Pathogenesis

Pathogenesis  Pathogenesis

is a multi-factorial process which depends on the immune status of the host, the nature of the species or strain (virulence factors) and the number of organisms in the initial exposure.

 Virulence:

The quantitative ability of an agent to cause disease. Virulent agents cause disease when introduced into the host in small numbers. Virulence involves invasion and toxigenicity. LD 50 (age /sex /health /route of entry, etc )

 LD50:

The number of pathogens required to cause lethal disease in half of the exposed hosts is called an LD50 .

 ID50:

The number of pathogens required to cause disease (or, at least, infection) in half of the exposed hosts is called the ID50

The Mechanisms of Bacterial Pathogenicity Pathogenicity

is the ability to produce disease in a host organism. Virulence: a term which refers to the degree of pathogenicity of the microbe.

 There

are two broad qualities of pathogenic bacteria underlie the means by which they cause disease: invasiveness and toxigenesis. – 1. Invasiveness : The ability to invade tissues, 2. Toxigenesis : The ability to produce toxins. Bacteria produce two types of toxins called exotoxins and endotoxins.

Invasiveness  capsule  Adesin

pili, hair-like appendages  invasive substances tissue-degrading enzymes

Adhesion BACTERIUM

adhesin receptor

EPITHELIUM

E. coli with fimbriae

E. coli fimbriae Type 1 mannose

P

• galactose – glycolipids – glycoproteins

S. pyogenes lipoteichoic acid F-protein

fibronectin

BACTERIAL VIRULENCE FACTORS

1. Adherence Factors

2. Invasion of host cells & tissues

2. Toxins  Exotoxins  Endotoxins

Exotoxins Like enzymes, bacterial exotoxins: •are proteins •are denatured by heat, acid, proteolytic enzymes •have a high biological activity (most act catalytically) •exhibit specificity of action

Exotoxins •strongly antigenic •In vivo, specific antibody (antitoxin) neutralizes the toxicity of these bacterial proteins.

Exotoxins •Toxoids •Protein toxins are inherently unstable: in time they lose their toxic properties but retain their antigenic ones. Toxoids are detoxified toxins which retain their antigenicity and their immunizing capacity.(formalin)

A-B toxins Cell surface

Active

Binding

A

B

Endotoxins  LPS

Lipopolysaccharide: core or backbone of CHO side chains of CHO: "O" antigen Lipid A  Cell wall lysis required  formaldehyde and heat resistant  poor antigen as free molecule

Endotoxins Endotoxin

effects

Fever-pyrogen 1 microgram/ kg Leukopenia and leukocytosis necrosis Shwartzman phenomenon and disseminated intravascular coagulation (DIC). Endotoxemia and shock

Endotoxemia

5. Antiphagocytic factors  Some

pathogens evade phagocytosis or leukocyte microbicidal mechanisms by adsorbing normal host components to their surfaces. A few bacteria produce soluble factors or toxins that inhibit chemotaxis by leukocytes and thus evade phagocytosis.

Antiphagocytic Substances  1.

Polysaccharide capsules of S. pneumoniae, Haemophilus

influenzae, Treponema pallidum ; B. anthracis and Klebsiella pneumoniae.

 2.

M protein and fimbriae of Group A streptococci  3. Surface slime (polysaccharide) produced as a biofilm by Pseudomonas aeruginosa

 4.

O polysaccharide associated with LPS of E. coli  5. K antigen (acidic polysaccharides) of E. coli or the analogous Vi antigen of Salmonella typhi  6. Cell-bound or soluble Protein A produced by Staphylococcus aureus. Protein A attaches to the Fc region of IgG and blocks the cytophilic (cell-binding) domain of the Ab. Thus, the ability of IgG to act as an opsonic factor is inhibited, and opsonin-mediated ingestion of the bacteria is blocked.

Protein A inhibits phagocytosis Fc receptor immunoglobulin

PHAGOCYTE Protein A BACTERIUM

M protein inhibits phagocytosis Complement

fibrinogen

M protein r

peptidoglycan

r

r

Original and devolopment of Bacterial Infection

Source of infection  Exogenous

infection : patient, carrier, diseased animal or animal carrier.  Endogenous condition : most are normal flora, cause infection under abnormal condition.

Transmission • Airborne droplets • Food • Water • Sexual contact

Routes of infection  Respiratory  Gastroenteric  Genitourinary

tract  closely contact  insect bitting  blood transfusion  Parenteral route  Mucous membranes

According to infectious state  Inapparent

or

subclinical

infection  Latent infection  Apparent infection : cause apparent clinic syndrome  Carrier state: carrier

  1. 2. 3. 4.

5.

According to infectious sites

Local infection Generalized or systemic infection Toxemia : is the presence of exotoxins in the blood. Endotoxemia : is the presence of endotoxins in the blood. Bacteremia : is an invasion of the bloodstream by bacteria. Septicemia : illness that occurs when poisonous substances (toxins) produced by certain bacteria enter the bloodstream. Pyemia : is caused by pyogenic microorganisms in the blood.