serology unit 6

List some immune defenses that protect us from viral infection?

skin, mucus barriers, immune cells, antibodies, type 1 interferons, NK cells

What will antibodies do when they find a virus

bind to it and prevent it from penetrating host cells

How do viruses escape host defenses?

1. genetic variation

2. can avoid immune response

3. can inhibit the immune response

4. can remain latent in the body

A patients serum has IgM present for a virus, what does that mean?

the patient has a current or recent viral infection

A patients serum has IgG present for a virus, what does that mean?

The patient has a current or past infection and could have built up viral immunity

How can current infections be detected

through immunoassays for viral antigens in serum, or the presence of viral nucleic acids

Hepatitis infections mainly affect which organ?

Liver

Early Hepatitis symptoms

Flu like symptoms, and pain in the upper right quadrant of the abdomen

Hepatitis can progress to

hepatomegaly, tenderness, jaundice, DARK URINE, LIGHT FECES

What initial laboratory findings suggest a hepatitis infection?

elevated bilirubin and liver enzymes, notably Alanine aminotransferase (ALT)

NOTE: these are nonspecific and further testing will be needed

Hepatitis A is transferred by

fecal-oral route, close person contact, ingestion of contaminated food/water, or rarely transfused blood

When testing for anti-HAV antibodies it is important to remember to

test individuals with active symptoms, asymptomatic patients will give a false pos

A positive anti-HAV and a negative IgM indicates

A patient has developed immunity to the hep A virus

Which Hepatitis is DNA based instead of RNA

Hep B

Which hepatitis variants are spread through parenteral, sexual or perinatally

Hep B, Hep C, Hep D*

*requires a hbv infection

In an infant what would suggest an infection?

the presence of IgM

In an infant where would they get IgG

their mother

HbeAG is a ___

Hepatitis B e antigen

How is CMV/cytomegalovirus transmitted

contact with bodily fluid, sexual contact, organ transplants, and perinatal exposure

How would you test for CMV?

-CMV specific IgM and IgG serology

- PCR for immunocomp. and newborns

EBV/Epstein Barr virus

mononucleosis aka mono

How would you test for EBV?

heterophile antibody test

How would you test for VZV?

-serological tests for VZV-specific IgM and IgG

- PCR for DNA from skin lesions is the most sensitive

How would you test for rubella, rubeola and mumps?

-serological tests for IgM and IgG

- RT-PCR recommended for confirmation

How would you test for HTLV-1?

initial screening with an antibody test, confirming with western blot

What is the clinical significance of heterophile antibodies?

strong indicator of acute infectious mononucleosis caused by EBV

Anti-HB

Hep B surface antibody, indicates recovery from HBV infection or successful vaccination, providing immunity

heterophile antibodies

non-specific IgM antibodies produced during acute EBV infection and detected by the monospot test

Parenteral

Administration or transmission that does not involve the digestive tract

ex: transmissions through needles and blood

VZV stands for ___

Varicella-zoster virus

TORCH tests for

Toxoplasmosis

Other infections- syphilis, hep, HIV

Rubella

Cytomegalovirus

Herpes simplex

When would you use TORCH

screening pregnant women and newborns for infections that can cause serious birth defects and miscarriage

interferons are

proteins released by infected cells that inhibit viral replication in neighboring cells

Which cell can detect and kill viruses without prior sensitization?

NK cells

Phagocytes can

engulf and digest virions and infected cells

What can the complement system do for viral infections?

lyse enveloped viruses and virus-infected cells and enhance phagocytosis

Which cells produce cytokines

t helper cells

Immunological memory

after an infection memory b and t cells provide a stronger immune response upon re-exposure

Latent phase

viruses can enter a latency and integrate their genetic material into the host cell and produce no markers to become invisible

antigenic variation

viruses can mutate surface proteins allowing them to evade antibodies and t cell recognition

NAAT or nucleic acid amplification tests detect what

viral genetic material directly

- highly sensitive and specific GOLD STANDARD FOR HEP

- tests like RT-PCR

How is hepatitis monitored

quantitative molecular tests to measure the viral load in a patients sample

- effectiveness of treatment and disease progression

core window is

a gap during the acute hep b, disappearance of HBsAg but before the appearance of protective HB antibodies

IgM anti HBc

Confirms a recent or acute Hep B

Which disease testing uses heterophile antibodies

EBV/mononucleosis

Which diseases are diagnosed by (disease) specific IgM and IgG serology

CMV, VZV, Rubella, Rubeola and Mumps

Which disease uses antibody test (ELISA)

