MLT1314 hemato lecture 2 (non-malignant agranular leukocytes)

CLL

chronic lymphocytic leukemia

ALL

acute lymphocytic leukemia

What is an immunoblast?

a lymphocyte in an activated phase --> they can undergo blast transformation (functionally mature but appear blast-like)

What are mott cells?

Plasma cells containing Russel Bodies + are characterized by the accumulation of immunoglobulin proteins w/in the endoplasmic reticulum

NK cell %

T lymph %

B cell %

NK

Monocytosis count

>0.9

Monopenia/monocytopenia count

When is vacuolation increased in monos?

in reactive conditions (aside from that, vacuolation is normal as their job is to engulf cellular remnants)

What happens when a monocyte enters tissue?

They become a macrophage

Only a monocyte in blood

Causes of monocytosis

Chronic bacterial infection

Inflammatory conditions

Immune conditions

Leukemia/lymphoma

Malignancies (hodgkins disease)

Stress repsonse

Chronic neutropenia (compensation)

Causes of monocytopenia

Aplastic anemia

Chronic use of corticosteroids

Hairy cell leukemia

How to treat lipid storage disease

Enzyme replacement therapy

Gene replacement therapy

What is the main goal when treating a lipid storage disease

Goal is to reduce organ damage, reduce splenomegaly and hepatosplenomegaly

NOTE: gene replacement therapy does not cross the BBB, so neurological symptoms persist when CNS is involved

Tay sachs inheritance pattern

autosomal recessive on a single gene (non sex-linked, so its very rare)

Lipid storage disease inheritance pattern

Recessive inheritance (rare)

What do memory B cells do?

they have memory of previous infections and jump into action when faced with a repeat infection

Name 4 viral infections that present with lymphocytosis and reactive abs. lymphocytes

Measles (rubella)

Mumps

Chicken pox (varicella)

Roseola (aka sixth disease)

B cells are antibody mediated. T or F

TRUE

Naive B cell

A b-cell that hasnt encountered an antigen

Name the 1 immune cell that produces antibodies

B cell

Where do naive B-cells migrate to once they leave the bone marrow

Secondary lymphoid tissue (spleen or lymph nodes)

Should plasma cells be seen on peripheral blood smear

no

Name antibodies that plasma cells can produce

IgGAME

How are plasma cells made

B-cells become plasma cells after encountering an antigen (this usually happens in secondary lymphoid tissue)

t cells can differentiate into 4 other cells

effector

helper

regulatory

memory

NK cell basics

No AB production

No prior exposure needed to activate

Cytotoxic action used

Hunts virally infected cells/cancer cells

Limited memory function

Where do lymphocytes circulate

Circulate in the blood or in the lymphatic system

Malignancy in blood is called

leukemia

Malignancy in lymph system is called

lymphoma

Effector cells aka cytotoxic T lymphs aka killer t-cells--> function

Directly ID and destroy infected/cancerous/damaged cells

Regulatory t cell function

Suppress and modulate the immune response (this prevents autoimmunity)

Memory t cell function

Remain in circulation and respond rapidly

Helper t cell function

secrete chem messengers

coordinate/regulate immune reponse

activate B-cells

T-cells (cell-mediated) do what?

No AB needed

cytotoxic action, precise killer

bind directly to free-floating AGs

Vacuolated lymphs are aka phagocytic vacuoles. T or F

FALSE. vacuoles arise from metabolic or organellar changes, not ingestion.

Cause of vacuolated lymphs

Viral infection (IM, CMV, COV-19)

Rare to see on blood smear though

Promyelocytes are associated with?

prolymphocytic leukemia

Can be seen in CLL and viral infection (rare)

Which is a medical emergency and progresses rapidly: viral or bacterial meningitis

BACTERIAL

In simple terms, how does lipid storage disease work

-metabolic enzyme is missing

-undigested metabolic product builds up in cell

-affects organ systems (esp RES)

Storage cell

Cells full of unmetabolized lipids

Symptoms of lipid storage disease

Fibrosis

Damaged tissue

Loss of motor skill/muscle tone

Why does lipid storage disease cause fibrosis

caused by lipid engorged mono/macrophages accumulating in BM → they crowd out normal cell production → leads to leukopenia and bone infarcts (causes bone pain)

