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Medicine Phase 2a > Immunology > Flashcards

Immunology Flashcards

1
Q

Describe features of innate immunity

A

Non-specific
Instinctive
Does not depend on lymphocytes

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2
Q

Describe features of adaptive immunity

A

Specific ‘acquired’ immunity
Requires lymphocytes
Antibodies

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3
Q

What is the general purpose of immune system?

A

To distinguish from self and non-self

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4
Q

What are the three types of leukocytes

A

Lymphocytes
Phagocytes
Auxillary cells

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5
Q

What cell do all leukocytes originate from

A

Haematopoietic Pluripotent/Multipotent Stem Cell

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6
Q

What progenitor cells are formed from haematopoietic pluripotent stem cells

A

Myeloid Progenitor

Lymphoid Progenitor

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7
Q

Which two cells in blood (or tissue) derive from haematopoietic pluripotent stem cells but not a progenitor cell (from hp stem cells)

A

Eosinophil

Basophil

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8
Q

What 4 cells/parts of the blood derive from Myeloid progenitors

A

Erythrocytes
Platelets
Monocytes
Neutrophils

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9
Q

What cell forms platelets

A

Megakaryocyte

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10
Q

What cell forms erythrocytes

A

Reticulocytes

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11
Q

What do monocytes differentiate into?

A

Macrophages

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12
Q

What are 2 types of cells macrophages can differentiate into

A

M1 and M2

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13
Q

What chemicals allow differentiation of macrophages into M1 cells

A

LPS

INF(gamma)

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14
Q

What chemicals allow differentiation of macrophages into M2 cells

A

IL-4
IL-13
TGF(beta)

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15
Q

What cells are formed from lymphoid progenitor

A 
B cell
T cells (regular, helper, cytotoxic)
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16
Q

How is B cell formed form Haematopoietic pluripotent stem cell

A

HP stem cell > Lymphoid progenitor >Pro-B cell > Pre-B cell > B-cell

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17
Q

What cell can lymphoid progenitor differentiate into which can then differentiate into T-cells

A

Thymocyte

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18
Q

Where are thymocytes found

A

Thymus

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19
Q

What 2 types of cells can B cells differentiate into

A 
Plasma cell
Memory cell (only some)
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20
Q

Where do plasma cells and T-cells drain into

A

Lymph nodes

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21
Q

What cells are considered Polymorphonuclear leukocytes

A

Neutrophils
Eosinophils
Basophils

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22
Q

How big are neutrophils

A

10-14 micro metres

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23
Q

What is the normal lifespan of a neutrophil

A

6h to 12d

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24
Q

What is the normal concentration of neutrophil in the blood and what % of cells does this make up

A

3000 to 11000 per mm^3 blood

65%

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25
Q

What is CD66b

A

activation marker for human granulocytes (but full understanding on eosinophils not known)
expressed by neutrophils

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26
Q

what is the role of Neutrophils in INNATE immunity

A

Phagocytosis

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27
Q

What are 2 main intracellular granules of neutrophils

A

Primary lysosomes

Secondary granules

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28
Q

What chemicals are found in primary lysosomes in neutrophils

A 
Enzymes:
Myeloperoxidase
Muramidase
Acid hydrolyses
Proteins (Defensins)
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29
Q

What is function of primary lysosomes in neutrophils

A

Combine with phagosomes containing microbes to digest them

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30
Q

What chemicals are found in secondary granules in neutrophils

A

Lactoferrin

Lysozyme

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31
Q

How do neutrophils kill microbes

A

By secreting toxic substances like superoxides

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32
Q

Which of these is not a feature of neutrophils:

  • Primary lysosomes combine with phagosomes containing microbes to digest them
  • They have Fc and complement receptors
  • They can kill microbes by secreting toxic substances
  • Primary granules contain lactoferrin and lysozyme
  • They are 10-14 micro m
A

Secondary granules contain lactoferrin and lysozyme (not primary)

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33
Q

Describe monocyte

A

Mononuclear leukocyte

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34
Q

What is size of monocyte

A

14-24 micro metres

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35
Q

What is concentration of monocytes in blood and what is % of monocytes amongst other cells of blood

A

100-700 per mm^3 blood

5%

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36
Q

What is CD14

A

Expressed by Monocytes (also dendritic cells, neutrophils (to much lesser extent) and macrophages)
Pattern Recognition receptor
for pathogenic activity and for bacterial lipopolysaccharide (LPS)

