Blood Flashcards

Question

Platelet Activation Regulation

Answer 1

* Platelets activated upon binding to collagen and laminin of damaged basement membrane * These are not exposed in healthy vessels * Healthy endothelial cells produce factors that inhibit platelet aggregation * Ex. **Prostacyclin** (PGI₂) from arachidonic acid

Answer 2

Inhibits cyclooxygenase activity. * Decreases platelet function * Prolongs bleeding times

Answer 3

* Most common bleeding disorder * Caused by deficiency of von Willebrand's factor * Results in abnormal platelet adhesion

Answer 4

* Due to deficiency of platelet receptor for von Willebrand's factor * Results in abnormal platelet adhesion

Answer 5

* Due to deficiency of platelet receptor for fibrinogen * Results in decreased of platelet aggregation

Answer 6

**Neutrophils, eosinophils, and basophils.** Characterized by: * Abundant cytoplasmic granules of 2 types: * _Azurophilic_ granules (primary) * small specialized lysosomes * _Specific_ _granules_ (secondary) * non-lysosomal secretory granules * Lobulated heterochromatic nucleus

Answer 7

**Lymphocytes and Monocytes** Characterized by: * Few azurophilic granules * No specific granules * Non-lobulated nucleus

Answer 8

* Process by which leukocytes leave the blood vessels by passing between endothelial cells * Requires specific interactions between molecules on plasma membrane of leukocyte and endothelium * Rate increases with inflammation * Due to histamine and chemoattractant molecules * Occurs most frequently in postcapillary venules 1. **Tethering** (weak adhesion) to the endothelium * Mediated by _L-selectins_ * Located on leukocytes * Receptors on endothelium 2. **Rolling** along the endothelium as weak interactions break and form again * Mediated by * _Integrins_ on leukocytes and their receptors on endothelium * _P-selectins_ and _E-selectins_ on inflamed endothelial cells and their receptors on leukocytes 3. **Arrest** as stronger interactions form 4. **Diapedesis**

Answer 9

**LAD 1**: lack of integrin expression of leukocytes. **LAD 2**: lack of leukocyte receptors for P & E selectins. Both result in: decreased diapedesis leukocytosis recurrent infections

Answer 10

* Migration along a concentration gradient of chemotactic factors * Positive = migration towards a greater concentration * Common * Negative = migration towards a lower concentration * Rare * After diapedesis leukocytes are guided to specific locations via chemotactic factors * WBCs can respond because they are motile

Answer 11

Different leukocytes respond to different factors. * Exogenous: * Bacterial peptides * Starts with **N-formyl-methionine** residues * Endogenous: * Some complement proteins * Ex **C5a** * Chemotactic cytokines (_chemokines_) * Ex. **IL-8**

Answer 12

* Induced by binding of activator molecules which are specific for each leukocyte type * Activator binding results in the synthesis and/or secretion of products specific for each leukocyte type ⇒ results in new or enhanced cell functions * Results in killing of microorganisms and contributes to inflammatory/immune reactions by altering behavior of other cell types. * Products carry out specific functions which fit into 3 broad categories: * _Respiratory burst_ * increased oxygen intake * production of reactive oxygen and nitrogen species which are microbicidal * ex. O₂^-, H₂O₂, HOCl^- * _Degranulation_ * release of mediators from azurophillic or specific granules * Ex. myeloperoxidase and lysozymes * _Synthesis and release_ of new mediators * Membrane lipid derivatives (usually arachidonic acid) * Ex. prostaglandins, leukotrienes * Cytokines * Proteins/peptides that affect the behavior of other cells

Answer 13

Compound which is secreted by lymphocytes and affects other lymphocytes or itself.

Answer 14

A secreted protein/peptide which influences the behavior of leukocytes.

