1. Immune Response against Infectious Diseases
Department of Immunology
IMMU 7070-Introductory Immunology
Immune Response against Infectious Diseases
Dr. Nyla Dil
437 Apotex Centre
Oct 20, 2011

2. Objectives
To understand how the immune system performs its major physiologic function.
To illustrate the physiologic relevance of various aspects of immune system function to different types of pathogenic microorganisms and how microbes try to resist the mechanisms of host defence.

3. Outline General Features of Immune Response to
pathogenic microorganisms
Immune response to:
-Viruses
-Extracellular Bacteria
-Intracellular Bacteria

4. Immune System
The principal function of the immune system is to protect the host against pathogenic microbes.
Immunity may be innate or specific.

5. Pathogens & Disease
Pathogens are defined as microbes capable of causing host damage.
When host damage reaches a certain threshold, it can manifest itself as a disease.

6. Pathogenesis of Infectious Diseases
Development of an infectious disease in an individual involves complex interactions between the microbe and the host.
Key events during infection include:
Entry of the microbe
Invasion and colonization of host tissues
Evasion of host immunity
Tissue injury or functional impairment

7. Important General Features of Immunity to Pathogens
Defense against pathogens is mediated by both innate and specific immunity.
The innate immune response to pathogens plays an important role in determining the nature of the specific immune response.
The immune response is capable of responding in distinct and specialized ways to different pathogens in order to combat these infectious agents most effectively

8. Important General Features of Immunity to Pathogens
The survival and pathogenicity of pathogens in a host are critically influenced by their ability to evade or resist effector mechanisms of protective immunity.
Tissue injury and disease consequent to infections may be caused by the host response to the pathogen and its products rather than the pathogen itself.

9. Agents That Cause Infectious Disease

10. Immunity To Viruses

11. Immunity To Viruses
Obligatory intercellular pathogens that replicate within cells.
Use the nucleic acid and protein synthesis machineries of the host cell.
Infect a variety of cell populations by utilizing normal cell surface molecules as receptors to enter cell.

12. Innate Immunity To Viruses
The principal mechanisms of innate immunity against viruses are :
-Inhibition of infection by type I IFNs
-NK cell-mediated killing of infected cells.

13. Innate Immunity To Viruses

14. Adaptive Immunity To Viruses
Adaptive immunity against viral infections is mediated by:
- Antibodies: block virus binding and entry into host cells
- CTLs: eliminate the infection by killing infected cells

15. Adaptive Immunity To Viruses

16. Mechanism of Immune Evasion by Viruses
Mechansim of Immune Evasion
Examples
Antigenic variation
Influenza, rhinovirus, HIV
Inhibition of antigen processing
Blockade of TAP transporter
Removal of class I molecules from ER
Herpes Simplex
Cytomegalovirus
Production of cytokine Receptor
homologs
Vaccinia, Poxviruses
Production of Immunosuppressive cytokines
Epstein-Barr virus
Infection of Immunocompetent cells
HIV

17. Immunity To Extracellular Bacteria

18. Immunity To Extracellular Bacteria
Extracellular bacteria are capable of replicating outside host cells.
They cause disease by two principal mechanisms:
They induce inflammation, which results in tissue destruction at the site of infection.
Many of these bacteria produce toxins:
- Endotoxins
- Exotoxins
The immune responses against extracellular bacteria are aimed at eliminating the bacteria and at neutralizing the effects of their toxins.

19. Innate Immunity To Extracellular Bacteria
The principal mechanisms of innate immunity to extracellular bacteria are:
-Complement activation
-Phagocytosis
-Inflammatory response

20. Innate Immunity To Extracellular Bacteria
Complement activation leads to opsonization and enhanced phagocytosis of bacteria
Complement by-products stimulate inflammatory response by recruiting and activating leukocytes
Phagocytes use surface receptors (mannose receptors,scavenger receptors), to recognize extracellular bacteria.
Phagocytes use Fc receptors and complement receptors to recognize opsonized bacteria.

21. Innate Immunity To Extracellular Bacteria
TLRs participate in the activation of the phagocytes as a result of encounter with microbes.
These various receptors promote the phagocytosis of the microbes and stimulate the microbicidal activities of the phagocytes.
Activated phagocytes secrete cytokines, which induce leukocyte infiltration into sites of infection (inflammation).
Injury to normal tissue is a pathologic effect of inflammation.

22. Adaptive Immunity To Extracellular Bacteria
Humoral immunity is the principal protective immune response against extracellular bacteria: Functions to block infection, eliminate the microbes, neutralize toxins
Adaptive immune responses to EC microbes consists of :
-Antibody production
-Activation of CD4+ helper T cells

23. Adaptive Immunity To Extracellular Bacteria

24. Adaptive Immunity To Extracellular Bacteria

25. Mechanism of Immune Evasion by Extracellular Bacteria

26. Immunity To Intracellular Bacteria

27. Immunity To Intracellular Bacteria
Intracellular bacteria survive and even replicate within phagocytes.
These microbes are able to find a niche where they are inaccessible to circulating antibodies.
Their elimination requires the mechanisms of cell-mediated immunity

28. Innate Immunity To Intracellular Bacteria
The innate immune response to intracellular bacteria is mainly mediated by:
-Phagocytes
-Natural Killer (NK) cells

29. Innate Immunity To Intracellular Bacteria
Mice with severe combined immuno deficiency, which lack T and B cells, are able to transiently control infection with the intracellular bacterium Listeria monocytogenes by NK cell-derived IFN-γ production. However, innate immunity usually fails to eradicate these infections, and eradication requires adaptive cell-mediated immunity.

30. Adaptive Immunity To Intracellular Bacteria
The major protective immune response against intracellular bacteria is T cell-mediated immunity.

31. Adaptive Immunity To Intracellular Bacteria

32. Mechanism of Immune Evasion by Intracellular Bacteria

33. ?
Group Activities

34. Summary