White Blood Cells Flashcards
Our bodies are exposed continually to bacteria,
viruses, fungi, and parasites:
– Skin – Mouth – respiratory passageways – the intestinal tract – lining membranes of the eyes – urinary tract. • Can cause more serious infections if they invade the deeper tissues • Other highly infectious bacteria and viruses
What are the agents that combat infection and toxic agents
– Blood leukocytes (white blood cells)
– Tissue cells derived from leukocytes
How do the agents that combat infection destroy invading bacteria/viruses?
– Phagocytosis
– Forming antibodies and sensitizing lymphocytes
Types of White blood cells?
- Granulocytes
- Monocytes
- Lymphocytes
- Plasma cells (occasionally)
Granulocytes include:
• Polymorphonuclear Neutrophils • Polymorphonuclear Eosinophils • Polymorphonuclear Basophils – called polys, because of the multiple nuclei
The genesis of White blood cells is called?
Leukopoesis
• Formation of the different
blood cells from the stem
cell
• NB: 2 major lineages of
white blood cells:
– Myelocytic
– lymphocytic
Where are White blood cells formed?
• Partially in the bone marrow
– granulocytes and monocytes
• Partially in the lymph tissue (lymph glands, spleen, thymus, tonsils)
– Lymphocytes and plasma cells
• Transported to where they are needed
– serious infection and inflammation
Life span of Granulocytes
Granulocytes: 4-8 hours circulating; 4-5 days in tissues where needed. Shortened to a few hours in serious infection.
Life span of Lymphocytes
• Lymphocytes enter the circulatory system continually (via the lymph). Pass out of the blood after a few hours – back into the tissue
(diapedesis). Repeated. Have a lifespan of weeks to months depending on need.
Life span of Monocytes
• Monocytes: 10-20 hours in blood live for months as macrophages on the tissues (unless destroyed performing phagocytosis)
How do White blood cells move?
- Enter the tissue by diapedesis
- Move through the tissue by ameboid motion (40um /min)
- Attracted to the inflamed tissue by chemotaxis
What is diapedesis?
Process where the cell squeezes through the pores of
the blood capillaries.
• But a pore is much smaller that a cell
How does it do this?
• A small portion of the cell slides through the pore at a
time: the portion sliding through is momentarily
constricted to the size of the pore
What is Chemotaxis?
When a tissue is inflamed, products are formed
– Bacterial or viral toxins
– Degenerative products from the inflamed tissue
– Reaction products from the complement complex
– Reaction products caused by plasma clotting
Causes a concentration gradient
• Concentration greatest near the source
which directs movement of the WBCs.
• Effective up to 100um away from an
inflamed tissue.
Because all tissues are not >50 um away
from a capillary, is an effective way to
move hordes of white blood cells from the
capillaries to the inflamed area.
Neutrophils and Macrophages act similarly how?
-In that they attack and destroy the bacteria via Phagocytosis
Phagocytosis
Attaches to the particle
• Projects pseudopodia in all directions around the particle
• Pseudopodia meet one another on the opposite side and
fuse
• Creates a chamber with the particle inside
• The chamber invaginates (turns inside out) and forms a
free-floating phagocyte
• Lysozymes and other cytoplasmic granules dump
digestive (proteolytic) enzymes and bactericidal agents (oxidizing agents, eg hydrogen peroxide) into the vesicle = digests the particle.
Neutrophils
• Already mature cells
• Can phagocytize 3 -20 bacteria before it dies.
• Are the most abundant of the white blood cells
- 62% of average adult white blood cell count
*(average adult white blood cell count is 7000 cells per microliter blood)
• Normal neutrophil count is 1500 – 8000 cells per microliter blood
• If count > 8000 – neutrophilia (most likely have an infection)
• If count is < 1500 – neutropenia (underlying disease causing the low production of neutrophils)
Neutrophilia
wbc > 8000
Neutropenia
wbc < 1500
Monocytes/Macrophages
Start out as monocytes
– Have large, eccentrically placed, bean-shaped nucleus
• When monocytes enter tissues
– they increase in size (swell)
– and develop large numbers of granules (lysosomes)
• Macrophages are the mature cells
• Attack and destroy bacteria in the blood.
