Bacterial Pathogenesis The term infection describes the process

Bacterial Pathogenesis

The term infection describes the process that pathogenic microorganisms multiply, release toxin within the body and produce a change in the normal physiology of the body.

Section 1 Normal flora and opportunistic pathogens Ø Definition: microorganisms that live on or in human bodies, and ordinarily do not cause human diseases but under certain condition cause disease

pathogen

The distribution of normal flora

Normal flora Skin Staphylococcus epidermidis Diphtheroids Streptococci Peptococcus

The significance of normal flora constitute a protective host defense mechanism: Competition of nutrients and receptors Metabolic substances by normal flora: e. g. , bacteriocins, antibiotics, etc. serve a nutritional function: several B vitamins and vitamin K keep our immune systems in tune normal flora share many antigenic determinants with pathogenic organisms

Opportunistic pathogens Definition: normally nonpathogenic microorganisms capable of causing infection disease in an immunosuppressed host. Conditions of causing diseases by opportunistic pathogens: o Alteration of colonization sites o Declination of host immune system function

o Dysbacteriosis Definition: the state in which the proportion of bacterial species and the number of the normal flora colonizing in certain site of a host present large-scale alteration.

Nosocomial infections Infectious diseases acquired as a result of a hospital stay are known as nosocomial infections. Surgical procedures and lower defenses permit resident flora Indwelling devices Fomites , medical equipment, other patients

Section 2 Bacterial pathogenesis Immune status of the host Cause disease inbody outerbody toxins bacteria 细菌 细菌 bacteria 细菌

Why do Animal get infectious diseases? From the organism’s perspectives The number of organisms The virulence of these organisms From the host’s perspective Innate immunity acquired immunity Antibody-mediated cell-mediated

Pathogenicity of bacteria Pathogenicity and virulence: refer to an organism's ability to cause disease. LD 50 (median lethal dose) or ID 50 (median infectious dose): refers to the number of bacteria or amount of bacterial products, such as toxins, that cause death or bacterial disease in 50% of animals in a defined period after the bacteria are administrated by a designated route.

Pathogenicity of bacteria Ø pathogenicity （determined by): virulence factors of the bacterium the number of infecting bacteria route of entry into the body

Virulence factors Invasiveness o Definition: the ability of a microorganism to invade human cells or tissues, and to multiply on or within them.

o Capsules and slime layers: e. g. , pneumococci o Interfere with the ability of phagocytic blood cells to engulf and destroy bacteria and protect bacteria against some antimicrobial substance

2. Adhesins Bacterial infections are usually initiated by adherence of the microbe to a specific epithelial surface of the host, otherwise the organism is removed Peristalsis and defecation ciliary action, coughing and sneezing or urination A specific “stickiness”

(1)Finbrial adhesins involved in mediating attachment of some bacteria to mammalian cell surfaces

(2)Non-fimbrial adhesin Including the filamentous haemagglutinin of Bordetella pertussia, a mannose-resistant haemagglutinin from Salmonella serotype Typhimurium and a fibrillar haemagglutinin from helecobacte pylori Pili: e. g. , Neisseria gonorrhoeae Other surface structures of bacteria: LTA

Other extracelluar aggressins o Invasive enzymes: e. g. Coagulase: working in conjunction with serum factors to coagulate plasma. contributes to the formation of fibrin walls around staphylococcal lesions.

ØToxins Exotoxin o Definition: a soluble protein toxin usually secreted from a living bacterium.

o Origin and release: produced by Gram-positive bacteria as well as Gram-negative cells o Physical and chemical properties: proteins and usually heat-labile.

Virulence factors ØToxins Exotoxin o Immunity: excellent antigens that elicit specific antibodies called antitoxins.

Antitoxin: Definition: a specific antibody capable of neutralizing the exotoxin that stimulates its production. Toxoid: Definition: a modified exotoxin that has been treated to destroy its toxicity and remains immunogenicity.

Virulence factors Exotoxin o Component characteristics: most exotoxins consist of two parts, an A (active) component and a B (binding) component. Toxicity: high and even fatal; highly tissue specificity

o Categories: Cytotoxins: exotoxins that destroy the target cells directly by various mechanisms. Neurotoxins: exotoxins that affect nerve transmission of the nerve system. Enterotoxins: exotoxins that stimulate hypersecretion of water and electrolytes from the intestinal epithelium and produce watery diarrhea.

