Lent Flashcards
What is a parasite?
An organism that lives and feeds on or in an organism of a different species and causes harm to its host
What are parasitic diseases caused by?
Eukaryotic protozoans and helminths
Give an example of a single-celled protozoa.
Plasmodium, Leishmania.
What are metazoa?
Multicellular parasites, e.g., nematodes, cestodes.
How is the diversity of parasites evidenced?
Evidenced by coprolites (fossilized faecal matter) and co-evolution with the host.
What are the two types of life cycles in parasites, and what is the main difference between them?
Direct life cycle (requires only one host) Indirect life cycle (requires two or more hosts).
Define definitive host.
The host in which the parasite reaches sexual maturity or undergoes sexual reproduction, e.g. mammals for Hookworms.
What is an intermediate host?
Hosts required for development, where the parasite may undergo asexual reproduction but not sexual, e.g. mosquito Plasmodium
How do protozoans evade the immune system?
Through antigenic variation (recombination of var genes coding for hypervariable surface proteins e.g. PfEMP1, instead of due to polymerase error causing mutation)
Hiding inside host cells (e.g., Plasmodium hiding in erythrocytes that don’t express MHC Class I)
What is the immune evasion strategy of Trypanosomes?
They change their Variant Surface Glycoprotein (VSG).
How do helminths modulate the immune system?
They dampen TH1 and TH2 pro-inflammatory responses, secrete anti-inflammatory proteins, and have systemic effects on the adaptive and innate immune systems.
What are the secondary effects of worm secretions?
Suppression of tumor-suppressing genes, reduced immunity and response to vaccines, and reduced immunity to other infections.
What are the positives of helminth infections?
They help in anti-inflammatory responses to allergies and other diseases.
What is immunopathology?
It is the response to a pathogen causing damage to the host tissue, rather than the actual effect of the pathogen.
What is crucial for preventing immunopathology?
A balanced response between anti-inflammatory and pro-inflammatory, with timing and size of the response being important.
How many deaths does malaria cause annually, and what is its global impact?
627,000 deaths annually, with 500 million people experiencing a mild illness
How do protozoans exhibit different forms of movement?
Amoeboid movement- Protozoans use cytoplasmic protrusions
Ciliary motion- Protozoans use hair-like projections
Flagellar movement- use a flagellum for navigation.
Gliding motility- through interactions between host and parasite, utilizing actin-myosin
How does Toxoplasma achieve success, and what is its unique feature?
Toxoplasma’s success is attributed to oocyst resistance against the environment and the ability to change morphology under stress.
Describe the replication process of Toxoplasma.
Toxoplasma undergoes sexual reproduction in the cat (definitive host)
1. Releases oocysts in faeces
2. Infects rats and develops into tachyzoites
3. Develop into bradyzoites for latent/chronic infection.
What is the transmission method and pathology associated with Toxoplasma?
Transmission occurs through cat feces (oocysts) and eating undercooked meat (bradyzoite cysts).
Immunocompromised individuals can experience neurological issues.
Outline the phases of Plasmodium’s life cycle
Plasmodium undergoes mosquito, liver, and blood phases in its life cycle.
What is the detection method for Plasmodium species, and what is unique about its replication?
The rate of turnover in Plasmodium species differs, causing fever paroxysms. Parasite replicates in mosquitoes, liver cells, and red blood cells.
What are the pathological effects of Plasmodium infection?
Plasmodium infection can lead to anemia (because they fed on RBC), respiratory distress, renal failure, and death.
How does Plasmodium evade the immune system?
Plasmodium infects erythrocytes that don’t express MHC I and exports proteins to the surface to form knob-like structures in P.falciparum= Erythrocyte Membrane Protein 1 (PfEMP1)
Cause rosette formation, binding of RBC and potential blockage
What is the natural resistance to Plasmodium, and give an example?
Sickle cell anemia provides resistance to Plasmodium due to the modified shape of red blood cells.
How does Leishmania move, and what are the different life cycle stages?
Leishmania moves by flagellar mobility, and it has promastigote (flagellated) and amastigote (non-motile) stages.
Describe the life cycle of Leishmania and its survival strategies.
Leishmania has an indirect life cycle, replicating asexually between hosts and sandflies.
Its survival involves lipophosphoglycan (LPG) on the surface and transmission through various species of sandflies.
What are the different types of pathologies associated with Leishmania?