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37
Q

What are roles of monocytes or macrophages in innate and adaptive immunity

A

Phagocytosis

Ag presentation

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38
Q

What is main role of monocytes

A

remove any foreign or dead microbes

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39
Q

How do monocytes kill microbes

A

Have lysosomes containing peroxidase that can kill microbes

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40
Q

What receptors are found on monocytes

A 
Fc (antibody) receptor 
Complement receptors
Pattern Recognition receptors (PRR)
Toll-like receptors
Mannose receptors

can bind to all kinds of microbes

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41
Q

What cells do monocytes differentiate into

A

Macrophages

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42
Q

What is general lifespan of monocyte

A

Months

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43
Q

What is the main role of macrophages

A 
Most often first line of non-self recognition
Remove foreign (microbes) and self (dead/tumour cells)
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44
Q

What are other features of macrophages

A

Can bind to all kinds of microbes as have Fc, complement, Scavenger, Toll-like, mannose receptors
Present Ag to T-cells
Have lysosomes containing peroxidase (free radicals)

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45
Q

What is general lifespan of macrophages

A

Months/years

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46
Q

Where do monocytes reside and where do macrophages reside generally

A

Monocytes - blood

Macrophages - tissue

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47
Q

What cells are considered mononuclear leukocytes

A

B lymphocytes
T lymphocytes
Monocytes

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48
Q

What is general size of eosinophil

A

10-14 micro metres

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49
Q

What is concentration of eosinophil and what is percentage in cells of blood

A

100-400 per mm^3 blood

5%

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50
Q

What is lifespan of eosinophil

A

8 to 12 days

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51
Q

What is CD125

A

Expressed by eosinophils

Alpha subunit of the Interleukin-5 receptor

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52
Q

What dyes do eosinophil granules stain for

A

Granules satin for acidic dyes (eosin)

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53
Q

What are roles of eosinophils

A

Countering Parasitic infections and allergic reactions

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54
Q

How do eosinophils counter parasitic infections

A

Granules contain Major Basic Protein which is a potent toxin for helminth worms

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55
Q

How do eosinophils counter allergic reactions

A

Major Basic Protein activates neutrophils.

This induces histamine release from mast cells and provokes bronchospasm.

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56
Q

Size of basophils

A

10-12 micro m

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57
Q

Conentration of basophils in blood and concentration in blood

A

20-50 per mm^3 blood

0.2% (lowest of cells)

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58
Q

What is average lifespan of basophil

A

2 days

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59
Q

Which of these statements regarding basophils is false:
Granules stain for basic dyes
Very similar to mast cells
They are generally 14-20 micro m

A

They are generally 10-12 micro m

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60
Q

What are basophils or mast cells involved in

A

Immunity to parasitic infections

Allergic Reactions

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61
Q

How are basophils involved in causing allergic reactions

A

Express high-affinity IgE receptors (FcεR1)

Binding of IgE to receptor causes de-granulation releasing Histamine (causes allergic reactions)

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62
Q

What is size of mast cell

A

10-14 micro m

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63
Q

Where are mast cells found

A

Only in tissues

Precursor in blood

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64
Q

How are mast cells similar to basophils

A

Also express high-affinity IgE receptors (FcεR1)

Binding of IgE to receptor causes de-granulation releasing Histamine (causes allergic reactions)

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65
Q

What is a key role of tissue macrophages and give 3 examples

A

Maintenance of tissue homeostasis through clearance of cellular debris (especially following infection or inflammation):

  • Alveolar macrophages (clear microorganisms and debris encountered in air)
  • Gut macrophages (bactericidal activity)
  • Osteoclasts (giant multinucleate cells that resorb bone)
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66
Q

What is size of T lymphocytes

A

5-12 micro m

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67
Q

What is concentration of T lymphocytes in blood and % in blood

A

300 to 1500 per mm^3 blood

10%

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68
Q

What is lifespan of T-lymphocytes

A

hours to years

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69
Q

Where do T lymphocytes mature

A

Thymus

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70
Q

What is CD3

A

T cell receptor complex

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71
Q

How do T-lymphocytes play a large role in adaptive immunity

A

recognise peptide Ag displayed by Antigen Presenting Cells (APC)

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72
Q

What are 4 main types of T lymphocytes

A

T helper 1 (CD4)
T helper 2 (CD4)
Cytotoxic T cell (CD8 - can kill cells directly)
T reg (Fox P3) - regulate immune response (dampens)

