Infectious Diseases: Prions & Viruses

symbiosis

interaction b/t 2 biological species

obligate

2 species cannot exist without each other

facultative

2 species do not depend on each other for survival

demodex mites

• common in eyelash and sebaceous glands

• one thought to be harmless commensals

• now connected to blepharitis and acne rosacea

• cause may be an allergic reaction to mites or bacteria that infects mites

base of eyelash

where do demodex mites live?

acne rosacea and dry eye

what conditions are demodex mites associated with?

acne rosacea

• more common in women

• often occurs around middle age with symptoms that flare up and quiet down

• facial redness, visible blood vessels and red, pus-filled bumps similar to acne

• can caused enlarged nose

tea trea oil

what is demodex mites treated with?

saprophytic

organisms that live on dead or decaying matter

river blindness (onchocerciasis)

• caused by worms transmitted by black flies

• intense itching around worm nodules

• causes chorioretinitis and corneal infections

filarial nematodes

blindness due to a severe immune reaction to endosymbiotic bacteria

obligate intracellular, facultative intracellular

true parasites are _____, some are also _____

direct spread, direct contamination, perinatal, zoonotic

what are the 4 methods of transmission of parasites?

skin/mucosa and host immune system

what are the human defenses for defending the body from microorganisms?

infectivity

ability of microorganism to establish in hose

virulence

disease producing potential of the organism

resistance

ability of host to fight infection

pathogenicity

ability to establish and infect by overcoming normal defenses of host

low, high

pseudomonas has ___ infectivity but ___ virulence once it infects the cornea

prions

transmissible spongiform encephalopathies are neurodegenerative diseases due to abnormal _______

prions

• 100% fatal

• long incubation period

• difficulty walking

• dementia

• mental confusion

Creutzfeldt Jakob Disease (CJD)

• prion

• can be inherited, but no clear cause

• can be acquired by exposure to infected tissue during a medical procedure or transplant

Mad cow disease

• prion

• related to infesting diseased meat

• usually occurs at a younger age

• longer disease course

Kuru

• prion

• caused by cannibalism and eating infected neural tissue

no

can prions be irradiated?

very high temp and pressure

what is necessary to remove prions?

PrP (prion)

normal cellular protein coded for on chromosome 20; normal role in helping the body absorb copper & Zinc

normal proteins to misfold, aggregation, and resistant to digestion

abnormal, misfolded prions cause what?

cytoplasmic vacuoles & neuronal death

protein aggregates in tissue lead to _____________

autofluorescent

spinal cords & retinas of prion infected animals are highly _____________

lipofuscin

what accumulates in the eyes of prion infected animals causing increased autofluorescence

tropism

capable of infecting many tissues; often shown by viruses

binding to cellular receptors

viruses enter host cells by?

deprive them of nutrients or induce apoptosis

how do viruses kill cells once inside of them?

years

viruses can be latent for ____

cell to cell or through blood stream

how do viruses spread through the body?

herpes virus

• large DNA viruses that commonly infect cells of ectodermal origin

• leads to pocks/vesicles

• latent infections

chickenpox

• primary infection in nasopharynx with viremia developing 10-13 days later

• vesicles/rash can scar due to secondary bacterial infection

• common in children

• spread by infected droplets

• complications: pneumonia, encephalitis, hepatitis, carditis, keratitis, orchitis, arthritis

shingles

• caused by a reactivation of latent virus in the ganglia

• travels down dermatome or cranial nerve

• very painful vesicles

• on one side of the body

• can affect the face and eye due to cranial nerves, leading to blindness

• complications: pneumonia, meningoencephalitis

post-herpetic neuralgia

seen in 20% of shingles patients; residual pain due to nerve damage

½

vaccine (Zostavax) for shingles prevents approximately __ of casues

herpes simplex type 1

• oral herpes

• primary infection causes fever blisters on oral cavity, lips, eyes, & skin

• same lesions can re-occur

• dendritic pattern of dead cells leading to an ulcer in the cornea

• latency can cause disciform keratitis

herpes simplex type 2

• genital herpes

• primary infection is sexually transmitted by contact with lesions

• doesn’t normally infect the eye

• can be reactivated

• can be passed perinatally

  • cannot be cured

antivirals

treatment for herpes simplex type 2

inactivate HSV-specific DNA polymerases

how do antivirals for herpes simplex type 2 help treat the disease?

epstein barr

• herpes virus that is transmitted by saliva

• typical symptoms: fevers, fatigue, sore throat, enlarged lymph nodes, enlarged spleens

• complications: liver failure, splenic rupture, kidney disease

B cells

EBV enters what cells via the CD21 receptor?

infected B cells die and trigger immune response with antibody formation and CD8+ cell appearance

what does EBV result in the immune system?

