Pathology 3240A Lecture Notes - Lecture 6: Varicella Zoster Virus, Shingles, Gram Staining

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THE PATHOLOGY OF INFECTION
Introduction and Basic Principles
Infectious pathology is the most common form of organic and cellular disease. Fortunately, it is often mild
and the ‘pathology’ goes virtually unnoticed. Many forms of infection, however, are associated with
significant tissue damage or loss of life and infectious disease is still a leading cause of death worldwide.
There are many infectious microorganisms with a variety of special abilities that enable them to infect,
proliferate, and move onto the next host. Whether or not you get an infection (i.e. show the signs and
symptoms of infectious disease) depends upon a highly complex and regulated process that involves not
only factors and features of the invading microorganism (e.g. its virulence or disease-producing potential),
but also the integrity of a number of host defense mechanisms
Both humoral and cell-mediated immune systems battle infectious organisms (e.g. humoral immunity more
often with bacterial infections and T cells with viral infections) and occasionally cause tissue toxicity that lead
to illness and disease. Since the immune system has a limited repertoire of tools, different origins of
infectious pathology show a great deal of similarity and overlap in symptoms and pathology. Specific
symptoms depend on the location of the invading organism and its predilection for specific organs or
tissues.
Not all interactions between humans and microorganisms are harmful. The internal and external exposed
surfaces of the body are normally inhabited by a multitude of bacteria, normal microflora, and the host is not
adversely affected. In fact, in some instances, the interaction is mutually beneficial, with the human host
providing nutrition and the microorganism secreting essential metabolic byproducts (e.g. vitamin K in the
intestinal tract) or keeping more virulent organisms at bay.
The treatment of infectious disease is most effective when there is identification of the pathogenic organism
and its site(s) of infection. Clinical signs and symptoms are the first step in identification; for instance, a
cough is usually indicative of a respiratory infection; vomiting or diarrhea of a gastrointestinal infection.
In 1884, the German physician Robert Koch published a set of criteria to determine whether bacteria caused
disease. There are some exceptions and limitations to these ‘postulates’ but in general, they are still useful
in establishing the infectious origin of a disease.
Koch’s Postulates state that the organism:
1. Must be found in lesions of the disease
2. Must be isolated and cultured in vitro
3. Must transmit the disease to another animal
4. Must be recovered from lesions in that animal – animal must develop similar disease as human
when exposed
Some infectious agents can be directly observed in microscopic sections (e.g. the inclusion bodies formed
by CMV (cytomegalovirus) or herpes virus; clumps of bacteria). Many agents require special stains to be
visualized based on particular characteristics in their cell walls (e.g. gram positive or gram negative, acid-
fast or silver stains, specific Ab-labelled immunohistochemical stains).
Laboratory studies (e.g. isolation and growth of organisms from sputum, blood, stool or urine samples) and
radiographic examination (e.g. chest X-ray) result in identification and determination of drug sensitivity of the
offending organism in the majority of cases, but not always. The organism may prove difficult to identify or
the site of primary infection remain unknown.
Increasingly, DNA sequence analysis and PCR-based methods are used to identify microbes that prove
elusive to grow in culture and to characterize specific virulent strains. Many of the genomes of bacteria,
viruses, fungi and parasites have been completely sequenced. Surprisingly bacteria exchange hundreds of
genes from one to another, particularly those genes involved in virulence.
