to Viruses
• Immunity to Bacteria & Fungi
• Immunity to Parasites
• Summary & Question
Key Concepts in antiviral immunity-I
1. The relationship between humans and viruses
(pathogens) is like a endless race.
2. Viruses need to find a niche in humans for their
survival and replications. Also they develop
strategies to counteract antiviral immunity.
3.
Humans consist of multiple levels of immune
protective mechanisms as below:
(1) Physical barrier
(2) Innate immunity
(3) Adaptive immunity
4. Some immune operations involve the cooperation of
both innate and adaptive components
Kinetics of
activation of
host defenses
Innate immunity against virus infection
1.
Soluble factors (microbicidal peptides) show antiviral
effects.
Influenza virus HA => Sialic acid
Surfactant protein
(SP-D)
Mucins & Pentraxins
2.
Type I interferons (IFNs) have critical antiviral and
immune regulatory roles
3.
NK cells eliminate virus-infected cells in an Agindependent manner.
4.
Macrophages kill viruses or virus-infected cells
Type I IFN from infected cells &
plasmacytoid dendritic cells
Innate immune recognition of viral
nucleic acids and type I IFN production
Mice lacking type I IFN receptor are highly
susceptible to viral infection.
Bowie, AG et al 2008
15
Type I IFNs affect infected cells &
many other immune cells
Adaptive immunity against viral infection
1.
T cells mediate antiviral immunity:
(1) CD8 T cells eliminate virus-infected cells in Agdependent manner
(2) CD4 T cells help B cell Ab responses (class
switching & affinity maturation)
(3) Memory T cells help combating reinfection
2.
B cells mediate antiviral immunity:
(1) Produce Ab to neutralize viruses
(2) Ab-dependent cell-mediated virus inhibition
(ADCVI)
Adoptive transfer of HSV-sensitized
T cells leads to protection
Antibody-mediated antiviral effects
Multiple antiviral effector mechanisms
Key Concepts in antiviral immunity-II
1. Virus strategies to evade host immune responses:
(1) Impair the host immune response
(2) Avoid recognition by Abs or T cells:
a. Reducing MHC expression on infected cells
b. Mutation of viral antigen
2.
Viral infections sometimes lead to immunopathological conditions:
(1) Excessive cytokine production (Cytokine storm)
(2) Ab can form immune complexes => tissue damage
(3) Overactive cytotoxic T cell responses => tissue
damage
Viruses inhibit Ag processing or
presentation
Outline
• Overview of infectious diseases
• Immunity to Viruses
• Immunity to Bacteria & Fungi
• Immunity to Parasites
• Summary & Question
Innate immunity against bacterial
infection
1.
The first line of defense against bacteria:
(1) Skin & mucus
(2) low PH
(3) Soluble factors (Complements & others)
(4) Commensals (Good neighbors)
2.
Pattern-recognition receptors recognize bacterial
components and then trigger innate immune
responses.
3.
Macrophage-mediated antibacterial defenses
Bacterial infection-mediated
pathogenesis
Innate immune responses against
bacterial infection
Host defense peptides to bacteria
& fungi
Toll-like Receptors
Recognition of bacteria by
Macrophage
Direct binding
Opsonization
S9780323080583-014-f007
Phagocytosis by innate immunity
Evasion of Phagocytosis by bacteria &
fungi
Endotoxin Shock
Phagocytosis of fungi
Antibody & T cell –dependent immunity
against bacterial infection
1.
Antibody-mediated antibacterial responses:
(1) Neutralize toxins Skin & mucus
(2) Block attachment or entry
(3) Activate the complement system
(4) Activate other immune cells w/ Fc receptors
2.
T cell-mediated antibacterial responses:
(1) CD8 T cells kill infected cells (intracellular
bacterial infection)
(2) CD4 T cells enhance Macrophage-mediated killing
(3) Other T cell populations
Cooperation of Antibody & Complements
CD8 T cell-mediated killing of bacteria
CD4 T cell–mediated antibacterial
Outline
• Overview of infectious diseases
• Immunity to Viruses
• Immunity to Bacteria & Fungi
• Immunity to Parasites
• Summary & Question
Overview of parasite-triggered immune
responses
Roles of T cells in parasite infection
Differentiation of T cells in
parasite infection
Roles of Antibody in parasite infection
Interaction between innate and
& adaptive immunity
1. Innate immunity => Ag presentation (by Dendritic cells)
2. Adaptive immunity => Ag recognition (by T & B lymphocytes)
SUMMARY
1. The interactions between humans and pathogens are
involved in multiple factors and cells.
2. Humans consist of multiple levels of immune
protective mechanisms to eliminate or restrict
pathogen spread in the body
(1) Physical barrier
(2) Innate immunity
(3) Adaptive immunity
3.
To kill a pathogen, often immune operations involving
both innate and adaptive components are used.
4.
Pathogens develop diverse strategies to promote
their survival in the host=> Immune Escape
Question
Have you learned something from
this series of Immunology Lectures?
(1) Yes, (2) More or less, (3) Not Sure, (4) Definitely
Not
 Lectures & textbook give you current answers to
biological & pathological operations of our immune
system
 The real & more answers to Immunology are still
waiting for you to learn from our body & patients.