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IMMUNE RESPONSE TO INFECTIOUS DISEASE

By: Erin Anthony Yasmin Deliz Jasminia Nuesa

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

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

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

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

VIRAL INFECTIONS

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

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)

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

VIRAL INFECTIONS

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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

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)

VIRAL INFECTIONS
Cell-Mediated Antiviral Mechanisms (Cont.)
Activated Th1 cells produce several cytokines

CTL activity
Arises within 3-4 days after infections Peaks by 7-10 days, and then declines Have viral specificity

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

Eliminites specific virusinfected cells, thus getting rid of potential new sources of new virus

TNF

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- & IFN

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

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

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

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?

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

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*