PATHOGENICITY

 

Microbe vs. Host

 

 

Steps to Disease

 

 

  • Must protect itself from host defense system while invading tissues (penetrating)

 

 

Portals of Entry for Pathogens

  • Respiratory tract
  • Easiest portal to enter and most commonly infected
  • Many microbes travel in aerosols which we breath
  • Ex. Cold, TB, Influenza, Smallpox, Pneumonia

 

  • Gastrointestinal tract
  • Through food, water and dirty fingers
  • Must overcome low pH of the gut
  • Ex. Amoebic dysentary, Hepatitis, Shigellosis

 

  • Genitourinary tract
  • For STDs
  • Broken (parenteral route) or unbroken membranes (depends on the microbe)
  • Ex. HIV, Genital warts, Herpes, Syphilis

 

  • §Skin
            §Impenetrable (for the most part)
§                Not true if skin is broken
§                Hookworm larvae can bore through skin
§            Hair follicles and sweat gland ducts (many of which have antimicrobial oils associated with them)
§            Some fungi (Example: ringworm) can infect actual skin.
§            Parenteral route:  When there is a break in the skin, the skin can be penetrated

  • §Preferred portal
            §Many microorganisms have to enter in a specific way and in a certain place to cause disease.
§                Ex. Vibrio cholerae infects the GI tract; therefore, rubbing an infected oyster on a wound will not cause cholera

 

Number of Invading Microbes

 

 

 

Bacillus Anthracis

 

 

 

 

ADHERENCE

  • First step in pathogenicity

 

  • Microbes must attach to a surface

 

  • Adhesins or ligands of microbe attach to receptor in host
  • Adhesins or ligands
  • Mostly glycoproteins or lipoproteins in cell wall, or sugars associated with glycocalyx, or fimbriae
  • Vary from microbe to microbe

 

  • Receptors
  • Usually sugars
  • Vary from host to host

 

  • Example - Streptococcus mutans (causes tooth decay)
  • Converts glucose to dextran (used in glycocalyx)
  • Actinomyces attaches to glycocalyx of S. mutans by fimbriae

 

  • Biofilm

 

  • Tapered end - Treponema pallidum

 

Invasion: Penetration of Host Defenses

  • Even though a microbe has a capsule doesn’t mean it is a pathogen and not all pathogens have a capsule

 

  • Adherence and protection from phagocytosis (immune system defense)

 

  • Often a key role in virulence

 

  • Ex. S. pneumoniae is only virulent when capsule present

 

Invasion: Penetration of Host Defenses

  • Some bacteria have cell walls that contribute to virulence

 

  • M protein
  • Used for attachment and resistance to phagocytosis by WBCs
  • Ex. S. pyogenes

 

  • Waxes
  • Resist digestion by phagocytes
  • Ex. Mycobacterium tuberculosis

 

 

Invasion: Protection from Host Defenses

  • •Enzymes

 

  • ØCoagulases
  • •Causes blood clots
  • •Clots help to protect the microbe from host defenses by surrounding it
  • •Ex. Boils caused by Staphylococci

 

  • ØKinases
  • •Dissolves fibrin clots which the host may form to isolate the pathogens—helps them escape from host defense
  • •Staphylococcus uses staphylokinase

 

  • ØHyaluronidase
  • •Dissolves hyaluronic acid which is used to keep host cells together --> blackening
  • •Ex. Gangrene caused by Clostridium
§
  • §Collagenase
  • §Breaks down collagen (connective tissue)
  • §Helps in spreading

 

  • §IgA proteases
  • §IgA --> an antibody that the host produces as a defense against invader
  • §Some organisms produces IgA proteases, which destroy these antibodies
  • §N. meningitidis

 

Invasion: Protection from Host Defense

  • Antigenic variation
  • Antigens on surface of pathogen are recognized by host antibodies and defense cells

 

  • Some pathogens can change the proteins (antigens) on their cell surface to trick the host

 

  • Ex. Influenzavirus

 

Penetration into Cytoskeleton of Host
(Fig 15.2)

  • Cytoskeleton
  • Actin

 

  • Invasins are enzymes that rearrange actin filaments

 

  • Example
  • Salmonella

 

 

Steps to Disease

  • Gain entry through portal
  • Adherence
  • Invasion
  • Must protect itself from host defense system while invading tissues (penetrating)
  • Damage

 

DAMAGE

  • Four Methods
  • Using Host’s nutrients

 

  • Direct damage around where invasion occurred

 

  • Toxins
  • Poisonous substances that are produced by pathogens (primary factor in pathogenesis)

 

  • Toxigenicity

 

  • Toxemia

 

  • Hypersensitivity
  • Immune system over reacts

 

DAMAGE

  • Host’s nutrients
  • Iron
  • Typically not available to pathogens
  • Hemoglobin, transferrin

 

  • Pathogen secretes siderophores

 

