How Microorganism Cause Disease
How Microorganism Cause Disease
How Microorganism Cause Disease
PRESENTED BY:
SANTOS, CARLA RIZA
CUERPO, MHELMAR JAY
PANTUA, HAZILLE
HOW MICROORGANISMS CAUSE DISEASE
Infectious agents establish infection and damage tissues by any of
three mechanisms:
• They can contact or enter host cells and directly cause death of infected cells.
Microorganisms can cause toxins, tissue degradation, and damage, causing
ischemic necrosis and mediated destruction of infected hepatocytes.
• Oncogenic viruses, like HPV and EBV, stimulate cell growth and survival
through various mechanisms, including hijacking cell cycle control, anti-
apoptotic strategies, and insertional mutagenesis. Bacterial damage to host
tissues depends on bacteria's ability to adhere, invade, or deliver toxins.
Pathogenic bacteria have virulence genes grouped together in pathogenicity
islands, with a few genes determining a bacterium's harmfulness. Plasmids and
bacteriophages carry virulence between bacteria.
• They can induce host immune responses that, although directed against the
invader, cause additional tissue damage. Thus, the defensive responses of the
host can be a mixed blessing, helping to overcome the infection but also
contributing to tissue damage.
MECHANISMS OF VIRAL INJURY
Viruses can directly damage host cells by entering them and replicating at the host’s
expense. The manifestations of viral infection are largely determined by the tropism of the
virus for specific tissues and cell types. Tropism is influenced by a number of factors.
• Quorum sensing
Bacteria regulate gene expression within large populations,
enabling specific genes like virulence genes to be expressed after high
concentrations. S. Aureus secretes auto inducer peptides, increasing
exotoxin production as bacteria grow.
• Biofilms
Biofilms form on host tissues or devices, making bacteria
inaccessible to immune mechanisms and increasing resistance to
drugs. They are crucial for infections like bacterial endocarditis,
artificial joint infections, and cystic fibrosis.
• Bacterial adherence to host cells
Adhesins are surface molecules that bind to host cells or extracellular
matrix. Different bacteria have different surface structures, such as S.
Pyogenes' protein F and teichoic acid binding to fibronectin. Pili,
filamentous proteins, have conserved stalks and vary in amino acids. E.
Coli strains have specific P pilus binding to uroepithelial cells, while N.
Gonorrhoeae's pili mediate adherence and host antibody response.
• Bacterial toxins
Toxins are bacterial substances that contribute to illness, classified
as endotoxins or exotoxins. Bacterial endotoxins are lipopolysaccharides
(LPS) found in gram-negative bacteria's outer membrane. LPS binds to
CD14 on host leukocytes and binds to toll-like receptor 4, promoting cell
activation and inflammatory responses. Benefits of LPS include protective
immunity, increased cytokines, and costimulatory molecules. However,
high levels can lead to septic shock, coagulation, and acute respiratory
distress syndrome. Exotoxins are secreted proteins that cause cellular
injury and disease, classified by their mechanism and site of action.
• Enzymes
Bacteria secrete enzymes (proteases, hyaluronidases, coagulases,
fibrinolysins) that act on their respective substrates in vitro, but their
role in disease is understood in only a few cases. For example,
exfoliative toxins are proteases produced by S. Aureus that cleave
proteins known to hold keratinocytes together, causing the epidermis
to detach from the deeper skin.
• A-B toxins:
Toxins with two components alter intracellular signaling or
regulatory pathways. These toxins have an active (A) component
with enzymatic activity and a binding (B) component that binds
cell surface receptors and delivers the A protein. The effect
depends on the binding specificity and cellular pathways affected.
Anthrax toxin has two alternate A components, edema factor and
lethal factor, mediating specific pathologic effects.
• Super Antigens
Stimulate very large numbers of T lymphocytes by binding to
conserved portions of the T cell receptor, leading to massive T
lymphocyte proliferation and cytokine release. The high levels of
cytokines lead to capillary leak and the systemic inflammatory response
syndrome. Superantigens made by S. Aureus and S. Pyogenes cause toxic
shock syndrome.
• Neurotoxins
Produced by Clostridium botulinum and Clostridium tetani inhibit
release of neurotransmitters, resulting in paralysis. These toxins do not
kill neurons; instead, the A domains cleave proteins involved in secretion
of neurotransmitters at the synaptic junction. Tetanus and botulism can
result in death from respiratory failure due to paralysis of the chest and
diaphragm muscles.
• Enterotoxins
Affect the gastrointestinal tract causing varied effects, including
nausea and vomiting (S. Aureus), voluminous watery diarrhea (V.
Cholerae), and bloody diarrhea (C. Difficile).
• Chronic Inflammatory Diseases
In the development of inflammatory bowel disease, an important
early event may be compromise of the intestinal epithelial barrier, which
enables the entry of both pathogenic and commensal microbes and their
interactions with local immune cells, resulting in inflammation. The cycle
of inflammation and epithelial injury may be an important component of
the disease, with microbes playing the central role.
• Cancer
Viruses, such as HBV and HCV, and bacteria, such as H. Pylori, that
are not known to carry or to activate oncogenes are associated with
cancers, presumably because these microbes trigger chronic inflammation
with subsequent tissue regeneration, which provides fertile ground for the
development of cancer.
Injurious Effects of Host Immune Responses
As mentioned earlier, the host immune response to microbes can
sometimes be the cause of tissue injury. A few examples of types and
mechanisms of injury are as follows:
ANTIGENIC VARIATION
Neutralizing antibodies prevent microbes from infecting cells and
killing pathogens. They use genetic mechanisms for antigenic variation, such
as low fidelity viral RNA polymerases, reassortment of genomes, gene
rearrangement, and gene-specific surface antigens in borrelia, trypanosoma,
and S. Pneumoniae serotypes.
MODIFICATION OF SURFACE PROTEINS
Host cationic antimicrobial peptides, like defensins,
cathelicidins, and thrombocidins, protect against invading microbes
by binding to the bacterial membrane and killing. Bacterial
pathogens avoid killing by creating surface molecules that resist
binding.