Bacterial Infection and Immunity

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Bacterial Infection and Immunity

• Xiao-Kui GUO

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Symbioses

• Commensalism one partner benefits and the other
  is neither harmed nor benefited.
• Mutualism both partners benefit.
• Parasitism one partner benefits at the expense
  of the other.

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Role of the resident flora

• Members of the resident flora in the intestinal
  tract synthesize vitamin K and aid in the
  absorption of nutrients.
• Members of the resident flora on mucous membranes
  and skin may prevent colonization by pathogens
  and possible disease through bacterial
  interference.
• The normal flora may antagonize other bacteria
  through the production of substances which
  inhibit or kill nonindigenous species.
• The normal flora stimulates the development of
  certain tissues, i.e., the caecum and certain
  lymphatic tissues (Peyer's patches) in the GI
  tract
• The normal flora stimulate the production of
  cross-reactive antibodies.

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• Hospital acquired infection Infections acquired
  during hospital stays.
• Pathgen A microorganism capable of causing
  sisease.
• Nonpathogen A microorganism that does not cause
  disease may be part of the normal flora.
• Opportunistic pathogen An agent capable of
  causing disease only when the hosts resistance
  is impaired (ie, when the patient is
  immunocompromised).
• Pathogenicity The ability of an infectious agent
  to cause disease
• Virulence The quantitative ability of an agent
  to cause disease. Virulent agents cause disease
  when introduced into the host in small numbers.
  Virulence involves invasion and toxigenicity.
• LD 50 (age /sex /health /route of entry,
  etc )
• LD50 The number of pathogens required to cause
  lethal disease in half of the exposed hosts is
  called an LD50.
• ID50 The number of pathogens required to cause
  disease (or, at least, infection) in half of the
  exposed hosts is called the ID50
• Adherence(adhesion, attachment) the process by
  which bacteria stick to the surfaces of host
  cells. Once bacteria have entered the body,
  adherence is a major initial step in the
  infection process. The terms adherence, adhesion,
  and attachment are often used interchangeably.
• Invasion The process whereby bacteria, animal
  parasites, fungi, and viruses enter host cells or
  tissues and spread in the body.
• Toxigenicity The ability of a microorganism to
  produce a toxin that contributes to the
  development of disease.

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• Koch's postulates
• Isolated
• diseased not healthy people
• Growth
• pure culture
• Induce disease
• susceptible animals
• Re-isolated
• susceptible animals

• Kochs Postulates
• Molecular Kochs Postulates
• Molecular Guidelines for Establishing Microbial
  Disease Causation

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Pathogenesis

• Pathogenesis is a multi-factorial process which
  depends on the immune status of the host, the
  nature of the species or strain (virulence
  factors) and the number of organisms in the
  initial exposure.

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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.

Routes of infection
Transmission

• Respiratory
• Gastroenteric
• Genitourinary tract
• closely contact
• insect bitting
• blood transfusion
• Parenteral route
• Mucous membranes

• Airborne droplets
• Food
• Water
• Sexual contact

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According to infectious sites
According to infectious state

• Inapparent or subclinical infection
• Latent infection
• Apparent infection cause apparent clinic
  syndrome
• Carrier state carrier

• Local infection
• Generalized or systemic infection
• Toxemia is the presence of exotoxins in the
  blood.
• Endotoxemia is the presence of endotoxins in
  the blood.
• Bacteremia is an invasion of the bloodstream by
  bacteria.
• Septicemia illness that occurs when poisonous
  substances (toxins) produced by certain bacteria
  enter the bloodstream.
• Pyemia is caused by pyogenic microorganisms in
  the blood.

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BACTERIAL VIRULENCE FACTORS
Environmental signals often control the
expression of the virulence genes. Common signals
includeTemperrature/Iron availability C
diphtheriae /low ion/Osmolality /Growth
phase/pH/Specific ions
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1. Adherence Factors
1. Tissue tropism 2. Species specificity 3.
Genetic specificity within a species

• Hydrophobic interactions
• Electrostatic attractions
• Atomic and molecular vibrations resulting from
  fluctuating dipoles of similar frequencies
• Brownian movement
• Recruitment and trapping by biofilm polymers
  interacting with the bacterial glycocalyx
  (capsule)

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Adhesion
E. coli fimbriae
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2. Invasion of host cells tissues
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3. Toxins  

• Exotoxins
• Endotoxins

• Exotoxins
• Produce in vitro cause food poisoning botulin,
  staphylococcal enterotoxin, etc.
• Produce in vivo
• Systematic toxic effects e.g. diphtheria,
  tetanus, and streptococcal erythrogenic toxins.
• Local toxic effects e.g. cholera, and
  toxigenic E. coli enterotoxins.

