This document discusses white blood cells (WBCs) and lymphoid tissues. It begins by introducing WBCs and their development stages. WBCs are categorized into granulocytes (neutrophils, eosinophils, basophils) and agranulocytes (lymphocytes, monocytes). The document then discusses specific WBC types in more detail, including their morphology, functions, and pathological variations seen in disorders. Disorders are categorized as non-neoplastic (increases or decreases in WBC counts) and neoplastic (leukemias and lymphomas). Overall, the document provides an overview of WBCs and lymphoid cells

1. Disorders of White Blood Cells
and Lymphoid Tissues
BY: MRS. GARIMA NAGPAL
Tutor, Pathology
MMU, MULLANA

2. objective
1. Introduction of white blood cells and lymphoid cells.
2. Development satges of wbcs and lymphoid cells
3. Categorized of wbcs disorder and discuss .

3. Leukocytes
• Blood cells are originate in the
bone marrow.
• To produce different blood cells
at different rates depending on
demand.
• This means we need :
- separate cell lines
- separate colony
stimulating
Factors for each line.
• There are various stem cells
with different abilities to
produce these cell lines .

4. Developmental stages of Blood
Cells

5. White blood cells : Further categorization
Granulocytes:
• Neutrophils : primary pathogen fighting cells – First
responders, phagocytes, (*release oxygen free
radicles ;super oxide, hydrogen peroxide, hypochloric
acid, hydroxide radicle)
• Eosinophils : Help control Allergic responses ; Fight
parasites(major basic protein), cationic peptide
protein .
• Basophils : Release Heparin, Histamine, and other
Inflammatory mediators.

6. Agranulocytes:
• Lymphocytes
- B cells :Produce antibody
- T cells :
T – helper cells (CD4+): active immune response.
Cytotoxic T cells (CD8+): cell mediated immunity.
- Natural killer cells : kill antigenic cells ( like tumors
cells).
• Monocytes (Macrophages):
Antigen- presenting cells ; produce inflammatory mediators

7. White blood cells

8. Lymphoid cells
T-cells( “T” for thymus)-
• Produced in bone marrow but
mature in thymus to become :
CD4+/T4 (Helper T-cells)
CD8+/T8 ( cytotoxic T-cells)
(These designations represent
specific proteins on their surface
membranes).

9. B-cells(“B” roughly refers to Bone marrow)-
• Produced and mature in bone marrow.
• Can become plasma cells (plasmocytic) that make
antibodies against specific pathogens .
Natural killer cell-component innate immune system
and kill tumors as well as other dysfunctional cells.
- NK cell work to control viral infections by secreting
IFN γ (interfering gamma )and TNFα(tumor necrosis
factor).

10. WBC’s disorders
• Categorized as :
- Non – Neoplastic:
It May include an increase or a decrease in number of white
blood cells :
Leukopenia, Neutropenia (agranulocytosis) ,infectious
mononucleosis.
-Neoplastic :
a. leukemia
b. lymphoma
c. plasma cell dyscrasia (Multiple myeloma)

11. Non – neoplastic white Blood cell deficiencies
Normal Total WBC count = 4,500-10,500 cells/µl
Leukocytosis:
Leukocytosis refers to an increase in the total number
of white blood cells (WBCs) due to –
-Infection ( bacterial, fungal, viral, protozoan,
parasitic).
-Bone tumor.
-Leukemia.
* it may also occur after strenuous exercise,
convulsions such as epilepsy, emotional stress, pregnancy
and labor, anesthesia, as a side effect of medication (and
epinephrine administration .

12. Neutrophil (polymorphs)
• Morphology-
A polymorphonuclear (PMN) neutrophil commonly
called polymorph or neutrophil .Size – 12-15 um in
diameter. It consist of a characteristic dense
nucleus, having 2-5 lobes and fine purple
cytoplasmic lysosomal granules contain various
enzymes.
- This lysosomal granules are 2 types –
• Primary or azurophilic granules
• Secondary or specific granules

13. • Primary or azurophilic granules –
They are large and coarse and appear early
in the promyelocyte stage. It contain –
a. Hydrolase enzyme.(Biochemical catalyst)
b. Elastase.(proteases break down)
c. Myeloperoxidase. (Degradation enzyme)
d. Microbicidal protein.(microbicide)

14. • Secondary or specific granules –
They are smaller and more numerous . These
appear later at myelocyte stage . It contain –
a. Lactoferrin .(Iron binding protein ;activated
neutrophil sites
b. NADPH oxidase.(Membrane bound protein).
c. Histamine. (Inflammatory response ).
d. Vitamin B12 binding protein .

