Lecture 30: Lymphadenopathy and HIV infection Flashcards Preview

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Flashcards in Lecture 30: Lymphadenopathy and HIV infection Deck (18):
1

What are the different types of Lymphocytes

B Lymphocytes

  • Plasma cells
    • Synthesise antibody IgG, IgM, IgA, etc.

T Cytoxic Lymphocytes

  • CD8 lymphocytes
  • T 8 lymphocytes
    • Kill cells displaying non-self peptides in MHC molecules, i.e. kill virus producing cells or cancerous cells

T Helper Lymphocytes

  • CD4 lymphocytes
  • T4 lymphocytes
    • Secrete cytokines to regulate other cells of the immune system, e.g. macrophages in a granuloma, B lymphocytes or T lymphocytes neutrophils

2

What is Lymphadenopathy?

Lymphadenopathy or adenopathy is disease of the lymph nodes, in which they are abnormal in size, number, or consistency.

 

Lymphadenopathy of an inflammatory type (the most common type) is lymphadenitis, producing swollen or enlarged lymph nodes.

3

What are the causes of Lymphadenopathy?

  1. Proliferation of lymphocytes in response to a local infection (focal)
  2. Proliferation of malignant cells that have metastasised to the node by lymphatic spread
  3. Proliferation of malignant lymphocytes
  4. Inflammation within nodes resulting from killing of lymphocytes infected by a virus

4

What are bacterial causes of lymphadenopathy?

  • Staphylococcus aureus
  • Mycobacterium tuberculosis
  • Others

5

What are viral causes of lymphadenopathy?

  • Epstein Barr virus (EBV)
  • Cytomegalovirus (CMV)
  • Human immunodeficiency virus (HIV)
  • Others

6

Name 2 types of herpesviruses

Epstein Barr virus (EBV)

Cytomegalovirus (CMV)

7

Describe Human Herpesviruses (HHV)

Human Herpesviruses (HHV)

Mechanism

Human herpesvirus is DNA viruses. It has acute infection, followed by:

  • Latent infection (asymptomatic) with reactivation
  • Chronic infection (asymptomatic)

 

Can cause lymphadenopathy

8

Describe the Acute Epstein-Barr Virus Infection

-What does it cause?

-How is it transmitted?

-How is it diagnosed?

Acute Epstein-Barr Virus (EBV) Infection (A Common Illness)

Glandular Fever

The Epstein–Barr virus (EBV), also called human herpesvirus 4. It is the cause of infectious mononucleosis (glandular fever) (“kissing disease”). 

Virus is transmitted in saliva.

  • Minor illness when acquired as a child
  • More severe illness when acquired as adolescent/adult (fever, sore throat, cervical adenopathy, malaise, fatigue)

Incubation period of 4-6 weeks. Illness for 1‐2 weeks (usually).

Recovery, but persistent salivary excretion of EBV.

 

Laboratory Diagnosis Of Acute EBV Infection

  • Lymphocytosis (>50% of WBCs)
  • Atypical lymphocytes (>10% of lymphocytes)
  • Abnormal liver function tests
  • Monospot test (Paul Bunnell) detects “heterophile” antibodies, which bind to guinea pig, sheep, horse RBCs, but NOT to EBV!
  • Specific EBV serology detects antibodies that bind to EBV; also detects EBV antigens

9

What causes Glandular Fever?

Acute Epstein-Barr Virus (EBV) Infection (A Common Illness)

Glandular Fever

The Epstein–Barr virus (EBV), also called human herpesvirus 4. It is the cause of infectious mononucleosis (glandular fever) (“kissing disease”). Virus is transmitted in saliva.

  • Minor illness when acquired as a child
  • More severe illness when acquired as adolescent/adult (fever, sore throat, cervical adenopathy, malaise, fatigue)

Incubation period of 4-6 weeks. Illness for 1‐2 weeks (usually).

Recovery, but persistent salivary excretion of EBV.

10

 

  • How do you diagnose Glandular Fever?

