Transcript 感染致病性

Macrophage Attacking E.coli (SEM x8,800)
Bacterial Infection
your textbook p45
Liuxin professor
Email [email protected]
Shenyang Medical College
Pathogenic Organism Department
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Pathogen病原体/Epidemic
流行病
Koch’s postulates 郭霍法则
Normal flora 正常菌群
Infectious diseases 传染病
Opportunistic infection 机会
感染
Nosocomial 医院的
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This chapter focuses on
 Definitions
normal flora, opportunistic pathogen, antitoxin, toxoid,
nosocomial infection, bacteremia, septicemia,
toxemia, endotoxemia, carrier
 Questions
What is the medical significance of normal flora?
Under what conditions do opportunistic pathogens
cause diseases?
What factors are associated with pathogenicity of
pathogens?
What do the virulence factors of pathogens include?
What is the difference between endotoxins and
exotoxins?
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What is the medical significance of carriers?
Agents that affect humans
What is an Infectious agent?
An Infectious agent may be defined as any
environmental agent capable of replicating in or on body
tissues
resulting
in an injurious response due to
competitive metabolism,
toxins,
intracellular replication,
immunologically mediated interactions.
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Pathgen病原微生物/病原体:
A microorganism capable of causing
disease.
Infection感染
Exogenous infection外源性感染
Endogenous infection 内源性感染
Pathogenicity致病性: The ability of an
infectious agent to cause disease
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§1 Pathopoiesis of bacteria
细菌致病作用
Main content
Invasiveness
侵袭力
Adherence &
permanent planting
黏附与定植
Multiplication &
diffusion
繁殖和扩散
toxin毒素
Anti-defense
function
of host
抗宿主的防御功能
Endotoxin
内毒素
其它微生物
Exotoxin
外毒素
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Source of infection
Exogenous infection : patient, carrier,
diseased animal or animal carrier.
Endogenous condition : most are normal
flora, cause infection under abnormal
condition.
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发红,灼痛
痛
Virulence毒力
Adherence factor
invasiveness
Capsule and slime layer
Invasive enzyme
Virulence factors
exotoxin
toxin
endotoxin
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Normal flora正常菌群,
Bacteria
Opportunistic pathogen条件致病菌
Pathogen病原体
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LD 50 (age /sex /health /route of entry,
etc )
LD50 半 数 致 死 量 : The number of
pathogens required to cause lethal
disease in half of the exposed hosts is
called an LD50.
ID50 半 数 感 染 量 : The number of
pathogens required to cause disease (or,
at least, infection) in half of the exposed
hosts is called the ID50
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皮脂腺
Pathogenesis
 Pathogenesis is a multifactorial process which
depends on the immune
status of the host,
 The nature of the species
or strain (virulence
factors)
 The number of organisms
in the initial exposure.
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Normal flora（textbook p118）
 Definition
Microorganisms that live on or in human bodies,
and ordinarily do not cause human diseases
 Physical Significance
 Antagonism拮抗作用
 Mechanism
• Competition for receptors on host cells
• Competition for nutrients
• Metabolic or toxic products
 Nutritional function
 Immunity
 Anti-tumor
Symbioses
共生
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Gloosary
normal flora正常菌群：Nonpathogen: A
microorganism that does not cause
disease; may be part of the normal flora.
Opportunistic pathogen机会病原体: An
agent capable of causing disease only
when the host’s resistance is impaired (ie,
when
the
patient
is
“immunocompromised”).
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韦荣球菌属
梭形杆菌
密螺旋体
紫质单胞菌
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Pathogenicity
 The routes of entry
Skin
Respiratory tract
Gastrointestinal tract
Urogenital track
Multiple routes
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Opportunistic infections
The normal flora living on their external
surfaces
Common bacteria found in the normal flora
include:
Staphylococcus aureus, S. epidermidis
Propionibacterium丙酸菌属acnes痤疮, 粉刺
(skin).
Bacteroides and Enterobacteriaceae,
found in the intestine
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Opportunists from the environment
We are constantly also exposed to
bacteria including:
air,
water
 soil
food.
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Pathogenic process of bacterium
Invasiveness侵袭力
Invasion侵入, settle down
Acceptive environment, multiply and
spreading
Destroy host defense
Toxin
other
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1. Adherence Factors
adhesive factor/ Adhesin黏附素
1）pili, colonization factor
2) the lipoteichoic acid （LTA）and F
protein (binds to fibronectin纤连蛋白)
causes adherence of the streptococci to
epithelial cells
3) The bacteria adhere by biochemical
reaction
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Capsule and slime layer
Invasiveness
 Adherence factors
Pili
Neisseria gonorrhoeae
Other surface structures
LTA
 Capsules and slime layers
Streptococcus pneumoniae
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黏附致病机制:
1. 通过黏附激活被
黏附细胞的信号
系统,使细胞释放
细胞因子,导致炎
性损伤.