15. Pathologic variation
• Variations in count
• Morphology
• Defective function

16. Variations In Count
An increase in neutrophil count (Neutrophil Leucocytosis
or Neutrophilia) or a decrease in count (Neutropenia) may
occur in various diseases.
Neutrophil leucocytosis
Absolute neutrophil count >7,500/cumm

17. The commonest type of leukocytosis and occurs most
commonly as a response to acute bacterial infections.
Some common causes of neutrophilia are as under:-
• Acute infections – ( local/Generalised) especially by
cocci but also by certain bacilli, fungi, spirochaetes,
parasites and some viruses.
• Other inflammations - tissue damage resulting from
burns, operations, ischaemic necrosis (such as in MI),
hypersensitivity reactions etc.

18. Cont…
• Intoxication -Uraemia, Diabetic ketosis, eclampsia,
poisonings by chemicals and drugs.
• Acute haemorrhage, internal or external.
• Acute haemolysis.
• Myeloproliferative disorders

19. Neutropenia
When the absolute neutrophil count falls below
2,500/μl, the patient is said to have neutropenia
and is prone to develop recurrent infections.
Common cause of neutropenia –
• Certain infections e.g. Typhoid, Brucellosis,Influenza,
Measles, Viral hepatitis, Malaria, Kala-azar etc
• Drugs, chemicals and physical agents which induce
Aplasia of the bone marrow cause neutropenia.

20. Cont..
• Certain haematological and other diseases e.g.
Pernicious anaemia, Aplastic anaemia, Cirrhosis of
the liver with splenomegaly.
• Certain hereditary, congenital or familial disorders
e.g.
Cyclic neutropenia, Primary splenic neutropenia,
Idiopathic benign neutropenia.

21. Variations In Morphology
• Granules -Heavy, dark staining, coarse toxic granules
are characteristic of bacterial infections.
• Vacuoles- In bacterial infections such as in
septicaemia, cytoplasmic vacuolation may develop.
• Döhle bodies- These are small, round or oval
patches,2-3 μm in size, in the cytoplasm. They are
mostly seen in bacterial infections.
• Nuclear abnormalities.

22. Defective Functions
• Defective chemotaxis e.g. in a rare congenital abnormality
called lazy-leucocyte syndrome; following corticosteroid
therapy, aspirin ingestion, alcoholism, and in myeloid
leukaemia.
• Defective phagocytosis due to lack of opsonisation e.g.in
hypogammaglobulinaemia, hypocomplementaemia, after
splenectomy,insicklecelldisease.
• Defectivekillinge.g.inchronicgranulomatousdisease,
Chédiak-Higashisyndrome,myeloidleukaemias.

23. Lymphocytes
MORPHOLOGY-
• 20-30 % of all WBCs
• Anatomy
-7-15 μm
- small amount of light blue
cytoplasm.
-coarsly clumped chromatin
. Take the majority of the cell
-nucleas is round –oval in
shape .

24. Pathologic Variations
A rise in the absolute count of lymphocytes
exceeding the upper limit of normal
(above4,000/μm) is termed lymphocytosis, while
absolute lymphocyte count below 1,500/μm is
referred to as lymphopenia.

25. Lymphocytosis
• Absolute count >5.5 x 109/L
• Some of the common causes of
lymphocytosisare as under:
Certain acute infections e.g.
Infectious Mononucleosis, Viral
hepatitis, Infectious lymphocytosis.
Certain chronic infections e.g.
Brucellosis, Tuberculosis,Syphilis.
Haematopoietic disorders e.g.
lymphocytic leukaemias,
lymphoma.

26. Lymphopenia
Lymphopenia is uncommon
and occurs in the following
conditions:
• Most acute infections.
• Severe bone marrow failure.
• Corticosteroid and
immunosuppressive therapy.

27. Monocytes
MORPHOLOGY:-
The monocyte is the largest
mature leucocyte in the
peripheral blood measuring 12-
20 μm in diameter. It possesses a
large, central, oval, notched or
indented or horseshoe-shaped
nucleus which has
characteristically fine reticulated
chromatin network. The
cytoplasm is abundant, pale blue
and contains many fine dust-
like granules and vacuoles.

28. Functions of monocytes are :-
• Phagocytosis of antigenic material or
microorganisms.
• Immunologic function as antigen-presenting cells
and present the antigen to lymphocytes to deal with
further.
• Mediator of inflammation, they are involved in
release of prostaglandins, stimulation of the liver to
secrete acute phase reactants.

