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Topics in medical biosciences > Blood and the immune system > Flashcards

Blood and the immune system Flashcards

1
Q

How many L of blood does an adult human have?

A

4-6L

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2
Q

What is the haemocrit?

A

The packed cell volume in blood

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3
Q

What % of the blood is plasma?

A

55%

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4
Q

What technique is used to collect blood for analysis?

A

Venipuncture from a superficial vein

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5
Q

Why is blood taken from a vein?

A

Superficial veins are easy to locate
Vein walls are thinner than arteries
Blood pressure is low, so wound seals easily

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6
Q

When would an arterial puncture be used?

A

To check gas exchange efficiency in the lungs

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7
Q

What are the 5 key functions of blood?

A
  • Transporting dissolved gasses
  • Regulating pH and ion composition of interstitial fluids
  • Restricting blood loss at sites of injury
  • Defence against pathogens and toxins
  • Stabilising body temperature
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8
Q

Explain how blood regulates pH and ion composition

A
  • Diffusion to eliminate local ion deficiencies or excesses
  • Absorb acids produced by active tissues e.g. lactic acid produced during exercise
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9
Q

Explain how blood stabilises body temperature

A
  • Heat redistribution from active skeletal muscles
  • Heat loss through skin if body temp is too high
  • Warm blood directed to sensitive organs e.g. brain is temperature too low
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10
Q

What are albumins?

A

Major plasma proteins that contribute to plasma osmolarity

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11
Q

What is the key role of albumins?

A

‘Molecular taxis’
Transport hydrophobic molecules including fatty acids, thyroid hormones, and steroid hormones

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12
Q

How do albumins maintain blood pressure?

A

Can pull water from interstitial tissues into the blood

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13
Q

How do albumins transport other molecules?

A

Hydrophobic pockets allow other molecules to bind to albumins and be transported around

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14
Q

What type of molecule is an antibody?

A

Immunoglobulin

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15
Q

How is each immunoglobulin domain coupled?

A

Disulphide bonding via cysteine residues

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16
Q

How many immunoglobulin domains make up a heavy chain?

A

4

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17
Q

How many immunoglobulin domains make up a light chain?

A

2

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18
Q

How many antigen binding receptors does IgG have?

A

2

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19
Q

What kind of binding molecule is an antibody?

A

Bivalent - it binds by both its arms at the same time

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20
Q

What is the role of globular transport molecules?

A

Bind small ions, hormones, and compounds that would otherwise be removed by kidneys or have low solubility in water

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21
Q

Give 3 examples of transport molecules

A
  • Hormone-binding proteins
  • Metalloproteins e.g. trasnferrin
  • Apolipopproteins
  • Steroid-binding proteins
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22
Q

What is the role of fibrinogen?

A

Soluble fibrinogen is converted to insoluble fibrin during blood clotting
A meshwork forms to prevent blood loss

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23
Q

What is the structure of fibrinogen?

A
  • Made of 6 chains
  • 2 gamma chains with a globular domain and an alpha helical region
  • 2 beta chains with a globular and alpha helical region
  • 2 alpha chains that are all alpha helical
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24
Q

How is fibrin generated during clotting?

A
  • Thrombin is produced during coagulation cascade
  • Thrombin is a serine protease
  • Thrombin clips the end of the fibrinopeptides off the alpha and beta chains of fibrinogen
  • Gly-His-Arg or Gly-Pro-Arg sequences are exposed
  • These sequences can bind to the globular domain of the gamma chain, forming a meshwork of insoluble fibrin
  • Blood clots
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25
Q

What is the role of plasma expanders?

A

Increase blood volume temporarily e.g. after blood loss or injury

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26
Q

Properties of plasma expanders

A

Large carbohydrate molecules to maintain proper osmotic concentration

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27
Q

What proportion of human cells do rbcs make up?

A

1/3

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28
Q

4 structural points of rbcs

A

Biconcave disc
Large SA:V ratio
Form stacks like dinner plates through narrow vessels
Bend and flex when entering small capillaries

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29
Q

Red blood cell composition (2)

A
  • Lose most organelles during differentiation, giving more space for oxygen an carbon dioxide
  • Retain only the cytoskeleton
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30
Q

How are rbcs produced?

