White Blood Cells and Haemostasis Flashcards
What is haemostasis?
Cessation of blood loss
What are innate responses?
General, non-specific processes against infectious agents
What components make up the innate responses?
Skin
Phagocytosis of micro-organisms
Destruction by stomach acids/enzymes
Hydrolytic enzymes released by immune cells
What is an adaptive response?
Directed response against specific infectious agents
What unique feature is present in adaptive responses?
improve on repeated exposure to the same infection
How many leukocytes are found per litre of blood?
4-10 x 10^9 cells
Which leukocytes have roles in phagocytosis?
Neutrophils
monocytes
eosinophils
How do basophils and lymphocytes attack foreign bodies?
Release hydrolytic enzymes, histamine and other chemicals from cytoplasmic granules
Are leukocytes nucleated?
Yes
What stain can help differentiate leukocytes under the microscope?
Wright’s stain
How does Wright’s stain differentiate between leukocytes?
Nuclear shape and cytoplasmic colour
What leukocytes are granulocytes?
neutrophils, basophils, eosinophils
What is the bone marrow precursor cell of granulocytes?
Myelocytes
What unique feature do granulocytes have?
Multi-nucleated
What other cell found in blood is formed from myelocytes?
Thrombocytes
What controls the formation of myelocytes?
Cytokine
How long do myelocytes stay in bone marrow?
6-10 days
How long do myelocytes reside in circulation?
6-10 hours
How long do myelocytes stay in tissues?
4-5 days
Where is the reserve pool of myelocytes?
Bone marrow
What is the most common circulating WBC in adults?
Neutrophils
How do neutrophils travel through tissues?
Squeeze through pores of capillaries by diapedesis
When do numbers off neutrophils increase?
During infection
Are eosinophils phagocytic?
Yes but weakly
What is the most common way that eosinophils attack bodies?
Attach to parasites and secrete hydrolytic enzymes
What is a unique function of eosinophils?
Reverse tissue damage during an allergic reaction
What is the least common granulocytes?
Basophils
How do basophils attack bodies?
Release hydrolytic enzymes from cytoplasmic granules
What is the defining characteristic of basophils?
Release chemicals that contribute to allergic reactions
Name the chemicals responsible for allergic reactions.
Histamine, seratonin, heparin, bradykinin, lysosomal enzymes, slow-reacting substance of anaphalaxis
What do monocytes develop into?
Tissue macrophages
What do monocytes phagocytose?
Infectious agents
Abnormal and dying cells/cell fragments including RBCs
Where do monocytes phagacytose?
Only in tissues
How long do macrophages remain in tissues?
Months
What is the reticuloendothelial system?
Monocyte-macrophage system
Attach to tissues indefinitely and can be recruited into tissues if required
Where are macrophages prominent?
Lymph nodes
Lung alveolar walls
Liver sinusoidal capillaries
Red pulp of spleen
What is chemotaxis?
The recruitment of neutrophils and macrophages to tissue inflammation/infection
What causes a chemotactic effect?
Bacterial/viral toxins
Degenerative products of inflamed tissues
Complement complex activated in inlfamed tissues
Reaction products of plasma clotting
What is the first line of defence against infection?
Local macrophages
What is the 2nd line of defence against infection
Neutrophils entering by margination/diapedesis
What are the products of inflammation that act on bone marrow?
Rapid neutrophilia
What do the factors secreted by activated macrophages do?
Promote granulocyte and monocyte production
What do the factors secreted by activated macrophages do?
Promote granulocyte and monocyte production
What is the first leukocyte which is up-regulated in bone marrow following infection?
Neutrophils
Are macrophages or neutrophils superior phagocytic cells?
Neutrophils
Where are natural killer cells produced from?
Lymphoid lineage
What do natural killer cells target?
Target tumour cells and virus infected cells
How do natural killer cells attack a cell?
Induced programmed cell death (Apoptosis) via release of contents of cytoplasmic granules
How are natural killer cells activated?
Interferons or macrophage-derived cytokines
What are the three main subtypes of lymphocytes?
B lymphocytes
T lymphocytes
Natural killer cells
How do b lymphocytes attack?
Mature into plasma cells which secrete antibodies
What are the two main subgroups of T lymphocytes?
Helper T cells
Cytotoxic T cells
How do helper T cells attack?
Secrete cytokines which activate other leukocytes
How do cytotoxic T cells attack?
Secrete factors that kill virus-infected cells and tumour cells
Where are lymphocytes produced from and stored?
Lymphoid tissue
How are lymphocytes positioned?
Positioned to intercept invading organisms or toxins
What kind of cytokine up-regulates lymphocyte production?
Interleukins
Where do pro-T cells migrate to and are processed?
Thymus
Where are pro-B cells processed?
Liver and bone marrow
What generates a very high diversity of antigen specificity?
Genetic recombination
What part of individual cells develop specificity of different antigens?
Surface receptors
What part of individual cells develop specificity of different antigens?
Surface receptors
What cells target proteins in the host organism?
Self reacting cells
Are self-reacting cells entered into the circulatory system?
No, they are eliminated, and remaining cells migrate to and are stored in lymphoid tissues
What differentiates B cells and T cells when activated?
T cells will bind themselves to the cell (Cell-mediated immunity)
B-cells will secrete antigen-specific antibodies (humoral-mediated immunity)
What differentiates each T cell and B cell?
