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
Give some signs and symptoms of splenomegaly.
Pancytopenia (pooling of blood in enlarged spleen)
Early satiety
LUQ/left-sided back pain
What is hyposplenism? Give some examples of causes of hyposplenism. What are hyposplenic individuals at risk of?
HYPOSPLENISM = lack of functioning splenic tissue
Sickle cell disease (eventually due to multiple infarcts causing necrosis)
Coeliac disease
Splenectomy
At risk of overwhelming sepsis from encapsulated organisms e.g. Pneumococcus, Haemophilus influenzae, Meningococcus
What is seen on the blood film in hyposplenism?
Howell-Jolley bodies
Basophilic nuclear remnants
What are some general causes of thrombocytopenia? What is seen on histology in each case?
Reduced production (reduced megakaryocytes on histology)
Increased removal (normal quantity of megakaryocytes on histology
Give some examples of causes of thrombocytopenia due to reduced production.
B12/folate deficiency
Infiltration by malignancy/fibrosis
Aplastic anaemia (no red marrow)
Drugs
- chemotherapy
- antibiotics (inc. chloramphenicol, septrin)
Viruses
- HIV
- infective hepatitis
- EBV
- CMV
Give some examples of causes of thrombocytopenia due to increased removal.
Splenic pooling (hypersplenism)
Immune destruction:
- self-limiting viral infection (children)
- immune thrombocytopenic purpura
- autoimmune disorders e.g SLE
- lymphoproliferative disorders e.g. lymphomas, CLL
- treated with corticosteroids, IV Ig (or observe in children with de novo presentation)
- platelet transfusion fail (transfused platelets destroyed)
Non-immune destruction:
- microangiopathic haemolytic anaemias (DIC, haemolytic uraemic syndrome, TTP) —> coagulation —> microthrombi —> consumption of clotting factors and platelets & mechanical destruction of RBCs (cannot bypass microthrombi) —> thrombocytopenia & haemolytic anaemia
- cardiopulmonary bypass (platelets aggregate within types of bypass machine)
What are the signs and symptoms of thrombocytopenia?
Easy bruising
Petechiae, purpura
Mucosal bleeding
Severe bleeding after trauma
Intracranial haemorrhage
Give some examples of causes of iatrogenic immunodeficiency.
Chemotherapy
Splenectomy
Immunosuppression (most commonly steroids)
Give some examples of causes of neutropenia.
Increased removal
- immune destruction
- splenic pooling
Reduced production
- B12/folate deficiency
- infiltration by malignancy/fibrosis
- aplastic anaemia
- drugs: chemotherapy, antibiotics, anti-epileptics, psychotropic drugs, DMARDs
- viruses
- congenital e.g. cyclic neutropenia
What are the signs and symptoms of neutropenia?
Severe life-threatening bacterial/fungal infection —> neutropenic sepsis
Anaemia
Leucopenia
Give some examples of causes of pancytopenia.
Increased removal
- immune destruction
- splenic pooling
Reduced production:
- B12/folate deficiency
- aplastic anaemia
- malignancy = haematological (leukaemias, lymphoma, myeloma, myelofibrosis, myelodysplastic syndromes), non-haematological (metastases e.g. prostate, breast, lung)
Describe the appearance of aplastic anaemia on histology.
Pancytopenia with hypocellular bone marrow in absence of an abnormal infiltrate and no increase in reticulin
Increased fat spaces on histology
What are the signs and symptoms of pancytopenia?
Anaemia
- fatigue
- dizziness
- chest pain
- shortness of breath
Thrombocytopenia
- bleeding
- bruising
Neutropenia
- infection
- ulcers (particularly oral apthous ulcers)
- fever
+ symptoms of underlying cause