• Can phagocytize up to 100 bacteria (more than
neutrophils)
• Can also engulf larger particles (unlike neutrophils)
• After digestion, extrudes residual products and can
continue to function (>months [many months]).
Where are macrophages found?
- Skin (Histiocytes)
- when the skin is broken and infection begins in subcutaneous tissue the local tissue macrophages divide in situ and can phagocytose the pathogen
- Lymph nodes
- Line the lymph sinuses where foreign particles are trapped
- Lungs (Alveolar macrophages)
- phagocytose particles that are entrapped in the alveoli
- liver (Kupffer cells)
- prevent bacteria from the gastrointestinal tract from entering the general systemic circulation.
- Spleen and bone marrow
- phagocytose organisms that succeed in entering the general circulation
- CNS (Microglia)
- located throughout the brain and spinal cord.
Reticuloendothelial system aka
(monocyte-macrophage system)
Define Reticuloendothelial system
Some macrophages (mobile cells) become attached to the tissues (monocytes) for months to years until stimulated.
- Break away – become mobile macrophages again.
- Combination of monocytes, mobile macrophages, fixed tissue macrophages and some specialized endothelial cells in the bone marrow spleen and lymph nodes make up the reticuloendothelial system.
Inflammation is the role of which cells
Role of Neutrophils and Macrophages
Inflammation is caused by?
– bacteria, trauma, chemicals, heat
– Release substances that dramatically change the surrounding uninjured tissue.
Inflammation is characterized by? The 5 steps of Inflammation
- Vasodilation of local blood vessel – causes excess blood flow
- Increased permeability of the capillaries – causes leakage of large amounts of fluid into the interstitial spaces
- Clotting of the fluid – caused by excessive amounts of fibrinogen leaking from the capillaries
- Migration of large numbers of granulocytes and monocytes into the tissue
- Swelling of the tissue cells.
The result of the steps?
• “Walling off”: tissue spaces and lymphatics
blocked by fibrinogen clots. Stops fluid
flowing through the spaces. Delays the
spread of bacteria/toxic products
1st line of defense (during 1st hr)
: Rapid enlargement of macrophages at the site of
infection. Attached macrophages become mobile.
• 2nd line defense (within a few hrs):
.
large number neutrophils invade the inflamed area. Stick to the capillary walls (margination). Pass from the blood into the tissue spaces (diapedesis).
Migrate towards the injured tissue (chemotaxis). Stored
neutrophils in the bone marrow are mobilized into the circulating blood, cause 4-5X increase in numbers of
neutrophils (neutrophilia)
3rd and 4th lines of defense
• 3rd line (several days): monocytes from the blood
enter the inflamed tissue and enlarge to macrophages (8hrs). Bone marrow increases production of new monocytes.
• 4th line (3-4 days): increased production (20-50X)
granulocytes and monocytes by bone marrow via
progenitor pathway. Can continue production for
months – yrs.
Basophils
• Found in the circulating blood. Similar to tissue mast
cells found immediately outside of the capillaries.
• Release heparin into the blood (prevents clotting).
Also histamine, bradykinin, seratonin (mainly mast
cells)
Role of Basophils
Role in allergic reactions because immunoglobulin
E (IgE) attaches to mast cells and basophils.
– When an antigen (Ag) attaches to IgE antibody (Ab), cells rupture.
– Releases large amounts of histamine, bradykinin, serotonin, heparin, slow-reacting substance of anaphylaxis (It induces prolonged, slow contraction of smooth muscle
and has a major bronchoconstriction role in asthma) – allergic manifestation
Eosinophils
• Under normal conditions found in the spleen, lymph
nodes and gastrointestinal tract where survive for
several days. Circulate for 8-12 hours
• Usually produced in large numbers in people with
parasitic infections.
– Weak phagocytes
– Instead, attach to the parasites by special surface
molecules and release:
– hydrolytic enzymes from their granules
– Highly reactive forms of oxygen (peroxidases)
– Highly larvicidal polypeptide = major basic protein
Role of Eosinophils in detoxification
Also collect in tissues in which allergic reactions
occur (lungs, skin).
– Partly due to release of eosinophil chemotactic factor by
mast cells and basophils
• Detoxify inflammation-inducing substances released
by mast cells and basophils.
• Phagocytose and destroy allergen-antibody
complexes.
