Lecture 5: Pathogen/Host interactions Mechanisms of Infections Disease

Question 1

What is a pathogen?

Answer 1

Always causes disease.
Example: Neisseria gonorrhoea, Ebola virus

Question 2

Potential Pathogen

Answer 2

Does not always lead to disease, needs to be the right time and place
Example: Escherichia coli

Question 3

Non-Pathogen

Answer 3

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)

Question 4

Virulence factors

Answer 4

Factors that help organisms cause disease or avoid immune responses
Example: Toxin production, capsule

Question 5

Normal flora/Microbiota

Answer 5

Organisms that are typically found at a body site - may cause disease if in other sites

Question 6

Mucus membranes

Answer 6

Mouth, nose, genital tract, GI tract all have bacteria that reside in those ecological niches

Question 7

Normal Flora: Skin

Answer 7

• 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

Question 8

Normal Flora: Respiratory Tract

Answer 8

• 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

Question 9

Normal Flora: Gastrointestinal (GI) Tract

Answer 9

• 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

Question 10

Normal Flora: Genitourinary Tract

Answer 10

• 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

Question 11

What are the parts of the microbiome

Answer 11

• Nose
• Mouth
• Vagina
• Skin

Question 12

What organisms do we term “commensals” or “normal flora” at least in the GI tract help us with extracting nutrients from our food

Answer 12

Intestinal flora
- Bacteroides
- Lachnospiraceae
- Clostridium
- Bifidobacteria
- Lactobacillus
- Actinomycetales
- Streptococcus

Question 13

What does normal flora do

Answer 13

• 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

Question 14

Clinical Manifestations of altered immune flora - C.difficile

Answer 14

• 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

Question 15

Non-specific host defences and examples

Answer 15

• 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

Question 16

Examples of Non specific host responses

Answer 16

• 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

Question 17

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?

Answer 17

1. 3 - 1st line (barriers at body surface), 2nd line (pre-made), 3rd line (you have to meet pathogen to have a response)
2. 1st and 2nd line are Innate (nonspecific) immunity, 3rd is acquired (specific) immunity
3. 1st - Skin, mucous membranes, secretions, reflexes, reflexes, normal microbiota
   2nd - Inflammation, phagocytes, fever, complement system, interferon
   3rd - T cell lymphocytes, B cell lymphocytes, antibodies

Question 18

Describe the host immune system

Answer 18

• 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

Question 19

Innate Immunity

Answer 19

Rapid response, no memory

Question 20

Adaptive immunity

Answer 20

Initial slow response, subsequent rapid response and long-term memory

Question 21

Innate immune system

Answer 21

• 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)

Question 22

Humoral response or antibody-mediated response

Answer 22

• 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

Question 23

What is cell-mediated immunity

Answer 23

• 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

Question 24

Mechanisms of Pathogen Control T cells Mediated immunity

Answer 24

• 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

Question 25

What is biofilm production?

Answer 25

- 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

Question 26

Method to avoid phagocytosis - Capsule production

Answer 26

- 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

Question 27

Toxin production and biofilms/capsules

Answer 27

- 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

Question 28

Bacteria toxins and all the levels below

Answer 28

1. Bacterial Toxins 2. Endotoxin or exotoxin 3. Under exotoxins: Enterotoxin, Neurotoxin, and Cytotoxin - Under Enterotoxin: - Adenylate cyclase - Guanylate cyclase - Food poisoning - Nothing under neurotoxin - Under Cytotoxin: - Macrophage cytotoxin - Vacuolation - Thiol-activated

Question 29

What is an Endotoxin

Answer 29

- Structural components of the outer membrane of Gram negative bacteria - Lipid A component of LPS - Heat stable

Question 30

What is an Exotoxin and Enterotoxin

Answer 30

Exotoxin: Excreted toxins Enterotoxins: Exotoxin with effects in the gut

Question 31

Immune Evasion - Antigenic Drift and Swift (Influenza Virus)

Answer 31

- Antigenic Variation - dramatic changes in sequences - Drift - gradual change in antigen (shrinks mutation) - Shift - major change in antigen (big amount of mutation)