Specific surface antigens
What will macrophages do while breaking down a pathogen?
Present fragments of that pathogen on the cell surface to T cells and B cells
What cell does the same job as macrophages?
Dendritic cells
What percentage of T cells are Helper T cells?
75%
What do Helper T cells do?
Secrete Lymphokines
What do lymphokines do?
Promote growth of activated B cells
Stimulate cytotoxic and suppressor T cells
Activate macrophages
Feedback stimulation of helper cells
What virus inactivates or destroys helper T cells?
HIV
What cells target macro-organisms that are protein-tagged?
Cytotoxic t cells
What are suppressor t cells?
They dampen cytotoxic t cell acitvity
What is the role of suppressor t cells?
Dampen the cytotoxic t cell activity
What could the failure of suppressor t cells lead to?
Autoimmune diseases
What do Activated B cells differentiate into?
Immunoglobulin secreting plasma cells
Are the antigen-binding sites specific?
Yes, they bind to the same receptor that propagated them
What is different between antibodies?
Variable portion
What are the five classes of antibodies?
IgM
IgG
IgA
IgD
IgE
What is complement?
A collection of proteins that lie dormant in plasma until it is activated by one another
What will the antigen-antibody complex activate?
C, protein involved in the complement system
What is opsonisation?
Tagging of pathogen for phagocytosis
How is complement involved with the immune response?
They recruit WBCs to respond
What do memory cells do?
Plasma B cells or functional T cells that circulate in blood and lymphoid tissue as dormant cells
Subsequent exposure to the same antigen causes a more rapid and potent response
What are memory B cells converted to in subsequent exposure?
Plasma cells
What are memory T cells converted to in subsequent exposures?
Helper, cytotoxic, and suppressor T cells
What are memory cells the basis of?
Immunisation
What are the steps of haemostasis?
Vascular spasm
Platelet plug formation
Blood coagulation
What is vascular spasm?
Constriction of damaged blood vessels
What happens during platelet plug formation?
Platelets adhere to damaged endothelium to form platelet plug
What is blood coagulation?
Formation of solid blood clot at site of platelet plug
When does vascular constriction occur?
Trauma to blood vessels causing contraction of vascular smooth muscle
What is a local myogenic contraction?
Local contraction of smooth muscle
What is a local axon reflex?
The releasing of factors locally following pain or sensory receptors singaling near damaged vessel
What platelet cell type is also a vasoconstrictor?
Thromboxane A
Where are platelets produced from?
Megakaryocytes - platelets are cell fragments
Are nuclei present in platelets?
No but residual cell orgaenlles are
What is the lifespan of thrombocytes?
3-4 weeks
What eliminates thrombocytes from the circulatory system?
Macrophages
What is the role of platelets?
Adhere to exposed collagen fibres of damaged vessel walls and form a platelet plug
What plasma protein factor in thrombocytes triggers aggregation and adherence?
von Willebrand factor
What secondary factors trigger further aggregation/adherence of platelets?
The release of ADP and thromboxane A2 from the structural changes of other thrombocytes
What kind of reaction forms a stable fibrin clot?
Cascade reaction
What activates the cascade reaction of thrombocytes?
Inactive coagulation factors
What are the two pathways for the formation of a blood clot?
Extrinsic pathway and intrinsic pathway
What activates the extrinsic pathway?
Vessel/tissue trauma
What initiates the intrinsic pathway?
Blood factors
What is the result of the cascade reaction of thrombocytes?
Stable fibrin clot
What is the final step in clot formation?
The proteolytic conversion of fibrinogen to fibrin by thrombin
What does thrombin do?
Activates factor XIII which makes fibrin more rigid
What vitamin is involved in the coagulation cascade?
Vitamin K
What does the vitamin involved in the coagulation cascade do?
Vitamin K synthesises some clotting factors including prothrombin
What synthesises vitamin K in the intestinal tract?
Bacteria
What causes a vitamin K defiency?
Obstruction of bile ducts and/or liver disease
When is vitamin K usually administered to a patient?
Newborn as they have only half the adult clotting factors
What prevents contact activation of the intrinsic pathway?
Layer of glycocalyx
Thrombomodulin removes thrombin from plasma
What can the incorrect or over-activation of the intrinsic pathway lead to?
Clot formation occurring within blood in absence of damage
Can lead to myocardial infraction or stroke
What absorbs the majority of the thrombin?
The clot itself (fibrin)
What removes the remaining thrombin?
Antithrombin III
What is heparin’s function?
Endogenous protein that acts as an agonist of antithrombin II activity
What is heparin’s clinical usage?
Pharmacological anti-clotting factor
What is a better way to describe “blood-thinners”?
Anti-platelet drugs
Name 3 blood thinners
Aspirin (acetylsalicylic acid)
Prostacyclin
Dipyridamole
How does Acetylsalicylic acid work?
Blocks the production of thromboxane by inhibiting cyclooxygenase, inhibiting platelet aggregation in low doses over a long period of time
How does prostacyclin work?
Binds prostacyclin receptor on platelets, increases cAMP concentration, blocks the increase in calcium concentration caused by thromboxane receptor, blocking platelet aggregation
How does dipyridamole work?
Inhibits thromboxane synthase and phosphodiesterase which degrades cAMP, blocking platelet adherence
