HYMS B9, W4

active vs passive immunity

Active = individual has memory cells - can make their own antibodies & provides long term immunity

Passive = person given antibodies, these work then die, no long term immunity, no memory cells.

Give examples of infections for which vaccination is a successful strategy.

- in 2017, the UK had reached elimination status with measles via vaccination

- in 2018, emergence of more strains and cases means the WHO could no longer consider the UK to have 'eliminated' measles.

what process is an essential feature of an acquired immune response against a pathogen?

clonal expansion

name types of vaccines + an example

1 - Live Attenuated Vaccines - weakened version of living bacteria or virus. e.g. MMR

2 - Inactivated Vaccines - killed version of pathogen. e.g. polio, hep A, rabies

3 - Subunit, Recombinant, Polysaccharide, and Conjugate Vaccines - use specific pieces of the pathogen (such as protein, sugar, or a casing). e.g. HPV, Hib, shingles.

4 - Toxoid Vaccines - safe version of the bacteria toxin. e.g. tetanus.

5 - Messenger RNA (mRNA) Vaccines - e.g. Pfizer-BioNTech and Moderna COVID-19 vaccines.

6 - Viral Vector Vaccines - virus is modified to contain the genetic material of the pathogen. e.g. Oxford-AstraZeneca's COVID-19 vaccine and the Johnson & Johnson's Janssen COVID-19 vaccine.

what are some of the methods of delivering a vaccine?

- intramuscular

- subcutaneous (under skin but above muscle)

- transdermal (in dermis of skin)

- oral

- nasal (a spray)

- intranasal (similar to nasal spray but in a droplet form)

- jet injection (instead of needle)

- patches

- implantable devices

- aerosol

what is an adjuvant?

an ingredient used in some vaccines that helps create a stronger immune response in people receiving the vaccine.

some examples:

- Lipid nanoparticles (LNPs) inCOVID-19 mRNA vaccines

- AS04 (aluminum hydroxide andmonophosphoryl lipid A) in HepBand HPV vaccine

- AS03 (squalene-based) in H1N1vaccines

- MF59 (squalene) in flu vaccines

Why could smallpox be eradicated by vaccination?

- diseases causes distinct symptoms (=facilitated rapid intervention and containment)

- Only one dominant variant

- vaccine was effective at inducing sterile immunity (no carriers remain)

- No animal reservoir

- Vaccination was coupled with active surveillance and containment

Are fungi prokaryotic or eukaryotic?

Eukaryotic

describe the epidemiology of infectious fungi

250,000 species

1500 new species discovered annually

1000 or so pathogenic to humans

12 or so colonise humans

why are most fungi described as saprophytes?

most fungi live on dead or decaying organic matter.

why do fungi act as secondary pathogens to humans?

- No fungi are primary pathogens of humans ie main survival technique is not though harming the host

- However, humans are sometimes accidental hosts for saprophytic fungi. this makes them secondary or opportunist pathogens (in vulnerable or immunocompromised patients)

describe the general structure + features of a fungi

- Eukaryotes

- Can be multicellular

- Cell wall containing chitin

- DNA on several chromosomes

- Distinct nucleus

- Cytoplasm has membrane-bound organelles

- 80S ribosomes

- Reproduction may be sexual or asexual

why are fungal infections rare in humans?

- Saprophytes are not well adapted to growth at 37°C

- Their enzymatic pathways function most efficiently at redox potentials found in non-living substrates

- Poorly adapted to using human nutrients

- Host defence mechanisms are efficient at dealing with inhaled/ingested fungi

- Slow growing

- Don't need to - highly successful in environment

what are the main three types of fungi that cause infection in humans?

Moulds

Yeast

Dimorphic (fungi that have a yeast (or yeast-like) phase and a mold (filamentous) phase)

how does mould grow?

- Growth by formation of filaments (called hyphae)

- Entangled mass of hyphae forms a mycelium which can be visible to the naked eye

how does mould reproduce?

- Asexually - conidia (aka asexual spores) are on aerial hyphae. they detach when mature.