• Antibodies (anti-toxins) neutralize
• vaccination

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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
• Endotoxin effects
• Fever-pyrogen 1 microgram/ kg
• Leukopenia and leukocytosis necrosis
• Shwartzman phenomenon and disseminated
  intravascular coagulation (DIC).
• Endotoxemia and shock
• Lethal 1 milligram/ kg Identification Limulcyte
  assay

• Non-specific inflammation.
• Cytokine release
• Complement activation
• B cell mitogens
• Polyclonal B cell activators
• Adjuvants

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   Peptidoglycan of Gram-positive bacteria

• May yield many of the same biologic activities as
  LPS.

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  4. Enzymes
5. Antiphagocytic factors

• Tissue-degrading enzymes
• IgA1 proteases split IgA1, an important
  secretory antibody on mucosal surfaces, and
  inactivate its antibody activity.
• H. influenzae
• S. pneumoniae
• N. gonorrhoeae
• N. meningitidis

• Some pathogens evade phagocytosis or leukocyte
  microbicidal mechanisms by adsorbing normal host
  components to their surfaces. A few bacteria
  produce soluble factors or toxins that inhibit
  chemotaxis by leukocytes and thus evade
  phagocytosis.

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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
• 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 and blocks the cytophilic
  (cell-binding) domain of the Ab. Thus, the
  ability of IgG to act as an opsonic factor is
  inhibited, and opsonin-mediated ingestion of the
  bacteria is blocked.

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Protein A inhibits phagocytosis
immunoglobulin
M protein inhibits phagocytosis
Complement
fibrinogen
M protein
peptidoglycan
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6. Intracellular pathogenicity

• Some bacteria live and grow within
  polymorphonuclear cells, macrophages, or
  monocytes by avoiding entry into phagolysosomes
  and living within the cytosol of the phagocyte,
  preventing phagosome-lysosome fusion and living
  within the phagosome, or being resistant to
  lysosomal enzymes and surviving within the
  phagolysosome.

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7. Antigenic heterogeneity

• Antigenic type of bacteria may be a marker for
  virulence, related to the clonal nature of
  pathogens, though it may not actually be the
  virulence factor.
• Some bacteria may make frequent shifts in the
  antigenic form of their surface structures in
  vitro and presumably in vivo, allowing the
  bacteria to evade the hosts immune system.

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8. The requirement for iron

• For the host, the iron metabolism denies
  pathogenic bacteria an adequate source of iron
  for growth.
• For the bacteria, they have developed several
  methods to obtain sufficient iron for essential
  metabolism, e.g., the low-affinity iron
  assimilation system or the high-affinity iron
  assimilation systems.

Bacterial siderophores compete effectively for
Fe3 bound to lactoferrin and transferrin.
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Development of the Immune System

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Components of the Immune System
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Balance between Infection and Immunity
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Response to Infection
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Significance of the Immune System

• Beneficial
• Protection from Invaders
• Elimination of Altered Self
• Detrimental
• Discomfort (inflammation)
• Damage to self (autoimmunity)

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Components of Innate and Adaptive Immunity
physical barriers
skin, gut Villi, lung cilia,etc
none
soluble factors
many protein and non-protein secretions
Immunoglobulins (antibody)
cells
phagocytes, NK cell eosinophils, K cells
T and B lymphocytes
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Chemotactic response to inflammatory stimulus
Macrophage Attacking E.coli (SEM x8,800)
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Adaptive Immunity
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Characteristics of Innate and Adaptive Immunity

• Antigen independent

• Antigen dependent

• No time lag

• A lag period

• Not antigen specific

• Antigen specific

• No Immunologic
• memory

• Development
• of memory

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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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INADEQUATE IMMUNE RESPONSES TO INFECTIOUS AGENTS

• Causes immune suppressionan example is infection
  with HIV, which alters T cell immunity and allows
  further infection with opportunistic pathogens.
• Release toxins that function as superantigens,
  initially stimulating large numbers of T cells to
  proliferate but, because of the release of
  cytokines from T cells, ultimately suppressing
  the immune response and allowing the pathogen to
  multilply.
• Evade the immune defenses by altering their
  antigenic structurean example is that influenza
  virus undergoes antigenic variation by two
  mutational mechanisms called antigenic shift and
  antigenic drift that creat new antigenic
  phenotypes which evade the hosts current
  immunity and allow reinfection with the virus.