micro chapter 18 mechanisms of bacterial pathogenesis
Successful infection requires
Sex, sense, swim, stick, scavenge, survive, stealth, strike back, subvert, spread
factors affecting signs and symptoms of disease: disease related conditions:
congenital defects immune status
strike back
damage the host tissues (exo and endotoxins)
Characteristics microorganisms posess to cause disease:
invasiveness-ability to invade tissue toxigenisis-ability to produce toxins
2 types of infection
localized or systemic
intracellular replication
microbe enters non-phagocytic cells and replicates completely unnoticed.
antigenic masking
microbes coats themselves with host proteins or polysaccharides hiding their own antigenic surfaces
swim
move towards site of infection (ex: flagella)
processes of Virulence:
multifactorial-bacterial army, like human army, needs more than just its firearms to enter and secure enemy territory. Multidimensional-A program of events organized in time and space
2 steps for mechanism of adherance:
nonspecific specific
toxins
part of bacteria causing direct harm to tissue substance that activates destructive biological activity Toxic activity-degradative enzymes that cause cell lysis. Specific receptor binding proteins initiating toxic rxn in a specific target tissue. Cell wall components initiate a systemic response (ex: fever)
exotoxin
poison released from bacterial cells and may act at tissue sites removed from the site of bacterial growth.
Virulent microorganisms:
posess independant systems/mechanisms that encourage and enhance their own multiplication at the expense of the patient. Loss of tissue function Loss of organ function. Development of host inflammatory responses.
inhibition of phagocytosis
prevent engulfment
inhibition of chemotaxis
prevent movement of the cell (mainly phagocytes)
encapsulation
prevents immune and phagocytic responses from IDing and destroying bacteria
production of anti immuno proteases
production antiimmuno proteases
destruction of phagocyte
production of aggressins-extracellular enzymes that kill the phagocyte
endotoxin
toxin produced by certain bacteria and released upon destruction of the bacterial cell (ex: lipopolysaccharides from gram negative)
endotoxin and other cell wall components
toxix component of the bacterial cell envelope most classic is the LPS
sex
transfer of virulence info
subvert
trick host ino bacterial uptake rather than destruction (phagocytosis). Trick host cells into believeing mircroorganism is "self"
mechanisms of invasiveness are:
-colonization-adherance and initial multiplication -production-of extracellular substances which facilitate invasion (invasins) -ability to bypass or overcome host defense mechanisms
disease can come about in several overlapping ways
-some bacteria are entirely adapted to the pathogenic way of life in humans. They are never part of the normal flora but may cause subclinical infections (ex: mycobacteria tuberculosis) -some bact. which are part of the normal flora acquire extra virulence factors making them pathogenic (ex: e. coli) -some bact. from the normal flra can cause disease if they gain access to deep tissues b trauma, surger, lines, espcially if associated w/a foreign body (staph epidermidis) -in immunocomprimised patients many free-living bacteria and components of the normal flora can cause disease, especially if introduced into deep tissues (ex: acinetobacter species)
colonization:
1st step. establishment of pathogen at appropriate portal of entry. Usually colonize host tissues that are in contact with the external environment. Microbss must possess some ability to overcome/withstand continued pressure of the host defenses at the surface. After initial invasion, activation of adherance mechanisms begin.
specificity of adherence: species specificity:
certain pathogenic bacteria infect only certain species. N. gonorrhea limited to humans E coli K-88 infections limited to pigs
Pathogen
a microorganism with ability to cause disease
factors affecting signs and symptoms of disease: inoculum size:
ability to cause disease is directly proportional to type of bacteria- EXAMPLE: Shigella- <200 bacteria Salmonella requires > 1 million or 1,000 in neutral pH
pathogenicity
ability to produce disease in the host organism
factors affecting signs and symptoms of disease: Bacterial strain:
ability to produce toxins capable of avoiding immune response resistance to chemotherapy
antigenic mimicry
acquistion or production of host antigen by bacteria enabling it to avoid detection
stick
adhere to mucosal surfaces
genetic specificity within a species
certain strains or raes within a species are genetically immune to a pathogen certain pigs are not susceptible to e coll k-88 infections presence of duffy ags on RBC's provide susceptibility or resistance to plasmodium vivax.
