Bacterial Pathogenesis and Immunology I Flashcards
1
Q
Bacterial-host interaction
A
- Normal flora (normal microbiota) - expected to be present; do not cause disease under normal circumstances
- -Skin; mucous membranes; digestive tract
- Pathogen
- -Opportunistic - normally does not cause disease; can cause disease when host defenses are breached
- -Obligate (frank) - must cause disease in order to survive and be transmitted to another host
2
Q
Basic steps in pathogenesis
A
- Attachment/entry
- Evasion of host defenses
- Multiplication/spread
- Damage
- Transmission
3
Q
Entry - Transmission Routes
A
- Ingestion
- Inhalation
- Breach of physical barrier: mucosal, ocular, cutaneous
- Vector borne: mechanical or biological vectors
- Transplacental
4
Q
Breach of barriers
A
- Tissue injury; release of chemical signals
- Dilation and increased permeability of capillary
- Phagocytosis of pathogens
Ex: cutaneous, ocular, or mucosal membranes
5
Q
Entry - traumatic
A
-Ex: foxtails and Actinomyces sp. –> draining tracts
6
Q
Entry - iatrogenic
A
- Surgical site infection
- Injection site infection
- -Joint infection in horses (need to ensure proper preparation of skin site)
- Iatrogenic = relating to illness caused by medical examination or treatment
7
Q
Hand washing
A
- Single most effective method of decreasing transmission of pathogens (hands can serve as fomites)
- Most germs located under fingernails
8
Q
Entry - vector borne
A
- Mechanical vector = transfers the pathogen like a fomite
- Fomite = An inanimate object that can carry an infectious agent from host to host
- Flies and Moraxella bovis (pink eye; infectious bovine keratoconjunctivitis)
- Face fly (musca autumnalis), house fly (Musca domestica), stable fly (Stomaxys calictrans) - Biological vector = the pathogen undergoes a biological change within the vector that is required for transmission
- A vector in which the pathogen undergoes a change that renders it capable of infecting a susceptible host
- Ixodid ticks and Anaplasma marginale
9
Q
Entry - attachment
A
- Agent’s adhesins interact with host’s receptors
- Extracellular colonization or internalization of the pathogen
- Variation of host cell receptors may explain host or organ specifically of infection
10
Q
Entry - ingestion –> attachment
A
- Enterotoxigenic E. coli (ETEC)
- -Bovine (ETEC K99 (F5) fimbriae
- -Porcine (ETEC F18 fimbriae)
- Nothing for it to bind to in the older calf or weaned pig so it cannot cause disease
11
Q
Entry - ascending into the bladder –> attachment
A
- Uropathogenic E. coli (UPEC): P-fimbriae facilitate attachment
- Proanthocyanidins (PACs) found in cranberries help prevent UTIs by blocking uropathogenic bacteria from adhering to the uroepithelium
12
Q
Entry - Ingestion –> attachment
A
- Enteropathogenic E. coli (EPEC)
- -Bacterial surface protein: intimin
- -Protein receptor on host cell surface: Tir (translocated intimin receptor)
- –The bacteria puts it there
- -Pedestal formation and effacement microvilli
13
Q
Evasion of host defenses
A
- Defense against innate immune mechanisms
2. Defense against adaptive immune mechanisms
14
Q
Breaching the cornea
A
- Pseudomonas aeruginosa –> equine corneal ulcers
- -Pili and LPS - adherence to epithelial cells and mucin
- -Protease (Phospholipase C) - tissue damage allowing entry
15
Q
Evasion of innate immunity
A
- Antimicrobial peptides (AMP)
- -AKA host defense peptides
- -Non-specific
- -Found in vertebrates and invertebrates
- -Active against bacteria, fungi, and many viruses
- -Ex: defensins and cathelicidins
- Repulsion of AMPs by reducing the net negative charge of the bacterial cell envelope
- Expelling AMPs through energy dependent pumps
- Cleaving AMPs wit proteases
- Decrease expression
- Ex: S. aureus
- -Staphylokinase binds and neutralizes defensins
- -Aureolysin detroys cathelicidins
16
Q
Evasion - innate immunity toll-like receptors (TLRs)
A
- A type of pattern recognition receptors (PRRs)
- -Bind pathogen-associated molecular patterns (PAMPs)
- Found on many cell types
- PAMP binds corresponding TLR –> signals passed to the cell –> pro-inflammatory molecules (cytokines) are produced by the cell