- Sexual - + and - hyphal tips fuse nuclei to form a sexual spore.

name a species of mould that can cause human disease

Aspergillus

usually affects the respiratory system

describe the shape of yeast

Single-cell organisms

Round or ovoid

how does yeast reproduce?

asexually by budding

name two pathogenic yeasts that affect humans

Candida species

Cryptococcus neoformans (cryptococcosis is a rare infection commonly associated with immunosuppressive individuals)

how is Candida albicans diagnosed under microscope?

Formation of true hyphae (aka 'germ tube' formation)

pseudohyphae vs true hyphae (yeast)

the width of pseudohyphae cells is always larger than the hyphal cells

what are dimorphic fungi?

Fungi that can exist in yeast form and mold form

non of them are endemic in the UK

name a dimorphic fungi

Coccidiodes immitis (coccidiodomycoses)

outline the non-infectious clinical signs of a fungal infection

- Mycotoxins are released by some moulds (such a ergotism)

- Hypersensitivity

- Asthma

- Farmer's lung

general feeling of being unwell is called...

malaise

mycosis meaning

a disease caused by infection with a fungus

what fungal species causes pityriasis versicolor?

Malassezia furfur

what is superficial mycoses?

- a superficial cosmetic fungal infections of the skin or hair shaft.

- No living tissue is invaded

- No cellular response from the host. Essentially no pathological changes are elicited.

what is dermatophytosis? what is also known as?

- a fungal infection of the hair, skin, or nails caused by a dermatophyte.

- all dermatophytes feed on keratin

- type of superficial mycoses

- also known as ringworm or tinea

describe a ringworm rash

- not itchy

- can be anywhere besides elbows and knees

- circular 'ring' with raised borders and a clear centre

Anthropophilic fungi meaning

one of the three types of dermatophytoses (superficial mycoses). the other two are Geophilic and Zoophilic.

Anthropophilic fungi are in contact with humans and are the only fungi which require humans for survival

what type of fungal infection causes brittle, discoloured nails (usually toes)?

Tinea unguis (aka onychomycosis)

Caused by Trichophyton rubrum [anthropophilic fungi]

how are fungal infections classified?

Mycoses are classified as superficial, cutaneous, subcutaneous, or systemic (deep) infections depending on the type and degree of tissue involvement and the host response to the pathogen.

what is a subcutaneous mycoses?

- fungal infection beneath the skin (dermis and subcutis)

- follows traumatic inoculation

- usually seen in tropics/sub-tropics

- chronic infection which can be locally invasive and involve bone

what is a deep / systemic mycoses?

affects internal organs

what problems can candida cause?

- Oesophagitis

- Candidaemia (candida in the blood)

- Endocarditis

- Hepatosplenic candidiasis

how can yeast infections be diagnosed?

- Microscopy of e.g. abscess aspirate

- Grows slowly on normal culture plates

- 'sterile blood cultures' (Diagnosis is confirmed by cultures from normally sterile sites)

- PCR

- Antigen tests: B glucan

risk factors for systemic candidiasis

use of central venous catheters

exposure to broad-spectrum antibiotics

neutropenia

how are moulds diagnosed?

- Seen mainly in tissue

- Grows very slowly on culture plates - extended culture

- Does not grow in blood culture

- There is no PCR test for it

- Antigen tests: gallactomanan

how is deep mycoses usually acquired?

through inhalation of spores (found in soil)

chronic lung infection may develop and disease may also disseminate to other organs

name a dymorphic fungi that causes a deep mycoses. where is this found?

- Coccidioidomycosis

- found in south western USA

- Spores inhaled

- Immunosuppression increases risk but not essential

- Causes respiratory and flu symptoms mainly, and a maculopapular rash

- causes nodules/cavities/fibrosis and chronic lung damage

name a toxic antifungal drug

- Amphotericin

- expected renal damage and causes chills/fever during course

- Lipid-associated formulations much less toxic so higher dose can be given

name a broad spectrum antifungal

Amphotericin

amphotericin mechanism of action

binds to ergosterol in the fungal cell membrane, which leads to the formation of pores, ion leakage and ultimately fungal cell death.

