P: White blood cells & haemostasis Flashcards
(37 cards)
1
Q
Innate response
A
general processes against infectious agents
2
Q
Adaptive response
A
directed response against specific infectious agents.
3
Q
Leukocytes
A
4-10 x 10^9 cells/L
Nucleated cells with 5 subtypes:
- Neutrophils (phagocytosis)
- Eosinophils (phagocytosis)
- Monocytes (phagocytosis)
- Basophils (released hydrolytic enzymes from cytoplasmic granules + histamine)
- Lymphocytes
4
Q
Granulocytes
A
- Neutrophils, eosinophils, basophils
- Granules visible in cytoplasm
- Called polymorphonuclear leukocytes. (PMN or PML)
- Multiple nuclei of varying shapes
- Originate from bone marrow precursor cells: myelocytes
5
Q
Genesis of myelocytes
A
- Under cytokine control
- 6-10 days in bone marrow/circulation
- 4-5 days in tissues
- Large numbers held in marrow as reserve pool
- Marrow has 10x as many myeloid cells as erythroid cells
- Neutrophils - most common white cell (40-75%)
- Eosinophils - 1-6% circulating cells
- Basophils - least common circulating cell (<1% in adult)
6
Q
Neutrophils
A
- Participate in phagocytosis in blood + tissues
- Circulate in blood and migrate into tissues by squeezing through pores via diapedesis
- Numbers increase dramatically during infection.
- Constitute about 50-80% of all leukocytes.
7
Q
Eosinophils
A
- Constitute 1-4% of all leukocytes
- Weakly phagocytic: mainly attack infecting parasites too large to be engulfed by attaching to parasite and secrete hydrolytic enzymes from cytoplasmic granules
- Can reverse tissue damage during allergic reactions: phagocytose allergen-antibody complexes & inflammation inducing substances.
8
Q
Basophils
A
- Least common circulating leukocyte <1%
- Non-phagocytic, act like eosinophils to release hydrolytic enzymes from cytoplasmic granules
- Release chemicals that contribute to allergic reactions: histamine, bradykinin, serotonin, heparin, slow-reacting substance of anaphylaxis, lysosomal enzymes.
9
Q
Monocytes
A
- Largest of leukocytes - 2-4%
- Circulate in blood for a few hours before migrating into tissues: increase in size by factor 5-10 and develop into tissue macrophages where they phagocytose infectious agents + abnormal/ dying cells including RBCs only in tissues.
10
Q
Monocyte –> macrophage cell system:
A
- Monocytes enter tissues + become macrophages
- Attach to tissues indefinitely + can be recruited into tissues if required
- Reticuloendothelial system
11
Q
Macrophages prominent in:
A
- Lymph nodes
- Lung alveolar walls
- Liver sinusoidal capillaries
- Red pulp of spleen
12
Q
Chemotaxis
A
Neutrophils & macrophages are recruited to tissue inflammation
13
Q
Inflammation
A
- Large number of neutrophils recruited by chemotaxis + enter by margination
- Activated macrophages secrete factors which promote granulocyte + monocyte production.
14
Q
Natural killer cells (innate immunity)
A
- Produced from lymphoid lineage
- Specifically target tumour cells + virus infected cells
- Induce programmed cell death (apoptosis) via release of contents of cytoplasmic granule
- Activated in response to interferons/ macrophage-derived cytokines.
15
Q
Lymphocytes (acquired immunity)
A
- 20-40% of leukocytes
- 3 main subtypes:
1. B lymphocytes: mature into plasma cells which secrete antibodies
2. T lymphocytes: helper T cells secrete cytokines which activate other leukocytes.
Cytotoxic T cells secrete factors that kill virus-infected cells + tumour cells
3. Natural killer cells: also secrete factors that kill virus-infected cells + tumour cells.
16
Q
Genesis of lymphocytes
A
Produced + stored in lymphoid tissue.
- Lymph glands, spleen, thymus, tonsils, bone marrow & peyers patches in intestinal epithelium
- Positioned to intercept invading organisms/ toxins
- Various cytokines drive growth + differentiation
17
Q
Lymphocyte processing
A
- Pro-T cells migrate to + process in thymus gland
- Pro-B cells processed in liver + bone marrow
- Both divide rapidly, surface receptors on individual cells develop specificity for thousands and millions of different antigens.