A

From development of haemopoietic stem cells in the bone marrow

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31
Q

How do rbcs obtain energy?

A

By anaerobic metabolism of glucose that they absorb from plasma - aerobic respiration would use the oxygen that they are transporting

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32
Q

Which protein has a dual role in platelet activation and the coagulation cascade?

A

Thrombin

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33
Q

What is the pathway of rbc development?

A

Early erythroblast —> Late erythroblast —> Normoblast —> Reticulocyte —> Erythrocyte

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34
Q

What antibodies and antigenss do rbc type A have?

A

Anti-B antibodies
A antigens

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35
Q

What antibodies and antigens do rbc type B have?

A

Anti-A antibodies
B antigens

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36
Q

What antibodies and antigens do rbc type AB have?

A

No antibodies in plasma
A and B antigens

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37
Q

What antibodies and antigens do rbc type O have?

A

Anti-A and Anti-B antibodies in plasma
No antigens in rbc

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38
Q

What is the role of wbcs?

A
  • Defend the body against pathogens
  • Remove toxins, wastes, and abnormal or damaged cells
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39
Q

Characteristics of circulating wbcs?

A
  • Can migrate out of the bloodstream to move to the damaged area
  • Capable of amoeboid movement
  • Chemotaxis
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40
Q

Which wbcs are capable of phagocytosis?

A

Neutrophils, eosinophils, and monocytes

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41
Q

Which wbcs are the most phagocytic?

A

Macrophages

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42
Q

What is a monocyte?

A
  • The cell type in the blood
  • They migrate outside of the bloodstream and become macrophages or dendritic cells
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43
Q

What is the role of neutrophils?

A
  • Part of the body’s non-specific (innate) defense system
  • First white blood cells to arrive at the site of injury
  • Specialised in phagocytosing bacteria marked with antibodies or a compliment
  • Dead neutrophils form pus - leave the body
  • Can extrude their nucleus to form a net of DNA that can trap bacteria last line of defense when overwhelmed
  • 2-5 lobed nucleus
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44
Q

What is the role of eosinophils?

A
  • Innate defence system
  • Attracted to the site of injury
  • They do phagocytosis
  • Attack objects that are coated with antibodies
  • They attack by exocytosis of toxic compounds - makes them specialised in attacking multicellular parasites
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45
Q

What is the role of basophils?

A
  • Innate defense system
  • Attracted to sites of injury
  • Promote inflammation by releasing histamine to dilate blood vessels
  • Associated with allergic reactions
  • Release other chemicals to attract white blood cells
  • Lifespan is not known
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46
Q

What is the role of monocytes?

A
  • Innate defense
  • Attracted to sites of injury - here they become phagocytic tissue resident macrophages and engulf pathogens and debris
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47
Q

What types of cells are lymphocytes?

A

T cells
B cells
NK cells

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48
Q

What is the role of T cells

A
  • Cell mediated immunity
  • Attack abnormal cells or control activity of other lymphocytes
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49
Q

What is the role of B cells?

A
  • Humoral immunity
  • Produce antibodies
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50
Q

What is the role of NK cells?

A

-Immune surveillance
- Attack abnormal cells

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51
Q

How are platelets made?

A

Develop from bone marrow megakaryocytes

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52
Q

What is haemostasis?

A
  • The stopping of bleeding
  • The prevention of excessive blood loss upon injury
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53
Q

What are the 3 stages of haemostasis?

A
  • Vasoconstriction to limit blood flow
  • Platelet plug formation
  • Coagulation cascade to stabilise the platelet plug
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54
Q

How do IgG antibodies bind to Nk cells?

A

Antibody constant domain binds to Fc receptors on NK cell

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55
Q

What cells make antibodies?

A

B lymphocytes

56
Q

How are antibodies made?

A
  • Pathogen with a surface antigen that is recognised by a b cell binds to the antigen
  • Binding triggers b cell to proliferate
  • Created either memory cells or plasma cells
57
Q

What do plasma cells secrete?

A

Soluble form of the surface B cell receptor

58
Q

3 ways in which antibodies can work

A
  • Neutralisation
  • Opsonisation
  • Complement activation
59
Q

How do antibodies work by neutralisation?

