GEP (Life Protection) Week 3

Question 1

What are the 2 main types of adaptive immunity

Answer 1

Part of adaptive immunity, which has two branches
Humoral immunity (mediated by B-cells)
Cellular immunity (mediated by T-cells)

Part of the immune response carried out by a cell, not by a molecule they release
T-cells involved: 2 main types:
T helper (CD4+)
Cytotoxic T (killer) cell (CD8+)

Question 2

What are antigen presenting cells and how are they involved in immune response

Answer 2

APCs are cells that are able to phagocytose pathogenic material and transport it to lymphatics
From here, they are able to present that antigen to naive T cells in order to activate an adaptive immune response
APCs present Ag on special proteins called Major Histocompatibility Complexes, which can match to specific T cell receptors (TcRs) and bind to them, causing activation of T cells

Question 3

How does APC interact with T cells during an immune response

Answer 3

Antigen Presenting Cells (APCs) will convert antigenic material into an Ag peptide, that is bound to a Major Histocompatibility Complex (MHC), and transported onto the cell surface
APC will then travel to secondary lymph organs (spleen and nodes) and present to naive T cells
Depending on the type of MHC the Ag is presented on, it will cause differentiation into a specific T cell

Question 4

What is MHC and the different type of classes

Answer 4

MHC is Major Histocompatibility Complexes

• There are two types of MHC, class 1 and class 2
• MHCI: Present Ag peptides to CD8+ T cells
  Are expressed by all nucleated cells, which expresses a self-antigen to tell the body it is a native cell
• MHCII: Present Ag peptides to to CD4+ T cells
  Are expressed by APCs only, to tell T cells that foreign/damaged cells are present

Question 5

Describe the activation of T cells

Answer 5

Step 1: Activation. Binding of Ag-MHC complex to TcR and CD. TcR binds to receptor and CD binds to MHC (this acts as complimentary anchor, preventing binding of self cells)

Step 2: Survival. More signals are required to activate the cell. CD28 (from T cell) is expressed, and binds to B7.1&2 (aka CD80&86), which are overexpressed when Ag is detected by APC. This leads to the rapid proliferation of the T cell. This process is highly regulated by other receptors that bind to B7s, to ensure there isn’t overstimulation/unwarranted stimulation
These steps together are called Co-stimulation

Step 3: Differentiation. Signal 1&2 together initiate expression of cytokines to differentiate the T cell into the specific cell it needs for the appropriate response
IL-2 (produced by T cell to increase gene expression)
IL-12 (produced by APC to stim Th1 cell)
IL-4 (produced by APC to stim Th2 cell)

Question 6

What are the roles Th1 and Th2 and CTL (cytotoxic T cell).

Answer 6

Th1 cells: Produces IFNy, which induces activation of phagocytes (mainly macrophages) to increase destruction of intracellular pathogens
also stimulate production of IgG to increase phagocytosis (complement)

Th2 cells: Helps in destruction of Helminths.
Produces IL-4 and IL-13, which recruits B cells to produce Ab to opsonise helminths so that eosinophils and mast cells are recruited for its destruction

CTL: Role in destruciton of viruses and mircobes that escape from phagosome (TB and malaria)
Also important in immunity to tumours and rejection of organ transplants
Deliver the ‘kiss of death’ by attaching and releasing cytolytic proteins into cell, triggering apoptosis
Peforins open pores in membrane, granzymes infiltration and initiate apoptosis

Depending on the varying signals, different T cells are produced with different roles:

Question 7

What are viruses

Answer 7

• Simply defined as an obligate intracellular parasite
• Consists of:
  Viral genome (ss/ds RNA/DNA)
  Protein coat (capsid)- shape varies
  Can be enveloped or non-enveloped
• Can vary greatly
• Capable of replication only within the living cells of bacteria, animals or plants
• Very small 20-400nm

