P: White blood cells and Haemostasis Flashcards
Innate responses
General processes against infectious agents
- Skin, phagocytosis of micro-organisms, destruction by stomach acids/enzymes, hydrolytic enzymes released by immune cells
Adaptive responses
Directed against specific infectious agents
- Improved on repeated exposure of the same infection
Subtypes of leukocytes
Nucleated cells
- Monocytes
- Eosinophils
- Neutrophils
- Lymphocytes
- Basophils
M+E+N = phagocytosis
B = release hydrolytic enzymes + histamine
Granulocytes
Neutrophils, Eosinophils, Basophils (BEN)
- Multiple nuclei of varying shapes
- Other name = polymorphonuclear leukocytes (PMN/PML)
Where do granulocytes originate from (what cells)?
Myelocytes (bone marrow precursor cells)
Genesis of myelocytes:
- Under ___ control
- Large ___ in bone marrow
- Marrow has 10x more ___ cells than ___ cells (RBC precursors)
- cytokine
- reserve pool
- myeloid, erythroid
Rank granulocytes from most to least common
Neutrophils > Eosinophils > Basophils
Neutrophils:
- ___ in blood and tissues
- Circulate in ___ —> migrate into ___ (squeeze through capillaries pores = ____)
- Numbers increase +++ during ___
- ___ immunity
- Phagocytosis
- blood, tissues, diapedesis
- infection
- Innate
Eosinophils:
- Weakly ___: attack ___ too large to be engulfed (attach to them and secrete ___ enzymes)
- Can reverse tissue damage during ___
- phagocytic, parasites, hydrolytic
- allergic reactions
Basophils:
- ____, but act like eosinophils to release ___
- Contribute to ___ by release of chemicals (histamine, heparin, bradykinin, serotonin, lysosomal enzymes, slow-reacting substance of anaphylaxis)
- Non-phagocytic, hydrolytic enzymes
- allergic reactions
Monocytes:
- Circulate in blood for hours before migrating into tissues where they ___ and develop ___
- ___ infectious agents and abnormal/dying cells (including RBCs) only in tissues
- increase in size +++, tissue macrophages
- Phagocytose
Which leukocytes act in innate immunity vs acquired immunity?
Innate: monocytes, eosinophils, neutrophils, basophils and NK cells (lymphocytes)
Acquired: lymphocytes
What’s the largest leukocyte
Monocytes
What is the system name of the collective monocytes?
Reticuloendothelial system
Where are macrophages especially prominent in?
- Lymph nodes
- Lung alveolar walls
- Liver sinusoidal capillaries
- Red pulp of spleen
What is chemotaxis?
Recruitment of neutrophils + macrophages to tissue inflammation/infection
What’s the first line of defence?
Local macrophages
What do the secreted factors of activated macrophages promote?
Production of granulocytes and monocytes
Different stages of inflammation
- Rapid neutrophilia (large production of neutrophils by bone marrow)
- Increased monocyte production/recruitment and tissue macrophage buildup (hours-days)
- Macrophages = superior phagocytic cells (longer to regulate and transport to site of infection, but more powerful)
Natural Killer (NK) cells:
- Produced from ___
- Specifically target ___ and ___ infected cells
- Induce programmed cell death (___)
- Activated by ___ or macrophage-derived ___
- lymphoid lineage
- tumour, virus
- apoptosis
- interferons, cytokines
Subtypes of lymphocytes
- B lymphocytes: mature into plasma cells and secrete antibodies
- T lymphocytes: Helper T cells secrete cytokines to activate other leukocytes. Cytotoxic T cells secrete factors that kill tumour and virus-infected cells
- NK cells: secrete factors that kill tumour and virus-infected cells
Where are lymphocytes produced and stored?
Lymphoid tissue (lymph, glands, spleen, thymus, tonsils, bone marrow and Peyer’s patches in intestinal epithelium)
What drives the growth and differentiation of lymphocytes?
Various cytokines like interleukins (ILs)
Where are Pro-T and Pro-B cells processed before and after birth?
Pro-T cells: thymus gland
Pro-B cells: liver and bone marrow
What causes the very high diversity of antigen specificity?
Genetic recombination
What happens to “self” reacting cells in lymphocyte processing?
They’re eliminated –> remaining cells migrate to and are stored in lymphoid tissues
What mediates the immunity of T and B cells?