Answer 15

1. Extent of nuclear lobulation * neutrophils 3-5 lobes * eosinophils 2-3 lobes * basophils 2 poorly defined lobes 2. Specific granules by LM * neutrophils have small & poorly staining specific granules * eosinophils have large eosinophilic specific granules * basophils have large basophilic specific granules * these often obscure the nuclear outline

Answer 16

* Very similar function to mast cells * After activation, release preformed and newly synthesized mediators that: * Increase vascular permeability and aid diapedesis * Are chemotactic for other cells types (especially eosinophils) * Excessive activation can cause certain allergies (Type 1 hypersensitivity reactions)

Answer 17

* Least lobulated nucleus of all granulocytes * Heterochromatic * Specific granules: * Intensely basophilic with Romanovsky stains * Can be metachromatic with toluidine blue * Appear grainy or like whorls of membrane by EM ⇒ _myelin figures_ (not really myelin)

Answer 18

* **Activation by immunoglobulin E (IgE)** 1. IgE made by plasma cells during first exposure to antigen (primary immune response) 2. IgE binds to receptors on basophils that are specific for its F_c portion 3. Basophils now primed (armed) 4. If antigen is subsequently encountered it binds to the IgE on basophils 5. Crosslinking of IgE molecules causes basophil activation * Other mechanisms independent of IgE * Binding of certain complement fragments to their receptors on basophil membrane * C3a * C5a

Answer 19

1. **Degranulation** * _Histamine_ * increases vascular permeability * _ECF_ (eosinophil chemotactic factor) * _NCF_ (neutrophil chemotactic factor) * _Proteases_ * helps break down ECM & facilitate WBC movement 2. Synthesis and secretion of **cytokines** * _IL-4_ * _IL-13_ 3. Activation of **phospholipases** that cleave basophil membrane lipids and convert them into: * _Platelet Activating Factor (PAF)_ * Not from arachidonic acid * Histamine like * _Leukotriene C4 (LTC4)_ * Arachidonic acid derivative * Histamine like * Takes longer to appear but lasts longer than histamine

Answer 20

1. **Vasodilation & increased vascular permeability** * Endothelial cells retract from one another forming gaps * Mediated by histamine, PAF, and LTC4 * Increased permeability leads to edema * Facilitates movement of WBCs, Ab, complement proteins etc to areas of need 2. **Contraction of airway smooth muscles** * Bronchioles most effected = bronchoconstriction * Mediated by LTC4 and histamine * Narrowing airway increases air flow velocity making coughs more effective * Excessive effects results in restrictions in airflow 3. **Increased mucus secretion** * By goblet cells and mucous glands * Mediated by histamine * Helps trap antigens * Excessive effects clogs bronchiolar lumens & causes nasal congestion 4. **B-lymphocyte class switching** * Causes activated B-lymphocytes to stop producing other classes of Ab and switch to IgE 5. **Chemotaxis of eosinophils/neutrophils** * Mediated by ECF and NCF 6. **Itch (Pruritis)** * Mediated by histamine

Answer 21

Immediate Hypersensitivities Caused by excessive basophil and/or mast cell activation. * Hay Fever * Asthma * Urticaria * Anaphylaxis

Answer 22

* Systemic activation of basophils and/or mast cells * Results in massive degranulation * Can result in fatal hypovolemic shock (anaphylactic shock) * Most often occurs in response to particular antigens * Drugs * Foods * Insect stings * There may be some genetic predisposition

Answer 23

* Nucleus usually bi-lobed (maybe 3) and heterochromatic * Contains azurophilic granules * Many large specific granules * Eosinophilic & sometimes refractile by LM * Irregular crystalloid embedded in an amorphous matrix by EM * Crystalloid made up by major basic protein (MBP)

Answer 24

* IL-5 stimulates eosinophil maturation in bone marrow and secretion into blood * Normally circulate in the blood for several hours * Responds to many chemotactic factors * IL-5 * Eotaxin * Made by epithelial cells especially in the respiratory and GI tract * Histamine * ECF * Can survive an additional 8-12+ days in CT * 100-1000 times more common in extravascular tissues than blood * Esp. lamina propria and respiratory tract * Die by apoptosis

Answer 25

* Can be activated by many stimuli * Ex. cross-linking of IgA bound to their plasmalemma

Answer 26

* Cleave membrane lipids and synthesize mediators * LTC₄ and PAF * Undergo a respiratory burst and produce reactive oxygen and nitrogen species * Degranulate * Synthesize and secrete many cytokines

Answer 27

1. Kill larvae of certain parasitic worms (helminths) by binding to their surface and secreting substances that damage them * From specific granules * Major basic protein (MBP) in the crystalloid * Eosinophil cationic protein (ECP) * Eosinophil peroxidase (EPO) * Eosinophil-derived neurotoxin (EDN) * From respiratory burst * Nitric oxide (NO) * Hydrogen peroxide (H₂O₂) 2. Phagocytize and destroy antigen-antibody complexes * Prevents excessive activation of complement * Poorly phagocytic cells otherwise 3. Modulate basophil and mast cell activity * Release enzymes from specific granules that can destroy mediators released from activated basophils/mast cells * Ex. Histaminase * Major basic protein activates basophils and mast cell * Can have either stimulatory or inhibitory effects on mast cells and basophils * May be explained by eosinophil's ability to release different mediators in response to different stimuli ⇒ piecemeal degranulation

