Type of Infection

advertisement
31
Infection and Pathogenicity
CHAPTER OVERVIEW
This chapter focuses on infection and pathogenicity. The development of a disease state is a dynamic process
that is dependent on the virulence of the pathogen and the resistance of the host. This dynamic process is
illustrated in the discussions of viral and bacterial pathogenesis. Modes of transmission and development of
diseased states are presented. The chapter includes a discussion of mechanisms used by viruses and bacteria
to evade host defenses.
CHAPTER OBJECTIVES
After reading this chapter you should be able to:







discuss the general characteristics of parasitic symbiosis
discuss the concepts of pathogens, disease, infection, and infectious disease
describes the modes by which pathogens are transmitted
describe the stages that pathogens usually go through in order to cause disease
distinguish exotoxins from endotoxins
describe the modes of action of various toxins
describe the mechanisms used by viruses and bacteria to evade host defenses
CHAPTER OUTLINE
I.
II.
Host-Parasite Relationships
A. A parasitic organism is one that lives at expense of its host; any organism that causes disease is a
parasite
B. Infection—the state occurring when a parasite is growing and multiplying on or within a host
1. Infectious disease—a change from a state of health as a result of an infection by a parasitic
organism
2. Pathogen—any parasitic organism that produces an infectious disease
3. Pathogenicity—the ability of a parasitic organism to cause a disease
4. Primary pathogen—organism that causes disease in a healthy host by direct interaction
5. Opportunistic pathogen—organism that is normally free-living or part of the host’s normal
microbiota, but adopts a pathogenic role under certain circumstances (host weakness)
C. Some infectious organisms can enter a latent state; this can be intermittent (e.g., cold sores) or
quiescent (e.g., chickenpox/shingles)
D. The final outcome of most host-parasite relationships is dependent on three main factors:
1. The number of pathogenic organisms present
2. The virulence of the organism
3. The host’s defenses or degree of resistance
E. Virulence—the degree or intensity of pathogenicity of an organism
The Infectious Disease Process
A. Characteristic patterns of an infectious disease
1. Signs—objective changes in the patient (e.g., fever, rash)
2. Symptoms—subjective changes in the patient (e.g., pain, loss of appetite
3. Disease syndrome—set of signs and symptoms characteristic of a disease
4. Incubation period—the period after pathogen entry but before signs and symptoms appear
5. Prodromal stage—onset of signs and symptoms but not yet clear enough for diagnosis
6. Period of illness—disease is most severe and has characteristic signs and symptoms
7. Period of decline (convalescence)—signs and symptoms begin to disappear
B. Source or reservoir
1. Source—location from which organisms are immediately transmitted to the host
332


2.
Period of infectivity—the time during which the source is infectious or is disseminating the
organism
3. Reservoir—site or natural environmental location where organism is normally found
4. Carrier—an infected individual who is a potential source of a pathogen; can be convalescent,
healthy, or incubatory; can be acute, transient, or chronic carriers
5. Zoonoses—infectious diseases that occur in animals and can be transported to humans; the
animals serve as a reservoir for the disease; transmission from animal to host can be direct or
indirect; vectors are organisms that spread disease from one host to another
C. Pathogen transmission
1. Airborne transmission—suspended in air; travels a meter or more
a. Droplet nuclei—may come from sneezing, coughing, or vocalization
b. Dust particles—may be important in airborne transmission because microorganisms
adhere readily to dust
2. Contact transmission—touching between source and host; direct (person to person)involves
physical interaction between infected person and host
3. Vehicle transmission—inanimate materials or objects are involved in transmission
a. Common vehicle transmission—a single vehicle serves to spread the pathogen to
multiple hosts, but does not support its reproduction
b. Fomites—common vehicles such as surgical instruments, bedding, eating utensils
c. Food and water also are common vehicles
4. Vector-borne transmission—living transmitters, such as arthropods or vertebrates
a. External (mechanical) transmission—passive carriage of the pathogen on the body of the
vector with no growth of the pathogen during transmission
b. Internal transmission—carried within the vector
1) Harborage—pathogen does not undergo morphological or physiological changes
within the vector
2) Biologic—pathogen undergoes morphological or physiological changes within the
vector
D. Infectious dose
1. Size of initial inoculum affects rate at which infection proceeds and its severity
2. Infectious dose 50 (ID50)—number of microorganisms required to cause clinical disease in
50% of inoculated hosts
E. Growth rate
1. Successful colonization requires favorable growth conditions
2. Intracellular parasites grow within host cells
a. Facultative intracellular parasites can grow within cells or the environment
b. Obligate intracellular parasites can only grow in host cells
F. Host susceptibility—depends on defense mechanisms of the host and the pathogenicity of the
pathogen
G. Exiting the host—must be able to leave host or disease cycle will be interrupted and the bacterium
will not be perpetuated
1. Active escape—movement of pathogen to portal of exit (e.g., many helminths
2. Passive escape—excretion in feces, urine, droplets, saliva, or desquamated cell
III. Virulence
A. Virulence is the magnitude of harm (pathogenicity) caused by a particular microorganism; intrinsic
characteristics that contribute to pathogenicity are called virulence factors
B. Pathogenicity islands
1. Large segments of DNA that carry virulence genes acquired during evolution by horizontal
gene transfer; are not present in nonpathogenic members of same genus or species
2. Have unique sequence characteristics including several open reading frames with putative
genes, a different G + C content than the host, and insertion-like elements at their ends
F. Virulence factors
1. Adherence and colonization
a. Bacterium must be able to adhere to and colonize (but not necessarily invade) host cells
and tissue
333


