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Flashcards in Immunity / Haematology Deck (27):

List two different classifications of the various anaemias.

  1. Classification by mechanism: 
  • Blood loss
    • Acute
    • Chronic
  • Increased RBC destruction (haemolysis)
    • Inherited genetic defects
      • Red cell membrane disorders - hereditary spherocytosis
      • Enzyme deficiencies - G6PD def'y, pyruvate, glutathione pathway def'ys
      • Hb abnormalities - Thalassemias, Sickle Cell
    • Acquired genetic defects - Paroxysmal nocturnal haemoglobinuria
    • Antibody mediated destruction - Haemolytic disease of the newborn (Rh disease), transfusionreactions
    • Mechanical trauma - Vessels: DIC, Heart: Valvular disease, Repetitive trauma: runners
    • Infections of RBCs: Malaria
    • Toxic/chemical injury: Snake venom, Pb poisoning
    • Membrane lipid abnormalities - Severe hepatocellular disease
    • Sequesteration - Hypersplenism
  • Decreased RBC prod'n
    • Inherited - eg Thalassemias
    • Nutritional deficiencies - eg B12 and folate, Fe def'y
    • EPO def'y - eg renal failure, anaemia of chronic disease
    • Immune mediated - aplastic anaemia
    • Inflam'n mediated - Anaemia of chronic disease
    • Neoplastic: Primary: Acute leukaemia, Malignancy: space occupying marrow lesions
    • Infection: Parvovirus B19
  1. Classification by morphology:
  • Size: Micro, macro normocytic
  • Colour: Hypo, normochromic
  • Shape


Discuss the intra and extra vascular hemolytic anaemias. What are the principal clinical findings in each type?

Intravascular haemolysis:

Clinical findings: 

  1. Anaemia
  2. Hemoglobinaemia
  3. Haemoglobinuria
  4. Heamosiderinuria
  5. Jaundice

NB released Hb binds to haptoglobin and phagocytosed (complexes are catabolised resulting in inc'd bilirubin and jaundice) but stores of haptoglobin are depleted -> free Hb inc's and some oxidised to methaemoglobin. Both filtered in kidneys, some resorbed but some not -> brown urine. 


  • Complement fixation - DIC
  • Trauma - cardiac valves, runners
  • Toxic - Pb poisoning, clostridial sepsis, malaria 

Extravascular haemolysis: 

Clinical findings: 

  • Anaemia
  • Splenomegaly
  • Jaundice

NB: RBCs are recognised by phagocytes in the spleen and prematurely broken down.

Less deformable RBCs (eg heridatary spherocytosis, G6PD def'y, Sickle Cell Disease, Thalassaemias)


Discuss the pathogenesis of pernicious anaemia.

Autoimmune destruction (thought to be a autoreactive T-cell response) of parietal cells in the gastric mucosa results in reduced or absent production of intrinsic factor. Intrinsic factor binds with B12 in the duodenum and this complex is endocytosed by mucosa in the ileum. 

Vitamin B12, or cobalamin, is a water soluble vitamin necessary for the formation of Hb and for normal function of the nervous system.


What are the general causes of iron deficiency anaemia. What type of anaemia does this process lead to?

  1. Insufficient dietary intake
  2. Impaired absorption
  3. Increased demand
  4. Chronic blood loss

Fe def'y anaemia results in a microcytic, hypochromic anaemia.


NB: Only 10-15% of dietary Fe is absorbed.


List the major causes of aplastic anaemia.


  • Idiopathic (60%)
    • Acquired stem cell defects
    • Immune mediated
  • Idiosyncratic
    • Chloramphenicol
    • Organic arsnenicals (pesticide)
    • Carbamazapine
    • Penicillamine
    • Phenytoin
    • Gold salts
  • Chemical agents
    • Benzene
    • Chloramphenicol
    • Inorganic arsenicals
    • Alklating chemotherapeutic agents (cyclophosphamide)
    • Antimetabolites
  • Physical agents
    • Whole-body irradiation
  • Viral infections
    • CMV
    • EBV
    • Varicella
    • Hepatitis (? virus)


  • Fanconi anaemia
  • Telomerase defects


What is the enzyme that regulates Fe absorption in the GIT? How does it work?