A

Bind to toxins, bacteria, or viruses to prevent them acting in the body

60
Q

How do antibodies work by opsonisation?

A
  • Antibodies bind to antigens on pathogen and coat it
  • Macrophages have Fc receptors on their surface that recognise the Fc portion of antibodies
  • Macrophage can bind and form a pathogen-antibody complex
  • This complex is internalised, phagocytosed, and degraded via lysosomes
61
Q

What is the classical pathway for the complement cascade?

A

Antigen-Antibody complexes formed

62
Q

How do antibodies work by complement activation?

A
  • Complement cascade can assemble on an antibody-antigen complex
  • The complement cascade forms a membrane attack complex that punches holes into the target that is about to be engulfed anyway
63
Q

What is the alternative pathway for the complement cascade?

A

Pathogens or injured tissue is detected

64
Q

What is the lectin pathway for the complement cascade?

A

Lectin binds to mannose on pathogens

65
Q

What happens when cells are too big to phagocytose?

A
  • Antibody binds antigens on surface of target cell
  • NK cells have Fc receptors that bind to the antibodies of the target cell
  • NK cell then degranulates and releases toxic components in its granules
  • Granules perforate the cell and the toxic compound called granzymes will enter the cell and cause apoptosis
66
Q

Benefits of antibody being bivalent?

A

If one arm disengaged the other arm would interact and give the other arm a change to reattach

67
Q

What are the 5 mechanisms of therapeutic antibodies?

A
  • Blocking
  • Signaling
  • Targeting
  • Complement-dependent cytotoxicity
  • Antibody-dependent Cell-mediated cytotoxicity
68
Q

What are the 3 roles of the immune system?

A

Recognition: distinguishes self from non-self
Elimination of non-self identities
Immunological memory: can respond quickly to new infection

69
Q

What type of stem cell can differentiate into any blood cell?

A

Pluripotent hematopoietic stem cells

70
Q

What cell is equally important in innate and adaptive immunity?

A

Cytokines

71
Q

What cells act as a bridge between innate and adaptive immune responses?

A

Dendritic cells
They phagocytose bacteria and present their antigens before moving to the lymph node to activate helper t cells

72
Q

What prevents autoimmunity?

A

Negative regulatory checkpoints

73
Q

What are DAMPS?

A

Danger-Associated Molecular Patterns

74
Q

What do DAMPs do as a response to severe injury?

A
  • When a cell undergoes this necrosis, DAMPs are released and these signals are recognised by patterns recognition receptors - PRRs
  • PRRs are found on the surface of cells such as macrophages
  • There are also soluble PRRs floating around
  • Binding of these danger signals triggers activation of the macrophage
75
Q

What do DAMPs do as a response to mild injury?

A

They just flag up to macrophages that they should be phagocytosed without alerting the immune system

76
Q

What is the role of PRRs?

A
  • Bind DAMPs and PAMPs
  • Soluble PRRs can bind to bacteria so they can be bound to macrophages to be engulfed
    Macrophage will release cytokines to activate othger immune cells
77
Q

What is the key role of cytokines?

A

Activate other cells and induce differentiation
- Dendritic cells
- Macrophages
- The endothelium

78
Q

What is the key role of chemokines?

A

Chemotactic factors to guide other cells to the site of infection

79
Q

How does endothelium activation help in the immune reponse?

A

Endothelium lines all blood vessels and when it is activated, it can capture neutrophils out of the blood and allows them to transmigrate through from the blood to the site of injury

80
Q

What is a sentinel cell?

A

Monitors the presence of potentially harmful cells in the body

81
Q

How are macrophages formed?

A

Monocytes transmigrate from the blood into the tissues and specialises into a macrophage, waiting for injury or infection

82
Q

Summaries the acute inflammatory reaction

A
  • Happens immediately after infection
  • Bacteria are attacked by tissue macrophages that phagocytose them
  • Release chemokines and cytokines that increase permeability of blood vessels by acting on endothelial cells
  • This allows neutrophils to get to site of injury by crossing between endothelial cells
  • Compliment proteins can activate other cells and increase vascular permeability
83
Q

What are the three types of granulocytes?