b.
G.
H.
Depends on ability of bacterium to successfully adhere to host and compete with normal
microbiota for essential nutrients
c. Adherence structures such as pili, fimbriae, and specialized adhesion molecules that
facilitate attachment to host cell receptors are important virulence factors
2. Invasion
a. Infectivity—ability of an organism to establish a focal point of infection
b. Invasiveness—ability of an organisms to spread to other tissues
c. Penetration of the host’s epithelial cells or tissues
1) Pathogen-associated mechanisms involve the production of lytic substances that:
(i) Attack the ground substance and basement membranes of integuments and
intestinal linings
(ii) Degrade carbohydrate-protein complexes between cells or on cell surfaces
(iii) Disrupt cell surfaces
2) Passive mechanisms of entry involve:
(i) Breaks, lesions, or ulcers in the mucous membranes
(ii) Wounds, abrasions, or burns on the skin surface
(iii) Arthropod vectors that penetrate when feeding
(iv) Tissue damage caused by other organisms
d. Invasion of deeper tissues can be accomplished by production of specific products or
enzymes that promote spreading (these are one type of virulence factor) or by entry into
the circulatory system; presence of bacteria in the blood is bacteremia; septicemia is
when toxins in the blood cause the disease process
Resisting host defenses
1. Successful infection by a microorganism requires that it avoid host immunity
2. Some pathogens infect immune cells and diminish their function; others avoid phagocytosis
with mucoidy capsules or specialized surface proteins
3. In some cases, pathogens use strategies to prevent detection by antimicrobial proteins
4. Some microorganisms survive inside host cells or can escape from hosts and spread
5. Many pathogens avoid the immune system by changing surface antigens, producing capsules
that resemble the host, or producing enzymes that degrade host proteins that bind bacteria
6. Biofilm communities bring microorganisms together enhancing nutrient acquisition, safety
from predators, and protection from the immune system and antibiotics
Toxins
1. Toxigenicity—the capacity of an organism to produce a toxin
2. Intoxications—diseases that result from the entry of a specific toxin into the host; Toxins are
specific substances, often a metabolic products of the organism, that damage the host in some
specified manner
3. Exotoxins
a. Soluble, heat-labile proteins produced by and released from a pathogen; generally
associated with gram-positive bacteria; may damage the host at some remote site
b. Toxins can be inactivated by neutralizing antibodies (antitoxins) or by chemical means
that create immunogenic toxoids (used for vaccines)
c. Can be grouped into four types based on structure and physiological activities
1) AB toxins can be separated into two distinct portions: one that binds the host cell
and one that causes toxicity (e.g., diphtheria toxin—binds host cell surface receptor
by the B portion and is taken into the cell by the formation of clathrin-coated
vesicles; toxin is then cleaved, releasing A fragment, which enters cytosol; the A
fragment inhibits protein synthesis)
2) Specific host site exotoxins: neurotoxins damage nervous tissue (e.g., botulinum
toxin and tetanus toxin), enterotoxins damage the small intestine (e.g., cholera
toxin), and cytotoxins do general tissue damage (e.g., shiga toxin); some host-sitespecific exotoxins are also AB toxins (e.g., cholera toxin)
3) Membrane-disrupting exotoxins—two subtypes, those that bind cholesterol in the
host cell membrane and then form a pore ( e.g., leukocidins and hemolysins) and
those that are phospholipases (e.g., gas gangrene-associated toxin)
334