Cutaneous- located lesions
Diffuse cutaneous- Expanded lesions
Mucocutaneous- erosion of soft tissue
Visceral types- infect internal organs
Manifestations range from localized lesions to fatal infections.
What are the two main categories of multicellular organisms causing chronic infections?
Roundworms (Nematodes)
Flatworms= Cestodes (tapeworms) and Trematodes (flukes).
Describe the characteristics of Nematodes and examples.
Nematodes are non-segmented, have resilient eggs, and typically use a direct life cycle, relying on a single host.
Hookworm, Whipworm, Ascaris, Pinworm
What is the life cycle of the Hookworm (Ancylostoma), Whipworm and Ascaris?
Larvae penetrate the skin, migrate to the lungs, are coughed up and swallowed to access the gastrointestinal tract.
Hookworm= They use teeth to latch onto the intestinal wall and release eggs through the fecal route.
Whipworm= burrow tail in the large intestinal wall
Ascaris= don’t attach to intestine but remain in gut
What is the pathology associated with Hookworm infections?
Hookworms secrete anticoagulants to feed on RBCs, causing anemia and malnutrition.
Symptoms may include a distended belly.
What is the pathology associated with Whipworm infections?
Feed on cellular secretion (not blood), and can cause anemia, due to effect of inflammation, tissue damage and toxic secretion (however don’t directly feed on blood)
Symptoms like diarrhea and rectal swelling.
What is the pathology associated with Ascaris infections?
Heavy worm burden leads to allergic reactions to waste secretion, malnutrition due to anti-trypsin secretion.
Describe the life cycle of Pinworm (Enterobius vermicularis).
Pinworms spread through the fecal-oral route and are easily spread between children. Eggs become infectious quickly after secretion.
What are the characteristics of Tapeworms (Cestodes)?
They have a segmented structure, flatworm
Tapeworms are more complex life cycle, requiring two hosts (human as the definitive host, and pig/cow as the intermediate host).
Outline the life cycle of Tapeworms (Taenia).
Ingestion by pig/cow leads to cyst formation, ingestion of undercooked meat leads to the ingestion of cysts, larvae are released and develop into adult worms in the intestine.
What is Cysticercosis, and how is it caused by Tapeworms?
Cysticercosis is caused by the ingestion of eggs/proglottids, making humans intermediate hosts (instead of definitive), leading to cyst formation in the CNS.
Describe the life cycle of Trematodes (Schistosoma cercariae).
- Trematodes hatch in water
- Develop into Miracidia
- Infect a snail (intermediate host)
- Hatch as Cercariae
- Infect humans (definitive host) by burrowing through the skin
- Lose the tail to become Schistosomulae
- Develop into adults in the liver/bladder.
What is the pathology associated with Schistosomiasis?
Schistosomiasis can lead to bladder or liver fibrosis, calcification, cancer, and morbidity due to egg deposition, initiating a Th2 response.
What is the size comparison among different helminths?
Schistosome eggs are much larger than the nematode eggs (hookworm, tapeworm etc.)
What is eradication in the context of disease control?
Eradication refers to the permanent elimination of a pathogen and the associated disease, where intervention measures are no longer necessary
Define elimination in the context of disease control.
Elimination involves reducing the incidence of a disease to zero within a defined geographical area. Unlike eradication, intervention measures may still be required to maintain this reduced incidence and prevent the re-emergence of the disease.
What is the concept of control in disease management?
Control refers to the active efforts to reduce the incidence and morbidity of a disease. Unlike elimination and eradication, control measures need to be continuously implemented
Outline some challenges in disease control efforts
-Development of resistance by parasites
-Diverse morphologies
- Immune evasion
- Limited resources and funding
- Existence of potential reservoirs
- Availability of diagnostic tools to monitor changes in disease prevalence
What are the challenges associated with creating vaccines for parasitic diseases?
- Ability of parasites to manipulate and evade host defenses
- Presence of multiple developmental stages
- Occupation of different niches in various life cycle stages
- Various permissive geographical locations
- Inability to grow certain parasites in a lab.
Provide examples of successfully eliminated parasitic diseases and the strategies employed.
Schistosoma japonicum: The elimination program began in the 1940s and successfully eradicated the disease in Japan in 1996. Strategies included cementing irrigation systems and using drugs to reduce snail populations.
What vaccines are there for malaria?
RTS,S
- targets pre-erythrocytic phase and prevents infection of hepatocytes.