2. 黏附与受体作用,
引起细胞凋亡
E. coli with fimbriae
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Adhesion
BACTERIUM
黏附与致病性:抗黏液冲刷,
细胞纤毛运动和肠蠕动等清
除作用,利于病菌定居
adhesin
receptor
EPITHELIUM 上皮细胞
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S. Pyogenes化脓性链球菌
lipoteichoic acid
F-protein
Fibronectin
纤维结合蛋白
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E. coli fimbriae
Type 1
mannose
P
• galactose半乳糖
– glycolipids
– glycoproteins
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2.Invasive enzyme
Invasiveness
 Invasive enzymes
Hyaluronidase透明质酸酶: hyaluronic acid
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2．reproducing and spreading 繁殖和扩散
coagulase: S. Aureus金葡菌
 fibrinogen纤维蛋白素原 fibrin surround
bacteria
hyaluronidase透明质酸酶(spreading
factor) ：hydrolyze hyaluronic acid tissue loose, B.
spreads,
streptokinase. SK. Lyse fibrin
streptodornase, SD, resolve DNA
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Shigella, and Salmonella organisms志贺菌
和沙门菌 are enteric bacteria that produce
an invasin protein侵袭性蛋白 that
promotes the binding of the bacteria to M
cells of the colon结肠, which in turn
stimulates the cell to invaginate and take
in the bacteria内陷吞噬细菌.
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3．Penetration host defence
1）ability to evade phagocytic
uptake：capsule or slime layers
and some pili are antiphagocytic。
2）anti-opsonisation
3）anti-IgA
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Antiphagocytic Substances
1. Polysaccharide capsules of
S. pneumoniae, Haemophilus influenzae,
Treponema pallidum ; B. anthracis and
Klebsiella pneumoniae.
2. M protein and fimbriae of
Group A streptococci
3. Surface slime (polysaccharide)
produced as a biofilm by Pseudomonas
aeruginosa
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4. O polysaccharide
associated with LPS of E. coli
5. K antigen (acidic
polysaccharides) of E. coli or the
analogous Vi antigen of Salmonella
typhi
6. Cell-bound or soluble Protein A
produced by Staphylococcus aureus.
Protein A attaches to the Fc region of IgG
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Protein A inhibits phagocytosis
Fc receptor
immunoglobulin
PHAGOCYTE
Protein A
BACTERIUM
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M protein inhibits phagocytosis
Complement
fibrinogen
M protein
r
peptidoglycan
r
r
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II. Toxins
Exotoxins
Endotoxins
Exotoxins

cause food poisoning: botulin肉毒菌毒素,
staphylococcal enterotoxin肠毒素, etc.
 Systematic toxic effects : e.g. diphtheria白喉,
tetanus, and streptococcal erythrogenic
toxins链球菌红疹毒素.
 Local toxic effects :
cholera, and toxigenic E. coli enterotoxins.
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Bacterial Toxins:
General Aspects
Definition
Soluble substances that alter normal
metabolism of host cells with deleterious effects
on the host
Toxin type
Exotoxin—protein produced by bacteria either
excreted or bound to bacterial surface and
released when lysed
Endotoxin—LPS of the outer membrane of
Gram— bacteria
Acts as toxin only under special circumstances
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Gene of exotoxin
Chromosome
Plasmid
Prophage 前噬菌体
Genes frequently carried on plasmids and temperate bacteriophage
character of exotoxin
virulence strong毒性强
Selectivity 选择性
Stability invalid稳定性差,不耐热
Antigenicity strong 抗原性强
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Toxin Production
Found on phage; toxin genes for:※※※
Diphtheria白喉
Botulism肉毒杆菌中毒
Scarlet fever猩红热
Toxic streptococci
Found on plasmids※※※:
E. coli toxin causes diarrhea腹泻
S. aureus toxin causes “scalded skin syndrome”皮肤
烫伤综合征
E. coli 0157:H7
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Kinds and biological role
Neurotoxins
Cytotoxins
Enterotoxin
others
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G+
and some
G- bacterium
synthesis then
released from
the cell.
