Lecture 5: Pathogen/Host interactions Mechanisms of Infections Disease Flashcards
What is a pathogen?
Always causes disease.
Example: Neisseria gonorrhoea, Ebola virus
Potential Pathogen
Does not always lead to disease, needs to be the right time and place
Example: Escherichia coli
Non-Pathogen
This one is difficult, most organisms can cause disease in the right setting. But non-pathogens generally don’t cause disease except in rare cases
Example: Lactobacillus (in yoghurt and cheese)
Virulence factors
Factors that help organisms cause disease or avoid immune responses
Example: Toxin production, capsule
Normal flora/Microbiota
Organisms that are typically found at a body site - may cause disease if in other sites
Mucus membranes
Mouth, nose, genital tract, GI tract all have bacteria that reside in those ecological niches
Normal Flora: Skin
- Staphylococcus is gram positive cocci in clusters
- In skin swab
- Corynebacteria will also be found on the skin
- Generally colonized by Gram positive bacteria, both bacilli (Corynebacteria AKA “diptheroids”) and cocci (Staphylococci)
- Below the best, likely have gram negatives
- Organisms that can cause infection colonies the skin including pathogens like Staphylococcus aureus (coagulase positive staphylococcus) but usually coagulase-negative staphylococci predminate
Normal Flora: Respiratory Tract
- All strep hang out in the mouth, can develop community pneumonia
- Obviously oral health plays a big role in bacterial populations of the oral flora
Normal Flora: Gastrointestinal (GI) Tract
- Flora is dependent on the site - upper vs. lower GI tract
- Upper GI - Facultative aerobes- grows anaerobically and aerobically
- Lower GI = anaerobes (grows only in the absence of O2)
- Few gram positive bacteria in the GI tract (although enterococci are present as they are resistant to bile)
- Bacteria can move using flagella that can transport them short distance
- Lactobacillus is very common in GI tract, common in women because it drops pH of genital tract, in pubescence women, prior to puberty has the same bacterial makeup as skin, post menopausal women have skin flora there, but 12 and 60 women get colonized by lactobacillus and it produces lactic acid, dropping pH by 1000 fold, not hospitable for most bacterial infections
- Entire defense system is mediated by this bacteria, that modules the entire pH of the environment
Normal Flora: Genitourinary Tract
- The urine washes organism from the urethra to maintain a sterile bladder
- Vaginal flora changes with age
- Prepubescent and postmenopausal women - flora similar to skin flora
- Women of childbearing age - many bacterial species with a predominance of lactobacillus
What are the parts of the microbiome
- Nose
- Mouth
- Vagina
- Skin
What organisms do we term “commensals” or “normal flora” at least in the GI tract help us with extracting nutrients from our food
Intestinal flora
- Bacteroides
- Lachnospiraceae
- Clostridium
- Bifidobacteria
- Lactobacillus
- Actinomycetales
- Streptococcus
What does normal flora do
- Provide a level of protection from potential pathogens from taking hold
- Ex: C.difficile - antibiotics wipes out the normal flora and allow the C.diff spores to colonize in the gut
- Can lead to death
- In genital flora, perturbations in the Microbiota of the Vaginal tract has been associated with bacterial vaginosis
- Normal flora of the GI tract prevents the colonization by pathogens
- Prevents onset of disease
Clinical Manifestations of altered immune flora - C.difficile
- Leading cause of antibiotic associated diarrhea
- Associated with changed to the GI flora
- Risk factors include using antibiotics, being in hospital, age
- Associated with ulcerative colitis and can lead to death or in some cases a colectomy
Non-specific host defences and examples
- Non-specific, non immune host defences
- Barriers include structural, enzymatic and pH of the environment
- Normal flora also prevent pathogens from taking a foothold and causing infection
Examples:
Resp Tract - Coughing, sneezing, mucus, ciliary action, phagocytes, lysozyme
GI - stomach acidity, normal flora, peristalsis, antimicrobial compounds
Skin - Structural barrier, lactic acid, propionic acid, lysozyme, normal flora
Urogenital Tract - Lavaging action of urine, acidity of urine, lysozyme, vaginal lactic acid
Eyes - Blinking, tears, lysozyme
Examples of Non specific host responses
- Urination typically washes organisms from the urethra to maintain a sterile bladder
- Mucociliary elevator: Ciliated cells move material towards the larynx and swallowed. Cough reflex: works in conjunction with mucociliary elevator
- Lysozyme: breaks peptidoglycan; Lactoferrin: binds free iron and limits bacteria from obtaining iron
- Secretory IgA: antibody in secretions
- Inflammation and cellular recruitment to the site of damage - neutrophils and ROS (toxic to cells)