-azoles mechanism of action

All act by inhibiting lanosterol demethylase: interrupt ergosterol biosynthesis, the primary sterol in the fungal cell membrane.

The depletion of ergosterol alters the fluidity of the cell membrane and alters the action of the membrane-associated enzymes.

Caspofungin class

Echinocandins

an antifungal

which fungi are becoming more resistant to Caspofungin?

Cryptococci

Dermatophytes

both of these are ALWAYS resistant

caspofungin indications

Invasive aspergillosis

Invasive candidal infections

caspofungin mechanism of action

Inhibits glucan synthase (inhibits cell wall synthesis)

which plasmodium species is the most virulent to humans?

Plasmodium falciparum

what makes a good anti-parasite drug?

1. Selective toxicity to parasites

2. Target many species and life stages

3. Cost effective

4. Easy to administer/ distribute

5. Unlikely to develop resistance

how do anti-helminthic agents generally work/target?

- current drugs mostly targeted to non-proliferating adult organisms.

- neuromuscular coordination (needed for feeding movements, location of the worm within the host)

- carbohydrate metabolism (major source of energy)

- microtubular integrity (needed for egg laying and hatching, larval development, glucose transport, enzyme activity and secretion)

how do anti-protozoa agents generally work/target?

- targeted at relatively rapid proliferating, young, growing cells.

- Nucleic acid synthesis

- Protein synthesis

- Specific metabolic pathways (e.g., folate metabolism)

- Detoxification mechanisms

diagnosis of malaria

blood smear (microscopy)

or Rapid Diagnostic Test

these should both be supported by the quality assurance test

what causes a fever in malaria ?

Rupture of RBC by schizont to release merozoites

What is tertian malaria?

- A brood of schizonts matures every 48 hr, so the periodicity of fever is tertian (“tertian malaria”)

- happens in P vivax and P ovale malaria

Quartan malaria

72 hour fever cycle

occurs with P malariae

describe the fever frequency in malaria

tertian - 48 hrs

quartan - 72 hrs

fever cycles

sequestration in malaria

- the adherence of infected erythrocytes containing late developmental stages of the parasite (trophozoites and schizonts) to the endothelium of capillaries and venules

- characteristic of Plasmodium falciparum infections.

- can happen in the brain, spleen, lungs, skin, heart, GIT

which 3 drug classes are used in malaria chemotherapy?

Quinolines

Anti-folates

Artemisinin compounds (newer)

these are usually used in combination to prevent resistance.

Artemisinin compounds mechanism of action

Interacts with Heme-Iron. Generation of free radicals that alkylate and oxidize proteins and lipids within infected red blood cells

African trypanosomiasis vector

tsetse fly

what is South American Trypanosomiasis also known as?

Chagas disease

a protozoa

South american trypanosomiasis vector

triatomine bug ("kissing bugs")

Other routes of infection (congenital transmission,blood transfusion, feces contaminated food, etc.)

what is African Trypanosomiasis also known as?

sleeping sickness

a protozoa

Leishmaniases vector

femalephle botomine sandflies

focal areas of more than 90 countries in thetropics, subtropics, and southern Europe- from rain forests to deserts.

diseases caused by Leishmaniasis

- may be asymptomatic

- Cutaneous leishmaniasis (causes skin sores)

- Visceral leishmaniasis (kala-azar)

- Others: Mucosal leishmaniasis

what disease does Toxoplasma gondi cause?

Toxoplasmosis

Mild lymphadeopathy in adults

Complications in immunocompromised individuals

Serious HIV-associated opportunist

Congenital toxoplasmosis - abortion, hydrocephalus

medication for Toxoplasmosis

Anti-folates

Entamoeba histolytica causes what disease?

Amoebiasis

can be asymptomatic

diarrheal illness + liver abscess

can be intestinal & extraintestinal infections

worldwide distribution

Giardia lamblia causes what disease?

