Virulence factors that damage the host Flashcards
Exotoxin structure and role in
disease
Exotoxins are potent protein toxins that are secreted by certain types of bacteria, including Staphylococcus, Streptococcus, and Clostridium species. Exotoxins can be classified into several types based on their mode of action and structure.
The structure of exotoxins varies depending on the type of toxin. Some exotoxins are single-chain polypeptides, while others are composed of multiple subunits. For example, diphtheria toxin is a single-chain polypeptide that consists of three domains: the receptor-binding domain, the translocation domain, and the catalytic domain. Botulinum toxin and tetanus toxin are multi-subunit proteins that consist of a heavy chain and a light chain.
Exotoxins can cause disease by disrupting essential cellular functions and damaging host tissues. They can act at various levels, including disrupting cell membranes, interfering with protein synthesis, and modifying intracellular signaling pathways. For example, the cholera toxin produced by Vibrio cholerae causes severe diarrhea by binding to specific receptors on the surface of intestinal cells and increasing the levels of intracellular cyclic AMP (cAMP), which leads to the secretion of large amounts of water and electrolytes.
Exotoxins can also have specific target cells or organs. For example, the tetanus toxin produced by Clostridium tetani targets the nervous system and can cause severe muscle contractions and spasms. The botulinum toxin produced by Clostridium botulinum targets the neuromuscular junction and can cause paralysis by blocking the release of the neurotransmitter acetylcholine.
The role of exotoxins in disease varies depending on the type of toxin and the host response. Some exotoxins can cause severe and life-threatening infections, while others can contribute to the virulence of the bacteria by promoting tissue damage and immune evasion. Understanding the structure and mode of action of exotoxins is important for the development of effective treatments and vaccines against bacterial infections.
Exotoxins
Exotoxins are peptides released by bacteria into periplasmic space. They contain active subunits which enter cytoplasm and exert toxic effects.
They have a bninding subunit which is larger and helps the toxin bind to host membrane A-B toxin
EG. diptheria toxin, cholera
Bacterial products that provoke an
autoimmune response
Lipopolysaccharides (LPS): LPS is a component of the outer membrane of Gram-negative bacteria. It activates the immune system by binding to Toll-like receptors (TLRs) on immune cells, leading to the production of pro-inflammatory cytokines. Studies have shown that exposure to LPS can trigger autoimmune responses and contribute to the development of autoimmune disorders such as rheumatoid arthritis and lupus.
Heat shock proteins (HSPs): HSPs are produced by bacteria and other organisms in response to stress. They are highly conserved proteins that are similar in structure to certain human proteins. When the immune system is exposed to HSPs, it can produce antibodies that cross-react with human proteins, leading to autoimmune responses. HSPs have been implicated in the development of autoimmune disorders such as multiple sclerosis and type 1 diabetes.
Superantigens: Superantigens are bacterial toxins that can activate a large number of T cells in the immune system, leading to a massive release of cytokines and inflammation. This can cause damage to tissues and organs and trigger autoimmune responses. Superantigens have been linked to autoimmune disorders such as Kawasaki disease and toxic shock syndrome.
Molecular mimicry: Some bacterial products can mimic human proteins, leading to the production of autoantibodies that attack both the bacterial product and human tissues. This is known as molecular mimicry and has been implicated in the development of autoimmune disorders such as Guillain-Barré syndrome and reactive arthritis.
Endotoxins and other toxic cell wall
components
Peptidoglycan: Peptidoglycan is a major component of the cell wall in most bacteria. It consists of repeating units of N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM), which are linked by peptide bonds. Peptidoglycan can cause inflammation and tissue damage when it is released into the bloodstream.
Lipoteichoic acid (LTA): LTA is a cell wall component found in Gram-positive bacteria. It is composed of a glycerol-phosphate backbone that is linked to teichoic acid chains. LTA can activate the immune system and cause inflammation.
Mycolic acids: Mycolic acids are long-chain fatty acids found in the cell walls of Mycobacterium tuberculosis and other acid-fast bacteria. They are highly immunogenic and can cause granuloma formation and tissue damage in infected individuals.
Capsular polysaccharides: Capsular polysaccharides are complex carbohydrate structures that are found on the surface of many bacteria. They can inhibit phagocytosis by the immune system and make the bacteria more resistant to antibiotics.
Endotoxin vs exotoxin
Explain how helminths evade the immune system
Modulation of host immune response: Helminths can actively modulate the host’s immune response by secreting immunomodulatory molecules. These molecules can suppress the host’s immune response, leading to reduced inflammation and damage to the host tissues.
Antigenic variation: Helminths can undergo antigenic variation by changing the surface proteins that are recognized by the host’s immune system. This allows the parasite to evade the host’s immune response and persist in the host for a longer period.
Encapsulation: Helminths can encapsulate themselves in a protective layer to avoid detection by the host’s immune system. This layer is composed of host-derived materials and can also prevent the penetration of drugs and other treatments.
Immune mimicry: Helminths can produce molecules that mimic the host’s own immune system, which can fool the host’s immune cells into thinking that the parasite is a part of the host’s own tissue. This can prevent the immune system from recognizing and attacking the parasite.
Suppression of effector mechanisms: Helminths can also suppress the host’s effector mechanisms, such as the production of antibodies or activation of T cells, which are necessary for the host’s immune response to be effective against the parasite.