A-B toxins
Host Cell surface
Active
Binding
A
B
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Tetanus toxin破伤风痉挛毒素
 inhibits glycine氨基乙酸 release
 inactivates inhibitory neurons阻断神经抑制性冲动
传递
 muscles over-active
 rigid paralysis
兴奋性递质
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Botulinum toxin肉毒毒素
inhibits acetylcholine乙酰胆碱 release
inhibits nerve impulses
muscles inactive
flacid paralysis 松弛麻痹
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Cellular toxin
Diphtheria toxin 白喉毒素and
Pseudomonas 假单胞菌exotoxin A
ADP-ribosylate elongation factor (EF2)
inhibit protein synthesis
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Enterotoxin
Cholera toxin and E. coli labile toxin
ADP-ribosylate adenylate cyclase
cyclic AMP
active ion and water secretion
diarrhea
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Shiga toxin - shigellosis
Shiga-like toxin - enterohemorraghic E. coli
 Lyses rRNA in ribosome
 Death of epithelial cells
 Poor water absorption
 Diarrhea
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Membrane damaging toxins
• Proteases
• Phospholipases
• Detergent-like action
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Endotoxin
 Origin and release
Gram-negative bacteria
Released only when bacteria lyse
 Chemical and physical properties
Lipopolysaccharide (LPS)
heat-stable: 160℃, 2-4hrs
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Endotoxins
LPS Lipopolysaccharide:
core or backbone of CHO
side chains of CHO: "O" antigen
Lipid A
Cell wall lysis required
formaldehyde and heat resistant
poor antigen as free molecule
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Endotoxin effects
Fever-pyrogen热原(质)
Leukopenia白细胞减少
leukocytosis白细胞增多
Shwartzman phenomenon
Endotoxemia and shock
disseminated intravascular coagulation
(DIC).
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Endotoxins
Non-specific inflammation.
Cytokine release
Complement activation
B cell mitogens
Polyclonal B cell
activators
Adjuvants
Endotoxemia
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The differences between exotoxin and endotoxin
Properties
Exotoxin
endotoxin
Origin
G+ and G-
G-
Release
Secreted from living cells or
released upon bacterial lysis
Released upon
bacterial lysis
composition
Protein
LPS
Heat-resistance Sensitive
Resistance
Immunity
High, antitoxin, toxoid
Low, no toxoid
High, tissue specificity
Low, no tissue
specificity
Toxicity
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内毒素与外毒素的比较
种类
内毒素
外毒素
来源
革兰阴性菌
革兰阳性菌部及分革兰阴性菌
存在部位
细胞壁成分、细菌裂解后释出
活菌分泌或细菌溶解后散出
化学成分
脂多糖
蛋白质
稳定性
好、160℃ 2-4小时破坏
差、60-80℃ 30分钟破坏
毒性作用
较弱、各种内毒素作用大致相同，强、对机体组织器官有选择性，
引起休克，发热，DIC等
引起特殊临床表现
抗原性
弱，能刺激机体形成抗体，
但无中和作用，
甲醛处理后不能形成类毒素
强，能刺激机体形成抗毒素，
经甲醛脱毒后能形成类毒素 52
§2 Bacterial route of transmission and
infection type细菌的传播途径和感染类型
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Sources of infectious diseases
 Exogenous infections
Patients
Carriers
Those in whom pathogens multiply and may be
transmitted to other individuals, but who shows no
clinical findings to their presence.
Convalescent carriers and Healthy carriers
Infected animals
 Endogenous infections
caused by opportunistic pathogens among normal
flora
Nosocomial infections
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Transmission • Airborne droplets
• Food
• Water
• Sexual contact
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Original and devolopment of
Bacterial Infection
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Routes of infection
Respiratory
Gastroenteric
Genitourinary tract
closely contact
 insect bitting
 blood transfusion
Potential route
Mucous membranes
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Hospital acquired infection
Infections acquired during hospital stays.
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Sources of infectious diseases
 Nosocomial infections
Definitions: infections acquired in a hospital. Also
called hospital-acquired infections.
Sources
Endogenous infections
Cross infections
Inappropriate hospital procedures
Hospital procedure
patient
Hospital personnel, visitors, or other patients
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Types of infections
 Determinants of infections
Pathogenicity of bacteria
Immunity defense of hosts
Environmental factors
 Inapparent infection
隐性感染
 Apparent infection
显性感染
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Inapparent infection
 Subclinical infection
 Definition
An infection that has no observable symptoms and
occurs when the host immunity is potent or the
pathogenicity of pathogens is weak.
