Mechanisms of Bacterial Pathogenesis PDF

Mechanisms of bacterial pathogenesis  HOW DO BACTERIA CAUSE DISEASE IN HUMANS? Microbes Elimination of microbes INFECTION IMPLIES BACTERIAL...

Mechanisms of bacterial pathogenesis  HOW DO BACTERIA CAUSE DISEASE IN HUMANS? Microbes Elimination of microbes INFECTION IMPLIES BACTERIAL MULTIPLICATION Infection Normal flora Asymptomatic infection SHORT-TERM RELATIONSHIP Elimination of microbes Disease  MICROBES-HOST RELATIONSHIP Saprophytes: microbes that grow in soil and live on dead organic matter Commensal bacteria: harmless microbes living on the host and causing no effect or injury to the host Pathogenic bacteria: microbes capable of causing disease Strict/Primary pathogens: cause disease in healthy person Opportunistic pathogens: microbes that take advantage of preexisting conditions, such as immunodepression (weakenend host immune system) to grow and cause disease Not all bacteria or bacterial infections cause disease  MECHANISM OF BACTERIAL PATHOGENESIS INFECTION is the growth and multiplication of a bacteria in/on the body with or without the production of disease DISEASE results from the damage or loss of tissue/organ function due to the infection or to the host inflammatory responses/deposition of the immunocomplex NOT ALL INFECTIONS RESULT IN DISEASE When bacteria which are harmless in one site (commensal members of the normal flora) move to another site turning pathogens When bacteria are transmitted from another source  INFECTION ≠ INFECTIOUS DISEASE Microorganisms Host defence system INFECTIOUS DISEASE IS CAUSED BY THE DAMAGE PRODUCED BY PATHOGENS AND BY THE CONSEQUENCES OF THE IMMUNE RESPONSES TO THE INFECTION (IMMUNOPATHOGENESIS)  EXOGENOUS INFECTIONS Sources of the infection are: o Patients: infection is transmitted from patients suffering from an active disease to healthy individuals o Infected animals: such infections are zoonoses o Soil: saprophytic microbes present in soil, vegetation and similar habitats may cause human infections o Carriers (convalescent, chronic, healthy): individuals harboring pathogenic bacteria in their body but themselves not showing any clinical manifestations of the disease and are capable of disseminating the causative agent to other people. Mode of transmission of the infection: o Ingestion (food or water) o Sexual transmission o Inhalation (respiratory tract) o Blood-borne transmission o Trauma o Vector borne transmission o Direct contact (skin-to-skin contact) o Vertical (mother-to-child) transmission MODE OF TRANSMISSION OF INFECTIONS  MOTHER-TO-CHILD TRANSMISSION Vertical transmission occurs when the mother has a pre-existing infection or becomes infected during pregnancy. Transmission occurs: o Across the placenta (prenatal/congenital infection) o During delivery (perinatal infection) o Through breast milk (postnatal infection) DEFENCE MECHANISMS AGAINST INFECTION Adaptative antigen-specific immune responces: Antibodies and T cells Innate antigen-nonspecific immune defences (local response): Macrophagocytes, natural killer (NK) cells, dendritic cells, interferon, complement system, AMPs, inflammation/fever  FIRST LINE OF DEFENCE AGAINST INFECTION physical and chemical defences Along with chemicals, physical actions aid in the removal of pathogens: coughing, sneezing, vomiting, diarrhea, and flushing of urinary tract. SOLUBLE DEFENSE MEDIATORS PROVIDE PROTECTION LACTOFERRIN Lactoferrin is widely used as a dietary supplement, as an immunomodulator. Lactoferrin is also used in the cosmetics sector for its antibacterial properties; it’s a highly sought ingredient in cleansers. INNATE (2° line) AND ADAPTATIVE (3° line) RESPONSES  INNATE (2° line) AND ADAPTATIVE (3° line) RESPONSES bacterial pathogen RESPONSE RESPONSE GRADUAL EARLY innate immunity adaptative immunity COMPLEMENT ACTIVATION ANTIBODIES PHAGOCYTOSIS T CELLS INFLAMMATION  COMPLEMENT SYSTEM The goal of the complement is to clear bacterial cells Membrane Attack Complex  PHAGOCYTES AND INFLAMMATION Macrophages use surface receptors to recognize bacteria, they engulf pathogens leading to their lysis and secrete cytokines, which induce leukocyte infiltration into the site of infection (inflammation). The recruited leukocytes ingest and destroy the bacteria.  INFLAMMATION Inflammation is a localized physical condition in which part of the body becomes reddened, swollen, hot, and often painful, especially as a reaction to injury or infection Inflammation is a defense mechanism in the body → The immune system recognizes damaged cells, irritants, and pathogens, and it begins the healing process  PATHOGENIC INFECTION Microbes produce disease by directly killing the host cells they infect, or by liberating toxins that can cause tissue damage and functional derangements in neighboring or distant cells and tissues that are not infected.  MICROBIAL TOXINS TOXINS are microbial products that directly harm tissues, alter the normal metabolism of host cells and often are responsible for the major symptoms of bacterial infection. An exotoxin is a toxin secreted by bacteria in the extracellular environment and has enzymatic activity that induces damage in the host cell. o Thermolable proteins (m.w. 10-900kDa) o Highly antigenic o In some cases, the toxin is completely responsible for causing the characteristic symptoms of the disease (diptheria, tetanus, cholera) o many exotoxins are cytotoxic, and others cause disease by various mechanisms The endotoxin is the component of outer layers of bacteria, released from lysed or damaged cells o LPS in Gram negative bacteria is a potent activator of inflammatory reactions o Scarcely antigenic  EXOTOXINS Exotoxins are produced by Gram positive and Gram negative bacteria as part of their growth and metabolism They are then released into the surrounding medium In many cases, the toxin genes are encoded on a plasmid or a lysogenic phage. Most exotoxins fall into one of three categories on the basis of their structure and activities: o cytolytic toxins, as membrane-disrupting enzymes, and pore-forming toxins o A-B toxins o superantigens EXOTOXINS Pore-forming toxins (PFTs) are water soluble molecules that bind membrane receptors leading to oligomerization and insertion of an aqueous pore into the plasma membrane →cell death Membrane-disrupting enzymes are proteins that break down sphingomyelin and other membrane phospholipids →cell death  EXOTOXINS Examples of A-B toxins internalization: B = Binding A = Action Both components A and B could be made up of different subunits  SUPERANTIGEN EXOTOXINS Superantigens are a class of antigens that trigger an excessive (but ineffective) activation of the immune system. They cause non-specific activation of T-cells and massive cytokine release →toxic shock syndrome (as for endotoxins); they also lead to a lowering of the immune defenses  ENDOTOXINS DESPITE THE NAME, ENDOTOXIN IS NOT INTERNALIZED  ENDOTOXINS At low concentrations, endotoxin stimulates the development of protective responses At high concentrations, endotoxin leads to shock and death ENDOTOXINS AND PYROGENIC (FEVER) RESPONSE ENDOTOXIN ACTIVITY