- Action by presenting P.falciparum RTS protein, as a VLP vaccine (lipids and saponin)
- efficacy below 50%, and protection diminishes significantly over time.
R21
- similar efficacy
- uses saponin based adjuvant
- efficacy of around 75% Nikita et al., 2023
What are some challenges associated with drug development for parasitic diseases?
- Different morphologies within the parasite’s life cycle
- Lack of effective drugs
- Development of drug resistance
- Co-infections complicating treatment
- Inadequate dissemination of drugs to those who need them.
Provide an example of vector control against parasitic diseases.
DDT (insecticide) against mosquitoes. In the 1950s, its targeted use in North America and Europe.
In Africa- Pyrethroid bednets, containing insecticides, also serve as a form of vector control
What are the key characteristics of apicomplexans?
Apicoplast- vestigial plasmid
Apical complex
Secretion of enzymes and form parasitophorus vesicle (protect from acidification and destruction)
E.g. plasmodium, toxoplasma
What is the general pathology associated with filarial worm infections?
Filarial worm death induces inflammation, often characterized by an overreaction, typically involving a Th2 immune response.
This immunopathology is irreversible and chronic.
Name the three types of filarial worm infections based on their classification.
Lymphatic filariasis: Infects the lymphatics.
Subcutaneous filariasis: Infection of subcutaneous tissue.
Serous Cavity filariasis: Infects the serous cavity of the abdomen, e.g., Dog heartworm.
What is the life cycle of filarial worms, and what morphologies do they exist as in humans?
Filarial worms have an indirect life cycle, requiring two hosts: a human and an insect.
They exist as adults and microfilariae in humans.
Unlike many parasites, filarial worms do not lay eggs; instead, they shed microfilariae.
Explain the immunomodulation strategies employed by filarial worms.
- Inhibiting cell proliferation
- Secreting peptides signaling immune cell apoptosis
- Block translocation of MHC and antigen presenting molecules to the surface
- Block antibody formation, modulating response of B cells and T cells
- Phosphorylcholine-Modulate expansion of immune cells, block B cells but allow Treg cells
- Modulate through chemokines and cytokines
Provide information on Wuchereria bancrofti, including transmission, prevalence, and development duration.
W. bancrofti causes lymphatic filariasis
Transmitted through mosquitoes. Approximately 863 million people are at risk, with 120 million infected.
The mosquitoes that transmit W. bancrofti exhibit diurnal behavior, moving to peripheral areas at night when mosquito bites are more likely.
The development from infection to an adult can take up to a year.
What is the pathology associated with W. bancrofti infection, and what are the treatment options?
Dead W. bancrofti worms release antigens, causing an inflammatory response.
This infection leads to lymphedema, with pulmonary eosinophilia in the lungs and elephantiasis in the legs.
Treatment involves using DEC, which kills microfilariae but not adults, blocking the transmission of the helminth.
Describe the pathology and treatment options for Onchocerca volvulus
O. volvulus causes subcutaneous filariasis.
The pathology includes river blindness, leading to inflammation and corneal hardening.
Dermatitis with skin thickening is also observed.
Treatment involves Ivermectin, which decreases microfilarial load but not adults, requiring repeated administration.
What are the characteristics of Loa loa, and what pathology and treatment options are associated with it?
Loa loa causes subcutaneous filariasis, transmitted by deerflies.
It migrates to the bloodstream with diurnal periodicity.
Pathology includes Calabar swelling due to IL-5 release.
Endemic individuals show tolerance, while visitors may experience greater pathology. (Clinical immunity)
DEC is used for treatment but may lead to encephalopathy if not administered repeatedly.
What are the challenges associated with treatment options for filarial worm infections?
Co-infections can complicate treatment. For example, DEC used against Onchocerca volvulus may lead to the Mazzotti reaction. Ivermectin against Loa loa can cause allergic encephalopathy.
What is the role of Wolbachia in filarial worms, and how is it targeted for treatment?
Wolbachia is a bacterial endosymbiont with a mutualistic relationship with filarial worms (except L. loa).
It is essential for worm fertility and viability.
Doxycycline (DOX) kills Wolbachia and is effective against O. volvulus and W. bancrofti.
However, DOX has challenges, requiring long treatment and repeated doses, and cannot be safely used in pregnant women and children.
What immune responses are triggered when Wolbachia is released during worm death, and what complications can arise?
When Wolbachia is released during worm death, it can cause an immune response. In the eyes, it may result in corneal haze, while in the skin, it can lead to dermatitis.