4)
I.
J.
Superantigens—pathogen proteins (e.g., staphylococcal enterotoxin) that provoke
massive cytokine releases, causing endothelial cell damage, circulatory shock, and
multiorgan failure
4. Endotoxins—LPS of many gram-negative bacteria
a. Released only when the microorganism lyses or divides
b. Usually capable of producing fever, septic shock, blood coagulation, weakness, diarrhea,
inflammation, intestinal hemorrhage, and/or fibrinolysis; many of these effects are
indirect and are mediated by host molecules and cells (e.g., macrophages, endogenous
pyrogens, host cytokines)
Mycotoxins—Secondary metabolites in fungi commonly found in food crops and water-damaged
buildings; include aflatoxin from Aspergillus (liver damage and cancer), satratoxins from
Stachybotrys (inhibit DNA, RNA, and protein synthesis), and ergot alkaloids from Claviceps
(hallucinogen)
Measuring virulence—determined as lethal dose 50 (LD50), the number of pathogens that kills 50%
of hosts in a specified period of time; a variety of virulence also can be measured
TERMS AND DEFINITIONS
Place the letter of each term in the space next to the definition or description that best matches it.
a. adhesins
____ 1. An organism that supports the growth of a parasitic
b. antitoxin
organism
c. bacteremia
____ 2. A host that is used by a parasitic organism as a vehicle for
d. endogenous pyrogen
reaching a final host
e. endotoxin unit
____ 3. A host infected by a parasitic organism that can also
f. endotoxins
infect humans
g. exotoxins
____ 4. The colonization of a host by a parasitic organism
h. fomites
i. hemolysins
j. host
k. infection
l. infectious disease
m. infectivity
n. intoxications
o. invasiveness
p. leukocidins
q. LPS-binding proteins
r. opportunistic pathogen
s. pathogen
w pathogenic potential
x. primary (frank) pathogen
y. reservoir
z. reservoir host
aa. septicemia
bb. toxemia
cc. toxigenicity
dd. toxin
ee. toxoids
ff. transfer host
gg. vector
hh. virulence
ii. virulence factors
335


____ 5.
____ 6.
____ 7.
____ 8.
____ 9.
____ 10.
____ 11.
____ 12.
____ 13.
____ 14.
____ 15.
____ 16.
____ 17.
____ 18.
____ 19.
____ 20.
____ 21.
____ 22.
____ 23.
____ 24.
____ 25.
____ 26.
____ 27.
____ 28.
____ 29.
____ 30.
____ 31.
____ 32.
A change from a state of health due to the presence of an
t
pathogenic potential
organism or its products in the host
u. primary (frank) pathogen
An organism that causes infectious disease
v. reservoir
An organism that causes disease in a healthy host by a
w. reservoir host
direct interaction
x. septicemia
An organism that causes disease only when the host’s
y. toxemia
resistance is impaired
z. toxigenicity
The degree or intensity of pathogenicity
aa. toxin
The ability of a pathogen to spread to adjacent or other
bb. toxoids
tissues
cc. transfer host
The ability of a pathogen to establish a focal point of
dd. vector
infection
ee. virulence
The degree that a pathogen causes damage
ff. virulence factors
A pathogen’s ability to produce toxins
Organisms (e.g., insects) that transfer pathogens from one
host to another
A place where a pathogen lives before and after causing
an infection
Inanimate objects that harbor and transmit pathogens
Molecules on the surface of a pathogen that mediate
attachment to host cells or tissues
Products or structural components of a pathogen that
contribute to its virulence or pathogenicity
The presence of viable bacteria in the bloodstream
Disease caused by the presence of pathogens or bacterial toxins in the blood
Diseases that result from the entry of preformed toxins into the body of the host
A substance, often a metabolic product of the organism, that alters the metabolism of host cells with
deleterious effects on the host
The conditions caused by toxins that have entered the blood of the host
Soluble proteins that are released by a pathogen into the host; they may damage the host at some
site remote from the site of infection
Antibodies capable of neutralizing toxins
Chemically altered forms of toxins that are immunogenic but are no longer toxic
Toxins that kill leukocytes
Toxins that kill erythrocytes
Substances that are part of the cell wall of gram-negative bacteria and cause toxic reactions
A substance released by macrophages during infection that triggers fever
Proteins in the plasma membranes of macrophages and monocytes that bind endotoxin
A unit of measure used to indicate the level of endotoxin contamination in drugs, media, or other
products.
FILL IN THE BLANK
1.
2
3.
4.