A

Neutrophils
Eosinophils
Basophils

84
Q

What is the role of granulocytes?

A

Granules contain toxic substances to kill pathogens e.g. microorganisms or parasites

When they are activated they release granules that have toxic substances, as well as releasing DNA content

85
Q

What is the role of neutrophils?

A

Key components of the innate immune system
Important during early injury stages
Can degranulate and release DNA content in the form of NETs that mop up bacteria
NET = neutrophil extracellular trap
Neutrophils can produce cytokines

86
Q

What are the 3 activation pathways of the complement cascade?

A

Classical by Ag-Ab binding
Lectin membrane protein binding to pathogens
Pathogens and injured tissue

87
Q

What is the key converging point of the 3 potential activation pathways in the complement cascade?

A

C3 convertase enzyme is activated
C3 must be broken down into C3a and C3b by C3 convertase enzyme

88
Q

Where do immature dendritic cells reside?

A

Peripheral tissue

89
Q

How do dendritic cells become activated?

A

PAMPs and other signs of infection e.g. cytokines released by activated macrophages e.g. interleukin 1 and tumor necrosis factor

90
Q

Immature dendritic cell state (4)

A

Non-motile
Low MHC
Highly phagocytic
Low B7 levels

91
Q

How do dendritic cells become activated?

A

Travel through lymphatics to lymph nodes where t cells reside

92
Q

What is signal 1 in regards to dendritic and t cells?

A

TCR recognises peptide-MHC and activate the t cell upon engagement

93
Q

What is signal 2 in regards to dendritic and t cells?

A

t cell membrane protein CD28 recognises b7 on activated dendritic cell and they engage

94
Q

Which cells express MHC class I?

A

All cells in the body continually present endogenous proteins on the cells surface

95
Q

Which cells express MHC class II?

A

Antigen presenting cells: dendritic, macrophages, b cells

96
Q

Where do MHC class II come from?

A

Anything foreign, dendritic cells take up proteins and bacteria and present them as 20bp long peptides on cells surface

97
Q

What are the key functions of t cells? (3)

A

Help with antibody production
Killing virally-infected cells
Regulatory role

98
Q

What triggers t cells to clonally expand?

A

T cell recognising MHC-peptide receptor on the surface of a dendritic cell

99
Q

What are the 3 main cell types produced by clonal expansion of t cells?

A

Helper t cells
Cytotoxic t cells
Regulatory t cells

100
Q

What triggers B cells to clonally expand?

A

Antigen b cell receptor, or cytokines from t cells

101
Q

What types of cells do clonal expansion of b cells produce?

A

Memory and plasma cells

102
Q

Explain antibody-mediated phagocytosis activation

A

Fc receptors on phagocytes and neutrophils can send signals to the cell interior of the cell it is bound to
This will induce phagocytosis of whatever the antibody is bound to

103
Q

How does ADCC kill virally infected cells?

A

Virally infected cell expresses a viral protein on cell surface
Fc receptors on NK cell recognise and bind to IgG antibody, then kill cell

104
Q

3 ways to kill a virally infected cell

A

ADCC
T-cell cytotoxicity
Nk cell activates receptor-mediated cytotoxicity

105
Q

How does granule-dependent killing of cells work?

A

NK cells recognise cell by non-self markers and cytotoxic t cells recognise antigens presented by MHC1
Perforin is released
Cytotoxic granules release granzymes
Granzymes are released through these pores and induce apoptosis

106
Q

What 3 cell types are sentinels of innate immune system/

A

Macrophages
Mast cells
Dendritic cells

107
Q

Mast cell functions as a sentinel (3)

A

Produce chemotactic factors
Produce histamine
Produce cytokines

108
Q

Macrophage functions as a sentinel (4)

A

Phagocytosis
Cytokine production
Antigen presentation
NET formation

109
Q

Dendritic cell functions as a sentinel (2)

A

Process and present antigens to t lymphocytes
Produce cytokines

110
Q

What is opsonisation?

A

The binding of complement proteins to bacteria

111
Q

What technique is used to sample bone marrow?

A

Trephine biopsy

112
Q

What is the name of the bone network within bone marrow?

A

Trabecular bone

113
Q

What is an indicator of healthy bone marrow?