29. Pathologic Variations
• A rise in the blood monocytes above 800/μl is termed
monocytosis.
• Some common causes of monocytosis are as follows:
1. Certain bacterial infections e.g. Tuberculosis, Sub acute
bacterial endocarditis, Syphilis.
2. Viral infections.
3. Protozoal aninfections e.g. Malaria, Typhus,
Trypanosomiasis, Kala-azar.
4. Haematopoietic disorders e.g. Monocytic Leukaemia,
Lymphomas, Myeloproliferative Disorders, Multiplemyeloma.
5. Malignancies e.g. Cancer of the Ovary, Stomach, Breast.
6. Granulomatous diseases e.g. Sarcoidosis(abnormal
masses), Inflammatory bowel disease.

30. EOSINOPHIL
MORPHOLOGY
-1-6 % of circulating WBCs .
- They have a bilobed ( spected
shaped )nucleus and the cytoplasm
shows specific orange /red coarse
granules .
These granules are composed of –
a. MBP( major basic protien).
b. peroxidase .
c. lysomal protien.
* immunoglobin E receptors presenent
on their surface play a role in allergic
reactions and killing parasites .

31. Pathologic Variations
Eosinophilia: An increase in the number of
eosinophilic leucocytes above 400/μl is referred to as
eosinophilia and below 40/μl is termed as
eosinopenia.

32. The causes of eosinophilia are as under:
1.Allergic disorders e.g. bronchial asthma, urticaria,
angioneurotic oedema, fever, drug hypersensitivity.
2. Parasitic infestations e.g. trichinosis, echinococcosis,
intestinal parasitism.
3. Skin diseases.
4. Löeffler’s syndrome.
5. Pulmonary infiltration with eosinophilia (PIE)
syndrome.
6. Tropical eosinophilia.
7. Haematopoietic diseases e.g. CML, polycythaemia
vera, pernicious anaemia, Hodgkin’s disease.

33. Eosinopenia.
Adrenal steroids and ACTH induce eosinopeniain
man. Eosinopenia is a form of agranulocytosis where
the number of eosinophil granulocytes is lower than
expected. Leukocytosis with eosinopenia can be a
predictor of bacterial infection. It can be induced by
stress reactions, Cushing's syndrome, or the use
of steroids. Pathological causes include burns and
acute infections.

34. Basophil
MORPHOLOGY
- 0.5-1 % OF ALL WBCs
Anatomy-
-8-10 μm diameter .
-Bilobed or irregular nucleus
-Round, blue-black granules may obscure
nucleus .
Physiology-
-Exit cappilaries to enter tissue fluid .
-Mature into mast cells
. Release heparin, histamine, serotonin
–stimulate inflamtion .
-Hypersensitivity (allergic) reaction.

35. Pathologic Variations
• Basophil leucocytosis or basophilia refers to an
increase in the number of basophilic leucocytes
above 100basophil/μl. Basophilia is unusual and is
found in the following conditions:
1.Chronic myeloid leukaemia
2.Polycythaemia vera
3.Myelosclerosis.(Fibrosis of the bone marrow).
4. Myxedema(severe hypothyroidism).

36. Qualitative WBC Disorders

37. Altered Cell Morphology
• Nuclear variation :
A.Pelger-Huet
B.Hyper segmentation
• Cytoplasmic variation :
A. Alder-Reilly
B. May-Hegglin
C. Vacuolization
D.Dohle Bodies

38. Pelger -Huet disease
•Pelger-Huet anomaly (PHA) is
an inherited blood condition in
which the nuclei of several types
of white blood cells (neutrophils
and eosinophils) have unusual
shape (bilobed, peanut or
dumbbell-shaped instead of the
normal trilobed shape) and
unusual structure (coarse and
lumpy)
• Indicated failure of neutrophil
to segment properley.

39. Hypersegmentation
Neutrophil hypersegmentation can
be defined as the presence
of neutrophils with six or more lobes
or the presence of more than 3%
of neutrophils with at least five lobes.
•The presence of hypersegmented
neutrophils is an important
diagnostic feature of megaloblastic
anaemias and myelodysplastic
syndromes .

40. Alder Anomaly
Alder anomaly is characterized
by large azurophilic granules that
stain dark-purple and are seen
throughout the leukocyte
cytoplasm, even covering the
nucleus. The inclusions (granules)
are seen in the cytoplasm of
almost all mature leukocytes .
• Toxic granulation is seen in
cases of severe infection, as a
result of denatured proteins in
rheumatoid arthritis .