Question 8

How are viruses classified

Answer 8

Classification is dependent on characteristics of viral particles:
-Type of Nucleic Acid (DNA/RNA, ss or ds)
-Capsid shape
-Presence or absence of envelope
-Process of replication
-Host organisms
-Type of disease caused

Question 9

How do Viruses replicate

Answer 9

• Can only replicate by infecting a host cell and utilising the cell’s replicating systems (ribosomes, enzymes, ATP etc)
• This process can vary also:
  RNA translated directly into viral proteins in ribosomes of host cell
  DNA transcribed into viral mRNA first
• This proteins then form new virions, which eventually cause lysis of cell wall so they can spread around host
• Some viruses can ‘live’ in a dormant state inside the body. This is called latency. They wait for an opportune moment to reactive and replicate, causing illness once again

Question 10

How do viruses cause disease and damage

Answer 10

Viruses cause many human diseases, ranging from mild to fatal
Diseases occurs due to:
Viruses causing host cells to burst open and die
Disrupting homeostasis of host cells

Characteristics of the illness depend on where they enter the body and what host cells they infect (and ultimately destroy)
e.g HIV affects immune cells, so when destroyed in high number, leads to immunodeficiency

Question 11

Give an overview of Herpes Simplex Virus (HSV)

Answer 11

Symptoms :
HSV-1:
cold sore on lips
painful scab
can spread further on face in immunosuppressed
HSV-2:
pain/itching around scabs
small bumps/blisters around genitals
painful urination
discharge

Spreads through cutaneous exposure

Is diagnosed through combination of symptoms, swab (HSV-2) and Nucleic Acid Amplification Test (NAAT)

Question 12

Give and overview Varicella Zoster Virus and what they cause

Answer 12

Chickenpox
itching fluid filled blisters covering body
eventall turn into scabs
fever
headache
swollen glands
Shingles
pain, burning or tingling
red rash with fluid filled blisters
fever
Headache

Spreads through direct with blisters, salvia or mucus of infected

Diagnosed by symptoms and swabs of ulcer (PCR)

Question 13

Give an overview of cytomegalovirus (CMV)

Answer 13

Symptoms:
* In adults is often asymptomatic or flu like
* In neonates:
Rash
Jaundice
Microcephaly
Retinitis
Seizures
Hepatosplenomegaly
Low birth weight

Spreads congenitally, or through close contact and bodily fluids

Diagnosed via a urine sample from babies ideally, or can test saliva or blood

Question 14

Give an overview of the Epstein-Barr Virus (EBV)

Answer 14

• Often asymptomatic in children, particularly under 5 years old. But can cause:
  fatigue
  fever
  inflamed throat
  swollen lymph nodes in neck
  hepatosplenomegaly
  rash
  post infection chronic fatigue syndrome
• Spreads via saliva, and can be sexually transmitted
• Diagnosed by Hx and age, physical examination, heterophile Ab and serological tests

Question 15

Give an overview of the adenovirus

Answer 15

Symptoms:
cough (croup, barking like)
runny nose
ear pain/infection
diarrhoea/vomiting
UTI
Conjunctivitis

Transmitted by droplets (coughs and sneezes) or the faecal/oral route

Diagnosed with Ag detection, PCR, virus isolation and serology

Question 16

Give an overview of Human papillomavirus (HPV)

Answer 16

Presents as warts (oral or genital, depending on how it has been spread)

Is sexually transmitted

Can be diagnosed with cervical screening and scab tests

Those with HPV have a increased risk of many different cancers (penile, vulval, anal, cervical)

Question 17

Give an overview of measles

Answer 17

Presents with:
Total body skin rash
Flu like symptoms
small white spots inside mouth (Koplik’s spots)

Is an airborne pathogen

Diagnosed by symptoms and lab testing:
positive measles IgM Ab
detection of viral RNA

Question 18

Give an overview of Mumps

Answer 18

Presents with:
Swelling of parotid glands
Fever
Headache
Dry mouth
Abdo pain
Loss of appetite
Fatigue

