Immunology Concepts Quiz

Leukocytic Disorders

• Leukocytic disorders are categorized as disorders of white blood cells.
• There are 5 types of leukocytic disorders.
• Dr Zin Zin Thu, from the UNIT of PATHOLOGY and the FACULTY of MEDICINE presented the information in 2025.
• The objectives of the lecture included discussing leukocytosis, agranulocytosis, leucopenia, leukemoid reactions, lymphadenitis, and the classification of lymphoid neoplasms.

Topic Outcomes

• Students will be able to identify causes for leukocytosis, leucopenia, and agranulocytosis.
• Students will be able to interpret a leukemoid reaction and recognize its underlying causes.
• Students will be able to diagnose acute and chronic non-specific lymphadenitis by correlating it with clinical presentations, common causes, and morphology.
• Students will be able to identify etiologic and pathogenetic factors in white cell neoplasia.
• Students will be able to differentiate types of lymphoid neoplasms based on the WHO classification.

Hematopoiesis

• Hematopoiesis is the process of blood cell formation.
• The hematopoietic system is divided into myeloid and lymphoid tissues.
• Myeloid tissues include bone marrow, which produces red cells, platelets, granulocytes, and monocytes.
• Lymphoid tissues include the thymus, lymph nodes, and spleen, which produce lymphocytes.
• Blood consists of Red Cells, Granulocytes, Monocytes, Platelets, and Lymphocytes.

Hematopoiesis (continued)

• Hematopoiesis involves a series of stages from stem cells to mature blood cells(e.g., erythrocytes (RBCs)).
• Stem cells differentiate into committed precursors, then late precursors, and finally mature forms.
• Colony-forming units (CFUs) play a role in the process
• Negative selection markers are used in the process (negative for lineage-specific markers)
• Natural killer (NK) cells are a type of lymphocyte.

Hematopoiesis (continued)

• Hematopoietic stem cells (HSCs) have two essential properties for maintaining hematopoiesis: pluripotency and self-renewal.
• Pluripotency lets a single HSC generate all mature blood cells.
• Self-renewal enables HSCs to divide into one daughter cell, allowing self-renewal and preventing depletion of stem cells.
• It’s a dynamic process, important for replenishing blood cells (automatic refill and proliferation).

Hematopoiesis (continued)

• Many diseases can affect blood cell production.
• The marrow is the primary source of many innate and adaptive immune system cells.
• It responds to infectious or inflammatory challenges by increasing granulocyte output under specific growth factors and cytokines.
• Many defects in hematopoiesis result in deficiencies of blood cells.
• Primary tumors of hematopoietic cells, genetic diseases, infections, toxins, nutritional deficiencies, and chronic inflammation interfere with marrow function, decreasing blood cell production.

Disorders of White Cells

• Disorders of white blood cells are categorized into proliferative disorders (expansion of leukocytes) and leukopenias (deficiency of leukocytes).
• Reactive proliferations are common in infections and inflammatory processes, resulting in increased numbers of leukocytes (needed for an effective host response).
• Neoplastic disorders are less common but clinically important.

Leukopenias

• Leukopenia is a condition with an abnormally low white cell count.
• It can result from reduced numbers of neutrophils (neutropenia, granulocytopenia) or lymphocytes (lymphopenia).
• Reference ranges for blood cells (including white blood cells, granulocytes, neutrophils, lymphocytes, monocytes, eosinophils, and basophils) are important in detecting anomalies from normal ranges.

Causes of Lymphopenia

• Congenital immunodeficiency diseases
• Advanced HIV infection
• Therapy with glucocorticoids or cytotoxic drugs
• Autoimmune disorders
• Malnutrition
• Certain acute viral infections

Leukopenias (continued)

• Neutropenia is a reduction in the number of neutrophils in the blood.
• Agranulocytosis is a severe reduction in neutrophils.

Causes of Neutropenia

• Inadequate or ineffective granulopoiesis (suppression of HSCs, infiltrative marrow disorders by drugs, conditions with ineffective hematopoiesis)
• Accelerated destruction or sequestration of neutrophils(immunologically mediated effects, splenomegaly, increased peripheral utilization)

Causes of Agranulocytosis

• Drug toxicity
• Acquired idiopathic neutropenia (autoantibodies).
• Large Granular Lymphocytes (LGL) leukemia
• Serious bacterial & fungal infections

Leukocytosis

• Leukocytosis is an increase in white blood cell count, a typical response to inflammatory conditions.
• The peripheral leukocyte count involves factors such as the myeloid and lymphoid precursor storage pools, release rate into circulation, proportion of cells adhering to blood vessel walls, and extravasation rate into tissues.