Lymphocytes
• Large nucleus, little cytoplasm, smallest of WBCs but size
increases when activated by foreign antigen
• Lymphocytes play the central role in all immunological
defence mechanisms, provide specific immune response
(acquired)
• Lymphocytes produced in bone marrow but may undergo
further development and division elsewhere (e.g. thymus –
Tcells; liver – Bcells (from bursa of Fabricius).
• They migrate to lymphoid tissue (mostly lymph nodes,
spleen, tonsils, lymphoid follicles in gastrointestinal tract)
encounter foreign antigen
Lymphocyte clones
• Occurs when specific antigens come into contact with the lymphocytes
• Lymphocytes are activated
• B lymphocytes produce antibodies when activated
• T lymphocytes produce activate T cells (can destroy infected cells).
• Activated lymphocytes react highly specifically against the antigens that
initiated their development.
• Produces tremendous amounts of duplicate lymphocytes = clones
Cell-mediated and Humoral immunity.
Explain the diagram
What is Leukopenia and what does it result in?
• When bone marrow produces very few WBCs
• What is the result?
– Allows invasion of bacteria normally present
(symbiotic bacteria) into adjacent tissues.
– Ulcers appear in the mouth and colon, respiratory
infection
– Bacteria invade surrounding tissue and blood
– Without treatment (transfusion; antibiotics) death
in <2weeks.
• Some stem cells, myeloblasts, and hemocytoblasts
are capable of regenerating the bone marrow – may
take weeks to months – therefore need treatment.
What is Leukemia?
• Caused by cancerous mutation of myelogenous or lymphogenous
cell.
• Results in increased numbers abnormal WBCs
What are the types of Leukemia?
- Lymphocytic
2. Myelogenous
Lymphocytic leukemia
– Cancerous production of lymphoid cells
– Usually begins in lymph node and spreads to other areas of the body
Myelogenous leukemia
– Cancerous production of young myelogenous cells in the bone marrow
– Spreads throughout the body so that WBCs produced in extramedullary tissue (outside of the bone marrow) – especially lymph nodes, spleen, liver.
– Occasionally produces partially differentiated cells
(neutrophilic, eosinophilic etc) – chronic, sometimes
developing slowly over 10-20 years.
-Mostly undifferentiated – the more undifferentiated, the more acute – can lead to death within a few months
What are the effects of leukemia on the body?
• Metastatic growth of leukemic cells in abnormal
areas,
– Eg leukemic cells from the bone marrow may invade
surrounding bone, causing pain and eventually a tendency for bones to fracture easily.
• Almost all spread to the spleen, lymph nodes, liver
and other vascular organs.
• Development of infection, severe anemia, bleeding
caused by thrombocytopenia (lack of platelets).
• Excessive use of metabolic substrates by the
cancerous cells (eg foodstuffs, amino acids,
vitamins).
• Causes lack of energy, deterioration of normal
protein tissues (amino acids).
Platelets aka Thrombocytes
• What are platelets?
– Minute disc 1-4um in diameter.
• How are they formed?
– Formed in the bone marrow from megakaryocytes (extremely large cells).
– Fragment into minute platelets in the bone marrow or soon after entering the blood.
– Megakaryocytes and platelets bind thrombopoietin
– When platelet count is low, there is increased free thrombopoietin which can stimulate megakaryocytes
– When the platelet count is high, there is decreased free thrombopoietin and decreased stimulation of megakaryocytes
- 300000 platelets per microliter blood. Replaced once every 10 days.
- Eliminated from the circulation by the macrophages, especially in the spleen.
What are the characteristics of Platelets?
• No nuclei
• Cytoplasm:
1. Have actin and myosin molecules and thrombosthenin which are contractile proteins.
2. Residuals of ER and Golgi apparatus – store large quantities calcium ions
3. Mitochondria and enzyme systems capable of forming ATP and ADP.
4. Enzyme systems that synthesize prostaglandins (local hormones)
–cause vascular and other tissue reactions.
5. Fibrin-stabilizing factor - coagulation
6. Growth factor – help repair damaged vascular walls.
• Cell membrane has:
– Coat of glycoproteins – selectively adheres to injured endothelium
– Phospholipids – activate multiple stages in the blood-clotting process
