Immune Response against Infectious Diseases

Department of Immunology

IMMU 7070-Introductory Immunology 2010-2011

Dr. Nyla Dil437 Apotex Centre272-3149

Oct 20, 2011

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.

Outline General Features of Immune Response to pathogenic microorganisms

Immune response to: -Viruses

-Extracellular Bacteria

-Intracellular Bacteria

Immune System

The principal function of the immune system is to protect the host against pathogenic microbes.

Immunity may be innate or specific.

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.

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

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

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.

Agents That Cause Infectious Disease

Immunity To Viruses

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.

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.

Innate Immunity To Viruses

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

Adaptive Immunity To Viruses

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

Immunity To Extracellular Bacteria

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.

Innate Immunity To Extracellular Bacteria

The principal mechanisms of innate immunity to extracellular bacteria are:

-Complement activation

-Phagocytosis

-Inflammatory response

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.

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.

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

Adaptive Immunity To Extracellular Bacteria

Adaptive Immunity To Extracellular Bacteria

Mechanism of Immune Evasion by Extracellular Bacteria

Immunity To Intracellular Bacteria

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

Innate Immunity To Intracellular Bacteria

The innate immune response to intracellular bacteria is mainly mediated by:

-Phagocytes

-Natural Killer (NK) cells

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.

Adaptive Immunity To Intracellular Bacteria

The major protective immune response against intracellular bacteria is T cell-mediated immunity.

Adaptive Immunity To Intracellular Bacteria

Mechanism of Immune Evasion by Intracellular Bacteria

Group Activities

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Summary