18
Q
Major histocompatibility complex
A
- Macrophages + dendritic cells phagocytose microorganisms + present antigenic fragments on cell surface to nearby lymphocytes
- Binding of antigens to specific cell surface receptors on lymphocytes activates these specific cells only
- Activated lymphocytes reproduce rapidly - large numbers of a clone of lymphocytes released into circulation
- Macrophages secrete IL-1 which promotes specific clonal growth.
19
Q
Helper T lymphocytes
A
- 75% of T-cells
- Secrete lymphokines (IL2-6)
- Promote growth of activated B cells
- Stimulation of cytotoxic + suppressor T cells
- Activation of macrophages
- Feedback stimulation of helper cells
20
Q
Types of T lymphocytes
A
Cytotoxic T cells
Suppressor T cells
21
Q
Cytotoxic T cells
A
- Killer cells which destroy micro-organisms containing activating antigen
- Virus infected cells, cancer cells + transplanted cells
22
Q
Suppressor T cells
A
- Prevent damage of tissues by cytotoxic cells
- Responsible for immune tolerance
- Failure causes autoimmune diseases
23
Q
Classes of antibodies
A
IgM, IgG, IgA, IgD, IgE.
24
Q
Secondary immune response with memory cells:
A
- Memory B cells rapidly converted to plasma cells
- Memory T cells rapidly converted to helper, cytotoxic + suppressor T cells.
25
Haemostasis
1. Vascular spasm (damaged blood vessel constricts)
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)
26
Vascular constriction due to trauma to blood vessels:
- Local myogenic contraction
- Local axon reflexes initiated by pain/sensory receptors at/near damaged vessels
- Local platelets in blood release a vasoconstrictor substance thromboxane A
27
Thrombocytes (platelets)
- Produced by megakaryocyte
- No nuclei but contain residual cell organelles
- Synthesise various factors that act on plasma proteins + local blood vessels + issue
- Lifespan of 3-4 weeks
- Eliminated from circulation by macrophages mainly in spleen
28
Formation of platelet plug
- Plasma protein (von Willebrand factor) triggers aggregation + adherence of platelets to one another + to sites of vascular damage
- Platelets undergo structural changes + release ADP and thromboxane A2 which act on nearby platelets triggering further aggregation/adherence
- Formation of a loose platelet plug.
29
Difference between extrinsic + intrinsic pathways for blood clots
Extrinsic pathway: activated by vessel/tissue trauma
Intrinsic pathway: initiated by blood factors
30
Coagulation cascade
- Fibrinogen is converted to fibrin by thrombin
- Loose fibrin stabilized by formation of covalent bonds catalysed by coagulation factor XIIIa which is activated by thrombin.
31
Vitamin K
- Needed for hepatic synthesis of clotting factors e.g. prothrombin
- Deficiencies leads to bleeding tendencies
- Synthesised by bacteria in intestinal tract
- Vitamin k deficiency caused by obstruction of bile ducts/ liver disease
- Newborns lack intestinal bacterial flora --> contain 50% of adult clotting factors so vitamin K is administered at birth.
32
Feedback inhibition by formation of fibrin:
- 85-90% of thrombin formed from prothrombin is absorbed to fibrin
- Antithrombin III binds + removes remaining thrombin
Cessation of clotting cascade.
33
To stop contact activation of intrinsic pathway
layer of glycocalyx on endothelium + thrombomodulin binds + removes thrombin from plasma.
34
Heparin
activates antithrombin III, removes free thrombin + upstream factors, used as anti-clotting agent.
35
Aspirin
blocks production of thromboxane by inhibiting enzyme cyclooxygenase, long-term aspirin inhibits platelet aggregation
36
Prostacyclin
binds prostacyclin receptor on platelets, increases intracellular cAMP, blocks increase in intracellular Ca2+ caused by thromboxane receptor. Blocks platelet aggregation/adherence
37
Dipyridamole
inhibits thromboxane synthase + phosphodiesterase which degrades cAMP. Blocks platelet aggregation/adherence.