By convention, an organism that causes harm or that lives at the expense of another organism is called a
__________ organism; when just the term __________ is used, it refers to harmful protozoa and helminths.
The relationship between a harmful organism and its host is called
. If the harmful
organism lives on the surface of its host, it is called an ____________; while if it lives within its host, it
is called an ____________.
Some pathogens release substances that kill leukocytes. These are called ____________.
Many pathogens possess mechanical, chemical, or molecular abilities to damage the host and cause
disease. Based on the way damage occurs, two distinct categories of disease can be recognized. If the
disease is due to the pathogen’s growth, metabolism, reproduction, or tissue alterations, it is called an
__________ disease. However, if the disease results from the entry of a preformed toxin into the host, it
336

5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
is called an ____________. The term ____________ is used if specific symptoms are caused by toxins in
the blood of the host.
Soluble proteins produced and released by an organism that can act at sites remote from the site of
infection are called ____________. They are divided into four types based on their structure and
physiological activities. One type is the
toxin, which has two parts, one that binds the target cell
and another that has toxic activity. A second type may also have this structure, but is distinguished by its
specificity for certain host sites. Those toxins that target the nervous system are called ____________;
those that cause cell death are called ____________; and those that damage the intestinal tract are
referred to as ____________. A third type does not have two different portions. These toxins target cell
membranes and are called __________ __________. The fourth type is the superantigen that stimulates
T cells to release cytokines.
Many bacteria have large segments of DNA, called
, that carry genes
responsible for virulence. An example of virulence genes carried this way is a set of genes that code for
proteins of
.
Viruses are usually spread throughout the body by the bloodstream and lymphatic system. The presence
of viruses in blood is called
. As viruses are spread, they specifically infect certain cells,
tissues, and organs. These specificities are called
.
The term __________ refers to the ability of an organism to cause disease. The term __________ refers
to the intensity of this ability and it is measured experimentally by the __________ (the dose of
pathogens that kills 50% of an experimental group of hosts) or by the __________ (the dose of pathogens
that infects 50% of an experimental group of hosts.
A number of bacterial pathogens produce
, which lyse red blood cells. This can be
observed by culturing the bacteria on blood agar plates. A complete zone of clearing around a bacterial
colony is called __________ __________, and a partial clearing is called __________ __________.
A
is an illness caused by a pathogen that can be transmitted from an infected
host or
(site where the pathogen is normally found). The immediate location from which
the pathogen is transmitted to a host (either directly or through an intermediate) is called the
____________.
A
is an infected individual who can transmit a pathogen to other hosts. If the infected
individual has an overt clinical case of the disease, the individual is referred to as an ____________
carrier. If the person has recovered from the infectious disease but can still transmit the pathogen, the
person is referred to as a ____________ carrier. If the individual can transmit the organism but is not
ill, the individual is a ____________ carrier. If the individual is not yet ill but will become ill, the
individual is referred to as an ____________ carrier.
The spread of a pathogen in the air for a meter or more from the source is called ____________
____________.
The transmission of pathogens by a coming together or a touching of the source and the host is called
____________ transmission.
Living transmitters of pathogens are called ____________, and this method of transmission is called
__________ transmission. If the pathogen is carried within the transmitter’s body and does not undergo
morphological or physiological changes, this is called ____________ transmission, and if the pathogen
does undergo morphological or physiological changes, this is called ____________ transmission.
MULTIPLE CHOICE
For each of the questions below select the one best answer.
1.
Which of the following has no effect on the
outcome of the host-parasite relationship?
a. the number of parasites on or in the
host
b. the virulence of the parasite
c. the defenses of the host
d. All of the above affect the outcome of
the host-parasite relationship.
2.
3.
337


