Immunity to Infection Flashcards
How would you classify the following:
Streptococcus pneumoniae
Clostridium tetani
Tryanosoma brucei
Pneumocytis jrovecii
What disease may they cause?
extracellular:
bacteria (gram pos. and neg)
parasites
fungi
pneumonia
tetanus
sleeping sickness
pneumocytsis pneumonia
How would you classify the following:
Mycobacterium leprae
Leismania denovani
Pasmodium falciparum
What disease may they cause?
Intracellular:
bacteria
parasites
Leprosy, leismaniasis, malaria
How would you classify the following:
Variola
Influenza
Varicella
What disease may they cause?
viruses (intracellular)
smallpox
flu
chickenpox
How would you classify the following:
Ascaris
Schistosoma
parasitic worms
Under most circumstances, microorganisms cannot cause disease unless there exists a breach in the protective barriers that normally prevent the pathogen from entering a foreign ecological niche (our body). The most notable barriers to infection have both Physical and Chemical
properties.
Describe physical barriers.
Skin:
Thick, multilayered
Low moisture
Acidic
(physical) The skin serves as a major barrier to a variety of noxious insults, including infection (bacterial, fungal, parasitic). The multiple layers of keratinocytes act as an impasse to pathogen invasion. Thus, infection via skin first requires direct tissue damage.
(physical)
Perhaps even more so than skin, mucosal surfaces are a primary site of infection (viral,
bacterial, fungal, parasitic).
Some mucosal surfaces (GI tract) secrete a thick mucus layer that acts as a physical barrier to cell surface interaction by microbes.
The movement of the ciliated epithelium of the lung expels particulate matter and foreign
material and prevents microorganisms from establishing an infectious niche.
Resistance to invading pathogens at mucosal surfaces is partially imparted by antibodymediated processes (e.g. secretory dimeric IgA).
Mucosal Surfaces: Major site of infection Mucus secretion (GI) Ciliated epithelium (Lung) Secretory IgA
Under most circumstances, microorganisms cannot cause disease unless there exists a breach in the protective barriers that normally prevent the pathogen from entering a foreign ecological niche (our body). The most notable barriers to infection have both Physical and Chemical
properties.
Describe chemical barriers.
Lysozyme - secreted in saliva/tears. A potent antimicrobial of Gram positive
(Staphylococcus aureus, Streptococcus pyogenes, Clostridium difficile) and
Gram negative (Salmonella,
Pseudomonas aeruginosa, Escherichia coli) bacteria. Degrades the
peptidoglycan layer that is unique to bacterial surfaces and is required for their survival.
Mostly Gram positive bacteria, some Gram negative. No Others!!
Antimicrobial peptides (AMPs), secreted by epithelial cells and phagocytes (Defensins, Cathelicidins, Histatins) +Defensins and Cathelicidins can act broadly, on bacteria, fungi, viruses. \+Histatins act dominantly on pathogenic fungi (e.g Cryptococcus neoformans). +All AMPs are believed to function by perturbing pathogen membranes
What are Defensins, Cathelicidins and Histatins?
Antimicrobial peptides- small peptides prod. by immune and epithelial cells that bind directly to membrane surface of pathogens. form pore on membrane of pathogen that leads to lysis of that microorganism.
Defensins and Cathelicidins – Broad acting ( can act on bacteria and fungi)
Histatins – Pathogenic fungi (Cryptococcus neoformans)
What can kill Cryptococcus neoformans
Histatins
opportunistic pathogen that usually causes disease in already immunocompromised individuals - generally manifests as disease of CNS. colonizes in brain or lung. when it enters infectious niche, histatins-prod to kill it.
Which TLR recognizes:
lipoteichoic acid, lipoproteins (GRAM POSITIVE and GRAM NEGATIVE bacteria)
TLR2
Which TLR recognizes:
Flagellin (BACTERIAL motility component)
TLR5
Which TLR recognizes:
Single-stranded RNA (VIRUSES)
TLR7/8
Which TLR recognizes:
lipopolysaccharide - LPS (GRAM NEGATIVE bacteria)
TLR4
Which TLR recognizes:
Bacterial/Viral DNA (BOTH bacteria and herpesviruses)
TLR9
Which TLR recognizes:
Double-stranded RNA (VIRUSES)
TLR3
Which, TLR/NOD recognizes extracellular
bacteria and viral pathogens vs intracellular?
NOD-like receptors – recognition of INTRACELLULAR bacteria
Toll-like receptors – recognition of extracellular
bacteria and viral pathogens
Which receptor would likely recognize Salmonella (gram negative, intracellular?
NOD1 – Peptidoglycan of GRAM NEGATIVE intracellular bacteria (eg Salmonella).
Which receptor is found highly enriched within cells of the gut?
NOD2 – Peptidoglycan of GRAM POSITIVE/GRAM NEGATIVE intracellular bacteria, AND Mycobacterium tuberculosis). NOD2 is found highly enriched within cells of the gut.
Which NOD receptor binds gram negative bacteria, which gram positive?
NOD1 - gram negative
NOD2- gram positive/gram negative
Listeria monocytogenes, Mycobacterium tuberculosis both potently induce what receptor?
both potent NOD2 inducers
What will a NOD2 mutation possibly induce clinically?
Clinical correlate –NOD2 mutation and Crohn’s disease
- Chronic inflammatory disorder of the GI tract.
- Typically ileal, ilealcolic, and colonic.
- Abdominal pain and diarrhea most common symptoms.
- No cure, treatments aim to alleviate symptoms and promote remission.
- NOD2 – maintains intestinal homeostasis and healthy microbiota.
- NOD2 mutations - Linked to the intestinal permeability and inflammation associated with disease due to improper recognition of bacterial by-products and dysbiosis.
Which receptor recognizes β-glucans that comprise the FUNGAL cell wall (e.g. acapsular Cryptococcus neoformans)?
Glucan receptor