Why does lipid storage disease damage tissues

macrophages become toxic to surrounding tissues (mostly spleen, this is best assessed by ultrasound)

lipid storage disease affects what 2 cells

macrophage, monocyte

Why does lipid storage disease cause loss of motor skill/muscle tone

buildup in the brain impacts function

Thymus increases or decreases in size as you age

decrease

Adults have less T-cells compared to children, but they do have more_______ cells

memory cells

What does it mean if a lymphocyte is darker blue

theres increased protein synthesis

Are there nucleoli in lymphs?

in reactive or activated lymphocytes

Why is lymphocytosis normal in infants and children

theyre yucky and put their mouths on everything, so the extra germs means extra lymphs

Causes of lymphocytosis

Viral infection (benign)

CLL (malignant)

Epstein barr virus

Hepatitis

HIV/AIDS

Name 2 (rare) non-viral causes of lymphocytosis

Treponema pallidum (syphilis)

Streptococcus agalactiae (group B strep)

Infectious mononucleosis common symptoms

Sore throat (esp if you have tonsils)

Fatigue

Loss of appetite

Head and body aches

Enlarged lymph nodes (esp those in neck)

Inf. mono. rarer symptoms

Hepatosplenomegaly

Autoimmune hemolytic anemia

Thrombocytopenia (due to spleen)

Cold agglutination (mycoplasma pneumonia)

How is infectious mono diagnosed

Rule out strep throat w/ swab

CBC-D

Rapid agglutination test (monospot)

What should show up for infectious mono on a CBC-D

Should see absolute lymphocytosis w/ reactive lymphocytes

What does the rapid agglutination test for in IM?

Looks at specific IgM ABs (not positive for other EBV)

Latex AG + PT serum (ABs) = agglutination

Most common cause of lymphocytosis is?

Infectious mononucleosis (caused by EBV, human herpesvirus type 4, transmitted by body fluids)

IgM ABs are aka

heterophile ABs

Heterophile AB definition

are ABs produced in response to external AGs (non-specific ABs)

Fake positive in latex monospot test can be caused by?

Rheumatoid factor (IgM anti‑IgG)

Polyclonal IgM from other infections

Autoimmune disease

Lymphoid malignancy

Hypergammaglobulinemia

Why do false pos happen in the monospot latex test?

the latex beads bind non-specific IgM and immune complexes, which leads to agglutination even without EBV

At what point to we report reactive lymphs?

> 5%

What does a reactive lymph look like?

Large, dark border colour where its touching other cells, conforms around other cells

The newer version of the heterophile AB test (the lateral flow immunoassay) works how?

Liquid is serum, plasma, or whole blood

Liquid absorbs along porous paper base

Soaks into secondary pas

Bioactive particles react w/ AG reagents

AG + AB = colour rxn

Abnormal lymphs seen in bordetella pertussi have a _______ nuclei

clefted! they look like coffee beans

(look at the PT age if you see these, if theyre younger its prob whooping cough)

Name 2 mononucleosis syndromes w/ similar presentation to IM

Toxoplasmosis (toxoplasma gondii)

Cytomegalic virus (CMV)

What do you do if you see plasmacytoid morphology on a blood smear?

note morphology so a pathologist can look at it

Is it normal to see activated/reactive lymphs in viral infection?

Yeah, Increased AB production/protein synthesis (ABs are protein) will stain dark blue

BUT! you shouldnt see plasma cells in peripheral blood

Name a few conditions to consider when looking at high lymphocyte counts

Viral (IM) vs CLL

Viral (IM) vs ALL

Acute lymphocytosis

Transient lymphocytosis

Stress lymphocytosis

Bordetella pertussi

Viral infections

HIV/AIDS

Mott cells

Activated T-cells w/ apoptopic B-cells

Rule for counting damaged cells

Cant ID it? Dont count it

Too many damaged cells? remake the slide or get fresher PT sample

How to minimize smudge cells in PT sample?

1 drop of 22% bovine albumin + 4-5 drops PT blood

Remake blood film, redo diff

Smudge cells are aka

basket cells or smear cells

What are smudge cells

These are lymphoid cells that have ruptured in vitro due to the preparation of the peripheral smear.

These are artifact

In what case are smudge cells most commonly seen

CLL (or any condition of increased lymph fragility)

How to count smudge cell?

If smudge cells are > 10% WBCs, add to total lymphs and comment on them in morphology

If

Plasmacytoid cells have tend to have ________ next to the nucleus

clearing!