How Microbes Cause Disease

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How Microbes Cause Disease

• gain access to host
• Mode of transmission
• Correct portal of entry
• adhering to and colonizing cell surfaces
• invading tissues
• producing toxins or harmful metabolites

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• Adherence is a critical point in the production
  of disease
• Surface molecules on microbes called adhesions or
  ligands bind with specific receptors on host
  cells
• Most are glycoproteins or lipoproteins
• If adhesions or receptors can be altered,
  infection may be prevented or controlled

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• microbes must be able to colonize the surface or
  penetrate into host cells
• Virulence factors
• Structural or physiological characteristics that
  help organisms infect or cause disease
• Fimbrae, adhesins, enzymes, toxins, capsule

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How Bacteria Penetrate Host Defenses

• Capsules
• protects against phagocytosis
• Streptococcus pneumoniae, Klebsiella pneumoniae
  and Bacillus anthracis
• Components of cell wall
• M proteins of Streptococcus pryogenes are acid
  and heat resistant
• Opa protein on fimbrae of Neisseria gonorrhoeae
  aids in attachment
• Mycolic acid of Mycobacteium resists digestion by
  phagocytosis and is heat and acid resistant
• Outer membrane of Gram- bacteria

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• Extra-cellular enzymes (exoenzymes)
• Coagulases coagulate blood
• streptococci
• Kinases break down fibrin dissolve clots
• Streptococci and staphylococci
• Hyaluronidase spreading factor dissolves
  hyaluronic acid
• Glue like substance that holds cells together
• streptococci
• Collagenase breaks down collagen proteins
• Clostridium
• IgA proteases destroy bodys antibodies
• Neisseria
• Leukocidins destroy WBCs
• Streptococci and Staphylococci

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• Penetration into host cytoskeleton
• major component of cytoskeleton is actin protein
• Some bacteria use actin to penetrate host cells
  and to move between host cells
• Salmonella and E. coli produce surface proteins
  called invasins that rearrange actin filaments
  causing a cytoplasmic extension to project from
  host cell and support the microbe
• Provides attachment for colonization

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How Bacteria Pathogens Damage Host Cells

• Using host cells nutrients
• Iron is required for growth of most pathogens
• Some secrete siderophores that bind iron pulling
  it away from host cells iron transport proteins
• Direct damage
• Penetration or attachment may cause damage
• Exoenzymes may cause damage
• Pathogens may reproduce and grow inside host cell
  until it ruptures
• Inducing hypersensitivity reactions (allergies)

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• Production of toxins poisonous substances
• Often primary factor contributing to
  pathogenicity
• Toxigenicity
• capacity of microbe to produce toxins
• Toxemia
• presence of toxins in blood
• May be exotoxins or endotoxins
• Exotoxins are produced inside bacteria
• Proteins released from G bacteria
• Produced as part of their growth and metabolism
• secreted externally into medium or released
  following cell lysis

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• Highly soluble so they diffuse easily in blood
  and are quickly transported through out the body
• Among the most lethal substances known
• 1 mg of botulinum exotoxin is enough to kill 1
  million guinea pigs
• Body produces antitoxins that provide immunity
• Inactivated exotoxins are called toxoids
• Still capable of stimulating body to produce
  antitoxins

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• Corynebacterium diphtheriae
• produces diphtheria toxin
• Inhibits protein synthesis in eukaryotic cells
• Streptococcus pyogenes
• Produces an erythrogenic toxin
• Damages plasma proteins of blood capillaries
• Scarlet fever
• Clostridium botulinum
• produces the botulinum toxin
• Neurotoxin acts at neuromuscular junction
• Prevents transmission of nerve impulses to muscle

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• Clostridium tetani
• produces the tetanus neurotoxin
• Binds to nerve cells in the central nervous
  system
• Results in uncontrollable contractions and
  convulsive symptoms
• Vibrio cholera
• produces heat labile cholera enterotoxin
• Disturbs muscular contractions leading to severe
  diarrhea and vomiting

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• Bacillus anthracis
• Produces Anthrax toxin
• Increases vascular permability
• Causes hemorrhages and pulmonary edema
• Staphylococcus aureus
• produces an enterotoxin
• associated with food poisoning
• has a similar effect as cholera toxin but less
  severe
• Produces an exofoliatin toxin
• Causes separation of skin layers
• Scalded skin syndrome

