PATTERNS OF MICROBIAL PATHOGENESIS: LOCALIZED AND SYSTEMIC VIRAL INFECTIONS

Reading Assignments: (1) Brooks, G., J. Butel, and S.A. Morse. 1998. Pathogenesis and Control of Viral Diseases, pp. 345-355. In Jawetz, Melnick, and Adelberg's Medical Microbiology, 21^st ed., Appleton and Lange, Stamford, Connecticut. (2) Text Chapters 32, 34, and 40 with Self- Study Assignments.

I. INTRODUCTION

After adherence to the mucous membranes, many pathogenic viruses multiply in the epithelial cells causing localized disease. Others have virulence factors and strategies that allow them to invade across the mucous membranes and spread systemically through the body.

II. REVIEW OF VIRAL ENTRY INTO CELLS

A. Direct penetration

B. Fusion with the cell membrane

C. Receptor mediated endocytosis

III. LOCALIZED VIRAL INFECTIONS

A. Localized infections of the mucous membranes- “The HIT AND RUN” Infection Strategy

a. Rhinoviruses

b. Influenza A and B viruses

c. Rotaviruses

B. Warts – a localized viral infection of the skin

IV. BASIC PRINCIPLES: HOW MICROBES SPREAD SYSTEMICALLY THROUGH THE BODY

A. What's under the epithelial cell surface?

1. The basement membrane

2. If the microbe reaches the subepithelial tissues it is exposed to 3 important host defenses:

a. Tissue Fluids

b. The Lymphatic System

c. Phagocytic Cells

INFLAMMATION!!!!

B. Methods of systemic spread:

1. Direct Spread

2. Via the Lymphatics

a. Lymphatic vessels

b. Lymph nodes

c. Thoracic Duct ------Blood

3. Via the Blood

a. By directly entering a subepithelial vessel

b. By entering via the lymphatics and the lymph nodes

c. Microbes localize in the organs of the Reticuloendothelial System (RES)

What happens to pathogens that pass through the RES via the blood?

i. They many not be phagocytosed.

ii. They are taken up and killed.

iii. They are taken up and grow in the macrophages and/or the endothelial cells (cells that line the blood vessels)

iv. There is transfer of the microbes from the macrophages to the neighboring tissue cells. (If into the hepatic cells – hepatitis)

d. What forms are microbes carried in the blood?

i. Free in plasma

ii. Associated with white cells

iii. Associated with red cells

iv. Associated with platelets

4. Other routes of systemic spread:

a. Invasion of the CSF:

1. By the bloodstream (hematogenous spread)

2. By peripheral nerve fibers (neuronal spread)

b. Spread from organ to organ in the pleural or peritoneal cavities

V. SYSTEMIC VIRAL INFECTIONS (Steps in the Process):

A. Entry into the Body and Infection of the mucous membranes

SOME THOUGHTS: Why do some pathogens invade and others don't?

1. Temperature

2. The site of budding (for viruses)

3. Microbes must reach susceptible target tissues

a. Sometimes a different target tissue from where they started.

b. Sometimes they end up back where they started from.

4. Infections may be confined because they are kept in check by host defenses.

B. Viruses reach the blood via a subepithelial vessel or the lymphatics

C. Primary viremia

May be short and silent for viruses

D. Growth of the viruses in primary target tissue

E. Reseeding of viruses into the blood

F. Multiplication in secondary target tissues

G. There may or may not be exit from the body

SOME INFORMATION ABOUT RASHES: There may be entry into the skin from above or below:

A. Through the epidermis:

1. A variety of skin and soft tissue infections

2. Formation of papillomas – warts

B. Through the dermis (caused by infections or toxins):

1. Macule

2. Papule

3. Vesicle

4. Ulcer