What is the action of Ivermectin on parasites?
- Binds to glutamate-activated chloride channels
- Causes hyperpolarization, by increasing permeability of chloride ion
- Paralyses the parasite to death
Who developed the pasteurization technique and what did it involve?
Louis Pasteur
Using a swan neck shaped flask to avoid air coming in and bacteria developing
Involves heating a liquid to a specific temperature to kill or inactivate potential pathogens, followed by rapid cooling, making the medium sterile.
What are Koch’s postulates, and what is their purpose in bacteriology?
Developed by Robert Koch to establish the association between a specific bacterium and a particular disease
Requirements
1. The bacterium must be present in every case of the disease.
2. The bacterium must be isolated and grown in pure culture.
3. The cultured bacterium should cause the disease when introduced into a healthy host.
4. The bacterium must be recovered from the newly infected individual.
The purpose is to prove the causative relationship between a bacterium and a disease.
What are some uses of bacteria in scientific research and technology?
- Fundamental Genetics: Bacteria are used to study gene regulation, operons, transcription, and translation.
- Insights into Host Biology: Bacterial studies provide insights into intracellular trafficking, innate immunity, and signal transduction.
- Genetic Manipulation: Bacteria are essential for studying genetic manipulation, involving restriction enzymes, plasmids, and polymerases (e.g., Taq for PCR).
- Genetic Editing: The CRISPR/Cas9 system, used for genetic editing, has been derived from bacterial systems.
What are the three types of disease outbreaks, and how do they differ?
- Point Source Outbreaks: These arise from a single origin and can include instances like Legionnaire’s Disease originating from contaminated water in AC systems or food poisoning.
- Continuous Source Outbreaks: These occur when the source is not eradicated, allowing the disease to spread continuously. Examples include carriers of diseases like typhoid.
- Propagated Outbreaks: These involve host-to-host transmission and various modes of transmission. Examples include whooping cough, tuberculosis, gonorrhea, cholera
What are the characteristics of an endemic, epidemic, and pandemic disease?
- Endemic: Occurs regularly at a low or moderate frequency in a specific population or geographic area (e.g., Streptococcus mutans causing tooth cavities).
- Epidemic: Sudden appearance or increase in disease cases above the endemic level, typically affecting a specific region (e.g., pre-WWII Diptheria epidemic in Europe).
- Pandemic: A global epidemic affecting a large population across multiple countries or continents (e.g., cholera).
Describe the size range of bacterial cells.
Bacterial cells typically have a size ranging from 0.5 to 3 micrometers.
This small size allows them to remain unicellular and undergo binary fission for replication.
What is the role of MreB in bacterial cells, and how does it contribute to their structure? What other factors regulate the bacterial cytoskeleton?
MreB is an actin homologue in bacterial cells. It plays a crucial role in maintaining the rod-like structure of bacteria. MreB filaments align along the cell’s long axis, directing the synthesis of peptidoglycan and influencing cell shape.
FtsZ a tubulin homologue - for division
Crescentin an intermediate filament homologue, for curved structure
Why do bacteria produce endospores, and what conditions do endospores help them survive?
In response to harsh environmental conditions.
Endospores can withstand desiccation, radiation, heat, starvation, and exposure to disinfectants, allowing bacteria to endure unfavorable circumstances.
What is the primary component of bacterial cell walls, and how is it structured?
Bacterial cell walls is peptidoglycan. It is a mesh-like structure formed from alternating sugars, N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM), vertically and horizontally cross-linked by oligopeptides.
Explain the Gram staining technique and its significance in bacterial classification.
Differentiates bacteria into Gram-positive and Gram-negative based on cell wall characteristics.
Gram-positive bacteria have a thick peptidoglycan wall, retaining the crystal violet stain, while Gram-negative bacteria, contain an outer membrane and don’t retain the crystal violet. Only retains the counter stain safronin
What is the role of the periplasm in gram negative bacteria?
-Space for reactions
-Compartmentalization of Enzymes:
- Detoxification, improve antibiotic resistance
Describe the structure of LPS found on the outer membrane of gram-ve bacteria?
Lipopolysaccharides
Composed of 3 sections
LipidA- attaches to membrane, is recognised by TLR4
Core polysaccharide- constant region
O-antigen- variable, aiding with evasion from the immune system
Elaborate on the role of bacterial capsules and how they are detected.
Bacterial capsules serve to prevent desiccation and protect against host defenses.