Answer 28

Eosinophils contribute to chronic lung damage in asthma. * Attracted to lungs by chemotactic factors including eotaxin from bronchiolar epithelium * Activated and release mediators that kill bronchiolar epithelial cells * MBP * ECP * Decrease in # of ciliated cells interferes with clearance of mucus from the airway * LTC₄ and PAF cause bronchoconstriction and vasodilation that leads to airway edema * MBP also affects airway smooth muscle making it hyper-reactive to mediators that cause contriction

Answer 29

1. Highly phagocytic cells * Specialized for bacteria 2. Promote inflammation by secreting mediators * IL-1: pyrogen which causes a fever by acting on temperature-regulating area of hypothalamus 3. Abundant in anemias associated with Vit B₁₂ or folate deficiency

Answer 30

* Heterochromatic nucleus * 2-5 lobes (usually 3) connected by thin strands * More than 5 lobes = hypersegmented neutrophils * In females, inactivated X-chromosome (Barr body) forms a drumstick-like appendage visible in some nuclei * Small and inconspicous azurophillic and specific granules

Answer 31

1. Large reserve of mature neutrophils exists in bone marrow * Azurophilic granules (primary granules) formed first in the bone marrow during differentiation only * Contains _myeloperoxidase_ (MPO) which can be used in histochemistry * Specific granules (secondary granules) are made second in the bone marrow 2. Rapidly mobilized when stimulated by IL-1 & IL-6 3. Half-life in blood ~ 12 hours 4. Leaves vessels via diapedesis 5. Shows positive chemotaxis towards: * Complement fragments such as C5a * N-formyl methionyl peptides 6. Activation induced by many stimuli * Including act of phagocytosis 7. Activated neutrophils: * Undergo respiratory burst * Release mediators from granules * Synthesize and secrete new cytokines 8. Activated neutrophils die by apoptosis * Dead neutrophils and damaged tissue are major components of pus * Pus is removed by macrophages

Answer 32

Rate of phagocytosis greatly increased by binding the particle to the neutrophil plasma membrane. Two methods for binding: 1. **Pathogen-associated molecular patterns (PAMPs)** * Highly conserved molecular configurations on the surface of pathogenic particles * Found on bacteria * Pattern recognition receptors (PRRs) on the neutrophils (& macrophages) bind to the PAMPs 2. **Opsonization** * Opsonins are extrinsic molecules that bind to pathogenic particles * Specific receptors on neutrophils & macrophages recognize each oposin * Opsonins act as bridges that physically bind the particle and the phagocyte together * Common opsonins: * **IgG** antibodies specific for antigens on the particle * Recognized by neutrophil Fc receptors for IgG * **C3b** fragment of the C3 complement protein * Produced during complement activation * C3b recognized by C3b receptors on the neutrophil

Answer 33

The Respiratory Burst * A measurable increase in oxygen consumption that is triggered by phagocytosis * Multi-step enzymatic process (cascade) * Phagocytosis causes polymerization and activation of the cytoplasmic & membrane bound _NADPH oxidase_ which catalyzes the first step in ROS production * Results in the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) * ROS/RNS kill microbes by reacting with microbial macromolecules, especially lipids & DNA * Includes: * _Superoxide anion radical_ (O₂^-) produced from O₂ by NADPH oxidase * _Hydrogen peroxide_ (H₂O₂) produced from O₂^- by superoxide dismutase * _Hypochlorous acid_ (HOCl) produced from (H₂O₂) by the myeloperoxidase of azurophilic granules * HOCl dissociates to form _hypochlorite_ (OCl^-)

Answer 34

* Caused by genetic defects in any 4 of the NADPH oxidase subunits * Characterized by a decreased or absent respiratory burst * Leads to recurrent bacterial and fungal infections * Shortened life expectancy