Hepcidin is a molecule produced by the liver which reduces absorption of iron from the enterocyte into the blood. Hepcidin levels are directly proportionate to serum Fe levels - ie high Fe levels ->  inc'd hepcidin levels -> inc'd inhibition of Fe absorption into the blood. Fe trapped in the enterocyte is then sloughed away when the cell dies.


What are the categories of the causes of aplastic anaemia? 



  • Idiopathic
  • Idiosyncratic
  • Physical
  • Chemical
  • Viral


List the general categories of causes of thrombocytopaenia.


  • Decreased production
  • Decreased survivial
  • Sequestration
  • Dilution


List the general categories of causes of thrombocytopaenia.


Decreased platelet production:

  • Selective impairment of platelet prod'n:
    • Drug-induced: ETOH, thiazides, diuretics, cytotoxic drugs
    • Infections: measles, HIV
  • Nutritional def'ys:
    • B12, folate
  • Bone marrow failure:
    • Aplastic anaemia
  • BMT
  • Ineffective haematopoesis
    • Myelodysplastic syndromes

Decreased platelet survivial:

  • Immunologic destruction:
    • Primary autoimmune:
      • Chronic Immune Thrombocytopaenic Purpura
      • Acute Immune Thrombocytopaenic Purpura

    • Secondary autoimmune:

      • SLE, B-cell lymphoid neosplasms

    • Alloimmune:

      • Blood transfusion, neonatal

    • Drug-induced

      • Quinine

      • Heparin

      • Sulphur compounds

    • Infections:

      • HIV

      • Infectious mononucleosis (transient)

      • Dengue Fever

    • Non-immunologic destruction

      • DIC

      • Thrombotic microangiopathies

      • Giant haemangiomas


  • Hypersplenism


  • Transfusion


List the causes of DIC.

Solid tumors and hematologic malignancies (particularly acute promyelocytic leukemia)

Obstetric complications: abruptio placentae, pre-eclampsia 
or eclampsia, amniotic fluid embolism, retained intrauterine fetal demise, septic abortion

Massive tissue injury
severe trauma, burns, hyperthermia, rhabdomyoloysis, extensive surgery

Sepsis or severe infection of any kind (virtually infections by any microorganism can cause DIC, though bacterial infections are the most common): bacterial (Gram-negative and Gram-positive sepsis), viral, fungal, or protozoan infections

Transfusion reactions (i.e., ABO incompatibility hemolytic reactions)

Severe allergic or toxic reactions (i.e. snake or viper venom)

Giant hemangiomas (Kasabach-Merritt syndrome)

Large aortic aneurysms


Draw the pathophysiology of DIC.


What are the two primary triggers for the clotting cascade?

  1. Release of Tissue Factor - tissue destruction, endothelium damage, sepsis
  2. Exposure of platelets to endothelial collagen


List the factors involved in:

  1. The intrinsic pathway
  2. The extrinsic pathway

  3. The common pathway


  1. XII, XI, IX, VIII 
  2. VII
  3. X, V, II, I 


What is another name for:

  1. Factor II and IIa
  2. Factor I and Ia

  1. Prothrombin and thrombin
  2. Fibrinogen and fibrin


List the causes of neutropenia.

Decreased production:

  • aplastic anemia
  • arsenic poisoning
  • cancer, particularly blood cancers
  • certain medications
  • hereditary disorders (e.g. congenital neutropenia, cyclic neutropenia)
  • radiation
  • Vitamin B12, folate or copper deficiency

Increased destruction:

  • autoimmune neutropenia
  • chemotherapy treatments

Marginalisation and sequestration:

  • Hemodialysis


  • Flecainide (class 1C cardiac antiarrhythmic)
  • Phenytoin
  • Indomethacin
  • Propylthiouracil
  • Carbimazole
  • Chlorpromazine
  • Trimethoprim/sulfamethoxazole (cotrimoxazole)
  • Clozapine
  • Ticlodipine


Outline the the general features of the immune system.

  • Inate immunity
    • epithelial barriers
    • phagocytic cells (macrophages and neutrophils)
    • dendritic cells
    • natural killer cells
    • plasma proteins (eg complement)
  • Adaptive immunity
    • Humoral: defend against extra-cellular microbes and toxins -> B lymphocyte/Ab mediated
    • Cell-mediated: defend against intra-cellular microbes ->T lymphocyte-mediated


Describe the principal types of lymphocytes and their mechanisms of action.

