Virology - Introduction

Viruses are obligate intracellular parasites

Viruses are considered nonliving because they cannot reproduce on their own

Viruses contain DNA or RNA either of which is double or single stranded


Host Range

Refers to range of tissue virus can infect

Most viruses can only infect a specific type of tissue within a host

Host range is determined by receptors found on found on tissue cell surfaces


Viral Size

Determined by electron microscopy; viruses cannot be seen under light microscope

Viruses range from 20 to 10000 nm


Virology - Structure

A viron is a complete fully developed particle composed of nucleic acid and surrounded by a protein coat

Nucleic acid

Capsid and Envelope


Nucleic Acid

Double stranded DNA

Single stranded DNA

Double stranded RNA

Single stranded RNA

Nucleic acid can be 1% to 50% of weight of virus particle


Capsid and Envelope

The protein coat surrounding the nucleic acid is a capsid

Capsid is composed subunits called capsomeres

Capsid of some viruses is enclosed by an envelope consisting of lipids, proteins & carbohydrates

Some envelopes are covered with carbohydrate-protein complexes called spikes

Virology - Structure


Virology - Phage Replication











Virology - Phage Replication

Attachment - bacteriophage attaches to cell wall

Penetration - phage makes opening in cell and injects DNA

Biosynthesis - phage DNA directs synthesis of viral protein & nucleic acid

Maturation - Viral components are assembled into virions

Release - Host cell lyses and virions are released into surrounding medium

Lysogeny - Instead of biosynthesis, maturation & release, nucleic acid is integrated into genome becoming a prophage



Virology - Replication  Animal Viruses

Attachment - uses receptors on cell surfaces often using “spikes” on virus

Penetration - whole virus enters cell via endocytosis; enveloped viruses can fuse with cell membrane

Uncoating - Virus capsid is removed

Biosynthesis - early & late transcription produce virus enzymes, viral nucleic acid & capsid proteins, respectively

Maturation - virus particles are assembled

Release - Virus particles are exported


Virology – Replication  RNA containing viruses

produce reverse transcriptase to make complimentary DNA

DNA then directs synthesis of viral components


Virology - Survey Human Viruses

Viruses are grouped by families  (See table in Text)

Similar DNA sequences & structure


Virology - Cancer

Cancer causing viruses first identified in chickens

Cancer causing viruses use genes derived originally from host

Cancer causing process is called tranformation

Virology - Cancer

Cancer causing viruses in humans

Epstein-Barr virus (a herpes like virsus and Burkitt’s lymphoma (a relatively rare cancer in children in Africa)

Herpes virus associated with cervical cancer

Human papilloma virus causes genital warts but can also cause cervical cancer (some strains)






Nature of Disease


Introduction - Definitions

Normal Bacteria & Host

Koch’s Postulates

Patterns of Disease

Spread of Infection

Nosocomial Infections


Disease - Introduction

Pathogens - disease causing with special properties that permit host invasion

Disease - when microorganism overcomes host defenses; an abnormal physiological state

Pathology - the study of disease

Etiology - the cause of disease

Infection - invasion & growth of pathogen in host

Pathogenesis - development of disease


Disease - Normal Bacteria

Animals - germ free in utero but are colonized almost immediately after birth

Different bacteria are normally associated with different parts of body

Transients - microorganisms that may occasionally be found associated with the host

Disease - Normal Bacteria


S. epidermidis/S. aureus

Gastrointestinal Tract

Gram negative bacteria (large intestine)

S. mutans (mouth)

Genito-Urinary Tract



Antagonism - normal bacteria prevent growth of others

Bacteria and host have symbiotic relationship (living together)

Three types of symbiosis

Commensalism (one benefits)

Mutalism (both benefit)

Parasitism (one benefits & other harmed)

Opportunistic - do not cause disease normally

Disease - Koch’s Postulates

Etiology or cause established using Koch’s postulates

same pathogen present in every instance of disease

pathogen isolated in pure culture

isolated pathogen causes disease when reintroduced into a healthy host

pathogen re-isolated from the now diseased host



Disease - Patterns

Predisposing factors make hosts more susceptible & include:




level of fatigue



Disease - Patterns - Development

Incubation period - time between infection & first signs

Prodromal period - first mild signs

Illness period - period when all symptoms are present

Decline period

Convalescence period


Disease - Spread of Infection

Reservoirs of Infection

a continuing source of infection

Reservoirs include:

Human - people who have disease or are carriers (infected but no symptoms)

