GEP (Life Protection) Week 3 Flashcards
What are the 2 main types of adaptive immunity
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+)
What are antigen presenting cells and how are they involved in immune response
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
How does APC interact with T cells during an immune response
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
What is MHC and the different type of classes
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
Describe the activation of T cells
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)
What are the roles Th1 and Th2 and CTL (cytotoxic T cell).
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:
What are viruses
- 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
How are viruses classified
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
How do Viruses replicate
- 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
How do viruses cause disease and damage
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
Give an overview of Herpes Simplex Virus (HSV)
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)
Give and overview Varicella Zoster Virus and what they cause
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)
Give an overview of cytomegalovirus (CMV)
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
Give an overview of the Epstein-Barr Virus (EBV)
- 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
Give an overview of the adenovirus
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
Give an overview of Human papillomavirus (HPV)
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)
Give an overview of measles
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
Give an overview of Mumps
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
Give an overview of Rubella
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
Give an overview of parvovirus (Slapped cheek Virus)
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
Give an overview of the rotavirus
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)
Give an overview of heamorrahagic Fever (Lassa Fever)
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
Give an overview of Ebola (type of haemorrahgic fever)
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
Give an overview on rabies
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
Give an overview of HIV (human immunodeficiency virus)
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
Give an overview of Rhinovirus (Common cold)
Is the predominant cause of the common cold
Is airborne, and diagnosis is based on symptoms
Give an overview of Influenza
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
Give an overview on Poxvirus
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
Give an overview on the STI: Chlamydia (Chlamydia Trachomatis)
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
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
What are the screening programme for chlamydia
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
Give an overview of the STI: Gonorrhoea (Neisseria Gonorrhoea)
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
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
Give an overview of the STI: Syhilis (Treponema pallidum)
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)
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
Give an overview of the STI: Trichomoniasis (Treponema pallidum)
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
Give an overview of Genital Herpes Background, risk facros and epidemiology
- 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
What are the clinical features of Genital Herpes
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
What is the pathophysiology of Genital Herpes
What is the main differences between HSV1 and 2
HSV1 (Oral Herpes) : Trigeminal ganglia
HSV2 (Genital Herpes) : Sacral ganglia
What are the investigations for Genital Herpes
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)
What is the management of Genital herpes management
Patient education
Usually self resolving
Self management
Saline baths
Analgesia
Petroleum jelly
Antivirals: Acyclovir
What is the MICRA for Acyclovir
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)
What are the prognosis for gentital herpes
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
Give an overview of pregnancy and transmission of infections such as syphillis etc.
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
Give an overview of Neonatal HSV
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