Answer 35

Contributes antimicrobial mediators: 1. **Myeloperoxidase** * Catalyzes production of HOCl from H₂O₂ during the later stages of respiratory burst 2. **Bactericidal permeability-increasing protein** (BPI) * Damages membranes of gram-negative bacteria 3. **Lysozyme** * Enzyme that attacks cell walls of bacteria, especially gram-positive 4. **Defensins** * Small cationic proteins that permeabilize bacterial membranes, probably by forming pores

Answer 36

Contributes: 1. **Lysozyme** * Present in azurophilic & specific granules * Attacks cell walls of bacteria, especially gram-positive 2. **Lactoferrin** * Bacteriostatic protein that competes with bacteria for iron and copper which are required for bacterial replication

Answer 37

* Genetic defect in the targeting of proteins to azurophilic granules * Leaves granules without the contents necessary to kill bacteria * Neutrophils contain abnormally large vacuoles resulting from fusion of azuorphilic granules with one another * Easily seen by LM * Often fatal in childhood

Answer 38

* Neutrophils can damage healthy tissues. * During phagocytosis neutrophils partially release granule contents into the extracellular space * Can cause significant damage to healthy tissues nearby * Examples: * Elastase from azurophilic granules * Type IV collagenase from specific granules

Answer 39

1. **Leukocytosis** * An increase in the number of circulating neutrophils * Due to neutrophils leaving bone marrow in greater numbers than usally seen * Used as a clinical marker of infection 2. **"Shift to the left" phenomenon** * Distribution of neutrophils by age in the plasma is shifted towards more immature forms

Answer 40

1. **Edema** * Due to vessels made leaky by histamine and other mediators 2. **Neutrophils arrive within 1 day** 1. Typical of the acute phase 3. **Monocytes arrive in a second wave of leukocytes around day 2** * Neutrophils secrete chemotactic factors that attract monocytes 4. **Monocytes differentiate into macrophages** * Typical of late phase of inflammation * Macrophages phagocytize dead neutrophils

Answer 41

* Considered monocytes in the blood * Can circulate for several hours to days (~12-100 hours) * Migrate out of vessels by diapedesis * Differentiation into macrophages can be during diapedesis and finishes in extravascular tissues

Answer 42

* Largest leukocyte * Irregularly shaped nucleus but not lobulated * Can be horseshoe shaped or folded on itself * Lacy chromatin with sharp boundaries between euchromatin and heterochromatin * Abundant paler staining cytoplasm * Few azurophilic granules * No specific granules * Large pale vacuoles * Well-developed Golgi * **Can produce Azurophilic granules throughout the monocyte lifespan unlike neutrophils**

Answer 43

Macrophages and related cells which derive from monocytes. * **Histiocytes**: ordinary macrophages in CT * **Kupffer cells**: in the liver * **Alveolar macrophages** (dust cells): in alveoli of the lung * **Microglia**: in the brain * **Mesangial cells**: in the kidneys

Answer 44

* Larger and more phagocytic than monocytes * Best recognized by presence of phagocytized material in cytoplasm * By EM have more: * Phagosomes * Secondary lysosomes * Plasma membrane pseudopods * Irregular nucleus * Can live for several months in extravascular tissues

Answer 45

**Classical Pathway** * Leads to productions of mediators that stimulate inflammation * Induced by many stimuli including: * Interferon-γ (IFN-γ) from the T_H1 subset of T-helper cells * Classically activated macrophages increase in size and become more efficient in their activities (eg phagocytosis, secretion, etc) **Alternative Activation** * Leads to production of anti-inflammatory mediators * Induced by stimuli including: * IL-4 and IL-13 from T_H2 subset of T-helper cells * Phagocytosis of apoptotic cells

Answer 46

* Can enlarge and congregate into groups to become **epithelioid cells** * Can fuse to form multinucleated **giant cells** * Stimulated by IFN-γ * Can occur when macrophages encounter an object too large to phagocytize alone

Answer 47

1. Functions in killing microorganisms 2. Adapted for specilaized functions: * Removal of apoptotic cells * Recognized by the presence of phosphatidylserine (PS) on the outer leaflet of apoptotic cell plasma membrane * Examples: * Apoptotic neutrophils in inflammation * Apoptotic lymphocytes in the lymphoid tissue

Answer 48

Phagocytosis can be enhanced by: * Opsonins * Pattern recognition receptors (PRRs) on the macrophage * Macrophage class A scavenger receptor: recognizes modified forms of LDLs

Answer 49

When excessive accumulation of LDLs occurs in macrophages causing them to become "foam cells" in atherosclerotic lesions of arterial walls.