- Damage results in damage signals
- These damage signals recruit cells
- Initiation of an immune response
Arsenal Host Defenses
1. How many lines of defense r there?
2. What are the categories or the lines of defense?
3. What is included in each defense?
- 3 - 1st line (barriers at body surface), 2nd line (pre-made), 3rd line (you have to meet pathogen to have a response)
- 1st and 2nd line are Innate (nonspecific) immunity, 3rd is acquired (specific) immunity
- 1st - Skin, mucous membranes, secretions, reflexes, reflexes, normal microbiota
2nd - Inflammation, phagocytes, fever, complement system, interferon
3rd - T cell lymphocytes, B cell lymphocytes, antibodies
Describe the host immune system
- Only about 2% of your white blood cells are circulating in blood
- Several specific cells with different functions - you should read about function of the different cells
Innate Immunity
Rapid response, no memory
Adaptive immunity
Initial slow response, subsequent rapid response and long-term memory
Innate immune system
- Inflammatory response
- Phagocytosis (ingest the bacteria like pac-man)
- The bacteria are ingested into specific vacuoles or “pockets” in the cell that contain digestive enzymes (lysozyme)
Humoral response or antibody-mediated response
- Immunoglobulins (antibodies - IgG, IgM, IgA, IgE, and IgD)
- Respond to an anti(antibody)-gen(generator)
- IgM = early; IgG = late and long lasting
- Agglutinate, precipitate, etc promote other factors to help immunoglobulins
G - antibody gives you protection (past infections)
E - allergic reaction
D - not sure
M - non specific, response early to pathogens turn into G
What is cell-mediated immunity
- Several different types of cells involved including Cytotoxic T-cells, Regulatory T cells, Natural Killer cells (NK cells)
- Important as a defence in combination with antibody but may also be important alone
Mechanisms of Pathogen Control T cells Mediated immunity
- Cytotoxic T cells destroy altered cells by recognizing foreign protein sequences presented on the cell surface
- Cytotoxic cells detect changes in the types of peptides presented on the cell. Also expand into a large population of clones and then will contract once the pathogen has been cleared. Small population will become memory cells
- Virus infected cells, foreign cells, tumour cells, and cells with internal bacteria or parasites
What is biofilm production?
- Often occur on prothetic devices, but can also occur on native tissue
- Biofilms are formed when organisms stick to a surface and produce an extracellular matrix
- The biofilm is both a mechanism of immune evasion and prevents the penetration of antibiotics and other cellular factors
- Biofilms also facilitate quorum sensing - bacterial communication and can support aerobic and anaerobic mixed bacterial populations
Method to avoid phagocytosis - Capsule production
- One method that bacteria avoid phagocytosis from immune cells is by generation a capsule
- A capsule is a thick polysaccharide layer that resides outside the cell
- Capsule production is a virulence factor in a host of bacteria
- Macrophages cannot take it in due to capsule
Toxin production and biofilms/capsules
- Biofilms and capsules help avoid phagocytosis but a more direct method is toxin production
- Toxins are small proteins or polysaccharides that are able to arrest cellular functions or lyse host cells
Bacteria toxins and all the levels below
- Bacterial Toxins
- Endotoxin or exotoxin
- Under exotoxins: Enterotoxin, Neurotoxin, and Cytotoxin
- Under Enterotoxin:- Adenylate cyclase
- Guanylate cyclase
- Food poisoning
- Nothing under neurotoxin
- Under Cytotoxin:
- Macrophage cytotoxin
- Vacuolation
- Thiol-activated
What is an Endotoxin
- Structural components of the outer membrane of Gram negative bacteria
- Lipid A component of LPS
- Heat stable
What is an Exotoxin and Enterotoxin
Exotoxin: Excreted toxins
Enterotoxins: Exotoxin with effects in the gut
Immune Evasion - Antigenic Drift and Swift (Influenza Virus)
- Antigenic Variation - dramatic changes in sequences
- Drift - gradual change in antigen (shrinks mutation)
- Shift - major change in antigen (big amount of mutation)
