Chapter 5 Bacterial infection and immunity

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Chapter 5 Bacterial infection and immunity
Xue qing-jie
Department of medical microbiology
????qjxue9797_at_126.com QQ676370420
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• The term infection describes the process that
  pathogenic microorganisms multiply,release toxin
  within the body and produce a change in the
  normal physiology of the body.

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Section 1 Normal flora and opportunistic pathogens

• Definition microorganisms that live on or in
  human bodies, and ordinarily do not cause human
  diseases but under certain condition can cause
  disease

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(?)??
pathogen
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• The distribution of normal flora

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Normal flora

• Skin
• Staphylococcus epidermidis
• Diphtheroids
• Streptococci
• Peptococcus

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The significance of normal flora

• constitute a protective host defense mechanism
  Competition of nutrients and receptors
• Metabolic substances by normal flora
  e.g., bacteriocins, antibiotics, etc.
• serve a nutritional functionseveral B vitamins
  and vitamin K
• keep our immune systems in tune
• normal flora share many antigenic
  determinants with pathogenic organisms

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Opportunistic pathogens

• Definition normally nonpathogenic microorganisms
  capable of causing infection disease in an
  immunosuppressed host.
• Conditions of causing diseases by opportunistic
  pathogens
• Alteration of colonization sites
• Declination of host immune system function

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• Dysbacteriosis
• Definition the state in which the proportion of
  bacterial species and the number of the normal
  flora colonizing in certain site of a host
  present large-scale alteration.

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Nosocomial infections

• Infectious diseases acquired as a result of a
  hospital stay are known as nosocomial infections.
• Surgical procedures and lower defenses permit
  resident flora
• Indwelling devices
• Fomites ,medical equipment,other patients

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Section 2 Bacterial pathogenesis

bacteria
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inbody
outerbody
Immune status of the host
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Why do people get infectious diseases?

• From the organisms perspectives
• The number of organisms
• The virulence of these organisms
• From the hosts perspective
• Innate immunity
• acquired immunity

Antibody-mediated
cell-mediated
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Pathogenicity of bacteria

• Pathogenicity and virulence refer to an
  organism's ability to cause disease.
• LD50 (median lethal dose) or ID50 (median
  infectious dose) refers to the number of
  bacteria or amount of bacterial products, such as
  toxins, that cause death or bacterial disease in
  50 of animals in a defined period after the
  bacteria are administrated by a designated route.

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Pathogenicity of bacteria

• pathogenicity (decide by)
• virulence factors of the bacterium
• the number of infecting bacteria
• route of entry into the body

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Virulence factors

• Invasiveness
• Definition the ability of a microorganism to
  invade human cells or tissues,and to multiply on
  or within them.

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• Capsules and slime layers e.g., pneumococci
• Interfere with the ability of phagocytic blood
  cells to engulf and destroy bacteria and protect
  bacteria against some antimicrobial substance

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2.Adhesins

• Bacterial infections are usually initiated by
  adherence of the microbe to a specific
  epithelial surface of the host,otherwise the
  organism is removed
• Peristalsis and defecation ciliary
  action,coughing and sneezing or urination
• A specific stickiness

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• (1)Finbrial adhesins
• involved in mediating attachment of some
  bacteria to mammalian cell surfaces

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• (2)Non-fimbrial adhesin
• Including the filamentous haemagglutinin of
  Bordetella pertussia,a mannose-resistant
  haemagglutinin from Salmonella serotype
  Typhimurium and a fibrillar haemagglutinin from
  helecobacte pylori
• Pili e.g., Neisseria gonorrhoeae
• Other surface structures of bacteria LTA

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Other extracelluar aggressins

• Invasive enzymes
• e.g.Coagulaseworking in conjunction with serum
  factors to coagulate plasma.contributes to the
  formation of fibrin walls around staphylococcal
  lesions.

