IMMUNE RESPONSE TO INFECTIOUS DISEASE

1. IMMUNE RESPONSE TO INFECTIOUS DISEASE By: Erin Anthony Yasmin Deliz 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. VIRAL INFECTIONS • 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 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

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+ Tc cells • 2. CD4+ Th1 cells (CD4+ Tc cells)

13. 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-γ • 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

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*