Laboratory Diagnosis Of Acute EBV Infection

  • Lymphocytosis (>50% of WBCs)
  • Atypical lymphocytes (>10% of lymphocytes)
  • Abnormal liver function tests
  • Monospot test (Paul Bunnell)
    • Get serum from someone with glandular fever- then mix the serum with RBC from sheep cows etc. the Red cells start to agglutinate.
    • detects “heterophile” antibodies, which bind to guinea pig, sheep, horse RBCs, but antibodies do NOT stick to EBV! (cause them to agglutinate)
  • Specific EBV serology
    • detects antibodies that bind to EBV; also detects EBV antigens

11

Describe Acute Cytomegalovirus Infections

 

-What they are

-How to diagnose this infection

Acute Cytomegalovirus (CMV) Infection

Human Cytomegalovirus

Human cytomegalovirus is a member of the viral family known as herpesviruses. Although they may be found throughout the body, CMV infections are frequently associated with the salivary glands.

 

Laboratory Diagnosis of Acute CMV Infection

  • Lymphocytosis (>50% of WBCs)
  • Atypical lymphocytes (>10% of lymphocytes)
  • Abnormal liver function tests
  • Detection of antibodies (IgM or IgG) to CMV
  • Detection of CMV in blood

12

What are the features of acute HIV infection?

  • Recent (3-6 weeks previously) exposure
  • Glandular fever-like illness
  • Persistent viraemia and virus in genital secretions
  • Presence of antibodies to HIV in blood

13

How do you diagnose HIV infection

Diagnosis of HIV Infection

  1. Detect antibodies to HIV in blood
  • Screening test via enzyme-linked immunosorbent assay (ELISA)
  • Confirmatory test via western blot
  1. Detect HIV genome in blood
  • Polymerase chain reaction (PCR)

14

Describe the ELISA test

Enzyme-Linked Immunosorbent Assay (ELISA)

  1. HIV antigen stuck to base of ELISA wells
  2. Serum sample added, so antibody in serum attaches to HIV antigen
  3. Anti-human antibody with adherent enzyme added, so enzyme attaches to serum antibody
  4. Reagent added, which is cleaved by enzyme on anti-human antibody. This results in colour change
  • If there isn't much antibodies to HIV, there won't be much anti-human IgG stuck, so not much enzyme there. If you put the reagent in there, not much will be split (light blue)
  • If there's lots of antibodies to HIV = Dark blue

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15

Describe the Western Blot Test

Western Blot Test

  1. HIV proteins separated (dependent on molecular weight and charge) by gel electrophoresis
  2. Proteins transferred from gel to a membrane (by Western blotting)
  3. Membrane strips incubated with serum from patients, and antibodies in serum attach to separated HIV protein bands
  4. Human antibodies stained with silver dye. Strips with >3 HIV protein bands (GP160, GP41, P24) stained are from people with HIV infection

16

Describe the HIV structure and how it replicates

HIV Structure and Replication

HIV is a rapidly evolving RNA retrovirus. It has (a) 2 strands of RNA; (b) viral core; (c) viral envelope; (d) GP120 “knob” on GP41 “stalk”.

 

It replicates via host cells (T helper cells) through the following steps:

  1. GP120 binds to CD4 and co-receptor on cell surface
  2. Viral envelope fuses with host cell cytoplasmic membrane
  3. Viral RNA is copied into DNA by viral reverse transcriptase
  4. HIV DNA copy is taken into host cell nucleus
  5. Host DNA is cut
  6. HIV DNA is integrated into host DNA
  7. Messenger RNA for viral proteins
  8. Synthesis of viral proteins
  9. Insertion of GP41 / GP120 into host cell membrane
  10. Assembly of viral proteins and viral RNA
  11. HIV buds out of host cell
  12. HIV “matures” into infectious virus after budding

Most are not active- suddenly get activated.

 

In 1983-4, scientists discovered HIV, which causes acquired immune deficiency syndrome (AIDS)

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17

Describe the HIV Pathognesis

HIV Pathogenesis

  1. 109 T helper lymphocytes produced each day
  2. HIV infects T helper lymphocytes
  3. Infected cells produce 109 HIV per day
  4. Productively infected cells are killed by cytotoxic lymphocytes

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18

Describe the Time course of untreated HIV infection

  1. Infection with HIV
  2. Level of HIV in tissues and blood rises
  3. Cytotoxic T lymphocytes kill many HIV producing cells
  4. Number of T helper lymphocytes in blood falls
  5. Level of HIV in blood falls
  6. Killing of infected lymphocytes causes a brief “glandular fever-like” illness
  7. B lymphocytes start producing antibodies to HIV
  8. Level of HIV remains stable for many years
  9. T helper lymphocyte number continues to fall
  10. T helper lymphocyte depletion is severe AIDS illnesses
  11. Level of HIV in blood rises further

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