Spreads via droplets of saliva

Diagnosed by symptoms, RT-PCR and IgM serology

Question 19

Give an overview of Rubella

Answer 19

Presents with:
Rash
Swollen lymph nodes (neck and behind ears)
Fever
Headache
Sore, red eyes
Aching fingers, wrists and knees

Spreads via droplets of saliva

Diagnosed via Serology and ELISA

Question 20

Give an overview of parvovirus (Slapped cheek Virus)

Answer 20

Presents with:
Facial rash (particularly cheeks)
Painful or swollen joints
Anaemia (more so adults)
Fatigue
Low grade fever

Spreads through droplets and can be passed on to a foetus

Diagnosed by serology and symptoms

Question 21

Give an overview of the rotavirus

Answer 21

Presents with diarrhoea, which left untreated can lead to severe dehydration

Spreads via the faecal oral route

Diagnosed by symptoms and PCR (viral NA and Ag detecting test)

Question 22

Give an overview of heamorrahagic Fever (Lassa Fever)

Answer 22

Presents as:
Weakness
Malaise
Headache
Sore throat
Muscle pain
Vomiting/diarrhoea
Abdo pain
Unexplained bleeding/bruising

Spread by coming into contact with food or items contaminated with rodent urine/faeces

Diagnosed by blood PCR

Question 23

Give an overview of Ebola (type of haemorrahgic fever)

Answer 23

Presents with:
Fever
Headache
Diarrhoea
Vomiting
Stomach pain
Muscle pain
Unexplained bleeding or bruising

Spreads through direct contact its blood or bodily fluids

Diagnosed by blood PCR

Question 24

Give an overview on rabies

Answer 24

Presents with:
Weakness
Fever
Headache
Cerebral dysfunction
Anxiety
Confusion
Agitation

Spreads through contact with saliva, or bite from infected animals (bats, dogs etc)

Diagnosed by PCR of CSf or Nuchal skin biopsy

Question 25

Give an overview of HIV (human immunodeficiency virus)

Answer 25

Presents with: Fever Headache Muscle aches and pains Rash Sore throat and painful mouth sores Swollen lymph nodes Weight loss Diarrhoea Sexuallty transmitted, as well as contact with bodily fluids Diagnosed via blood test Is an enveloped virus with protein

Question 26

Give an overview of Rhinovirus (Common cold)

Answer 26

Is the predominant cause of the common cold Is airborne, and diagnosis is based on symptoms

Question 27

Give an overview of Influenza

Answer 27

Causes ‘the flu’: Headache Cough Sore throat Loss of appetite Joint pain/ aches Fever Fatigue Is airborne Diagnosed based on symptoms, RT-PCR, Viral culture and immunofluorescence assay

Question 28

Give an overview on Poxvirus

Answer 28

Presents with: Fever Headache Muscle aches Backache Swollen glands Exhaustion Joint pain Rash that spreads from the face to the entire body (raised spots that turn into blisters, similar to chicken pox) Spreads through: close contact with blisters cough/sneezes contact with items used by patients Diagnosed by swab from the rash

Question 29

Give an overview on the STI: Chlamydia (Chlamydia Trachomatis)

Answer 29

Atypical gram negative bacteria * SIGNS/SYMPTOMS: Asymptomatic Vaginal/Penile discharge (white/yellow) Abdominal pain Post coital bleeding (women) Intermenstural bleeding Dysuria * ONSET: Few weeks after exposure Usually picked up in screening from 2 weeks post exposure * COMPLICATIONS: Pelvic inflammatory disease (PID) Epididymitis or orchitis Infertility Ectopic pregnancy & pregnancy complications Sexually acquired reactive arthritis (SARA) * MANAGEMENT: Antibiotics: azithromycin or doxycycline ## Footnote PID occurs in 16% of women with untreated chlamydia Pregnancy: Increased PROM, premature delivery, low birthweight. Infections of the eyes, lungs, nasopharynx, and genitals in the neonate, due to exposure in the birth canal during delivery

