W2-L5; VIRUSES AND HEMAPOIETIC STEM CELLS Flashcards
The subset of cells from which all other blood cells are formed are referred
to as
haematopoetic stem cells (HSCs) and progenitor cells
Features of HSC
- Self‐renewal capacity
- and the ability to regenerate all the different cell types that comprise the blood‐forming system
Two waves of hemapoiesis along the development of mammals
- 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
What are the 2 ways that viruses use to affect HSCs proliferation, differentiation?
- 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
What’s the underlying mechanism leading to pancytopenia?
- reduced production or
- increased destruction
Definition of aplastic anaemia is____
Bone marrow failure with
pancytopaenia in the absence of bone marrow infiltrative
disease
Pancytopenia
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
T/F:
Pancytopenia caused by the viruses is usually transient and reversible with resolution of the infection
TRUE
Two forms of aplastic anaemia
-Acquired: Is immune
mediated in most cases; autoreactive lymphocytes mediate the destruction of
haematopoetic stem cells
- Congenital
Can result from direct or
indirect destruction of haematopoietic stem/
progenitor cells
Acquired Aplastic anaemia
What is the pathological hallmark of aplastic anaemia?
Hallmark pathologically is
peripheral pancytopaenia and an ‘empty’ bone marrow
Haemophagocytic lymphohistiocytosis (HLH)
Clinical syndrome which cover a range of hyperinflammatory conditions which include viral-associated haemophagocytic syndrome, macrophage
activation syndrome and cytokine-release syndrome.
Features of HLH
- Rare and life-threatening with multi-organ involvement
- Has a variety of
triggers, both genetic and environmental. - HLH may be congenital or
acquired
How do you know its HLH? What characterises it?
- haemophagocytosis in bone marrow, liver, or lymph nodes
- splenomegaly
- pancytopenia
- hyperferritinaemia (vry high ferritin)
- Fever
What is the pathological hallmark of HLH?
- prolonged and excessive activation of immune cells particularly; natural killer, cytotoxic T-lymphocytes and
macrophages in response to a trigger
What triggers both the primary and secondary HLH?
Infectious agent
*Viruses are a common trigger ~35% of adults
Two viral infection that account for 62% of reported viral cases of HLH in adults
EBV and CMV account for
62% of reported viral cases of HLH in adults
*Clinically, HLH may mimic acute viral disease
Leading cause of infection-associated HLH
EBV
*Without early and
effective therapy, EBV-HLH has a high mortality rate
Describe the EBV epidemiology
Epidemiology
* Gamma human herpes virus-4
* Ubiquitous, worldwide distribution
* Transmission, direct contact with oropharyngeal secretions
Describe EBV pathology
Pathogenesis
* Primary infection following latency and periodic reactivation from B-cells.
- Disease profile is host-dependent, and varies in different population groups
EBV-HLH can be due to:
- 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
Has similarities to, and may
mimic secondary HLH
Clinical presentation of moderate-severe COVID-19
(Within the Immunopathology of COVID-19)
Has a key role in
subsequent inflammatory response and organ injury
uncontrolled macrophage and monocyte activation due to a
dysfunctional interferon response to SARS-CoV-2 infection
Discuss the epidemiology of pavovirus
Parvovirus B19 is ubiquitous and has a worldwide distribution
* Transmission routes:
* Vertical transmission
* Horizontal transmission-respiratory and transfusion mediated
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
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
Discuss the epidemiology of cytomegalovirus
Epidemiology
* Ubiquitous
* Asymptomatic in immunocompetent individuals
* Severe disease in immunocompromised
Discuss the pathogenesis of cytomegalovirus
Pathogenesis
* Mediate myelosuppression from lytic infection
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
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
CMV diagnosis
Diagnosis
* CMV serology
* CMV PCR
Impact of HIV-1 and HTLV-1 infection on hematopoietic and progenitor cells
- deregulation of normal haematopoiesis
- Development of leukaemia/lymphoma
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
Clinical and Diagnostic Approach of retroviruses
- History
*Symptoms
*Familial
*Preceding/concurrent illness - Examination
- 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