Answer 50

Monocytes & macrophages can act as antigen presenting cells (APCs) to help activate T-helper (T_H) cells. 1. Take up antigen by endocytosis. 2. Partially degrade antigen in phagolysosomes leaving some peptide fragments intact. 3. Peptides bind to major histocompatibility II (MCHII) proteins that are part of the vacuolar membrane. 4. Vacuoles fuse with the plasma membrane, delivering the peptide/MHC-II complex to the cell surface where it can activate T_H cells

Answer 51

Monocytes & Macrophages secrete productions that regulation processes other than inflammation: * **Colony-stimulating factors** (GM-CSF, G-CSF, M-CSF) that promote hematopoiesis * **Proteases** important in normal turnover of ECM * _Collagenases_ * _Elastase_ * **Growth factors** important in wound healing * _Tumor necrosis factor_ (TNF) stimulates fibroblasts * _Transforming growth factor_ (TGF) stimulates keratinocytes

Answer 52

* Lymphocytes represent 25-30% of blood WBC's but 99% of lymph WBC's. * Major cell type of immune system * Undergo diapedesis mainly from high endothelium venules (HEVS) * Many lymphocytes recirculate into the blood after leaving HEVs and entering lymphatic capillaries * Constantly travel throughout the body "patrolling" for antigens and presenting to cells in lymphoid tissues ⇒ **immune surveillance**

Answer 53

* Post-capillary venules with cuboidal to collumar endothelial cells * Typical of lymph nodes and certain other lymphoid tissues/organs * Only lymphocytes can cross the walls of HEVs

Answer 54

Can exist as small, medium, or large lymphocytes depending on activation state. Undergo blast transformation after activation. * Small lymphocytes * Account for \> 90% in the blood * Currently inactive * Round or kidney bean heterochromatic nucleus * Very thin rim of "sky blue" cytoplasm * Large lymphocytes * More euchromatic nucleus with "smudged" pattern by LM * Cytoplasm increases

Answer 55

* When activated by the immune response small lymphocytes increase in size and divide to form medium and large lymphocytes (lymphoblasts). * Immunoblasts then divide to form a clone of cells. * From clones, various effector cells develop and carry out the immune response. * Example: Plasma cells are effector cells derived from activated B lymphocytes.

Answer 56

Immune reactions that require live lymphocytes. Immunity cannot be transferred passively from one individual to another by plasma alone.

Answer 57

Required for cell-mediated immunity Can be divided into several subclasses: T helper cells T cytotoxic cells

Answer 58

* Carry CD4⁺ surface markers * Effector cells derived from activated T_H cells * Function by secreting cytokines * Two subsets which secrete different cytokines: * T_H1 cells * T_H2 cells

Answer 59

Carry CD8⁺ surface marker Effector cells derived from activated T_c cells are called **cytotoxic T lymphocytes (CTL).** * CTL can lyse some altered-self cells * Virus-infected cells * Tumor cells * Genetically different cells in a tissue graft * CTL recognizes antigens on target cells * Killing requires binding of CTL to target cell * One method by which CTL kill target cells involves secretion of: * **Perforin**: protein that aggregates to form pores in the targe cell membrane * Proteases called **granzymes** (fragmentins) that enter target cells through the pores and induces apoptosis

Answer 60

Immune reactions that require antibodies. Immunity can be transferred passively from one individual to another by the antibodies alone. Does not require transfer of live plasma cells.

Answer 61

* Major cell type in humoral (antibody-mediated) immunity * Plasma cells are effector cells derived from activated B-cells

Answer 62

* Effector cells derived from activated B-cells * Secrete antibodies * Are relatively short-lived (10-30 days) * Old plasma cells become **Russell body cells** * Contain large distended RER cisternae called _Russell bodies_ * Full of antibody and stain very eosinophillic

Answer 63

* Do not carry CD4 or CD8 on their plasma membranes * Make up 5-10% of lymphocytes in peripheral blood * Functions to kill target cells * Virus-infected cells * Tumor cells * Uses some of the same mediators as CTL (perforins and granzymes) * Recognize target cells via different mechanisms than CTL * Previously called large granular lymphocytes (LGLs) due to large diameter and high content of azurophillic granules obvious by LM

Blood Flashcards

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