W2-L5; VIRUSES AND HEMAPOIETIC STEM CELLS Flashcards

1
Q

The subset of cells from which all other blood cells are formed are referred
to as

A

haematopoetic stem cells (HSCs) and progenitor cells

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2
Q

Features of HSC

A
  • Self‐renewal capacity
  • and the ability to regenerate all the different cell types that comprise the blood‐forming system
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3
Q

Two waves of hemapoiesis along the development of mammals

A
  • Premitive: early embryogenesis
    *Initiated in the yolk sac

-Definitive: Late foetal stages
*Initiated within intra-embryonic sites
*Aorta-gonad-mesonephros (AGM)
*Foetal liver
*Bone Marrow

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4
Q

What are the 2 ways that viruses use to affect HSCs proliferation, differentiation?

A
  • Viruses act directly:
    -Direct infection of HSCs
    *Viral recognition (immune cells in the marrow see the virus and hamper it action)
  • or indirectly:
    -Production of pro-inflammatory cytokines
    *Changes in the microenviroment
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5
Q

What’s the underlying mechanism leading to pancytopenia?

A
  • reduced production or
  • increased destruction
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6
Q

Definition of aplastic anaemia is____

A

Bone marrow failure with
pancytopaenia in the absence of bone marrow infiltrative
disease

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7
Q

Pancytopenia

A

Decrease in all three blood cell types: red blood cells (anaemia), white blood cells
(leukopaenia), and platelets (thrombocytopaenia)

*Clinically may be asymptomatic or symptoms may related to the affected blood
line

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8
Q

T/F:
Pancytopenia caused by the viruses is usually transient and reversible with resolution of the infection

A

TRUE

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9
Q

Two forms of aplastic anaemia

A

-Acquired: Is immune
mediated in most cases; autoreactive lymphocytes mediate the destruction of
haematopoetic stem cells

  • Congenital
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10
Q

Can result from direct or
indirect destruction of haematopoietic stem/
progenitor cells

A

Acquired Aplastic anaemia

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11
Q

What is the pathological hallmark of aplastic anaemia?

A

Hallmark pathologically is
peripheral pancytopaenia and an ‘empty’ bone marrow

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12
Q

Haemophagocytic lymphohistiocytosis (HLH)

A

Clinical syndrome which cover a range of hyperinflammatory conditions which include viral-associated haemophagocytic syndrome, macrophage
activation syndrome and cytokine-release syndrome.

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13
Q

Features of HLH

A
  • Rare and life-threatening with multi-organ involvement
  • Has a variety of
    triggers, both genetic and environmental.
  • HLH may be congenital or
    acquired
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14
Q

How do you know its HLH? What characterises it?

A
  • haemophagocytosis in bone marrow, liver, or lymph nodes
  • splenomegaly
  • pancytopenia
  • hyperferritinaemia (vry high ferritin)
  • Fever
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15
Q

What is the pathological hallmark of HLH?

A
  • prolonged and excessive activation of immune cells particularly; natural killer, cytotoxic T-lymphocytes and
    macrophages in response to a trigger
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16
Q

What triggers both the primary and secondary HLH?

A

Infectious agent

*Viruses are a common trigger ~35% of adults

17
Q

Two viral infection that account for 62% of reported viral cases of HLH in adults

A

EBV and CMV account for
62% of reported viral cases of HLH in adults

*Clinically, HLH may mimic acute viral disease

18
Q

Leading cause of infection-associated HLH

A

EBV

*Without early and
effective therapy, EBV-HLH has a high mortality rate

19
Q

Describe the EBV epidemiology

A

Epidemiology
* Gamma human herpes virus-4
* Ubiquitous, worldwide distribution
* Transmission, direct contact with oropharyngeal secretions

20
Q

Describe EBV pathology

A

Pathogenesis
* Primary infection following latency and periodic reactivation from B-cells.
- Disease profile is host-dependent, and varies in different population groups

21
Q

EBV-HLH can be due to:

A
  • It’s secondary to EBV infection, in apparently EBV-immune individuals
  • EBV infection in genetically predisposed for lymphoproliferative disease
    (BIRC4 or SHD21A), usually males (X-linked lymphoproliferative
    syndrome)
  • Chronic active EBV infection
  • Aggressive NK cell leukaemia, and T/NK cell lymphoma
22
Q

Has similarities to, and may
mimic secondary HLH

A

Clinical presentation of moderate-severe COVID-19

23
Q

(Within the Immunopathology of COVID-19)

Has a key role in
subsequent inflammatory response and organ injury

A

uncontrolled macrophage and monocyte activation due to a
dysfunctional interferon response to SARS-CoV-2 infection

24
Q

Discuss the epidemiology of pavovirus

A

Parvovirus B19 is ubiquitous and has a worldwide distribution
* Transmission routes:
* Vertical transmission
* Horizontal transmission-respiratory and transfusion mediated

25
Discuss the pathogenesis of pavovirus
- Targets mostly Erythroid progenitor (pro-erythroblasts) and less megakaryocytes * P-antigen (globoside) receptor and co-receptors * Direct cytolytic affect of susceptible cells, leading to interruption of haematopoesis * Chronic persistent infection in immunocompromised patients
26
List the hematological manifestations of Pavovirus 19
- Pure red cell aplasia (Red cells reduced in numbers) * Transient aplastic crisis * Persistent anaemia * Hydrops foetalis / Congenital anaemia (abnormal accumulation of fluid in at least two fetal compartments, such as the abdomen, chest, or under the skin) * Other rare haematological syndromes *Thrombocytopenia *Neutropenia *Haemophagocytic syndrome *Haematological manifestations of Parvovirus B19 are host-dependent, based on immune status
27
Discuss the epidemiology of cytomegalovirus
Epidemiology * Ubiquitous * Asymptomatic in immunocompetent individuals * Severe disease in immunocompromised
28
Discuss the pathogenesis of cytomegalovirus
Pathogenesis * Mediate myelosuppression from lytic infection
29
CMV management
In transplant pts *Presumptive therapy – viraemia is detected *Note: viraemia is a strong predictor of CMV ds * Treatment: Ganciclovir * AIDS pts *HAART to improve immune suppression *Be watchful for IRIS
30
List the cytomegalovirus hematological syndromes
Haematological syndromes * Thrombocytopaenia- congenital infection,severe thrombocytopenic purpura in 10-15% symptomatic babies * Leukopaenia immunocompromised hosts * Pancytopaenia-Ganciclovir, guanosine analogue for CMV treatment and prophylaxis * Leukocytosis-Infectious mononucleosis
31
CMV diagnosis
Diagnosis * CMV serology * CMV PCR
32
Impact of HIV-1 and HTLV-1 infection on hematopoietic and progenitor cells
- deregulation of normal haematopoiesis - Development of leukaemia/lymphoma
33
What's the haematological Disease associated with HIV-1?
- Cytopaenias are the most common haematological abnormality affecting ≥1 cell lineage * They are a direct or indirect effects of HIV * The severity and prevalence of cytopaenias are associated with disease stage, and generally improve with ART
34
Clinical and Diagnostic Approach of retroviruses
1. History *Symptoms *Familial *Preceding/concurrent illness 2. Examination 3. Investigation * Initial Investigation * Full Blood Count with peripheral smear * Additional *Biochemistry *Viral Studies (HIV serology, EBV serology,ParvoB19 serology and PCR, viral hepatitis serology, CMV studies, SARS-CoV-2 PCR) *Bone Marrow *Auto-immune studies *Nutritional studies