systemic infection
an infection that has spread to several regions or areas of the body of the host
superantigens:
antigens causing a nonspecific activation of T cells. Normal T-cell response: activation of .oo1-.ooo1 of the body's Tcells. superags activate 10-20% of the bodys' Tcells. Activation releases large amts of interleukins (cytokine storm). Life threatening situation. Autoimmune like response, shock, multiple organ failure... ex: staph A causing Toxic shock syndrom.
determinance of virulence
any genetic, biochemical or structural features that enables the microorganism to produce disease in a host.
survive
avoid stressful situations (ex: acid pH in stomach, heat shock during fever, phagocytosis)
stealth
avoid the immune system response (ex: capsule)
sense
aware of the environment, virulence genes switched on and off
antigenic shift
bacteria changes ag on the surface to avoid detections
specificity of adherance: tissue tropism:
bacteria known to have apparent preference for certain tissue over others. strep mutans found in dental plaque but not on tongue strep salivarius found on tongue but not on dental plaque
spread
dispersal of microorganism thruout tissues and organs.
pathogenicity island "island of evil"
distinct class of genomic island/chromosomal regions codes for and harbors virulence factor responsible for pathogenesis present in pathogenic strains, absent in non-pathogenic strains important in the evolution of pathogenesis acquired thru horizontal transfer (plasmids)
Relation between host and pathogen
dynamic- each modifies the activities and functions of the other. outcom depends on virulence of the pathogen and degree of resistance of the host (effectiveness of the host defense mechanisms)
Exotoxins:
effects are usually seen acutely, sufficiently potent that serious effects (death) often result survival of the acute infection results in neutralizing abs which disable the exotoxin
10 mechanisms for escaping host defenses
encapsulation, antigenic mimicry, antigenic masking, antigenic shift, production of anti-immunoglobulin proteases, destruction of phagocyte, inhibition of chemotaxis, inhibition of phagocytosis, inhibition of phagolysomal enzymes, intracellular replication.
adhesion
enhanced system or ability a the molecular level whereby the microorganism sticks to or attaches itself to a mucosal surface. this method prevents the host from eliminating the microbe. or at least makes it difficult to accomplish.
2 types of toxins
exotoxin endotoxin
inhibition of phagolysosomal enzymes
inhibition of phagolysosomal enzymes
invasion
extracellular substances assist invasion by acting against the host thru the breakdown of prmary and or secondary defenses.
evidence that ID's clinically significant pathogen:
follows koch's postulates organism isolated in pure culture or in abundance isolated on more than one occasion (multiple sites or multiple times) discovered in deep tissue evidence of inflammation demonstration of immune response to the pathogen clinical signs and symptoms match
localized infection
infection that is restricted to a specific location or region within the body of the host
substances referred to as: invasins:
proteins/enzymes acting locally to damage host cells. immediate effect of facilitating the growth and spread of the pathogen this damage may become part of the pathology of the infectious disease.
2 factors required for adhesion:
receptor ligand (also known as adhesin)
tissue destruction:
results of fermentation (acids and gases are toxic to tissue) release of degradative enzymes (clostridium perfringens produce phospholipase C, collagenase, hyaluronidase staph produce hyaluronidase, fibrinolysin and lipases strep produce streptolysin S and O
nonspecific adherance:
reversible attachment of the bacterium to the eucaryotic surface (sometimes called docking). involves nonspecific attractive forces which allow approach of the microorganism to the cell surface
specific adherance
reversible permanant attachment of the microbe to the surface (sometimes called anchoring). involves permanent formation of many specific lock and key bonds between complementary molecules.
scavenge
search out required nutrients (ex: iron)
virulence
the degree of pathogenicity of the microbe
Immunopathogenesis
the process of development of a disease in which an immune response or the products of an immune rxn are involved. The discription is different for each infectious disease process EX: Mycobacterium tuberculosis: formation of a granuloma induced by CD4T cells and macrophages. Further tissue destruction Strep Pyogenes- Mimicry of antigenic proteins result in autoimmune responses: rheumatic fever, glomerulonephritis
mechanisms for escaping hosts defenses
thru the evasion of incapacitation of host defenses a pathogen has a greater potential for causing disease accomplished thru several different mechanisms structures and or features.
pathogenic actions of bacteria
tissue destruction, toxins, exotoxins, endotoxin and other cell wall components, superantigens