1. IMMUNE RESPONSE TO INFECTIOUS DISEASE By: Erin Anthony By: Erin Anthony Yasmin Deliz Yasmin Deliz Jasminia Nuesa Jasminia Nuesa

2. 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

3. 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

4. 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

5. VIRAL INFECTIONS  Viruses: Structure & Function (cont.)  In contact with a cell, the virus, with help from surface molecules, will inject it’s genetic material into the cell  Thus taking over the cell’s functions  The infected cell produces more viral proteins and genetic material rather than it’s usual products  In the cell, the virus has two phases:  1. The lysogenic phase  2. The lytic phase

6. VIRAL INFECTIONS

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

8. 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 IFN’s 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)

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

10. VIRAL INFECTIONS

11.  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

12. 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+ T c cells  2. CD4+ T h 1 cells (CD4+ T c cells)

13. VIRAL INFECTIONS  Cell-Mediated Antiviral Mechanisms (Cont.) Activated Th1 cells produce several cytokines Activated Th1 cells produce several cytokines IL-2 IL-2 Acts indirectly by assisting in the recuitment of CTL precursors Acts indirectly by assisting in the recuitment of CTL precursors Activates NK cells Activates NK cells IFN-γ IFN-γ Directly induces an antiviral state in cells Directly induces an antiviral state in cells Activates NK cells Activates NK cells TNF TNF CTL activity CTL activity Arises within 3-4 days after infections Arises within 3-4 days after infections Peaks by 7-10 days, and then declines Peaks by 7-10 days, and then declines Have viral specificity Have viral specificity Eliminites specific virus- infected cells, thus getting rid of potential new sources of new virus Eliminites specific virus- infected cells, thus getting rid of potential new sources of new virus

14. 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-α & IFN- β  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

15. 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

16. 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

17. 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?

18. 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

19. 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*