 Medical significance
specific defense
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Apparent infection
 Definition
An infection that has obvious symptoms and occurs
when the host immunity is compromised or the
pathogenicity of pathogens is potent
Septicemia
 Localized infection
 Generalized / systemic infection
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Generalized infection
 Bacteremia
Definition: the presence but not multiplication of
bacteria in blood
 Septicemia
Definition: the presence and multiplication of bacteria
in blood
 Toxemia
Definition: the presence of bacterial exotoxins in
blood
 Endotoxemia
Definition: the presence of bacterial endotoxins in
blood
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Opportunistic pathogens
 Definition
normally nonpathogenic microorganisms capable of
causing infection disease under certain conditions.
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Opportunistic pathogens
 Conditions
Alteration of colonization sites
Declination of the host immunity defense
Dysbacteriosis
Definition: the state in which the proportion of
bacterial species and the number of the normal flora
colonizing in a certain site of a host present largescale alteration.
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Pathogenicity of pathogens
 Pathogenicity
A qualitative term that refer to an organism's ability to
cause disease
 Virulence
A quantitative measurement of pathogenicity
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病原菌在机体血液中大量繁殖产生毒性物
质，并随血流到达其他器官，引起多发性
脓肿，称为____________。
a.bacteremia
b.pyemia
c.endotoxemia
d.toxemia
e.septicemia
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Which one of the following BEST
describes the mode of action of endotoxin?
____________。
a. Degrades lecithin卵磷脂in cell membranes
b.Inactivates elongation factor 2
c.Blocks release of acetyl choline
d. Cause the release of tumor necrosis
factor,IL-1,et al
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The effects of endotoxin include each of
the following EXCEPT: ____________。
a.opsonization
b.fever
c.activation of the coagulation cascade
d.hypotension
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Each of the following statements
concerning exotoxins is correct
EXCEPT:____________。
 a.When treated chemically, some exotoxins lose
their toxicity and can be used as immunogens in
vaccines
 b.Some exotoxins are capable of causing
disease in purified form, free of any bacteria
 c.Some exotoxins act in the gastrointestinal tract
to cause diarrhea
 d.Some exotoxins contain lipopolysaccharides
as the toxic component
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Each of the following statements
concerning endotoxins is correct
EXCEPT____________。
a.The toxicity of endotoxins is due to the
lipid portion of the molecule
b. Endotoxins are found in most grampositive bacteria
c.Endotoxins are located in the cell wall
d.The antigenicity of somatic(O) antigen is
due to repeating oligosaccharides
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Each of the following statements
concerning exotoxins is correct
EXCEPT:____________。
a. Exotoxins are polypeptides
b.Exotoxins are more easily inactivated by
heat than endotoxins
c. Exotoxins are less toxic than the same
amount of endotoxins
d. Exotoxins can be converted to toxoids
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Each of the following statements
concerning the normal flora is correct
EXCEPT ____________。
 a.The normal flora of the colon consists
predominantly of anaerobic bacteria
 b.The presence of the nomlai flora prevents
certain pathogens from colonizing the upper
respiratory tract
 c. Fungi. eg, yeasts, are not members of the
normal flora
 d.Organisms of the normal flora are permanent
residents of the body surfaces
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Which one of the following characteristics
does not suitable for
exotoxin____________。
a.protein in nature
b.strong virulence
c.causing specific symptomes and signs
d.used for preparation of toxoid
e.stable
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Evasion of immune responses by
pathogens
Barriers
Invasion
& infection
Innate immunity
+
+
Inflammation
Adaptive immunity
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Adaptive Immunity
Adaptive Immunity, which occurs after
exposure to an antigen ( eg. An infectious
agent) is specific and is mediated by
either antibody or lymphoid cells. It can be
passive or active.
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 Immunity of extracellular bacterial infection:
antibodies (IgG, IgM, SIgA); phagocytes
(neutrophils); complement; humoral immunity
mainly.
 Immunity of intracellular bacterial infection:
cell-mediated
immunity
(delayed-type
hypersensitivity, DTH response (DTH) involving
TH1and macrophages) mainly.
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Symbioses
共生
 Commensalism共栖:
one partner benefits
and the other is
neither harmed nor
benefited.
 Mutualism互利共生:
both partners benefit.
 Parasitism: one
partner benefits at the
expense of the other.
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Role of the resident flora
1. Members of the resident flora in the intestinal
tract synthesize vitamin K and aid in the
absorption of nutrients.
2. Members of the resident flora on mucous
membranes and skin may prevent colonization
by pathogens and possible disease through
“bacterial interference”.
3. The normal flora may antagonize other bacteria
through the production of substances which
inhibit or kill nonindigenous species.
4. The normal flora stimulates the development of
certain tissues, i.e., the caecum and certain
lymphatic tissues (Peyer's patches) in the GI tract
5. The normal flora stimulate the production of
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