T: ___-mediated
B: ___-mediated
T: cell-mediated
B: humoral-mediated
Major histocompatibility complex:
- ___ + ___ cells phagocytose microorganisms + present antigenic fragments on cell surface to nearby ___
- Binding of ___ to specific cell surface ____ on lymphocytes activates these specific cells only
- Activated lymphocytes ___ rapidly - large numbers of a clone of lymphocytes released into circulation
- Macrophages secrete ___ which promotes specific clonal growth
- Macrophage, dentritic, lymphocytes
- antigens, receptors
- reproduce
- IL-1
Helper T lymphocytes:
- 75% of T-cells secrete ___ (IL-2 to 6)
- Promote growth of ___
- Stimulation of ___ and ___ cells
- Activation of ___
- ___ of helper cells
- ___ destroys helper T cells
- lymphokines
- activated B cells
- cytotoxic and suppressor T cells
- macrophages
- Feedback stimulation
- HIV
Cytotoxic T cells
- Killer cells
- Destroy micro-organisms containing activating antigen (virus infected, cancer and transplanted cells)
Suppressor T cells
- Prevent damage of ___ by ___
- ___ tolerance
- Failure = ___ diseases
- tissues, cytotoxic cells
- Immune
- autoimmune diseases
B lymphocytes:
- Activated B cells differentiate into ___ (___) secreting plasma cells
- Same specificity as B cell receptor is activated by the ___ = membrane-bound ___
- antibody (immunoglobulin)
- antigen, immunoglobulin
What’s a complement?
- A ___ protein ___ in plasma, activated by ___ complexes
- Constant portion of antibody activates ___
- ___ of sequential reactions with ____ at each stage
- Activated products ___ next component and stimulate ___
- ___: tagging of pathogen for pathogenesis
- Cell ___
- ~20, cascade, antibody-antigen
- C1
- cascade, amplification
- activate, innate immunity
- Opsonisation
- lysis
Primary response
- Small number of activated B and T cells become memory cells
- Circulate in blood and lymphoid tissue as dormant cells
Secondary response
- B cells become plasma cells
- T cells become helper, cytotoxic and suppressor T cells
Steps of haemostasis
- Vascular spasm: constriction damaged blood vessels
- Platelet plug formation: platelets adhere to damaged endothelium to form platelet plug
- Blood coagulation: formation of solid blood clot at site of platelet plug
Vascular constriction
Trauma to blood vessels causes contraction of vascular smooth muscle:
- Local myogenic contraction
- Local axon reflexion initiated by pain/sensory receptors at/near damaged vessels
- Local platelets in blood release thromboxane A (vasoconstrictor substance)
Platelets
- ~4000 platelets produced from each ___ in bone marrow
- No ___
- Synthesize various factors that act on ___ + local blood vessels and tissue
- megakaryocyte
- nucleus
- plasma proteins
What eliminates platelets from circulation?
Macrophages mainly in spleen
Formation of platelet plug
- Platelets adhere to exposed ___ fibre of damaged ___ and form a platelet plug
- Plasma protein (___ factor) triggers ___ and ___ of platelets to one another and to sites of vascular damage
- Platelets are structurally changed and release ___ + ___ –> trigger further ___/___
- Formation of a ___ platelet plug
- collagen, vessel walls
- von Willebrand, adherence, aggregation
- ADP, thromboxane A2, adherence/aggregation
- loose
Formation of blood clot:
- Inactive ___ factors are activated in a cascade reaction
- ___ pathways: activated by ___/___ trauma
- ___ pathway: initiated by ___
- End stage = production of a stable ___ meshwork (blood clot) –> stabilizes temporary platelet plug
- coagulation
- extrinsic, vessel/tissue
- intrinsic, blood factors
- fibrin
Coagulation cascade:
- Last step in clot formation = ___ conversion of ___ to ___ by ___
- Loose ___ stabilized by formation of covalent bonds catalysed by ____ which is activated by ___
- Thrombin has a ___ on prothrombin = ___ feedback
- proteolytic, fibrinogen, fibrin, thrombin
- fibrin meshwork, coagulation factor XIIIa, thrombin
- proteolytic, positive
Vitamin K:
- Needed for hepatic synthesis of ___ e.g. ___
- Deficiencies leads to ___
- Synthesised by bacteria in ___
- Vitamin K deficiency caused by obstruction of ___ and/or ___ disease
- Newborns lack ____ –> contain 50% of adult clotting factors so vitamin K is administered at birth.
- clotting factors e.g. prothrombin
- serious bleeding tendencies
- intestinal tract
- bile ducts, liver
- intestinal bacterial flora
Feedback inhibition by formation of fibrin:
- 85-90% of ___ formed from ___ is absorbed to ___
- ___ binds + removes remaining ___
- Cessation of ____
- thrombin, prothrombin, fibrin
- Antithrombin III, thrombin
- clotting cascade
Intravascular anticoagulants: to stop contact activation of intrinsic pathway, ____
- layer of glycocalyx on endothelium
- thrombomodulin binds + removes thrombin from plasma.
Heparin:
- Activates ___
- Removes ___ + ___
- Used as ___ agent
- Antithrombin III
- free thrombin + upstream factors
- anti-clotting
Aspirin
- Blocks production of ___ by inhibiting ____
- Long-term aspirin inhibits ___
- thromboxane, enzyme cyclooxygenase
- platelet aggregation
Prostacyclin:
- binds ___ on platelets
- increases ___
- blocks increase in ___ caused by ___
- Blocks ___
- prostacyclin receptor
- intracellular [cAMP]
- intracellular [Ca2+], thromboxane receptor
- platelet aggregation/adherence
Dipyridamole:
- inhibits ___ + ___ which degrades ___
- blocks ___
- thromboxane synthase, phosphodiesterase, cAMP
- platelet aggregation/adherence
