P: White blood cells and Haemostasis

Question 1

Innate responses

Answer 1

General processes against infectious agents
- Skin, phagocytosis of micro-organisms, destruction by stomach acids/enzymes, hydrolytic enzymes released by immune cells

Question 2

Adaptive responses

Answer 2

Directed against specific infectious agents
- Improved on repeated exposure of the same infection

Question 3

Subtypes of leukocytes

Answer 3

Nucleated cells
- Monocytes
- Eosinophils
- Neutrophils
- Lymphocytes
- Basophils

M+E+N = phagocytosis
B = release hydrolytic enzymes + histamine

Question 4

Granulocytes

Answer 4

Neutrophils, Eosinophils, Basophils (BEN)
- Multiple nuclei of varying shapes
- Other name = polymorphonuclear leukocytes (PMN/PML)

Question 5

Where do granulocytes originate from (what cells)?

Answer 5

Myelocytes (bone marrow precursor cells)

Question 6

Genesis of myelocytes:
- Under ___ control
- Large ___ in bone marrow
- Marrow has 10x more ___ cells than ___ cells (RBC precursors)

Answer 6

• cytokine
• reserve pool
• myeloid, erythroid

Question 7

Rank granulocytes from most to least common

Answer 7

Neutrophils > Eosinophils > Basophils

Question 8

Neutrophils:
- ___ in blood and tissues
- Circulate in ___ —> migrate into ___ (squeeze through capillaries pores = ____)
- Numbers increase +++ during ___
- ___ immunity

Answer 8

• Phagocytosis
• blood, tissues, diapedesis
• infection
• Innate

Question 9

Eosinophils:
- Weakly ___: attack ___ too large to be engulfed (attach to them and secrete ___ enzymes)
- Can reverse tissue damage during ___

Answer 9

• phagocytic, parasites, hydrolytic
• allergic reactions

Question 10

Basophils:
- ____, but act like eosinophils to release ___
- Contribute to ___ by release of chemicals (histamine, heparin, bradykinin, serotonin, lysosomal enzymes, slow-reacting substance of anaphylaxis)

Answer 10

• Non-phagocytic, hydrolytic enzymes
• allergic reactions

Question 11

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

Answer 11

• increase in size +++, tissue macrophages
• Phagocytose

Question 12

Which leukocytes act in innate immunity vs acquired immunity?

Answer 12

Innate: monocytes, eosinophils, neutrophils, basophils and NK cells (lymphocytes)
Acquired: lymphocytes

Question 13

What’s the largest leukocyte

Answer 13

Monocytes

Question 14

What is the system name of the collective monocytes?

Answer 14

Reticuloendothelial system

Question 15

Where are macrophages especially prominent in?

Answer 15

• Lymph nodes
• Lung alveolar walls
• Liver sinusoidal capillaries
• Red pulp of spleen

Question 16

What is chemotaxis?

Answer 16

Recruitment of neutrophils + macrophages to tissue inflammation/infection

Question 17

What’s the first line of defence?

Answer 17

Local macrophages

Question 18

What do the secreted factors of activated macrophages promote?

Answer 18

Production of granulocytes and monocytes

Question 19

Different stages of inflammation

Answer 19

1. Rapid neutrophilia (large production of neutrophils by bone marrow)
2. Increased monocyte production/recruitment and tissue macrophage buildup (hours-days)
3. Macrophages = superior phagocytic cells (longer to regulate and transport to site of infection, but more powerful)

Question 20

Natural Killer (NK) cells:
- Produced from ___
- Specifically target ___ and ___ infected cells
- Induce programmed cell death (___)
- Activated by ___ or macrophage-derived ___

Answer 20

• lymphoid lineage
• tumour, virus
• apoptosis
• interferons, cytokines

Question 21

Subtypes of lymphocytes

Answer 21

1. B lymphocytes: mature into plasma cells and secrete antibodies
2. T lymphocytes: Helper T cells secrete cytokines to activate other leukocytes. Cytotoxic T cells secrete factors that kill tumour and virus-infected cells
3. NK cells: secrete factors that kill tumour and virus-infected cells

Question 22

Where are lymphocytes produced and stored?

Answer 22

Lymphoid tissue (lymph, glands, spleen, thymus, tonsils, bone marrow and Peyer’s patches in intestinal epithelium)

Question 23

What drives the growth and differentiation of lymphocytes?

Answer 23

Various cytokines like interleukins (ILs)

Question 24

Where are Pro-T and Pro-B cells processed before and after birth?