Giardiasis

diarrheal illness

worldwide distribution

Trichomonas vaginalis causes what disease?

Trichomoniasis

genital infection; sexuallytransmitted

worldwide distribution

Amoebiasis, Giardiasis and Trichomoniasis drugs treatment

Metronidazole

Tinidazole

name some protozoa (7)

1. Trypanosomiasis (african = sleeping sickness); (south american = Chagas disease)

2. Leishmaniases

3. Toxoplasmosis

4. Amoebiasis

5. Giardiasis

6. Trichomoniasis

7. malaria

what is the main difference between protozoa and helminths?

Protozoa are single-celled organisms, while helminths are multicellular animals.

Protozoa are members of the kingdom Protista, while helminths are members of the kingdom Animalia.

name three types of helminths

Tapeworms: Cestodes

Flukes: Trematodes

Round worms: Nematodes

What is a Helmith?

parasitic worm

How can helminths be transmitted?

1. swallowing infective eggs or larvae via faecal-oral route.

2. swallowing infected larvae in the tissues of another host.

3. active penetration of the skin by larval stages.

4. the bite of an infected blood-sucking insect vector.

what serious infection can flukes cause?

- Schistosomiasis, also known as bilharzia

- Although the worms that cause schistosomiasis are not found in the United States, people are infected worldwide.

- second mostly impactful parasitic disease (to malaria)

Hookworm, ascaris, whipworm, onchocerciasis, dracunculiasis and lymphatic filariasis are all types of what?

Round worms: Nematodes

Echinococcosis and Taeniasis are types of what?

Tapeworms: Cestodes

how is Taeniasis acquired?

Eating raw or undercooked beef (T. saginata) or pork (T. solium and T. asiatica).

complications of taenuasis infection?

Taenia solium tapeworm infections can lead to cysticercosis, which is a disease that can cause seizures, so it is important seek treatment.

name two arthropods

scabies

nits/lice

transmission of scabies

direct, prolonged, skin-to-skin contact with a person who has scabies.

scabies symptoms

The microscopic scabies mite burrows into the upper layer of the skin where it lives and lays its eggs. The most common symptoms of scabies are intense itching and a pimple-like skin rash.

what is the term for the signs and symptoms that occur with cancer, not directly caused by the tumour itself?

Paraneoplastic syndrome

It is generally immune (autoantibody or T cell mediated) or hormone mediated

Examples of paraneoplastic syndromes

Cachexia

Neurological: pretty much anything

Skin: various rashes

Endocrine: calcium, Cushing, carcinoid

Haematological: abnormal blood counts, thrombosis

what are some ways cancer is classified?

1. Organ of origin

2. Tissue of origin

3. Benign versus malignant

4. Degree of differentiation

5. (Genomic/biomarker features)

what is the difference between a benign and malignant tumour?

Benign: basement membrane intact, no spread

Malignant: basement membrane breached, potential for cancer cells to spread. Some (but not all) benign tumours progress to malignant tumours

adenoma

a benign tumor that arises in or resembles glandular tissue (epithelial tissue)

carcinoma

a malignant (cancerous) tumor that occurs in epithelial tissue

how are muscle & connective tissue tumours described?

Benign tumour = -oma e.g. fibroma

Malignant tumour = sarcoma e.g. fibrosarcoma

what is a teratoma?

Embryological tumours containing all 3 germ layers. Usually arise in gonads and can be benign or malignant. It is very rare.

what is hamartoma?

Disorganised tissue overgrowth

Benign- 1-3 germ layers

May be part of a genetic syndrome eg Cowden's

what is an anaplastic carcinoma?

Undifferentiated (anaplastic) carcinoma is a variant of ductal adenocarcinoma in which there is a loss of glandular differentiation and tumor cells display large, polygonal to spindled, often bizarre (anaplastic) and multinucleated features.

poor differentiation of cells in a tumour usually indicates... (more/less aggressive cancer)

high grade cancer

aggressive

what does the grade of cancer refer to?

degree of differentiation

what does the stage of cancer refer to?

degree of spread around the body