Lecture 30: Lymphadenopathy and HIV infection Flashcards
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 molecule_s, 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
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.
What are the causes of Lymphadenopathy?
- Proliferation of lymphocytes in response to a l_ocal infection (focal)_
- Proliferation of malignant cells that have metastasised to the node by lymphatic spread
- Proliferation of malignant lymphocytes
- Inflammation within nodes resulting from killing of lymphocytes infected by a virus
What are bacterial causes of lymphadenopathy?
- Staphylococcus aureus
- Mycobacterium tuberculosis
- Others
What are viral causes of lymphadenopathy?
- Epstein Barr virus (EBV)
- Cytomegalovirus (CMV)
- Human immunodeficiency virus (HIV)
- Others
Name 2 types of herpesviruses
Epstein Barr virus (EBV)
Cytomegalovirus (CMV)
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
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
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.
- 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
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.
- CMV infection is typically unnoticed in healthy people, but can be life-threatening for the immunocompromised
- Diseases associated with CMV include glandular fever, and pneumonia.
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
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
How do you diagnose HIV infection
Diagnosis of HIV Infection
- Detect antibodies to HIV in blood
- Screening test via enzyme-linked immunosorbent assay (ELISA)
- Confirmatory test via western blot
- Detect HIV genome in blood
* Polymerase chain reaction (PCR)
Describe the ELISA test
Enzyme-Linked Immunosorbent Assay (ELISA)
- HIV antigen stuck to base of ELISA wells
- Serum sample added, so a_ntibody in serum attaches to HIV antigen_
- Anti-human antibody with adherent enzyme added, so enzyme attaches to serum antibody
- 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
Describe the Western Blot Test
Western Blot Test
- HIV proteins separated (dependent on molecular weight and charge) by gel electrophoresis
- Proteins transferred from gel to a membrane (by Western blotting)
- Membrane strips incubated with serum from patients, and antibodies in serum attach to separated HIV protein bands
- Human antibodies stained with silver dye. Strips with >3 HIV protein bands (GP160, GP41, P24) stained are from people with HIV infection
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 envelop_e; (d) GP120 “knob” on GP41 “stalk”.
It replicates via host cells (T helper cells) through the following steps:
- _GP120 binds to CD4 a_nd co-receptor on cell surface
- Viral envelope fuses with host cell cytoplasmic membrane
- Viral RNA is copied into DNA by vira_l reverse transcriptase_
- HIV DNA copy is taken into host cell nucleus
- Host DNA is cut
- HIV DNA is integrated into host DNA
- Messenger RNA for viral proteins
- Synthesis of viral proteins
- Insertion of GP41 / GP120 into host cell membrane
- Assembly of viral proteins and viral RNA
- HIV buds out of host cell
- 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)
Describe the HIV Pathognesis
HIV Pathogenesis
- 109 T helper lymphocytes produced each day
- HIV infects T helper lymphocytes
- Infected cells produce 109 HIV per day
- Productively infected cells are killed by cytotoxic lymphocytes
Describe the Time course of untreated HIV infection
- Infection with HIV
- Level of HIV in tissues and blood rises
- Cytotoxic T lymphocytes kill many HIV producing cells
- Number of T helper lymphocytes in blood falls
- Level of HIV in blood falls
- Killing of infected lymphocytes causes a brief “glandular fever-like” illness
- B lymphocytes start producing antibodies to HIV
- Level of HIV remains stable for many years
- T helper lymphocyte number continues to fall
- T helper lymphocyte depletion is severe AIDS illnesses
- Level of HIV in blood rises further