Burkitt’s lymphoma

cancer type associated with EBV that is more common in kids in equatorial region

nasopharyngeal carcinoma

cancer type associated with EBV that is more common in people of Asian descent

Zika

• RNA virus related to viruses causing dengue/yellow fever

• spread by aedes mosquitos

• also spread by sexual contact and blood transfusions

• can be asymptomatic or similar to mild dengue fever

• muscle, bone, joint pain, headaches, vomiting, conjunctivitis, rash, fever

• can cause microcephaly in fetus if mother is infected

• Guillian Barre syndrome

ebola

• RNA virus

• enters cell endosomes & lysosomes by fusing with cell membrane and release viral nucleocapsid

• enters cell via NPC1 receptor

• zoonotic

• symptoms include flu like symptoms that progresses to vomiting, diarrhea, and abdominal pain

• 5-7 days in get shortness of breath, chest pain, confusion, maculopapular rash, internal & external bleeding

fruit bats

origination of ebola virus

bushmeat, contact with fruit bats, monkeys, gorillas, chimpanzees

how can ebola spread from animals to humans?

direct contact with body fluids (blood, semen, breast milk, etc)

how can ebola spread from person to person?

macrophages/dendritic cells

ebola infects what WBCs that carry the virus to lymph nodes and then infects lymphocytes?

no

has airborne transmission been shown for ebola?

low bp and fluid loss

what causes death with ebola?

increased clotting, pooling of blood in body, hypovolemic shock

endothelial cell infection with ebola leads to what?

fatigue, joint pain, headaches, pericarditis, vision loss, photophobia, chorioretinal scars

what are complications that survivors of ebola may experience?

eye

what is one immunologically privileged site that ebola may persist in? (even at 14 weeks)

SARS-CoV2

• zoonotic in origin

• causes covid19

• can be asymptomatic or pt may experience fever, dry cough, difficulty breathing, and GI symptoms

• highly infectious with significant mortality rate

ACE2 receptor

how does SARS-CoV2 enter epithelial cells?

conjunctiva, limbus, cornea

where in the eye is the ACE2 receptor present in? (key for SARS-CoV2)

HIV

• non-transforming retrovirus that affects CD4+ lymphocytes, macrophages, and dendritic cells

• viral RNA is inserted into the host leading to viral protein and virus production

• either remain latent or use host to replicate virus

reverse transcriptase, protease, integrase

HIV viral enzymes include what 3 things?

phagocytized

HIV is __________ but not killed by macrophages and dendritic cells

carry live virus to lymph nodes and deliver it to T cells

what do HIV infected macrophages do with the virus?

gp120, CD4 receptor, chemokine receptor

____ on the viral envelope of HIV binds to the ____ leading to a conformational change and binding to a _________

no

is binding to chemokine co-receptors constant during HIV infection?

m-tropic strains

co-receptor CCR5; important for entry of virus into mucosal tissues in early infection with HIV

t-tropic strains

co-receptor CXCR4; replicate aggressively in CD4+ cells; important in late HIV infection

gp41, fusion

____ pierces host cell membrane with HIV infection; leads to ____ and entry of viral core and genome

reverse transcriptase

changes viral RNA → viral DNA → double stranded viral DNA

integrase

viral protein used to insert double stranded viral DNA into the host DNA

protease

required for virus maturation; cleaves non-functional polypeptide chains into functional viral proteins

memory & activated T cells

what immune cells does HIV infect?

blocks antigen presentation

HIV does what to evade detection by the immune system?

CD4+

what immune cells are lost with HIV infection and lysis?

destruction of lymphoid organs

what comes secondary to HIV?

entire

decreased helper T cells affects ___ immune response

ELISA, Western Blot

what 2 tests are used to diagnose HIV?

6 weeks, 3 months, 6 months

because HIV can be latent, patients have to be tested when following known exposure?

HAART

what is the overall AIDS therapy?

entry, fusion inhibitors, reverse transcriptase inhibitors, protease inhibitors, integrase inhibitors

what types of drugs are part of HAART therapy cocktails?

nucleoside RT inhibitors

faulty versions of the building blocks used by reverse transcriptase to convert RNA to DNA; these drugs stop replication

non-nucleotide RT inhibitors

drugs that bind or block enzyme reverse transcriptase

acute

phase of HIV infection with viremia and symptoms

2-10years

how long can HIV be latent for?

500

CD4+ cell count drops below ____ and body can no longer fight infections

200

CD4+ cell count less than ____ will make a person very ill

AIDS

state of risk for opportunistic infections; due to immune cell destruction, multiple infections by viruses, bacteria, fungi, and protozoans all at once

SIV

original infection of HIV probably occurred by transfer of simian T lymphotrophic virus from monkeys

flu like symptoms, fever, fatigue, headache, night sweats, swollen lymph nodes, rash

what are some symptoms of initial acute infection of AIDS?

oral thrush, hairy leukoplakia (EBV), angular stomatitis, gingivitis

AIDS oral cavity infections

dermatitis, itchy folliculitis, shingles, herpes, perianal warts, ringworm, MRSA

AIDS skin infections

molluscum contagiosum

STD that causes volcano shaped bumps, can occur on the eyelids

kaposi’s sarcoma

rapidly growing tumors common in AIDS patients; reddish, purplish lesions that may develop all over the body; may not be an actual tumor but a proliferation of vascular endothelial cells and capillaries due to angiogenic factors

HHV8

what is the co factor for Karposi’s sarcoma?

non-hodgkin’s lymphoma, cervical cancer, anal cancer, karposis sarcoma

what are the common AIDS tumors?