What is an organism that transmits a parasitic
organism from one host to another called?
a. fomite
b. vector
c. transmitter
d. carrier
Which of the following is a membranedisrupting exotoxin?
a.
b.
c.
d.
e.
4.
5.
6.
7.
leukocidin
streptolysin-O
streptolysin-S
phospholipase
All of the above are membranedisrupting exotoxins.
Which of the following is a factor that helps
determine the virulence of a pathogen?
a. invasiveness
b. infectivity
c. pathogenic potential
d. All of the above are correct.
Which of the following is NOT a mode of
action associated with endotoxins?
a. shock
b. paralysis
c. diarrhea
d. All of the above are modes of action
associated with endotoxins.
When is endotoxin released from a gramnegative bacterium?
a. when the bacterium lyses
b. when the bacterium reproduces
c. Both (a) and (b) are correct.
d. Neither (a) nor (b) is correct.
Neisseria gonorrhoeae uses a mechanism
called serum resistance to evade host
defenses. Which host defense is evaded by
this mechanism?
a. formation of the membrane attack
complex
b. phagocytosis
c. destruction within a phagosome
d. the action of secretory IgA
8.
Which of the following is a large segment of
DNA that carries virulence genes acquired
through gene transfer?
a. fomite
b. pathogenicity island
c. peripheral transducer
d. immune complex
9. Which term refers to carriers that harbor a
pathogen for only a brief time (hours, days,
or weeks)?
a. casual carriers
b. acute carriers
c. transient carriers
d. All of the above are this type of carrier.
10. Which of the following is NOT normally a
way that humans or animals introduce
airborne organisms into the air?
a. sneezing
b. evaporation of sweat
c. coughing
d. vocalization (talking)
11. Which of the following does NOT refer to
inanimate objects involved in the
transmission of disease-causing organisms?
a. vectors
b. vehicles
c. fomites
d. All of the above refer to inanimate
objects involved in the transmission of
disease-causing organisms.
TRUE/FALSE
____ 1.
____ 2.
Parasitic organisms are metabolically dependent on their hosts.
Some pathogens have mechanisms that allow them to penetrate into host epithelial cells, while
others can enter only if the epithelial cells have been damaged by other means (wounds, insect
bites, etc).
____ 3. Generally, exotoxins tend to be more heat stable than endotoxins.
____ 4. A pathogen is generally found in the area of the host’s body that provides the most favorable
conditions for its growth and reproduction.
____ 5. Endotoxin effects can be mediated by cytokines released from monocytes and macrophages to
which the endotoxin has bound.
____ 6. Colonization specifically refers to the multiplication of a pathogen on or within a host.
____ 7. For most pathogenic bacteria, many clonal types exist in the environment.
____ 8. Genes for virulence are expressed constitutively.
____ 9. Exotoxins can cause disease only after the bacterium colonizes its host.
____ 10. Pathogens that are spread by direct contact tend to be more virulent than those that are vectorborne.
____ 11. Direct contact spread of a pathogen implies that there is actual physical contact between the current
host and the new host. Therefore, transfer of a respiratory pathogen by a sneeze or a cough is not
considered direct transmission.
338


____ 12. In order to maintain its life cycle, a pathogen must escape from the host either passively (i.e.,
secreted out of the host in feces, urine, droplets, salvia, or desquamated cells) or actively (pathogen
moves on its own to a portal of exit and then escapes).
____ 13. The manifestations of an infectious disease are the same in all hosts belonging to the same species.
339


TYPES OF INFECTIONS ASSOCIATED WITH PARASITIC ORGANISMS
Using your own words, complete the following table by describing each type of infection.
Type of Infection
Description
Acute
Bacteremia
Chronic
Latent
Localized
Opportunistic
Primary
Secondary
Sepsis
Septicemia
Septic shock
Subclinical (unapparent or
covert)
Systemic
Toxemia
Zoonosis
340


CRITICAL THINKING
1.
Compare and contrast exotoxins and endotoxins. Discuss the chemical and physiological characteristics
of the molecules, as well as their mechanisms of pathogenesis.
2.
Describe the different mechanisms by which pathogens can be transmitted. Which type of transmission
seems the most effective in causing large outbreaks? Pathogens transmitted by which mechanism might
be the most easily controlled and eliminated?
ANSWER KEY
Terms and Definitions
1. j, 2. cc, 3. w, 4. k, 5. l, 6. s, 7. u, 8. r, 9. ee, 10. o, 11. m, 12. t, 13. z, 14. dd, 15. v, 16. h, 17. a, 18. ff, 19. x,
20. c, 21. n, 22. aa, 23. y, 24. g, 25. b, 26. bb, 27. p, 28. i, 29. f, 30. d, 31. q, 32. e
Fill in the Blank
1. parasitic; parasite 2. parasitism; ectoparasite; endoparasite 3. leukocidins 4. infectious; intoxication; toxemia
5. exotoxins; AB; neurotoxins; cytotoxins; enterotoxins; membrane-disrupting exotoxins 6. pathogenicity
islands; secretion systems 7. viremia; tropisms 8. pathogenicity; virulence; LD50; ID50 9. hemolysins; beta
hemolysis; alpha hemolysis 10. communicable disease; reservoir; source 11. carrier; active; convalescent;
healthy; incubatory 12. airborne transmission 13. contact 14. vectors; vector-borne; harborage; biologic
Multiple Choice
1. d, 2. b, 3. e, 4. d, 5. b, 6. c, 7. a, 8. b, 9. d, 10. b, 11. a
True/False
1. T, 2. T, 3. F, 4. T, 5. T, 6. T, 7. F, 8. F, 9. F, 10. F, 11. F, 12. T, 13. F
341


Download