  • B-lymphocytes
  • CD4+ helper T-lymphocytes
  • CD8+ cytotoxic T-lymphocytes


Discuss the four types of hypersensitivity reactions.


Outline the pathophysiology of TB.

  • Droplets containing M.tuberculosis travel to the alveoli (usually the lower regions of the upper lobe or the upper regions of the middle or lower lobe)
  • Macrophages endocytose the bacterium where they replicate and inhibit the cells' normal phago/lysosomal activity by inhibiting normal Ca signalling
  • Some infected macrophages are transported to LNs where TH1 cells are exposed to antigen and mount a response which activates macrophages to kill bacterium within them. 
  • At this point there are three possible outcomes:
  1. Localised caseation is usually (90%) limited by the TH1 response and the bacterium within the Ghon focus and LN (together forming the Ghon complex) are either:
    1. killed, resulting in a scar, or
    2. walled-off in a granuloma, resulting in dormant infection.
  2. In 5% of cases, the TH1 response is not able to limit the infection and Primary Progressive TB ensues. This results in extensive local tissue damage and can also result in haematogenous spread -> miliary TB.

Secondary TB usually occurs in the setting of immunocompromise and can result from either:

  • reactivation of dormant infection, or
  • re-infection.

As the individual is now sensitised, the TH1 response mobilises more rapidly but also results in more extensive tissue damage and caseation. Again, miliary TB can result from secondary TB.


Which groups of adults are at risk of contracting HIV?

  • Homosexual and/or bisexual males
  • IVDU
  • Haemophiliacs and other blood product recipients
  • Heterosexual contacts of other high risk groups
  • Children via vertical transmission:
    • In utero transplacental spread
    • During birth -> transmission during passge through an infected birth canal
    • Ingestion of breast milk


Outline the pathogenesis of HIV-1 infection. 

  • HIV virus binds to a T-helper cell expressing CD4+
  • gp120 and gp41 proteins bind the virus to the cell and facilitate membrane fusion with the T-cell -> RNA genome and essential enzymes enter the cytoplasm
  • Reverse transcription of the RNA ensues. Once complete RNA passes out of the cell, taking a new capsule from the cell membrane. It is now ready to infect a new T-cell
  • The original T-cell eventually dies as the result of the virus
  • Chronic activation of non-infected T-cells -> apoptosis
  • Multiple mechanisms lead to a reduction in the number of T-helper cells and thus the level of immunity of the host decreases making opportunistic infections and secondary neoplasms possible.


Outline the abnormalities of the immune system that occur in AIDS.


List AIDS defining opportunistic infections and neoplasms. 


  • Karposi sarcoma
  • Non-Hodgkins B-cell lymphoma
  • Cervical Ca
  • Anal Ca


See pic


What are the clinical manifestations of SLE?


Describe the natural history of HIV.

Early acute phase

  • transient viraemia
  • temporary fall in CD4+ T cells
  • self limiting acute illness

Middle chronic phase

  • clinical latency
  • vigorous viral replication
  • gradual decline of CD4+ counts
  • generalised lymphadenopathy

Final crisis phase

  • rapid decline in host defenses
  • low CD4+ counts
  • opportunistic infections and neoplasms


What is a granumloma?

A large collection of macrophages that forms around a substance or organism that is recognised as foreign but cannot be eliminated.


Persistent antigen ->:

  • perivascular lymphocytes
  • epithelioid cells
  • collar of lymphocytes around epithelioid cells


What is Type I hypersensitivity?

Rapid reaction that occurs after antigen binds to mast cells coated with IgE in a previously sensitised host.

Sensitisation occurs when antigen is presented to a CD4+ TH2 helper cell. This results in B-cell production of IgE that is specific to the antigen. The IgE then binds to the surface of mast cells and basophils which are then "sensitised".

Type I hypersensitivity results in:

Initial Phase:

  • Vasodilataion
  • Vascular leakage
  • Sm mm spasm
  • Glandular secretions

Late Phase:

  • Infiltration by eosinophils, neutrophils, basophils, monocytes, CD4+ T Cells
  • Tissue destruction (eg epithelial cell damage)


Most, but not all, Type I reactions are mediated by the cross-linking of antigen to IgE on the surface of mast cells -> vasoactive amines and lipid medsiators -> immediate reaction and cytokines -> late phase reaction.

Mast cells release:


Chymase, tryptase


Leukotrienes C4 and D4

Prostoglandin D2

Platelet activating factor