HTLV-1

Which HIV form is more virulent

HIV-1

Which HIV-1 group is responsible for the global pandemic

group M (main)

- group n, o, and P are rarer

Recombinant forms are

when a person is infected with 2 different HIV subtypes and a new hybrid can be created

Circulating recombinant forms (CRF)

become widespread in a population

Unique recombinant forms (URF)

Hybrid viruses found in only one person

What does HIV transmission require

direct contact with bodily fluids containing the virus, and a mucous membrane, damaged tissue or the bloodstream

How does HIV transmit

sexual contact, shared needles/syringe, perinatal

What increases the risk of HIV transmission

High viral loa, untreated STI

HIV envelope contains which glycoprotiens

gp120 and gp41

Gp120

External protein that binds to CD4 receptor

Gp41

anchors gp120 to the envelope and facilitates fusion with the host cell membrane

What's inside the HIV core

RNA and enzymes

what does reverse transcriptase do

converts viral RNA into DNA

Protease does what

cleaves precursor polypeptides during viral maturation

What does integrase do

integrates viral DNA into the host cells DNA

Replication cycle of HIV

1. binding

2. fusion

3. reverse transcription

4. integration

5. replication

6. assembly

7. budding and maturation

HIV binding

Gp120 binds to CD4

fusion

gp41 enables the viral envelope to fuse with the host cell membrane, viral core will enter the cell

reverse transcription

inside the cell single stranded viral RNA is converted to double stranded DNA

integration

HIV integrase enzyme integrates the HIV DNA into the host DNA

replication

host cell is used to produce new HIV RNA and HIV proteins

Assembly

New HIV RNA + proteins move to cell surface where they become an immature virion

budding and maturation

immature virion pushes out the cell; it will steal the cell membrane with it. HIV protease will cleave the protein chains allowing it to mature

How does the immune system initially respond to an HIV infection?

1. Killer t cells recognize and destroy HIV cells however, are easily evaded through mutation

2. antibodies are produced, but they can be ineffective

HIV primarily infects and destroys

CD4 t cells

What will HIV infection lead to

Chronic generalized immune activation which will cause a snowball effect

(more immune cells to infect, worse disease)

What tissue does HIV effect

Lymphoid tissue, it will damage it directly effecting the immune system since its where the cells reside

What can HIV develop into

AIDS

What defines the progression into AIDS

when CD4 cells fall below a critical threshold (200 cells ul), causes the immune system to be severely compromised

Primary/acute stage of HIV

2-4 weeks, flu like illness (ARS) or asymptomatic

Clinical latency of HIV

Happens after ARS the spread/multiplication slows and can remain latent for years

still causes immune damage

symptomatic HIV infection

The immune system will weaken causing milder infections and chronic symptoms including: persistent fatigue, fever, swollen lymph, diarrhea, and oral thrush

AIDS leaves room for

other infections and cancers including pneumocystis pneumonia, Kaposi's sarcoma, and cytomegalovirus

Stage 0

early HIV infections, inferred from a negative or indeterminate test w/i 6 months of a confirmed positive

Stage 1

Cd4 cell count is above or equal to 500 cells/ul and no AIDS defining symptoms

Stage 2

Cd4 t cell count from 200-499 cells and no aids defining conditions

stage 3

Cd4 count less than 200, or the presence of an AIDS defining condition

stage unknown

when there is insufficient info on the CD4 cell count or AIDS conditions to classify the person

What is the major structural protien (core) of the HIV-1 virus

p24

Another name for ART

Antiretroviral treatments

3 bodily fluids that will not transmit HIV

saliva, tears, urine, and saliva

What does the p24 protein encode?

Group specific antigen (GAG)

Toxoplasmosis is clinically significant because

It causes congenital deformities

Ig cannot cross the placenta

IgM

Zoonotically transmitted by eating undercooked meat from infected animals

Hep E

Gene that encodes the precursor protein for the internal structural proteins of HIV such as the capsid (p24) and matrix (p17)

GAG

Primary transmission route for Hep A

fecal oral route

Increase AST and ALT plus anti-HAV antibodies, recently drinking from a forest lake

Hep A

IgM vs IgG

IgM: current or recent infection

IgG: past infection or immunity

serological marker indicating a recent hep B infection

IgM and anti-HBc

Which antibody is the first produced in response to a viral infection

IgM

Herpesvirus responsible for causing chickenpox and shingles

varicella zoster virus (VZV)

Which test would be most reliable in detecting HIV in an infant younger than 18 months

DNA PCR testing