Viruses and Hematopoietic Stem cells Flashcards
define hematopoiesis
The process in which a stem cell proliferate and differentiate into all cellular components of the blood, this process is stimulated by hematopoietic growth factor and related cytokines
Haematopoiesis occurs in a series of two waves, list the waves
- Primitive early embryogenesis
* initiated in the yolk sac - Definitive late fetal stages
* bone marrow
* fetal liver
There are families of viruses that have been associated with bone marrow failure,they achieve this by disturbing survival, proliferation, and differentiation of HSC by reducing production or increasing destruction : list the 2 mechanisms these viruses use to do this :
> Directly :
- Direct infection of HSC
- Viral recognition
> Indirectly
- Production of cytokines
- changes in the microenvironment
What is Pancytopenia and list its various causes
Pancytopenia is a decrease in all three cell types RBC (anaemia), WBC ( leukopenia ) and platelets ( thrombocytopenia )
> Causes: these causes may result in increased destruction or decreased production
- Direct infection of HSC eg Epstein Barr virus during mononucleosis
- Underlying systemic illness eg aplastic anaemia
- Secondary to antiviral medication eg Ganciclovir ,Zidovudine
What is aplastic anaemia
- Aplastic refers to the inability of the bone marrow to produce and form blood.
Aplastic anaemia is bone marrow failure with pancytopenia in the absence of bone marrow infiltrative disease. Its hallmark is peripheral pancytopenia and empty bone marrow
What are the causes of aplastic anemia?
Maybe congenital / acquired
AA may result from indirect/direct destruction of HSC/ progenitor cells
Acquired AA is immune-mediated, where autoreactive lymphocytes react against HSC
HAA: hepatic Associated AA occurs after an episode of acute hepatitis due to T cell-mediated cytokines
define Haemophagocytic lymphohistiocytosis (HLH)
The clinical syndrome includes hyperinflammatory conditions which include viral-associated hemophagocytosis, macrophage activation syndrome, and cytokine releasing syndrome. Maybe congenital / acquired
What is the hallmark of haemophagocytosis lymphohistiocytosis
Prolonged and excessive activation of immune cells eg NKC, T lymphocytes, and macrophages in response to a trigger
Causes of HLH?
Both primary and secondary HLH may be triggered by an infectious agent eg virus which is common in adults .EBV and CMG accounts for 62% of reported viral cases
How does EBV lead to HLH?
Mention the MOT and pathogenesis
EBV is the leading cause of infection associated with HLH. Without early and effective therapy,EBV-HLH has a high mortality rate
MOT: Direct contact with oropharyngeal secretions
Pathogenesis: Primary infection following latency and periodic activation . The disease profile is host-dependent and its infection varies
EBV- HLH can be due to :
- Secondary to EBV infection
- EBV infection in genetically predisposed for the lymphoproliferative disease usually males.
- Chronic active EBV infection
- Aggressive NKC leukaemia and T/NKC lymphoma
Discuss how is Covid-19 associated with HLH?
- Clinical presentation of moderate to severe Covid-19 may have similarities and may mimic secondary HLH
- In Covid -19 infection an uncontrollable macrophage and monocyte activation due to a dysfunctional interferon response to SARS- Covid 19 infection may play a role in subsequent inflammatory response and organ failure
- Similar to HLH, MERS, and ARDS
Discuss the association between Parvovirus and HLH and mention the pathogenesis?
Parvovirus B19 is ubiquitous and has a worldwide distribution and is transmitted through vertical transmission and horizontal transmission-respiratory and transfusion mediated.
Pathogenesis:
- Erythroid progenitor and fewer megakaryocytes
- P-antigen (globoside) receptor and co-receptors
- Direct cytolytic effect of susceptible cells leading to interruption of hematopoiesis
- Chronic persistent infection in immunocompromised patients
What are the haematological manifestations of Parvovirus B19
- They are host-dependent
- Pure red aplasia
- Transient aplastic crisis
- hydrops foetails / congenital anaemia
Discuss the association between CMV and HSC
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