They are detected through (acid) staining, where the background is stained with an acidic stain, and the cell is stained with a basic stain, resulting in a visible halo around the cell due to lack of capsule staining.
How do bacteria achieve motility, and what role do flagella play in this process?
Rotation of flagella.
Require an electrochemical (pH) gradient and proton gradient
Tumble (clockwise rotation)
Swimming (anti-clockwise rotation)
How do bacteria secrete proteins?
Various secretion systems
Sec- unfolded and Tat- folded
BAM- Integration of protein into membrane
Type III and IV- used needle like for direct secretion into host
Flagellin structure from inner membrane is detected by TLR5 formation is from sequential addition of units
Explain the process of chemotaxis in bacterial cells.
- Sense chemical signals and move towards them. Bacteria detect gradients of chemicals
- Transducing the signal via phosphorelay systems
- Directed movement toward more favorable conditions.
Describe the phases in bacterial growth
Lag- adaptation to media
Log- rapid binary fission
Stationary- exhaustion of nutrients
Death- secretion or build up of toxic waste
What is quorum sensing, and how does it influence bacterial behavior?
Quorum sensing is a communication system in bacteria where they alter their behavior in response to changes in population density.
As bacterial populations increase, they release signaling molecules, coordinating activities like biofilm formation and other collective behaviors.
e.g. Production of AHL by LuxI, reach threshold binds to LuxR to activate LuxAB and LuxI
How are bacteria able to adapt rapidly?
Transcription and translation compound are linked
Signalling changes by Histadine-aspartate phosphorelay (HAP) pathway
What genetic changes can incur in bacteria?
Horizontal transfer
- Conjugation - plasmid and pili
- Transformation- take up from env
- Transduction - transfer by phage
- Transposition- movement of transponse elements from acquired plasmids etc.
What is Polycistronic?
Many proteins encoded within the gene
What are the key events in bacterial pathogenesis?
1.Colonization:
- Adhesion is crucial, and if bacteria remain extracellular, multiplication occurs.
2. Invasion:
- Bacteria are either uptaken or forcefully enter the host for replication.
3. Replication
4. Damage:
- Can be direct (caused by bacteria, e.g., toxin secretion) or indirect (caused by the host response to infection).
5. Transmission
What are virulence genes, and how are they commonly spread?
Genes that contribute to the ability of a microorganism to cause disease in a host e.g. toxins, adhesins and invasion proteins
Virulence genes are not always expressed and are horizontally spread between bacteria.
They are often carried on extrachromosomal plasmids and bacteriophages.
What are pathogenicity islands, and how do they evolve (3)?
Pathogenicity islands are groups of pathogenic genes (e.g., adhesins, invasion proteins, toxins) that evolved through the integration of transposons, bacteriophages, and horizontal plasmid transfer.
They have a G+C content that differs from the rest of the genome.
What is swarming motility, and how is it characterized?
Swarming motility is a community movement of bacteria effective in colonizing surfaces, often with a radial outwards trajectory.
Where are cell surface adhesins commonly found, and what is an example?
Found on the end of pili and are used for attachment to glycoproteins on the surface of host cells. An example is the P-pilus adhesin in uropathogenic E.coli (UPEC), which binds to kidney receptors.
Describe the process of pili formation.
- Chaperone proteins bind to adhesin and transport it to the Usher protein.
- Pilus subunits are transported to the Usher protein, where they polymerize to form a structure.
- Aggregation occurs when the pilus is long enough.
What are the steps involved in recurrent infections?
- Lumenal replication
- Invasion of bacteria into the epithelium
- Intracellular replication
- Exfoliation and lysis of the cell (action of inflammasome)
- Tissue repair (burying some pathogens in the layer below)
- Resurgence (when immunocompromised, infection recurs)
Explain the process of pedestal formation in bacterial pathogenesis. And where this is located
Located in the intestines
By enteropathogenic E.coli (EPEC) and enterohaemorrhagic E.coli (EHEC) through the Type III secretion of Translocated Intimin Receptor (Tir).
1. Secrete the effector that acts as a receptor
2. Bind by intimin on the bacteria surface
3. Binding causes actin polymerisation
What is a biofilm, and why is it difficult to eradicate?
A biofilm is a community of bacteria encased in a self-produced extracellular matrix.
- e.g. alginate polysaccharide from P.aeruginosa
It is difficult to eradicate due to the protective nature of the matrix and communication through quorum sensing.
