Host-Pathogen Relationships - Chapter 4 PDF

**Chapter 4\ Host-pathogen relationships** **Chapter overview** - Basic concepts in infectious diseases - Host-pathogen relationships - Portals of entry - Virulence factors **Definitions** - Pathology: study of disease - Etiology: cause of disease - Pathogenesis: disease proce...

**Chapter 4\ Host-pathogen relationships** **Chapter overview** - Basic concepts in infectious diseases - Host-pathogen relationships - Portals of entry - Virulence factors **Definitions** - Pathology: study of disease - Etiology: cause of disease - Pathogenesis: disease process - Infection: colonization by microbe - Disease: illness - Virulence: degree of pathogenicity =some bacteria are friendly and other are pathogen - Bacteremia: presence of bacteria in the blood - Sepsis/septicemia: generalized inflammatory response to an infection. *Some example* *Covid is most infectious when you have symptoms* *Chicken pots that cause a rash just when you have it is contagious* **Infection and disease** - Infection - Invasion by parasitic microbes - Can occur without causing disease - HIV infection *retrovirus can't stay inactive for 20years* ; AIDS disease - Disease - Changes in health; damage to host **Phases of disease** - Incubation: - Time between introduction of organism to onset of symptoms (depends on many factors) - Illness - Follows incubation - The individual experiences signs and symptoms of disease - Convalescence - Period of recuperation and recovery (Infectious agents may still be spread) **Types of disease** Men at 50 get immunoscense **Sepsis** - In 1914, Hugo Schottmüller provided the first scientific definition of sepsis: "sepsis is a state caused by microbial invasion from a local infectious source into the bloodstream which leads to signs of systemic illness in remote organs". - According to this definition, bacteremia was a *condition sine qua non* to the diagnosis of sepsis, which arises from the host response to infection, which is directed to kill the invading pathogens. - For this reason, patient outcomes from sepsis are determined not only by the viability of the invading pathogen, which can be directly toxic and destructive to tissue, but also even more so by the host response, which may be exaggerated and result in collateral organ and tissue damage. **[Host-pathogen relationships]** - Commensalism - One benefits and the other neither benefits o is harmed (indiferente) - *Corynebacterium* in eyes - Mutualism - Both benefit - *E. coli* in the gut *Some pruduce vitamins ex K or others substance* - Parasitism - One benefits and the other is harmed - Any pathogen - Pathogenicity depends on the susceptibility of host and virulence of pathogen **Normal Microbiome: populations of microorganisms routinely found growing on the body of a healthy individual** *Pro/Pre biotic the first one for protecton if you take antibiotics* *The second one is giving good bacterial (or buy it or eat 10 different vegetables)* **Opportunistic pathogens** - Don't normally cause disease, but they may under some circumstances: - Normal flora in the wrong environment - E. coli in urinary tract or wounds - Compromised immune system - Pneumocystis carinii and AIDS - Disruption of homeostasis = *aemonia after a flu, some bacterial normally found in the respiratory tract can penetrate more* - Secondary infection after the flu **Pathogenic microorganisms** - To cause disease a microbe has to gain access to host. Possible portals of entry include: - Mucous membranes - Skin - Parenteral - Placenta - Once inside it must evade host defenses and damage host tissues **[Portals of entry]** **Portal of entry: mucous membranes of the respiratory tract =** 2 m is the safest distance - Microbes inhaled into mouth or nose in droplets of moisture or dust particles - Easiest and most frequent portal of entry - Common diseases contracted via the respiratory tract: - Common cold - Flu - Tuberculosis - Whooping cough - Pneumonia - Measles *=rush in the skin* - Strep Throat - Diphtheria **Portal of entry: mucous membranes of the gastrointestinal tract** - microbes gain entrance through contaminated food and water or fingers and hands - most microbes that enter the gastrointestinal tract are destroyed by hydrochloric acid and enzymes of stomach or bile and enzymes of small intestine - Common diseases contracted via the G.I. tract: - Salmonellosis - Shigellosis - Botulism - Cholera *Omeprazole change the acidity of the bowel so if you are immunosuppressive you get sick* **Portal of entry: mucous membranes of the genitourinary tract** - Sexually transmitted diseases - Common diseases contracted via the genitourinary tract: - Gonorrhea - Syphilis - Chlamydiasis - HIV **Portal of entry: mucous membranes of the conjunctiva** - Mucous membranes that cover the eyeball and lines the eyelid - Common diseases contracted via the conjunctiva - Chlamydiasis - Herpes ocularis *If a mother have an infection the baby can born with infection* **Portal of entry: skin** - Skin - the largest organ of the body. When unbroken is an effective barrier