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• Endotoxins
• part of the outer portion of the G- cell wall
• membrane consists of lipoproteins, phospholipids
  and lipopolysaccharides (LPS)
• The lipid portion (lipid A) is the endotoxin
• Released when cells die and their cell walls lyse
  
• Antibiotics used to treat diseases caused by Gram
  - bacteria can lyse cells
• May release endotoxins and cause an immediate
  worsening of symptoms

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• All endotoxins produce the same symptoms
• Chills, fever, weakness, aches
• May activate blood clotting proteins causing
  small clots to form
• May cause septic shock that can be fatal
• Phagocytosis of G- cells may cause the release of
  tumor necrosis factor (TNF) from the phagocyte
• Endotoxins do not prompt the formation of
  antitoxins
• Antibodies may enhance action of toxins
• Salmonella typhi, Proteus spp. and Neisseria
  meningitidis all produce endotoxins

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Pathogenic Properties of Viruses

• Cytopathic effects observable changes due to
  viral infection
• Cytocidal effects stop mitosis or macromolecule
  synthesis
• May cause lysozymes to release enzymes destroying
  host cell
• Formation of inclusion bodies sometimes filled
  with viral parts
• May cause several host cells to fuse syncytium
• May cause no visible changes in the infected
  cells
• Some virus-infected cells release interferons to
  warn neighbor cells
• May induce antigenic changes on surface of host
  cell to induce an immune response (antigen
  presenting cells)
• Some viruses induce chromosomal changes in host
  cell
• Loss of contact inhibition resulting in
  unregulated cell growth

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Pathogenic Properties of Other Microbes

• Fungi
• Some produce toxins that are an indirect cause of
  disease
• A few mushrooms produce mycotoxins Amanita
  phalloides
• most fungi grow on or in host parasites
• may cause allergic response
• Candida albicans and Trichophyton secrete
  protease enzymes that modify host cell membranes
  to allow fungal attachment
• Protozoa
• Some reproduce within host causing cell lysis
• Plasmodium causes Malaria
• Others evade immune system through antigen
  alterations
• Trypanosoma and Giardia

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• Helminths
• Steal host cell nutrients
• May produce large growth masses
• Algae
• A few species produce neurotoxins
• Alexandrium produces toxin that causes paralytic
  shellfish poisoning
• Produces symptoms similar to botulism

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Symptoms, Signs, Syndromes, Sequelae

• Symptoms are subjective changes that are not
  apparent to an observer
• Pain, malaise
• Signs are objective and can be observed and
  measured
• Lesions, swelling, fever, and paralysis
• A Syndrome refers to a specific group of symptoms
  or signs that always accompany a particular
  disease
• Sequelae are after effects of disease
• Bacterial infections of the heart may lead to
  long term valve damage
• Poliovirus leads to permanent paralysis

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• Severity or Duration of a Disease
• acute diseases develop rapidly but last a short
  time
• signs and symptoms sometimes severe
• common cold
• chronic diseases develop slowly, but can continue
  for long periods
• tuberculosis, hepatitis B
• Latent disease is one in which the causative
  agent remains inactive for a time but can become
  active again at some point
• shingles from chicken pox and other herpes
  viruses
• AIDS may harbor the HIV virus for years

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• Extent of Host Involvement
• local infections are limited to a small area
• boils and abscesses
• systemic infections can be spread throughout the
  body by blood and lymph
• measles
• primary infection is an acute infection that
  causes the initial illness
• secondary infection is one caused by an
  opportunistic pathogen after the primary
  infection has weakened the immune system
• common in AIDS patients
• subclinical infection is one that does not cause
  any noticeable illness
• poliovirus and hepatitis A virus can be carried

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• People are affected by disease in different ways
• Predisposing factors make the body more
  susceptible to a disease and may alter the course
  of the disease
• gender
• genetic background
• climate and weather
• inadequate nutrition
• age
• habits and lifestyle
• chemotherapy
• emotional disturbances

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Stages of an Infectious Disease

• incubation period
• time between initial infection and the first
  appearance of any signs or symptoms
• prodromal period
• a relatively short period that follows the period
  of incubation in some diseases
• early, mild symptoms by occur such as aches and
  malaise
• period of illness
• the disease is most acute
• overt signs and symptoms occur
• period of decline
• signs and symptoms subside
• patient is vulnerable to secondary infections
• period of convalescence
• person regains strength and recovery has occurred
• people can still serve as reservoirs of disease
  at this point