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• Toxins
• Exotoxin
• Definition a soluble protein toxin usually
  secreted from a living bacterium.

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• Origin and release produced by Gram-positive
  bacteria as well as Gram-negative cells
• Physical and chemical properties proteins and
  usually heat-labile.

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Virulence factors

• Toxins
• Exotoxin
• Immunity excellent antigens that elicit specific
  antibodies called antitoxins.

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• Antitoxin
• Definition a specific antibody capable of
  neutralizing the exotoxin that stimulates its
  production.
• Toxoid
• Definition a modified exotoxin that has been
  treated to destroy its toxicity and remains
  immunogenicity.

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Virulence factors

• Exotoxin
• Component characteristics most exotoxins consist
  of two parts, an A (active) component and a B
  (binding) component.

Toxicity high and even fatal highly tissue
specificity
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• Categories
• Cytotoxins exotoxins that destroy the target
  cells directly by various mechanisms.
• Neurotoxins exotoxins that affect nerve
  transmission of the nerve system.
• Enterotoxins exotoxins that stimulate
  hypersecretion of water and electrolytes from the
  intestinal epithelium and produce watery
  diarrhea.

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Exotoxin

• Neurotoxin
• Tetanus toxin ,clostridium tetani
• glycine spastic paralysis
• Botulinum toxin, clostridium botulinum
• acetylcholine flaccid paralysis

• Cytotoxin diphtheria toxin inhibits
• protein synthesis

Enterotoxins v. cholerae perturb the
processes that regulate ion and water exchange
across the intestinal epithelium
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Virulence factors

• Endotoxins
• Origin and release
• produced only by Gram-negative bacteria and
  released only when bacteria lyze.
• Chemical and physical properties
• lipopolysaccharide of the outer membrane of
  Gram-negative bacteria heat-stable

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Endotoxins

• Immunity weakly immunogenic
• Biologic activity
• lipid A is the primary toxic component
• all endotoxins present similar biologic
  effects.
• Pyrogenicity
• Leukocyte reaction
• Endotoxemia and endotoxin shock
• DIC (dissemiated intravascular coagulation)
  

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Endotoxin (especially lipid A))
Activates Hageman fatcor
Activates complement
Activates macrophages
C3a Hypotension Edema
TNF Fever and hypotension
C5a Neutrophil chemotaxis
Coagulation cascade DIC
IL-1 Fever
Nitric oxide hypotension
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Endotoxin toxicity

• leukocytoreaction
• pyogenetic reaction
• endotoxemia and endotoxin shock
• Shwartzman phenomenon
• DIC

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Endotoxins

• Detection of endotoxin The Limulus lysate test

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The different between indotoxin and exotoxin
kinds exotoxin indotoxin
source Gor a few G- G-

component protein LPS
stebility Short of good?160? 2-4h destroyed
virulence strong weak
antigenicity strong weak
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Virulence of pathogenic bacterial
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?.Portals of Entry and the size of the inoculum

• If certain pathogen enter the wrong portal,they
  will not be infectious.
• Occasionally,an infective agent can enter by more
  than one portal.e.g.mycobacterium tuberculosis.

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Portals of entry

• skin
• respiratory system
• ingestion system
• genitourinary system
• C. tetani

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The size of the inoculum

• The quantity of microbes in the inoculating dose.

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?.the originate and progress of infection

• A.The source of the infection
• B.routes of pathogen transmission
• C.Patterns of infection

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A.The source of the infection

• Living reservoirs
• Persons or animals with frank symptomatic
  infection are obvious sources of infection
• Nonliving reservoirs

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• Sources of infectious diseases

• Exogenous infections
• Patients
• Carriers those in whom pathogens are present and
  may be multiplying, but who shows no clinical
  response to their presence.
• Contaminated animals
• Endogenous infections