for most microorganisms. - Some microbes can gain entrance through openings in the skin: hair follicles and sweat glands - Common diseases contracted via the skin: - Staphylococcal infections - Mycosis **Portal of entry: parenteral** *trough the blood* - Microorganisms are deposited into the tissues below the skin or mucus membranes, through: - Punctures - Injections - Bites - Scratches - Surgery - splitting of skin due to swelling or dryness - Common diseases contracted via parenteral: - Cytomegalovirus (*90% human have it but can be bad)* - Hepatitis - HIV **Factors that determine the establishment of disease** - Just because a pathogen enters your body it does not mean it's going to cause disease: - Is it the preferred portal of entry for the pathogen? - *Streptococcus pneumoniae* - If it is inhaled can cause pneumonia - If it enters the G.I. tract it does not cause disease - *fimbraetyphi* - if it enters the G.I. tract it can cause typhoid fever - if it is on skin it does not cause disease - How many bacteria? Size of the inoculum - LD50: Number of microbes in a dose that kill 50% of the organisms infected in a sample - ID50: Number of microbes in a dose that causes disease in 50% of the organisms infected - The higher the virulence the lower the ID50 or LD50 Because highly virulent pathogens are more efficient at causing infection or death, requiring fewer organisms (ID₅₀) or a smaller dose (LD₅₀) to reach those outcomes **Step One: Adherence** - Pathogens have attachment structures - Pili () - Protein structure that binds to host glycoproteins - Example: type I fimbriae in enteric bacteria **Step 2: Invasion/Colonization** - Three goals - Get beyond point of attachment - Multiply - Need food, water, and space - Must breakdown complex nutrients (soluble/simple not readily available) they must produce enzymes to **break down complex nutrients** in tissues (such as proteins, lipids, or polysaccharides) into simpler forms they can use for energy and growth. - Iron is sequestered by transferrin - Protect from host defenses - Must compete with normal flora, nonspecific immunity (macrophage = Immune cells that engulf and destroy pathogens., fever = A systemic response that can slow the growth of pathogens and inflammation = local immune response that brings immune cells to the site of infection and creates an environment that is hostile to pathogens) and specific immunity (T or B cells and antibodies) **Step 3: Cause Damage** - - **Proteases** break down proteins. - **Lipases** degrade fats. - **Hyaluronidase** breaks down hyaluronic acid in connective tissues. - Production of toxins: bacterial products that directly harm tissue or trigger destructive biological activities. **Exotoxins** neurotoxins, cytokines, enteroxins / **Endotoxins** - Immunopathogenesis: excessive innate, immune and inflammatory responses triggered by the infection (superantigens; These are bacterial toxins that overactivate T cells, leading to a massive, uncontrolled immune response; immune complexes precipitation These are clusters of antigens and antibodies that can precipitate and deposit in tissues, causing inflammation and tissue injury.) - Escape of host defenses *they are going to secrete a lot of substances* - **Proteases** that degrade antibodies. - **Capsules** that hide the pathogen from immune cells. - **Antigenic variation**: The pathogen changes its surface proteins to avoid recognition by the immune system. - **Toxins** that kill immune cells or inhibit their function. **[Virulence factors]** [ ] - Definition: a pathogen-produced substance that promotes the establishment and maintenance of disease - Types: 1. Adhesion factors 2. Evading immune response 3. Degradative enzymes 4. Toxins 1. **Adhesion factors** - Pili: short, rigid and numerous - Adhesins: molecules that bind to specific receptors on tissue surfaces. Some of them are present at the tip of the pili Example: Fibronectin Binding Proteins, cell surface-bound protein that binds to both fibronectin and fibrinogen 2. **Evading immune response** **Microbial defenses against host immunological clearance** - Encapsulation - Antigenic mimicry - Antigenic shift - Inhibition of phagolysosome fusion - Production of antiimmunoglobulin proteases - Destruction of phagocyte - Inhibition of chemotaxis - Resistance to lysosomal enzymes - Intracellular replication **Capsule** - Prevents phagocytosis by macrophages or neutrophils, bacteria are "not seen" by immune system cells. - Mainly maid of polysaccharides, with exceptions. - Examples: - *Streptococcus pneumoniae* - *Klebsiella pneumoniae* - *Haemophilus influenzae* - *Bacillus anthracis* - *Streptococcus mutans* - *Yersinia pestis* **Antigenic mimicry** = pretent to be host molecule that will not cause harm - Antigenic similarity between molecules found on some disease-causing microorganisms and on specific previously healthy body cells or tissues. **Antigenic shift** ex flu virus have it ! emergence of a new subtype with significantly altered surface antigens. - Genetic alteration occurring in an infectious agent that causes