A

High quantities of fat deposits

114
Q

In which bones do haemopoietic stem cells reside/?

A

Bone marrow of long bones e.g. sternum, skull

115
Q

What is the role of transient amplifying cells?

A

Proliferate to generate a bulk of cells that can differentiate

116
Q

What is a precursor cell?

A

Cell type before it becomes terminally differentiated

117
Q

Stem cells are a population of cells able to:

A

Sustain themselves by a process of self-renewal
Generate progeny that sustain both the mass and functional competence of the tissue

118
Q

What is restriction in relation to stem cells?

A

Them losing the ability to differentiate into certain cell types as they become more specialised

119
Q

What does selective IgA deficiency cause?

A

Recurrent respiratory and gastrointestinal infections

120
Q

What is CVID?

A

Common Variable Immunodeficiency
Low antibody levels
Recurrent infections
Caused by mutations in lymphocyte membrane proteins or cytokine receptors

121
Q

What is SCID

A

Severe Combined Immunodeficiency
Defective T and B cells
Caused by IL-2 receptor common gamma chain mutations
This protein is shared by IL-2/4/7/9/15/21
Severe bacterial, viral, fungal infections
Treatment by bone marrow transplant

122
Q

What are the major causes of autoimmune disease?

A

Genetic susceptibility genes
Linked to hormones

123
Q

Give 2 organ-specific autoimmune diseases in the thyroid

A

Graves disease
Hashimotos disease

124
Q

How does graves disease progress?

A

Immune system mistakenly targets thyroid gland and generates antibodies: thyroid-stimulating immunoglobulins
TSI’s bind to Thyroid Stimulating Hormone receptors on thyroid
Results in hyperthyroidism

125
Q

How does Hashimotos disease progress?

A

Thyroid cells are destroyed
Antibodies or autoantibodies are made against thyroid peroxidase and thyroglobulin
Cytotoxic t cells mistakenly attack the antigenic peptide presented by MHG

126
Q

Give an example of a non organ-specific autoimmune disease

A

Lupus erythematosus

127
Q

How does lupus erythematosus progress?

A

Apoptotic cells have blebs that contain histones
Apoptotic cells are usually cleared by complement
Mutation in c1q means they are not cleared
Dendritic cells present the histones and activate helper T-cells and immune system
Antibodies are made for the blebs
Clumping of blebs by antibodies gets lodged in kidneys

128
Q

How is lupus erythematosus treated?

A

Immunosuppressants

129
Q

Progression of cancerous cells

A

Normal
Hyperplastic
Dysplastic
Neoplastic
Metastatic

130
Q

What is genetic heterogeneity?

A

Where two different mutations can cause the same disease
Solid tumors have genetic heterogeneity

131
Q

How do DAMPs help in the immune response against cancer?

A

Dying tumor cells release DAMPs
DAMPs are not usually exposed to blood
Dendritic cells become activated by DAMPs in blood
Dendritic cells upregulate antigens from dying cancer cells
Dendritic cells present the peptides as MHC class II
T-cells become cytotoxic and kill cancer cells

132
Q

What is the role of immune checkpoints?

A

Molecules in the immune system that either turn up a signal or turn down a signal

133
Q

How do tumor cells use checkpoints?

A

As tumor cells evolve, they can suppress immune checkpoints to stop the immune cell attacking them

134
Q

Outline the process of T-cell inhibitor CTLA-4

A

CTLA-4 is present on T cells
CTLA-4 can bind B7, stopping the immune system from becoming overactive
CTLA-4 deficient mice die from lymphoproliferative at 3-4 weeks

135
Q

Outline the process of T-cell inhibitor PD-1

A

Tumor cells are upregulated by antigen-presenting cells
CD28 (+ve) and CTLA-4 (-ve) regulators of T-cell activation via cytokines
Effector T-cell TCR binds to MHC-I to kill tumor cell
PDL-1 is expressed by normal cells as well as tumor cells
PD-1 on effector T cell binding to PD-L1 on tumor cell will shut down that T-cell

136
Q

When does CTLA-4 checkpoint occur?

A

Before dendritic cell is activated

137
Q

When does PD-1 checkpoint occur?

A

At the effector phase

Topics in medical biosciences (3 decks)

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