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• Carrier state
• Definition of carriers those in whom pathogens
  are present and may be multiplying, but who shows
  no clinical response to their presence
• Definition of carrier state a type of infections
  causing no signs of symptoms, in which pathogens
  multiply and may be transmitted to other
  individuals

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• two major types of carrier
• Convalescent carriers those who recover
  from infectious disease and in whom the pathogens
  remain and multiply without causing overt
  symptoms.
• Healthy carriers those who do not have the
  clinical symptoms but carry pathogens indeed.
• Typhoid Mary (Mary Mallon)

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B.routes of pathogen transmission

• 1.respiratory infections
• the tiny particles of liquid released into
  the air form aerosols or droplets
• 2.wound infectonsin soil and feces of human and
  animal
• 3.intestinal infections contaminate drinking
  water and food or when used to fertilize crops

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• 4.contact infectiondirectly contact between the
  skin and mucous membranes of the infected person
  or animal and that of healthy person
• 5.animal bites infectionsthe majority of animal
  vectors are arthropods such as fleas,mosquitos,fli
  es,and ticks

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C.Patterns of infection

• acute infection
• chronic infection

Apparent infection
1.apparent infection When an infection causes
pathological changes leading to disease,it is
often accompanied by a variety of signs and
symptoms Infectons that come on rapidly,with
severe but short-lived effects,are called acute
infections The infection persists several months
to several years called chronic infection
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• Inapparent infection also called subclinical
  infection that has no detectable clinical
  symptoms

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• local infection
• generalized/systemic infection

Localized infection stands for the case that the
microbe enters the body and remains confined to a
specific tissue
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Generalized infection

• Bacteremia
• Definition a transitory disease in which
  bacteria present in the blood are usually cleared
  from the vascular system with no harmful effects.
  
• Septicemia
• Definition a disease in which the blood serves
  as a site of bacterial multiplication as well as
  a means of transfer of the infectious agent from
  one site to another.

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• Toxemia
• Definition the presence of microbial toxins in
  the blood
• Pyemia
• Definition the presence of pyogenic bacteria in
  the blood as they are being spread from one site
  to another in the body

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Local lesion
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toxin
Defense function??
toxin
special toxic symptom
pathogenic bacterium can grow in blood
Organism is seriously dadamaged, toxic symptom
all over the body?
Toxemia
Bacteremia
Septicemia
e.g.tetanus
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toxin
When Pyosis bacteria cause Septicemia,multiple
pyosis focus of infection will happen.e.g.
staphylococci aureus
New pyosis focus of infection
Pyosepticemia
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Section3 Antibacterial immunity of host
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Host resistance mechanisms

• Nonspecific host defenses
• Anatomical defenses
• Skin and mucosal membrane
• Mechanical barriers
• Secretions
• Normal flora

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• Blood-brain barrier
• Placenta barrier
• Cellular defenses the reticuloendothelial
  system
• Molecular defenses complements, lysozymes, etc

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Innate immunity

• Skin mucous membranes
• Intact skin
• Fatty acids sebaceous glands
• Mucous membrane of respiratory tract
• ciliary action
• traps many microorganisms
• Lysozyme
• Normal flora

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Innate immunity

• Inflammatory response phagocytosis
• (early host responses to bacteria infection)
• Bacteria infection?vasoactive factors ?
• the increased permeability
• Chemokines ? Neutrophils and macrophages

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Host resistance mechanisms

• Specific host of defenses
• Humoral immunity antibody-mediated immunity
• Cellular immunity cell-mediated immunity

Inflammatory response phagocytosis
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Host defences
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Acquired immunity

• Humoral immunity
• antibody to aggressin
• antibody to toxin
• Cell-mediated immunity
• T cells
• lymphokines (IFN- ?)
• macrophages

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Some question
TERMS EXPLAINATION

• opportunistic pathogens Toxemia Bacteremia
• Septicemia Pyosepticemia
• Question
• whats the differences between indotoxin and
  exotoxin ?
• Whats the functions of Normal flora ?