Zoonoses - wild or domestic animals that transmit disease to humans

Nonliving - soil & water


Disease - Spread of Infection


Direct contact

Fomites - inanimate objects

Droplet - saliva, mucus coughing or sneezing

Medium - food, water air

Airborne - carried > 1 meter

Arthropod - insect vectors


Disease - Nosocomial Infection

     Acquired during hospitalization or a stay in other health care facilities

     Occurs at 5-15%

     Can be normal organisms introduced into wrong part of body during invasive procedures

     Opportunitic drug resistant G-, e.g. Pseudomonas


Compromised host



immune suppressed (disease or drugs)

Chain of Transmission

Direct contact




Aseptic techniques

Proper cleaning storage


Properly trained staff



Multiple drug resistance

Nonuse of effective cleaning agents

Training of staff




Mechanisms of Pathogenicity



Entering the Host

Penetrating Host Defenses

Damaging Host Cells


Pathogenicity - Introduction

Pathogenicity is the ability of a pathogen to produce disease by overcoming host defenses

Virulence is the degree of pathogenicity

Expressed as LD50 (lethal dose necessary to kill 50% of the inoculated hosts)

ID50 is also used (dose necessary to infect 50% of the inoculated hosts)


Pathogenicity – Entering Host

Route of entry is called Portal of Entry

Usual portals include mucous membranes

Conjunctiva (eyes)

Respiratory tract

Gastrointestinal tract

Genitourinary tract


Respiratory most common

Microorganisms are inhaled on moisture droplets or dust particles

Genitourinary through mucous membranes and direct contact

Gastrointestinal through food water and contaminated fingers

Pathogenicity – Entering Host

Most microorganisms cannot penetrate skin but can gain access through hair follicles and sweat ducts

Can gain entry through inoculation also called parenteral

insect bites




Penetrating Host Defenses

Bacterial Elements that Overcome Host Defenses


Cell Wall Components


Cytoskeletal Components



Prevent or reduce phagocytosis

Usually polysaccharide


Dextran (S. mutans)

Polyglutamic acid (B. anthracsis)


Penetrating Host Defenses

Cell Wall Components

Adhesins (adhere to complementary receptors on host cells

Fimbriae – interact with membrane glycoproteins especially mannose

Some microbes reproduce only in host cells




Leukocidins – destroy white blood cells

Hemolysins – destroy red blood cells

Kinases – digest blood clots

Hyaluronidase – digests mucopolysccharides

Collogenase – destroy collogen of connective tissue


Via Cell Cytoskeleton


Cause actin of microfilaments to form basket to carry bacteria into cell

Found in Salmonella


Damaging Host Cells

Damage by metabolizing and reproducing in hosts

Damage by the production of toxins

Two major types of toxins





Usually from Gram positive bacteria

Usually a secreted protein product

Heat Labile (60 to 80 deg C)

Very toxic – low LD50

Usually specific for cell type or cell function

Can be neutralized by antibodies

Symptoms usually appear sooner


Exotoxins – Examples

Diptheria toxin –stops protein sysnthesis; damages heart and other organs

Cholera toxin – affects intestinal cells; disrups cAMP a cell secondary messenger

Tetnus toxin – affects nerve transmission

Toxic shock –affects T-cells & macrophages

Listeriolysin – pore forming cytotoxin allows cell to escape phagocytic vesicle



Almost exclusively Gram negative

Present in LPS and released with destruction of cell

Heat stable – often can withstand autoclave

Not easily neutralized by antibodies

Produces general effects fever, aches, shock

Much larger LD50 than exotoxins


Endotoxins – Examples

Salmonella typhi and typhoic fever-incubation period ~ 1 week symptoms due to LPS induced release of cytokines enter blood and multiply in spleen and liver

S. enteriditis & S. typhimurium – food borne gastroenterits – symptoms usually appear within 24 to 48 hours takes longer than with S. aureus exotoxin



The Immune Response


Duality of Immune System

Antigens & Antibodies

T-Cells & Cell Mediated Immunity


Immunology - Introduction

Innate resistance – genetically predetermined resistance

Immunity – ability of host to counteract specific substances or organisms

Antigens - foreign substances that interact with the immune system

Immunity is acquired


From infection – natural active

From mother to fetus – natural passive


From vaccination – artificial active

From immunoglobin injection – artificial passive

Vaccines made from pathogens





Antiserum if contains antibodies

Serum is separated into fractions – the fraction containing antibodies is the gamma fraction – gamma globulin