Question 30

What are the screening programme for chlamydia

Answer 30

National Chlamydia Screening Programme (NCSP) Public health initiative to reduce the prevalence of chlamydia Primarily targets age 15-24 (highest risk group) Normalise regular sexual health screening Involves: Free testing (SH clinics, GP’s, Online) Sexual health education Access to treatment: prompt treatment and free of charge Confidentiality

Question 31

Give an overview of the STI: Gonorrhoea (Neisseria Gonorrhoea)

Answer 31

Gram Negative Bacteria * SIGNS/SYMPTOMS: Asymptomatic (1:10 men; 1:2 women) Vaginal/Penile discharge, thin and watery (green/yellow) Pelvic pain (women) Intermenstrual bleeding Dysuria Inflammation of the foreskin/testicles Rectal infection Pain/discomfort Discharge Throat infection Asymptomatic Sore throat * ONSET: ~2 weeks post exposure * COMPLICATIONS: PID Epididymitis, orchitis or prostatitis Infertility (men & women) Disseminated gonorrhea * MANAGEMENT: IM injection ceftriaxone Sometimes dual therapy is used due to antibiotic resistance or co-infection with chlamydia: IM ceftriaxone PO azithromycin/doxycycline ## Footnote PID occurs in up to 30% of women with untreated gonorrhoea infections Pregnancy complications similar to chlamydia Disseminated gonorrhea: 0.5–3% of untreated gonorrhoea cases. It occurs with bacteraemia and spreads, leading to septic arthritis, polyarthralgia, tenosynovitis, petechial/pustular skin lesions, or, on rare occasions, endocarditis, or meningitis

Question 32

Give an overview of the STI: Syhilis (Treponema pallidum)

Answer 32

Atypical gram negative bacteria * SIGNS/SYMPTOMS: Primary (1-3 weeks) Chancre (painless ulcer) Secondary (6-12 weeks) Skin rashes- particularly palms/soles (reddish brown) Mucous membrane lesions (mouth/genitals) Fever Fatigue Swollen lymph nodes Latent No symptoms Tertiary (years after initial infection) Neurosyphilis Cardiovascular syphilis Gummatous syphilis Systemic infection/symptoms * ONSET: 10-90 days * COMPLICATIONS: Cardiac: AA, angina, heart failure Neuro: dementia, seizures, personality changes, paralysis Nerve pain Joint pain Systemic complications: liver, skin, bones, eyes, testicles, etc! * MANAGEMENT: Number of doses determined by stage Primary/Secondary: 1 dose IM penicillin G Tertiary: 3 doses IM penicillin G over 3 weeks Penicillin allergy: use either doxycycline, erythromycin or azithromycin (all oral) ## Footnote PID occurs in up to 30% of women with untreated gonorrhoea infections Pregnancy complications similar to chlamydia Disseminated gonorrhea: 0.5–3% of untreated gonorrhoea cases. It occurs with bacteraemia and spreads, leading to septic arthritis, polyarthralgia, tenosynovitis, petechial/pustular skin lesions, or, on rare occasions, endocarditis, or meningitis

Question 33

Give an overview of the STI: Trichomoniasis (Treponema pallidum)

Answer 33

Protozoan (parasite) * SIGNS/SYMPTOMS: Asymptomatic (particularly in men) Genital itching/swelling Vaginal discharge, foul smelling (green, frothy) Penile discharge (white and thin) Dysuria Pain with sex (dyspareunia) Pain with ejaculation * ONSET: 5- 28 days * COMPLICATIONS: Rare for complications Increased risk of other STIs including HIV PID Complications if pregnant Low birth weight Premature delivery * MANAGEMENT: Oral metronidazole