Current Problems with Infectious Disease
Increased incidence of antimicrobial resistance
oNew antibiotics are produced slower than resistance is developed
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Re-emergence of disease
oWe see diseases which are declining suddenly reappear, such as syphilis
Organisms appearing from other parts of the world
oMany infectious diseases are location specific such as West Nile virus in Egypt
oHowever, people travel to and from these areas and bring these infectious organisms back
Infection is always in the news
oPresence of viruses and disease changes how we interact with the environment
oGenerates standards such as wearing masks or gloves
oFor example, H1N1 was key in our development of masks for medical professionals
New pathogens identified in the last 30 years include
oEbola virus, Hanta virus – lung infection, E. coli O157 – uncooked hamburgers
oHIV, Hepatitis C, Legionella pneumophilia
oHelicobacter pylori – causes gastric cancers/ulcers and showed us an alternate mechanism for
ulcer development than type A personalities
Diseases and cancer are now linked to infectious organisms
The Organisms
Prions
oInfectious proteins (or proteinacious infectious particles), lack DNA or RNA (e.g. Creutzfeld-Jakob
disease (CJD), ‘Mad Cow’ disease (new variant CJD) or bovine spongioform encephalopathy
(BSE))
oRepresents an abnormal form of a normal host prion protein (PrP)
oModify the host protein to undergo a conformational change conferring resistance to degradation
Viruses
oObligate intracellular organisms, take over genetic apparatus of host cell for their own replication
oCell-specific in that they only infect specific cells (e.g. HIV T-cells)
oThe viral genome may be DNA or RNA surrounded by a protein coat (capsid)
Never both DNA and RNA
oIllnesses may be acute (colds, influenza), chronic (hepatitis B or C) or latent (herpes zoster)
oSome viruses have the capacity to transform host cells into neoplastic cells (HPV)
Bacteria
oHave a cell membrane but lack membrane-bound nuclei or organelles; also bound by a cell wall
oOften classified by shape (round – cocci; rods – bacilli, spirochetes); reaction on gram staining
(gram positive – have a chick cell wall that retains the stain; or gram negative – do not stain); or
oxygen requirement for growth (aerobic or anaerobic)
oPathogenic strains “in the wild”, but normal flora may infect if defenses are down
Bacteriophages, plasmids, and transposons
oMobile genetic elements that infect bacteria and may impact bacterial virulence factors
Chlamydia, Rickettsia, Mycoplasma
oAtypical or intracellular bacteria, lacking certain features typical of bacteria (e.g. no cell wall)
Fungi
oHave thick cell walls and cell membranes
oMany are normal flora but are common opportunistic infections (e.g. Candida albicans)
Protozoa
o Single-celled organisms that may have complex life cycles (may cycle in multiple hosts and be
transmitted from one host to another), e.g. plasmodium falciparum – malaria – replicate in insect
vector before transmission to human host; giardia (via drinking water); toxoplasma (intestinal)
Helminths
oParasitic worms, find 3 classes
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Roundworms (nematodes – ascaris, hookworms)
Tissue invaders, these will go from intestinal tract into tissue
Flatworms (cestodes – pork, beef or fish tapeworms)
Find host environment, and can grow to be meters in length
Flukes (trematodes – schistosomes)
Schistosomes – parasitic organism common in Egyptian water, it will burrow into
your feet while you are swimming and eventually enter the intestinal or bladder
system
Ectoparasites
oTicks, fleas, lice – attach to and live on the skin
oMay cause disease directly or be vectors for other organisms (e.g. a deer tick transmits Lyme
disease spirochete)
oArthropods can cause diseases such as scabies or be vectors for other pathogens
Bed bugs
Virulence
Virulence are factors that are characteristic of the organisms that allow it to colonize, proliferate, invade and
destroy host tissues
Colonization
oThe organism must be able to colonize the site it was introduced to
oDependent on
Size of inoculum
Ability to adhere to the tissue
Viruses: bind to cell surface receptors
Bacteria: express adhesion gene products to enhance binding to cell surfaces
Proliferation
oDependent upon moisture, oxygen content, pH, and availability of nutrients
oMust be able to evade host defenses
For example, difficult to digest beta encapsulated viruses and bacteria
Reproduce quickly and covertly
Overwhelm immune system
oMust compete with the normal flora
Tissue injury
oInfectious agents can establish an infection and damage tissue via
Directly causing cell death
Release of toxins and enzymes
Induce host cellular responses
oViruses
Damage host cells by entering the cell and replicating at the hosts expense
Viral tropism beta specific cells for specific viruses
Kill the host cell in a number of ways
Inhibit host cell metabolic function
Affect integrity of host cells plasma membrane
Lyse the cell
Host immune response destroys the host cell
Induce cell proliferation and transformation
oBacteria
Release toxins – two types of toxins
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