IMMUNE RESPONSE TO INFECTIOUS DISEASE

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IMMUNE RESPONSE TO INFECTIOUS DISEASE

• By Erin Anthony
• Yasmin Deliz
• Jasminia Nuesa

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INTRODUCTION

• Despite innate and adaptive immune responses to
  pathogens, infectious diseases which have plagued
  human populations throughout history still cause
  millions of deaths per year.
• There are 4 main types of pathogens that cause
  infectious disease
• 1. Viruses
• 2. Bacteria
• 3. Protozoa
• 4. Helminths

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VIRAL INFECTIONS

• One of the 4 main pathogens responsible for
  infectious diseases
• Responsible for smallpox, the common cold,
  chickenpox, influenza, shingles, herpes, polio,
  rabies, Ebola, hanta fever, and AIDS.
• Several specific immune effector nonspecific
  defense mechanisms
• Viruses act to subvert one or more of these
  mechanisms to prolong their survival

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VIRAL INFECTIONS

• Viruses Structure Function
• Viruses depend on host cells for reproduction
• Outside of host cells, the viruses remain
  metabolically inert
• They exist as a protein coat or capsid, sometimes
  enclosed within a membrane
• The capsid encloses either DNA or RNA which codes
  for the virus elements

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VIRAL INFECTIONS

• Viruses Structure Function (cont.)
• In contact with a cell, the virus, with help from
  surface molecules, will inject its genetic
  material into the cell
• Thus taking over the cells functions
• The infected cell produces more viral proteins
  and genetic material rather than its usual
  products
• In the cell, the virus has two phases
• 1. The lysogenic phase
• 2. The lytic phase

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VIRAL INFECTIONS
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VIRAL INFECTIONS

• Innate Immune Response
• - 2 primary events
• 1. Induction of Type I Interferons
• 2. Activation of NK cells

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VIRAL INFECTIONS

• Induction of Type I Interferons
• The double-stranded RNA (dsRNA) of the virus
  induces the expression of the interferons by the
  infected cell.
• The bound IFNs will activate the JAK/STAT
  pathway responsible for the synthesis of several
  genes
• One encodes 2-5(A) synthetase an enzyme that
  activates ribonuclease (RNAse L)

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VIRAL INFECTIONS

• IFNs and NK Cells
• In addition, IFN-a IFN-ß binding induces a
  specific protein kinase called RNA-dependent
  protein kinase (PKR)
• The binding of IFN-a IFN-ß to NK cells induces
  lytic activity
• Effective in killing virally infected cells
• Enhanced by IL-12

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VIRAL INFECTIONS
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VIRAL INFECTIONS

• Viral Neutralization by Humoral Antibody
• What is crucial to the preventing of the spread
  of the virus during acute infection and in
  protecting against reinfection?
• ANTIBODIES
• If antibody is produced to the viral receptor, it
  can block infection altogether by preventing
  viral binding to the host cells
• i.e. Secretory IgA in mucous secretions
• Viral Neutralization by antibody sometimes occurs
  after viral attachment
• Some may block viral penetration by binding to
  epitopes necessary to mediate fusion of the viral
  envelope with the plasma membrane
• Some cause the lysis of the enveloped virions
• Some agglutinate viral particles and function as
  an opsonizing agent

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VIRAL INFECTIONS

• Cell-Mediated Antiviral Mechanisms
• Antibodies, although crucial in containing the
  spread of the virus, are not able to eliminate
  the virus once infection has occurred
• Once infection occurs, cell-mediated immune
  mechanisms become the most important
• 2 main components of cell-mediated antiviral
  defense
• 1. CD8 Tc cells
• 2. CD4 Th1 cells (CD4 Tc cells)

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VIRAL INFECTIONS

• Cell-Mediated Antiviral Mechanisms (Cont.)

• Activated Th1 cells produce several cytokines
• IL-2
• Acts indirectly by assisting in the recuitment of
  CTL precursors
• Activates NK cells
• IFN-?
• Directly induces an antiviral state in cells
• Activates NK cells
• TNF

• CTL activity
• Arises within 3-4 days after infections
• Peaks by 7-10 days, and then declines
• Have viral specificity
• Eliminites specific virus-infected cells, thus
  getting rid of potential new sources of new virus

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VIRAL INFECTIONS

• Viral Invasion of Host-Defense Mechanisms
• Viruses encode proteins that interfere at various
  levels with specific or nonspecific host defenses
• Some develop strategies to avade the action of
  IFN-a IFN-ß
• Some inhibit the antigen presentation by infected
  hosts by preventing antigen delivery to class I
  MHCs
• Some reduce levels of class II MHCs on cell
  surface
• Others evade complement-mediated destruction
• Some cause generalized immunosuppression-direct
  viral infection of lymphocytes or macrophages
• Some constantly change their antigens
• i.e. Influenza

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VIRAL INFECTIONS

• Properties of the Influenza Virus
• Virions are roughly spherical or ovoid in shape
  with an ave. diameter of 90-100nm
• Virions are surrounded by an outer envelope
• 2 proteins are inserted into this envelope
• 1. Hemagglutinin (HA)
• 2. Neuraminidase (NA)
• Inside the envelope
• Matrix protein surrounds the nucleocapsid
• Consists of 8 different strands of ssRNA
  associated with protein and RNA polymerase

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VIRAL INFECTIONS

• Influenza
• 3 major types A, B, C
• Distinguished by differences in their
  nucleoprotein and matrix proteins
• Distinguishing feature of influenza virus is its
  variability
• Two different mechanisms for variation in HA NA
• 1. Antigenic Drift
• 2. Antigenic Shift

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VIRAL INFECTIONS

• Influenza (Flu) Symptoms
• Fever
• Muscle aches and pain
• Headache
• Fatigue
• Dry cough
• Sore throat
• Runny nose
• What makes this different from a cold?

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VIRAL INFECTIONS

• Host Response to Influenza Infection
• Humoral Antibody specific for the HA molecule is
  produced during infection
• Serum antibodies antibodies imporant for
  resistance to reinfection by the same strain, but
  not required for recovery
• In addition, CTLs also play a role

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VIRAL INFECTIONS

• Epstein-Barr (Infectious Mono)
• Herpes virus family
• Life-long dormant infection in some cells
• Symptoms
• Fever
• Sore Throat
• Swollen Lymph glands
• Swollen liver/spleen
• Age Group

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