Answer 24

Pro-T cells: thymus gland
Pro-B cells: liver and bone marrow

Question 25

What causes the very high diversity of antigen specificity?

Answer 25

Genetic recombination

Question 26

What happens to "self" reacting cells in lymphocyte processing?

Answer 26

They're eliminated --> remaining cells migrate to and are stored in lymphoid tissues

Question 27

What mediates the immunity of T and B cells? T: ___-mediated B: ___-mediated

Answer 27

T: cell-mediated B: humoral-mediated

Question 28

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

Answer 28

- Macrophage, dentritic, lymphocytes - antigens, receptors - reproduce - IL-1

Question 29

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

Answer 29

- lymphokines - activated B cells - cytotoxic and suppressor T cells - macrophages - Feedback stimulation - HIV

Question 30

Cytotoxic T cells

Answer 30

- Killer cells - Destroy micro-organisms containing activating antigen (virus infected, cancer and transplanted cells)

Question 31

Suppressor T cells - Prevent damage of ___ by ___ - ___ tolerance - Failure = ___ diseases

Answer 31

- tissues, cytotoxic cells - Immune - autoimmune diseases

Question 32

B lymphocytes: - Activated B cells differentiate into ___ (___) secreting plasma cells - Same specificity as B cell receptor is activated by the ___ = membrane-bound ___

Answer 32

- antibody (immunoglobulin) - antigen, immunoglobulin

Question 33

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 ___

Answer 33

- ~20, cascade, antibody-antigen - C1 - cascade, amplification - activate, innate immunity - Opsonisation - lysis

Question 34

Primary response

Answer 34

- Small number of activated B and T cells become memory cells - Circulate in blood and lymphoid tissue as dormant cells

Question 35

Secondary response

Answer 35

- B cells become plasma cells - T cells become helper, cytotoxic and suppressor T cells

Question 36

Steps of haemostasis

Answer 36

1. Vascular spasm: constriction damaged blood vessels 2. Platelet plug formation: platelets adhere to damaged endothelium to form platelet plug 3. Blood coagulation: formation of solid blood clot at site of platelet plug

Question 37

Vascular constriction

Answer 37

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)

Question 38

Platelets - ~4000 platelets produced from each ___ in bone marrow - No ___ - Synthesize various factors that act on ___ + local blood vessels and tissue

Answer 38

- megakaryocyte - nucleus - plasma proteins

Question 39

What eliminates platelets from circulation?

Answer 39

Macrophages mainly in spleen

Question 40

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

Answer 40

- collagen, vessel walls - von Willebrand, adherence, aggregation - ADP, thromboxane A2, adherence/aggregation - loose

Question 41

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

Answer 41

- coagulation - extrinsic, vessel/tissue - intrinsic, blood factors - fibrin

Question 42

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

Answer 42

- proteolytic, fibrinogen, fibrin, thrombin - fibrin meshwork, coagulation factor XIIIa, thrombin - proteolytic, positive

Question 43

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.

Answer 43

- clotting factors e.g. prothrombin - serious bleeding tendencies - intestinal tract - bile ducts, liver - intestinal bacterial flora

Question 44

Feedback inhibition by formation of fibrin: - 85-90% of ___ formed from ___ is absorbed to ___ - ___ binds + removes remaining ___ - Cessation of ____

Answer 44

- thrombin, prothrombin, fibrin - Antithrombin III, thrombin - clotting cascade

Question 45

Intravascular anticoagulants: to stop contact activation of intrinsic pathway, ____

Answer 45

- layer of glycocalyx on endothelium - thrombomodulin binds + removes thrombin from plasma.

Question 46

Heparin: - Activates ___ - Removes ___ + ___ - Used as ___ agent

Answer 46

- Antithrombin III - free thrombin + upstream factors - anti-clotting

Question 47

Aspirin - Blocks production of ___ by inhibiting ____ - Long-term aspirin inhibits ___

Answer 47

- thromboxane, enzyme cyclooxygenase - platelet aggregation

Question 48

Prostacyclin: - binds ___ on platelets - increases ___ - blocks increase in ___ caused by ___ - Blocks ___

Answer 48

- prostacyclin receptor - intracellular [cAMP] - intracellular [Ca2+], thromboxane receptor - platelet aggregation/adherence

Question 49

Dipyridamole: - inhibits ___ + ___ which degrades ___ - blocks ___

Answer 49

- thromboxane synthase, phosphodiesterase, cAMP - platelet aggregation/adherence