a dramatic change in a protein called an antigen, which stimulates the production of antibodies by the immune systems of humans and other animals. - Antigenic shift has been studied most extensively in influenza type A viruses, which experience this change about once every 10 years. **Inhibition of phagolysosome fusion** **3. Degradative enzymes** **Leukocidins** - Attack certain types of white blood cells, preventing phagocytosis - Release and rupture lysosomes - lysosomes - contain powerful hydrolytic enzymes which then cause more tissue damage **Hemolysins** - Cause the lysis of red blood cells. - Example: *Streptococci*, alpha haemolytic, secrete hemolysins that cause the incomplete lysis of RBC's, beta haemolytic, secrete hemolysins that cause the complete lysis of RBC's **Coagulase** - Cause blood to coagulate - Blood clots protect bacteria from phagocytosis from white blood cells and other host defenses - *Staphylococci* - are often coagulase positive - boils - abscesses **Kinases** - Dissolve blood clots - Streptokinase - *Streptococci* - Staphylokinase - *Staphylococci* - Helps to spread bacteria - Bacteremia - Streptokinase - used to dissolve blood clots in the heart (heart attacks due to obstructed coronary blood vessels) **Hyaluronidase** - breaks down hyaluronic acid (found in connective tissues). Is a spreading factor. - Also allows the bacteria to use hyaluronan as a carbon source - Produced by *Streptococci*, *Staphylococci* and *Clostridium* **Collagenase** - breaks down collagen (found in many connective tissues) - *Clostridium* *perfringens* - Gas Gangrene - uses this to spread through muscle tissue **Necrotizing factor** - Causes death (necrosis) to tissue cells - Caused by *Streptococcus* class A, the so called "Flesh Eating Bacteria". **4. Toxins** - Poisonous substances produced by microorganisms: exotoxins and endotoxins - toxins - primary factor - pathogenicity - 220 known bacterial toxins - 40% cause disease by damaging the eukaryotic cell membrane - Toxemia - Toxins in the bloodstream **[Exotoxins]** - Released extracellular - Mostly enzymes - Soluble in body fluids - Highly specific - Host can produce antitoxin - Toxoids (inactivated by heat or formaldehyde) that still can produce antitoxin. The are used as vaccines - General types of toxins - Superantigens (Type I) - Membrane disrupting toxins (Type II) - A-B toxins (Type III) **Classification of Exotoxins** - Descriptive classifications - Leukotoxin - Cytotoxin - Neurotoxins - Enterotoxin - Hepatotoxin - Cardiotoxin **Leukotoxins: Superantigen** - Invoke very strong immune response - Affect T cells, which release lots of cytokines which can cause severe symptoms - Ex: *Staphylococci* and food poisoning toxins **Cytotoxins: Membrane Disrupting Toxins** - Cytoxic; Disrupt host plasma membrane by targeting - Protein channels - Phospholipid disruption - Examples: - Target protein channels in phagocytes - Target protein channels in RBCs **Neurotoxins: A-B toxin** - Toxin of *Clostridium* *botulinum* is responsible for the symptoms of botulism, preventing transmission of signal from nerve cell to muscle cell (inhibits release of acetylcholine) - Toxin of *Clostridium* *tetani* is responsible for the symptoms of tetanus - A-B neurotoxin travels to central nervous system - Prevents inhibition of random contractions by muscles **[Endotoxins]** - Present in Gram negatives bacteria - Are part of the outer portion of cell wall (outer membrane), particularly the Lipid A - They cause the same symptoms for different species of microbe - No antitoxins are produced by host - Very stable---can't be destroyed easily - Macrophages release TNF (tumor necrosis factor) when they attack some Gram negative cells. TNF binds to many tissues of host and may cause damage to blood capillaries and damage to blood-brain barrier (leading to infection of CNS) - antiiResponse: - Macrophages ingests Gram negative bacteria - They release then interleukin-1 in bloodstream - Interleukin-1 travels to hypothalamus and produces prostaglandins - Prostaglandins reset the body´s thermostat - Leukopenia followed by leukocytosis = initially, there is a drop in white blood cells (leukopenia) due to the immune response, but this is soon followed by a surge in white blood cell production (leukocytosis) as the body tries to fight off the infection. - Activation of complement = The endotoxins also activate the complement system, a part of the immune system that enhances the ability of antibodies and phagocytic cells to clear microbes and damaged cells. - Thrombocytopenia = Endotoxins can cause a decrease in platelets (thrombocytopenia), which are essential for blood clotting, as they get used up in abnormal clotting processes. - Disseminated intravascular clotting, because endotoxins activate blood clotting which blocks capillaries. - loss of water and decrease in blood pressure, leading to shock - death **Who will win? Susceptibility or Resistance of Host** - Age - Stress - Diet - Pre-existing disease (Genetic and Infectious) - Gender - Behavior - Weather - Your first line of defense