Question 34

Give an overview of Genital Herpes Background, risk facros and epidemiology

Answer 34

* BACKGROUND: Can be caused by both HSV1 & HSV2, although more often by HSV2 Both are members of the Herpesviridae family Enveloped virus, with double stranded linear DNA Cutaneous exposure Can be spread through oral, vaginal or anal sex * RISK FACTORS: Sex with multiple partners Anonymous sexual partner Presence of another STI Female * EPIDEMIOLOGY: HSV1: 7 in 10; HSV2: 1 in 10 (UK) 6% of all newly diagnosed STIs in the UK HSV2 more common in women than men

Question 35

What are the clinical features of Genital Herpes

Answer 35

Small bumps/blisters around genitals, anus, thighs or bottom Pain/itching around scabs Dysuria Discharge Infections are recurrent Can self resolve Reactivation often triggered by event: Stress (physical/emotional) Immunocompromised state Trauma to genitals Menstruation Hormonal changes UV light exposure Prodrome of pain 2 hours - 2 days prior in recurrent infections

Question 36

What is the pathophysiology of Genital Herpes

Answer 36

Question 37

What is the main differences between HSV1 and 2

Answer 37

HSV1 (Oral Herpes) : Trigeminal ganglia HSV2 (Genital Herpes) : Sacral ganglia

Question 38

What are the investigations for Genital Herpes

Answer 38

Symptoms: Swab of ulcer Nucleic acid amplification test (NAAT) Polymerase chain reaction (PCR) Antibody testing: IgM: primary infection IgG: recurrent infection REMEMBER! IgM : Modern (new infection) IgG : Geriatric (old infection)

Question 39

What is the management of Genital herpes management

Answer 39

Patient education Usually self resolving Self management Saline baths Analgesia Petroleum jelly Antivirals: Acyclovir

Question 40

What is the MICRA for Acyclovir

Answer 40

**M** Converted to acyclovir triphosphate: -Inhibits viral DNA replication **I** Most species of Herpesviridae family: -HSV1/2, VZV, EBV **C** -Hypersensitivity -Caution in hepatic/renal failure -Safe in pregnancy **R** Oral (tablet or liquid) IV **A** Nausea, vomiting, diarrhoea, headache Nephrotoxicity (acyclovir crystals in kidneys)

Question 41

What are the prognosis for gentital herpes

Answer 41

Lifelong infection, no cure but active infections can be managed Recurrent infections tend to improve and become less frequent over time Few complications in healthy people Immunocompromised individuals may experience: Severe active infections Further spread of ulcers Increased frequency of active infections

Question 42

Give an overview of pregnancy and transmission of infections such as syphillis etc.

Answer 42

Best way to remember is STORCHH **S** -Syphilis -Transplacental **T** Toxoplasmosis Transplacental **O** Other- -Viruses: VZV, parvovirus, zika, Influenza, covid-19 -Bacteria: Group A Strep, GBS VZV - transplacental Parvo - transplacental Zika - transplacental Influenza - transplacental Covid - transplacental GBS - perinatal **R** -Rubella -Transplacental **C** CMV Transplacental, Postnatal (breastmilk) **H** -HSV -Perinatal **H** -HIV -Perinatal

Question 43

Give an overview of Neonatal HSV

Answer 43

Neonatal Herpes is a potentially life threatening disease, contracted during delivery Mothers from 36 weeks with known HSV2 should have prophylactic acyclovir Viral shedding can occur without active infection Primary HSV2 infection of the mother during the third trimester or within 6 weeks of delivery = highest risk of neonatal herpes **Disease can be classified in 3 ways:** Skin, eye and mouth (SEM) disease Central nervous system (CNS) disease Disseminated disease - 30% mortality with treatment Neonates that survive may experience serious morbidities **Management:** ~14 days of IV Acyclovir with SEM disease 21 days of IV Acyclovir with CNS or disseminated disease