  • Pathogen may secrete toxins to help get iron

 

  • Direct Damage
  • Metabolism and production of waste in host

 

  • Multiplication

 

ENDOTOXIN VS. EXOTOXIN - (Figure 15.4)

 

 

 

 

 

 

 

 

 

 

EXOTOXINS – Fig 15.5

  • 3 categories of toxins
  • A-B toxins
  • Membrane disrupting toxins
  • Superantigens

 

  • A-B Toxins
  • Part A: active enzyme component
  • Part B: Binding component

 

  • Steps
  • Toxin released
  • B binds to host receptor and transported to cytoplasm
  • A inhibits protein synthesis of host and host cell dies and B is released from cell

 

  • Example
  • Diptheria toxin
  • Corynebacterium diphtheriae

 

Membrane Disrupting Toxins

  • Disrupt host plasma membrane
  • Protein channels

 

  • Phospholipid disruption

 

  • Varieties
  • Leukocidins
  • Target phagocytes
  • Protein channels
  • Ex. Staphylococci leukocidins

 

  • Hemolysins
  • Target RBCs
  • Protein channels
  • Ex. Stretococci (streptolysin)

 

SUPERANTIGENS

  • Invoke very strong immune response
  • T cells
  • Release lots of cytokines which can cause severe symptoms
  • Ex. Staphylococci and food poisoning toxins

 

Another Way to Classify Exotoxins

  • Cardiotoxins

 

  • Neurotoxins

 

  • Enterotoxins

 

  • Cytotoxin

 

  • Hepatotoxin

 

  • Leukotoxin

 

More Important Exotoxin Examples

  • Botulinum toxin (Clostridium botulinum)--botulism
  • A-B Neurotoxin
  • Prevents transmission of signal from nerve cell to muscle cell at NMJ (inhibits release of acetylcholine)

 

  • Tetanus toxin (Clostridium tetani)--tetanus
  • A-B Neurotoxin that goes to central nervous system
  • Prevents inhibition of random contractions by muscles

 

  • Cholera toxin (Vibrio cholera)—cholera
  • A-B toxin enterotoxin
  • "A" induces cyclic AMP formation from ATP
  • Causes discharge of many fluids and electrolytes from intestine
  • Very heat sensitive

 

ENDOTOXIN

  • Problems with antibiotic treatment
  • Lysing cells

 

  • Cause macrophage to release high levels of cytokines

 

  • General Effects
  • Disseminated intravascular clotting
  • Endotoxins activate blood clotting proteins which blocks capillaries

 

  • Septic Shock: loss of blood pressure due to bacteria (endotoxic shock)
  • Macrophages release TNF (tumor necrosis factor) when they attack some Gram – cells

 

  • TNF binds to many tissues of host and may cause
  • Damage to blood capillaries (loss of water and decrease in BP)

 

  • Damage to blood-brain barrier (leading to infection of CNS)

 

  • Extreme pyrogenic response

Pyrogenic Response

  • §Macrophage ingestion and release of endotoxin from bacteria

 

  • §Release of interleukin-1(pyrogens) in bloodstream

 

  • §Interleukin-1 to hypothalmus and production of prostaglandins

 

  • §Resetting of bodies thermostat --> Fever

 

 

 

 

ENDOTOXINS

  • Test for endotoxins
  • Limulus amoebocyte lysate assay (LAL)
  • Horseshoe crab amoebocytes has lysates that cause clotting in the presence of endotoxins

 

Viruses

  • Viruses
  • Can penetrate and grow inside of cells where host defense cannot get them

 

  • Cytopathic effects
  • Cell death by
  • Multiplying viruses

 

  • Inhibition of DNA, RNA or protein synthesis

 

  • Effects on permeability of membrane

 

  • Cytocidal vs. Noncytocidal effects
  • Macromolecular synthesis to stop

 

  • Lysosome leaking = destruction of organelles

 

  • Inclusion bodies (virus parts)

 

  • Syncytium (fusing of cells)

 

  • Host cell function

 

  • Interferons (protects uninfected cells)

 

  • Antigenic changes on cell surface

 

  • Chromosomal breaks

 

  • Contact inhibition

 

 

Pathogenic Properties of Fungi

  • §Fungal waste products may cause symptoms.
  • §Chronic infections provoke an allergic response.
  • §Proteases
§        - Candida, Trichophyton

 

  • §Aflatoxin
§        - Aspergillus
 
§

Pathogenic Properties of Algae

  • Paralytic shellfish poisoning
§        - Dinoflagellates

 

  • §Respiratory tract
§        - Coughing and sneezing

 

  • §Gastrointestinal tract
§        - Feces and saliva

 

  • §Genitourinary tract
§        - Urine and vaginal secretions

 

  • §Skin

     

  • §Blood
§        - Biting arthropods and needles or syringes
 

 

 

Mechanisms of Pathogenicity