Immunodeficiency Flashcards
Give some examples of congenital causes of immunodeficiency.
X-linked hypogammaglobulinaemia (B cells) =
- recessive
- early presentation
- low IgA & IgM
- no tonsils
Di George syndrome (T cells) = absent thymus + CHARGE defects
Severe Combined Immunodeficiency (SCID) =
- recessive
- low B & T cells
- treated by bone marrow transplant
Ataxia telangiectasia =
- recessive
- thymic hypoplasia
- low B cells
- treated by bone marrow transplant
Chronic granulomatous disease =
- X-linked recessive
- persistent infection of skin
- resp. & GI tract
- defective bacterial killing by neutrophils
- treated by bone marrow transplant
Give some examples of causes of acquired immunodeficiency.
Hypogammaglobulinaemia (B cells - low levels of all Igs) = - chronic lymphatic leukaemia (increased proliferation of lymphoblasts at expense of other cells)
- myeloma (increased specific Ig at expense of other Igs),
- nephrotic syndrome (loss of Igs through glomerulus)
T cells =
- HIV
- chemotherapy
- Hodgkin’s disease
- immunosuppression e.g. transplantation
B & T cells =
- radiotherapy
- chronic lymphatic leukaemia
- malnutrition
Neutrophils =
- neutropenia
- myelodysplasia
Give some examples of fungal infections associated with immunosuppresion.
Pneumocystis jirovecci =
- atypical pneumonia
- diagnosed via microscopy of broncho-alveolar lavage
- treated with cotrimoxazole
Candida albicans =
- thrush in GI tract (sometimes systemic)
- white plaques
- silver stain (highlights saccharide capsules of fungus)
- treated with fluconazole
Aspergillus fumigatus = pneumonia
Histoplasma capsulatum = disseminated
Cryptococcus neoformans =
- meningo-encephalitis
- pneumonia
- silver stain
Give some examples of mycobacterial infections associated with immunosuppression.
TB =
- giant cells
- caseous necrosis
Mycobacterium avium intracellulare =
- large no. of organisms present
- systemic
- GI disturbance
Give some examples of parasitic infections associated with immunosuppression.
Cryptosporidia = GI tract
Isospora = colon
Toxoplasma gondii
- CNS
- eye
- lymph nodes
Give some examples of viral infections associated with immunosuppression.
Cytomegalovirus =
- subclinical CMV common (reactivated)
- GI (oesophagitis, colitis, hepatitis)
- CNS
- pneumonitis
- treated with acyclovir/gancyclovir
Herpes zoster =
- shingles (limited by midline, dermatomal)
- may involve conjunctivae
Herpes simplex =
- muco-cutaneous (skin lesions)
- encephalitis
- systemic
- treated with acyclovir/gancyclovir
Epstein-Barr virus (reactivation)
- post-transplant lymphoproliferative disorder: B-cell proliferation driven by EBV, may progress to lymphoma, responds to reduced immunosuppression
JC virus
BK virus
What are the sites of haemopoiesis at different stages of life?
Foetus =
0-2 months = yolk sac
2-5 months = liver & spleen
5-9 months = bone marrow
Infants = bone marrow of most bones
Adults = bone marrow of central skeleton (vertebrae, ribs, sternum, sacrum, pelvis, proximal ends of femur)
Outline the types of blood cells haemotopoietic stem cells can differentiate into.
Common myeloid progenitor:
- megakaryocyte —> thrombocytes
- erythrocytes
- mast cells
- myeloblast
- –> basophil
- –> neutrophil
- –> eosinophil
- –> monocyte —> macrophage
Common lymphoid progenitor
- natural killer cell
- small lymphocyte
- –> T-lymphocyte
- –> B-lymphocyte —> plasma cell
Outline the steps in differentiation of WBCs from myeloblasts. Which cells are raised in leukaemia? Which cells are lowered in leukaemia?
Myeloblast —> promyelocyte —> myelocyte —> band cell —> neutrophil
Same for other WBCs
Leukaemia:
+++ myeloblast
— all subsequent cells
Outline the steps in differentiation of RBCs from proerythrocytes. What does maturation involve?
Proerythrocytes —> normoblasts —> reticulocyte —> red cell
Normoblasts (early, intermediate, late)
Reticulocyte = RNA visible
Maturation involves haemoglobinisation of cytoplasm and nuclear maturation and extrusion
Outline how megakaryocytes produce platelets.
Stay in bone marrow
Thrombopoietin stimulates platelet production
Cells increase in size and replicate DNA —> platelets bud from cytoplasm
What are the different components of the spleen?
Red pulp = sinuses lined by endothelial macrophages and cords (reticuloendothelial cells)
White pulp = similar structure to lymphoid follicles, full of WBCs
Blood entering via splenic artery: WBCs and plasma pass through white pulp preferentially and vice versa for RBCs and red pulp
What are the functions of the spleen?
- sequestration and phagocytosis of old/abnormal RBCs
- blood pooling in spleen can be rapidly mobilised during bleeding
- extramedullary haemopoiesis = pluripotent stem cells proliferate during haemotological stress e.g. severe blood loss, failure of bone marrow e.g. myelofibrosis (replacement of bone marrow by scar tissue)
- 25% of T cells and 15% of B cells in spleen
Give some examples of causes of splenomegaly.
Myeloproliferative disease (increase in cells supposed to be there)
Infiltration by other cells e.g. blood cancers, metastases
Extramedullary haemopoiesis
Infiltration by other material e.g. Gaucher’s disease (genetic disorder; anaemia, thrombocytopenia, hepatomegaly, splenomegaly)
Portal hypertension —> back pressure of blood into spleen
Overworking red pulp and white pulp (autoimmune haemolytic anaemia, malaria)
Equate the levels of severity of splenomegaly with causes.
MASSIVE
- chronic myeloid leukaemia
- myelofibrosis
- chronic malaria
MODERATE
- as with massive splenomegaly
- lymphoproliferative disorders
- myeloproliferative disorders
- liver cirrhosis with portal hypertension
MILD
- as with massive and moderate splenomegaly
- infection e.g. glandular fever, infectious hepatitis, endocarditis
- sarcoidosis
- SLE
- idiopathic thrombocytopenic purpura
- autoimmune haemolytic anaemia