Leukocyte Homeostasis

• Homeostasis is maintained by cytokines, growth factors, and adhesion molecules.
• Acute infections promote rapid increases in mature granulocytes from the bone marrow pool, mediated by TNF and IL-1.
• Infections or inflammatory processes stimulate macrophages, bone marrow stromal cells, and T cells to produce more hematopoietic growth factors.
• These factors boost granulocytic progenitor proliferation and differentiation, and neutrophil production.

Causes of Leukocytosis (continued)

• Increased marrow production (chronic infection/inflammation, paraneoplastic syndromes, myeloproliferative neoplasms)
• Increased release from marrow stores (acute/chronic inflammation)
• Decreased margination (exercise, catecholamines)
• Decreased extravasation into tissues (glucocorticoids)

Causes of Leukocytosis (specific types)

• Neutrophilic leukocytosis (bacterial infections, sterile inflammation, burns)
• Eosinophilic leukocytosis (allergic disorders, drug reactions, malignancies, autoimmune disorders)
• Basophilic leukocytosis (myeloproliferative neoplasms)

Causes of Monocytosis (specific type)

• Chronic infections (TB, bacterial endocarditis, Rickettsiosis, Malaria)
• Autoimmune disorders (SLE)
• Inflammatory bowel diseases (ulcerative colitis)

Causes of Lymphocytosis (specific type)

• Chronic immunologic stimulation (TB, brucellosis)
• Viral infections (hepatitis A, CMV, EBV)

Leukemoid Reactions

• Leukemoid reactions are severe increases in WBC count where the numbers are similar to the count in leukemia.
• They are often caused by severe infections and can be distinguished from leukemia by looking at circulating cell types of the bone marrow.

Acute and Chronic Nonspecific Lymphadenitis

• Inflammation in lymph nodes (acute or chronic)
• Clinical presentations: swollen, painful lymph nodes; abscess formation, red overlying skin, draining sinuses from the lymph nodes after infections have penetrated through the capsule of the node

Lymphadenitis

• Infections and inflammation can stimulate immune reactions in lymph nodes.
• Resident immune cells are activated leading to morphologic changes.

Lymph Nodes Morphology

• Normal lymph node histology includes lymphoid follicle, cortex B cells, paracortex T cells and medulla macrophages and plasma cells.

Chronic Nonspecific Lymphadenitis

• Chronic immunologic stimuli can produce nonspecific lymphadenitis.
• It exhibits patterns of morphologic changes (follicular hyperplasia, paracortical hyperplasia, sinus histiocytosis), commonly in a single lymph node.

Causes of Chronic Nonspecific Lymphadenitis (follicular hyperplasia)

• Rheumatoid arthritis
• Toxoplasmosis
• Early HIV

Chronic Nonspecific Lymphadenitis (Morphologic findings)

Follicular Hyperplasia (features of reactive hyperplasia): preserved lymph node architecture, marked variation in follicle shape/size, frequent mitotic figures, recognizable light and dark zones, large germinal centers surrounded by a collar, dark and light zones in the germinal center.

Causes of Chronic Nonspecific Lymphadenitis (paracortical hyperplasia)

• T cell-mediated immune response (e.g., acute viral infections, infectious mononucleosis).

Causes of Chronic Nonspecific Lymphadenitis (sinus histiocytosis)

• Prominent in lymph nodes that drain cancers (e.g. breast carcinoma). The presence of numerous macrophages inside the sinuses.

Etiologic and Pathogenetic Factors in White Cell Neoplasia

• Development involves chromosomal translocations, inherited genetic factors, viruses, chronic inflammation, iatrogenic factors, and smoking.
• Chromosomal translocations can involve abnormal genes, leading to loss or gain of function.
• Recurrently affected genes play a role in malignancy development, growth, and survival.
• Inherited genetic factors can promote genomic instability.
• Viruses, chronic inflammation, and certain drugs/treatments (iatrogenic) can lead to white blood cell cancers.
• Smoking increases risk for some white blood cell cancers.

Lymphoid Neoplasms

• They are neoplasms of white blood cell-types (lymphocytes).
• Leukemias have widespread involvement of bone marrow and peripheral blood.
• Lymphomas present as discrete tissue masses.
• (WHO classification) lymphoid neoplasms are divided into precursor B-cell neoplasms, peripheral B-cell neoplasms, precursor T-cell neoplasms, peripheral T-cell and NK-cell neoplasms, and Hodgkin lymphomas.

Descriptions of Lymphoid Neoplasms

• Detailed descriptions of various types of lymphoid neoplasms (like acute lymphocytic leukemia or lymphomas, chronic lymphocytic leukemia, various types). (see tables)