41. Vacuolization
• The presence of vacuolated
polymorphonuclear neutrophils in
blood smears of patients suffering
from infection appears to be
associated with massive bacterial
growth and to constitute a very early
symptom of rapidly life-threatening
septicaemia.

42. Döhle bodies
Döhle bodies(karl Gottfried paul
Döhle) are light blue-gray, oval,
basophilic, leukocyte inclusions located
in the peripheral cytoplasm of
neutrophils. They measure 1-3 μm in
diameter.
• Seen in toxic changes
-Bacterial infection.
-Inflammation.
-Administration of G-CSF.
-During pregenancy .

43. INFECTIOUS MONONUCLEOSIS
Infectious mononucleosis (glandular fever) is an
acute, benign, self-limiting lymphoproliferative
disorders caused by Epstien- Barr-virus(EBV).
Infection may occur from childhood to old age but
the classical acute infection is more common in
teenagers and young adults. The infection is
transmitted by person-to-person contact such as by
kissing with transfer of virally-contaminated saliva.
• Incubation period : it ranges from 4 to 8 weeks .

44. • Type of infection –
- Productive infection : infection seen only in a
minority B cells. The infected B cell produce and
release virions accompanied by death of B cell.
- Latent infection: The virus become latent inside the
B cells . There are no viral replication and the infected
B cells are not killed . These latently infected B cells
are transformed or “immortalized” so they are
capable of prolification identify.
• Immoratalization of B cell is the hallmark of EBV
infection.

45. Clinical features
Incubation period :
adult 30-50 days
children- 15-40 days
• During prodromal period (first 3-
5 days), the symptoms are mild
such as headache and fatigue.
• Frank clinical features (next 7-21
days) commonly are fever, sore
throat and bilateral cervical
lymphadenopathy.

46. Pathogenesis of EBV associated lesions

47. Leukaemoid Reactions
• Leukaemoid reaction is defined as a reactive
excessive leukocytosis in the peripheral blood
resembling that of leukaemia in a subject who does
not have leukemia.

48. Myeloid Leukaemoid Reaction
• CAUSES- Majority of leukaemoid reactions involve the
granulocyte series. It may occur in association with a
wide variety of diseases. These are as under:
1. Infections e.g. staphylococcal pneumonia,
disseminated tuberculosis, meningitis, diphtheria,
sepsis, endocarditis,plague, infected abortions etc.
2. Intoxication e.g. eclampsia, mercury poisoning,
severeburns.
3. Malignant diseases e.g. multiple myeloma,
myelofibrosis,Hodgkin’s disease, bone metastases.
4. Severe haemorrhage and severe haemolysis.

49. Lymphoid Leukaemoid Reaction
CAUSES: Lymphoid leukaemoid reaction may be found
in the following conditions:
1. Infections e.g. infectious mononucleosis, pertussis
(whooping cough) caused by Bordetella pertussis,
chickenpox, infectious lymphocytosis, tuberculosis.
2. Malignant diseases may rarely produce lymphoid
leukaemoid reaction.

50. Leukemia
It is a group of malignant disorder, affecting the
blood and blood-forming tissue of the bone marrow
lymph system spleen.
• Cause of leukemia:-
- Congenitel disorder : Down syndrome ,
Immunodeficiency syndrome
- Ionizing radiation : X-ray, Radiotherapy
- Chemicals : Alkelyting agent ,Benzene
- Viruses : Human T-lymphocyte leukemia virus
(HTLV1), EBV.

51. TYPES
• ACCUTE LEUKEMIA:
- Affect younger age group frequently.
- Rapid course and the peripheral blood and bone
marrow show the presence of large number of blast
cells.
- If left untreated ,these are fatal within
weeks/months.
Type-
• Acutel ltmphoblastic eukemia (ALL)
• Acute meylegenous leukemia (AML)

52. • CHORNIC LEUKEMIA :
- Generally affect older people .
- Onset is insidious .
- Usually less aggressive
Type-
• Chornic lymphocytic leukemia (CLL)
• Chornic myelogenus leukemia (CML)

53. Laboratory investigations of ALL
1.CBC
• ↑↑ WBCs with lymphoblasts in the peripheral
blood
• ↓RBCs ( anaemia)
• Plateletes ↓
2. Bone marrow
• Bone marrow aspirate
- All normal elements are depressed and replaced by
abnormal cells.

54. ALL; lymphoblasts have condensed chrometin
inconspicious nuclei

55. AML; leukemic blast cell

56. CLL; Condense chromatin, scant cytoplasm

57. CML; hypercellular marrow, elevated Eosinophil and
Basophil

58. Thank you