- Bacterial LPS binds TLR4 on stem cells in bone marrow –> stimulates increased leukocyte production
- This is why an increased leukocyte count is a consistent feature of bacterial infections
- Interference with TLR signaling pathways:
- -Modified PAMPs that will not trigger TLRs
- -Blockage of TLR signaling pathways
- -Accelerated destruction of intermediate signaling molecuels
- -Destruction of NF-kB
- -Misdirection towards anti-inflammatory pathways
17
Q
Phagocytosis
A
- Chemotaxis and adherence of microbe to phagocyte
- Ingestion of microbe by phagocyte
- Formation of a phagosome
- Fusion of the phagosome with a lysosome to form a phagolysosome
- Digestion of ingested microbe by enzymes
- Formation of residual body containing indigestible material
- Discharge of waste materials
18
Q
Evasion - chemotaxis
A
- Both microbes and damages tissues release specific chemical substances (chemoattractant)
- Movement of phagocytes toward stimulus
- Phagocyte already at the infection sites will release cytokines that attract additional phagocytes to the site of infection
- Bacteria can suppress chemotaxis of phagocytes:
- -Alginate - Pseudomonas aeruginosa (also important in biofilm formation)
19
Q
Evasion - opsonization
A
- Opsonins bind to and coat the surface of the pathogen
- -Complement (innate) or antibodies (adaptive)
- The ligand binds the receptor –> phagocytosis
- -Antibody receptor = CD32 –> type 1 phagocytosis
- -Complement receptor = CD35 –> type 2 phagocytosis
- Avoiding opsonization: Protein A produced by Staphylococcus aureus attaches to the Fc region of IgG and blocks the cytophilic (cell-binding) domain of the Ab
- The biofilm matrix inhibits opsonic killing
20
Q
Ingestion
A
- Adherence of the bacterium to the phagocyte causes the membrane of the phagocytes to move around the microbe, forming pseudopods
- Pseudopods fuse and enclose the microbe within cytoplasmic vacuole called phagosome
- Avoiding ingestion:
- -Polysaccharide capsules of S. pneumoniae, Haemophilus influenzae, Treponema pallidum, and Klebsiella pneumoniae (difficult to phagocytose)
- -Alginate of Psedomonas aeruginosa
21
Q
Digestion
A
- Phagosome fuses with lysosome (full of destructive hydrolytic enzymes) to form a phagolysosome
- The bacterium is digested, and any undigested material within the residual body is excreted from the cell
22
Q
Evading intracellular destruction
A
- Escape from phagosome into the cytoplasm
- -Listeriolysin O (Listeria sp.)
- Prevention of phago-lysosomal fusion
- -Mycobacterium sp., Aspergilus flavus, B. abortus, Chlamydia psittaci
- Resistance to lysosomal enzymes
- -Mycobacterium sp. (mycolic acid)
- -Yersinia sp. (capsule)
23
Q
Respiratory burst
A
- Macrophages use oxygen to form:
- -Hydrogen peroxide
- -Superoxide anion
- -Hypochlorite ions
- -Nitric oxide
- Survival strategies:
- -Carotenoid pigments as antioxidants (S. aureus)
- -Salmonella Typhimurium can downregulate host NOS2 activity
- -Pasteurella multiocida and Histophilus somni can inhibit the respiratory burst
- -Catalase (Staphylococcus sp.) breaks down H2O2
24
Q
Iron sequestration
A
- Iron is an important micronutrient and is a cofactor for many metalloproteases needed for bacterial growth and survival
- Sequestering iron is a key defense against microbial invaders
- Vertebrates use iron-binding proteins: transferrin, lactoferrin, haemoglobin
- Siderophores (iron producing)
- -Produced by bacteria in iron poor conditions
- -Bind iron ions and cell receptor –> ferrisiderophore complex is transported into the cell
25
Q
Evasion - adaptive immunity
A
- Antigenic variation
- Antibody destruction
26
Q
Adaptive immunity - antigenic variation
A
-The process by which an organism changes its surface antigens (proteins, carbohydrates, etc.) and thereby avoids destruction by the host immune response
-Campylobacter fetus ssp. venerealis
-Anaplasma marginale
(lifelong infection)
27
Q
Adaptive immunity - proteases
A
- Some bacteria secrete proteases that can destroy immunoglobulins or cytokines
- IgA proteases (Neisseria gonorrhoeae, Haemophilus influenzae, Histophilus somnus, Strep. pneumoniae) –> prevent opsonization and Fc receptor-mediated phagocytosis