Exotoxin Neurotoxin Tetanus toxin , clostridium tetani glycine spastic paralysis Botulinum toxin, clostridium botulinum acetylcholine flaccid paralysis Cytotoxin diphtheria toxin inhibits protein synthesis Enterotoxins v. cholerae perturb the processes that regulate ion and water exchange across the intestinal epithelium

Virulence factors Endotoxins o Origin and release: produced only by Gramnegative bacteria and released only when bacteria lyze. o Chemical and physical properties: lipopolysaccharide of the outer membrane of Gram-negative bacteria; heat-stable

Endotoxins o Immunity: weakly immunogenic o Biologic activity: lipid A is the primary toxic component all endotoxins present similar biologic effects. Pyrogenicity Leukocyte reaction Endotoxemia and endotoxin shock DIC (dissemiated intravascular coagulation)

Endotoxin (especially lipid A)) Activates macrophages IL-1 Fever TNF Nitric oxide Fever and hypotension Activates complement Activates Hageman fatcor C 3 a C 5 a Hypotension Edema Neutrophil chemotaxis Coagulation cascade DIC

Endotoxins o Detection of endotoxin: The Limulus lysate test

The different between indotoxin and exotoxin kinds exotoxin Endotoxin source G+or a few G- G- component protein LPS stability good、160℃ 2 -4 h Short of destroyed strong weak antigenicity strong weak virulence

Virulence of pathogenic bacterial

Ⅱ. Portals of Entry and the size of the inoculum If certain pathogen enter the wrong portal, they will not be infectious. Occasionally, an infective agent can enter by more than one portal. e. g. mycobacterium tuberculosis.

Portals of entry skin respiratory system ingestion system genitourinary system C. tetani

The size of the inoculum The quantity of microbes in the inoculating dose.

Ⅲ. the originate and progress of infection A. The source of the infection B. routes of pathogen transmission C. Patterns of infection

A. The source of the infection Living reservoirs Persons or animals with frank symptomatic infection are obvious sources of infection Nonliving reservoirs

Sources of infectious diseases Exogenous infections: o Patients o Carriers: those in whom pathogens are present and may be multiplying, but who shows no clinical response to their presence. o Contaminated animals Endogenous infections

Carrier state o Definition of carriers: those in whom pathogens are present and may be multiplying, but who shows no clinical response to their presence o Definition of carrier state: a type of infections causing no signs of symptoms, in which pathogens multiply and may be transmitted to other individuals

two major types of carrier: Convalescent carriers: those who recover from infectious disease and in whom the pathogens remain and multiply without causing overt symptoms. Healthy carriers: those who do not have the clinical symptoms but carry pathogens indeed. Typhoid Mary (Mary Mallon)

B. routes of pathogen transmission 1. respiratory infections the tiny particles of liquid released into the air form aerosols or droplets 2. wound infectons: in soil and feces of human and animal 3. intestinal infections: contaminate drinking water and food or when used to fertilize crops

4. contact infection: directly contact between the skin and mucous membranes of the infected person or animal and that of healthy person 5. animal bites infections: the majority of animal vectors are arthropods such as fleas, mosquitos, flies, and ticks

C. Patterns of infection Apparent infection acute infection chronic infection 1. apparent infection When an infection causes pathological changes leading to disease, it is often accompanied by a variety of signs and symptoms Infectons that come on rapidly, with severe but shortlived effects, are called acute infections The infection persists several months to several years called chronic infection

Inapparent infection: also called subclinical infection that has no detectable clinical symptoms

local infection generalized/systemic infection Localized infection stands for the case that the microbe enters the body and remains confined to a specific tissue

Generalized infection Bacteremia o Definition: a transitory disease in which bacteria present in the blood are usually cleared from the vascular system with no harmful effects. Septicemia o Definition: a disease in which the blood serves as a site of bacterial multiplication as well as a means of transfer of the infectious agent from one site to another.

Toxemia o Definition: the presence of microbial toxins in the blood Pyemia o Definition: the presence of pyogenic bacteria in the blood as they are being spread from one site to another in the body

Local lesion toxin 毒 素 血液 局局 部部 病病 灶灶 toxin 毒素 toxin special toxic symptom Toxemia e. g. tetanus Defense function↓↓ pathogenic bacterium can grow in blood Organism is seriously dadamaged, toxic symptom all over the body。 Bacteremia Septicemia

toxin 毒 素 局局 部部 病病 灶灶 blood toxin 毒素 New pyosis focus of infection Pyosepticemia When Pyosis bacteria cause Septicemia， multiple pyosis focus of infection will happen. e. g. staphylococci aureus

Section 3 Antibacterial immunity of host

Host resistance mechanisms Ø Nonspecific host defenses Anatomical defenses o Skin and mucosal membrane Mechanical barriers Secretions Normal flora

o Blood-brain barrier o Placenta barrier Cellular defenses: the reticuloendothelial system Molecular defenses: complements, lysozymes, etc

Innate immunity Skin & mucous membranes Intact skin Fatty acids sebaceous glands Mucous membrane of respiratory tract 1. ciliary action 2. traps many microorganisms Lysozyme Normal flora

Innate immunity Inflammatory response & phagocytosis (early host responses to bacteria infection) Bacteria infection→vasoactive factors → the increased permeability Chemokines → Neutrophils and macrophages

Host resistance mechanisms Ø Specific host of defenses Humoral immunity: antibody-mediated immunity Cellular immunity: cell-mediated immunity Inflammatory response & phagocytosis

Host defences

Acquired immunity Humoral immunity antibody to aggressin antibody to toxin Cell-mediated immunity T cells lymphokines (IFN- γ) macrophages