Immunology – Lymph System

Bone morrow

Thymus gland


Lymph nodes



Immunology – Duality

Two parts to immune response


Cell Mediated

Usually accomplished by white blood cells derived from hemopoetic stem cells



Mediated by B-cells (bursa)  derived from stem cells found in bone marrow

Produce circulating antibodies found in the gamma globulin fraction of blood serum

Defend against bacteria, viruses and toxins in blood and lymph


Mediated by T-cells (Thymus derived, i.e. white blood cells that mature in the thymus gland

Defend against intracellular viruses, multi-cellular parasites, transplanted tissue and cancer cells


Immunology – Antibodies

Immune response characterized by interaction between antigens and antibodies


Foreign substances

Molecular weight > 10,000 daltons

Proteins, lipoproteins, glycoproteins

Antigenic determinants are that portion of antigen which reacts with a specific antibody

Antigens have many determinants

Hapten – a low molecular weight substance combined with a carrier molecule


Antibodies are proteins produced by B-cells in response to an antigen

Antibodies have two binding sites per molecule

Immunology – Antibodies

Antibody molecule is a dimer

Connected by –S-S- bonds

Variable and constant region

Fab and Fc

Immunology – Antibodies

Antibody classes –circulating antibodies consist of five classes

IgG - most prevalent

IgM – 5 monomers involved in complement fixation & agglutination

IgA – secreted protects mucosa

IgD – antigen receptors on B-cells

IgE – bind to mast cells & basophils; involved in allergic reaction


Antibody Production

Mature B-cells circulate in blood; each producing a slightly different antigen receptor

B-cells not needed undergo cell death

B-cells becomes activated when antigen reacts antigen receptors on cell surface

Activated B-cells produce a clone of plasma cells and memory cells



Antigen ingested by antigen presenting cell (apc)

Antigen broken down into smaller pieces for presentation

Immunology – Antibodies

Immunology – Antibodies

Antigen presenting cell presents antigen and self antigen to helper T-cell

Self antigen keeps immune system from forming antibodies against itself, i.e. immune system will not form antibodies against a self-self combination

Immunology – Antibodies

Helper T-cell interacts between antigen presenting cell and B-Cell to activate B-cell to produce plasma cells

Plasma cells secrete antibody

Immunology – Antibodies

Antibody Production (continued)

Plasma cells secrete antibody (IgG)

Memory cells recognize antigen from previous encounters; produce plasma cells faster

T-cells and B-cells that react with self are destroyed during fetal development



Immunology – Antibodies

Antigen-Antibody Binding

Antigen binds to variable region forming antigen-antibody complex

IgG binding inactivates viruses and toxins

Agglutination reduces number of active particles and enhances phagocytosis

Activates the complement cascade

Opsonization enhances phagocytosis


Immunological Memory

Circulating antibody is called titer

First antigen contact is primary response; second is secondary

Secondary response is usually faster with a significantly greater antibody titer


Cell Mediated Immunity



Components of Cell Mediated Immunity


Cell Mediated Immunity


Involves specialized lymphocytes call T-cells

T-cells mature in thymus

Response to intracellular viruses, multicellular parasites, transplanted tissues and cancer


Cytokines are chemical messengers

Interleukins are cytokines that allow leukocytes to communicate

Interferons are cytokines that protect against viruses

Chemokines cause leukocytes to move to site of infection




Helper T Cells (TH )

Cytotoxic T Cells (TC )

Delayed Hypersensitivity T Cells (TD)

Suppressor T Cells (TS)

Activated Macrophages

Natural Killer Cells


Helper T Cells

Activate B-cells

Activate cytotoxic T cells

Activate other helper T cells


Cytotoxic T Cells

Used to attack intracellular  pathogens such as viruses, some bacteria, multicellular parasites

Attaches to target  cell

Releases protein perforin which pokes holes in target cell inducing lysis

T cells continue as long as antigen is present


Delayed Hypersensitivity T Cells

Involved in allergic reactions like response to poison ivy and transplanted tissue rejection

Originally named because transfer of cell transferred immunity to TB

Probably a subpopulation TH cells and TC cells


Suppressor T Cells

Appears to regulate immune response

Probably a subpopulation of helper cells


Activated Macrophages

Stimulated by ingestion antigens and cytokines from helper T cells

Acquire enhanced ability to digest via phagocytosis virus infected cells and intracellular bacteria infected cells

Can be antigen presenting cells


Nautral Killer Cells

Kill virus infected cells, tumor cells and large parasites

Not immunologically specific like cytotoxic T cells