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73
Q

Where are T lymphocytes and B-lymphocytes found

A

Blood, Lymph nodes and spleen

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74
Q

What is difference between T helper 1 and T helper 2 cells

A

T helper 1 CD4 - help immune response intracellular pathogens
T helper 2 CD4 - help produce antibodies - extracellular pathogens

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75
Q

What is size of B lymphocyte

What is concentration of them in blood and what % of cell content do they make up

A

5-12 micro m
300-1500 per mm^3 blood)
15%

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76
Q

What is lifespan of B lymphocytes

A

Hours to Years

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77
Q

How do B-lymphocytes play a large role in adaptive immunity

A

Recognise peptide Ag displayed by Antigen Presenting Cells (APC)
Express membrane bound antibody on cell surface
Differentiate into plasma cells that make antibodies

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78
Q

Where do B cells mature?

A

Bone Marrow

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79
Q

What CD proteins are expressed by B lymphocytes

A

CD19 and CD20

depends on maturity

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80
Q

What % of lymphocytes are Natural Killer Cells?

A

15%

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81
Q

What protein is expressed by Natural Killer cells

A

CD56

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82
Q

Where are natural killer cells found

A

spleen/tissues

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83
Q

Describe appearance of natural killer cells

A

look like ‘large granular lymphocytes’

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84
Q

What is purpose of natural killer cells

A

Recognise and kill:
Virus infected cells
Tumour cells
(by apoptosis)

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85
Q

Name 3 kinds of soluble factors

A

Complement Factors
Antibodies
Cytokines/Chemokines

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86
Q

What are 3 main pathways of activating complement factor C’3

A

Classical - Ab bound to microbe
Alternative -Complement (C’) binds to microbe
Lectin - activated by mannose binding to lectin bound to microbe

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87
Q

What are immunoglobulins (Ig’s)

A

Soluble Glycoproteins

Bound to B cells as part of B-cell antigen receptor

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88
Q

What are 5 distinct classes of immunoglobulins/antibodies

A 
IgG (IgG1-4)
IgA (IgA1 and 2)
IgM
IgD
IgE
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89
Q

Define Antibody (Ab)

A

Protein produced in response to an antigen. It can only bind with an antigen that induced its formation (i.e. specificity)

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90
Q

Define Antigen (Ag)

A

A molecule that reacts with preformed antibody and specific receptors on T and B cells.

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91
Q

*Define Epitope

A

The part of the antigen that binds to the antibody/receptor binding site

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92
Q

Define Affinity

A

Measure of binding strength between an epitope and an antibody binging site.
(Higher affinity = better)

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93
Q

What is Fab and Fc regions of antibody

A

Imagine Y shape
Vertical bit is Fc region of only heavy chain parts (binds to Fc receptor of phagocyte)
Two diagonal bits are Fab region of Light chains and parts of heavy chains (with antigen-binding site that binds to epitope of antigen)
**see picture of basic structure of IgG1 with hinge region, variable region etc

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94
Q

What is most common Ig in human serum?

A

IgG

70-75% of total Ig in serum

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95
Q

Describe the shape of IgG

A

Light chains of 212 residues
Heavy chains of 450 residues
Hinge region between Fc and Fab regions
(Is like Y shape but Fc region looks circular so is like a gamma symbol)

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96
Q

What % of Ig in serum does IgM make up?

A

10%

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97
Q

In which antibodies or immunoglobulins would you find a J chain?

A

IgM and sIgA (secretory)

sIgA held together by J chain and secretory component

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98
Q

What is shape of IgM

A

Pentamer

formation requires J chain

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99
Q

Where is IgM mainly found

A

Blood as too big to cross endothelium

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100
Q

Where is monomeric form of IgM (mIgM) found

A

Present as an antigen-specific receptor on B cells

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101
Q

Where are IgMs mainly used?

A

Mainly primary response - initial contact with Ag

102
Q

What % of Ig in serum does IgA make up?

A

15%

103
Q

What % of serum IgA is a monomer?

A

80%

can also be a dimer, held by J chain

104
Q

Where is IgA found

A

Predominant Ig in mucous secretions such as saliva, milk, bronchiolar and genitourinary secretions
(sIgA - secretory)

105
Q

What % of Ig in serum does IgD make up?

A

1%

106
Q

What is mIgD and where is it found?

A

Transmembrane monomeric form of IgD present on mature B cells

107
Q

What % of Ig in serum does IgE make up?

A

approx 0.05% (lowest)

108
Q

What cells express IgE-specific receptors with a high affinity for IgE?

A

Basophils

Mast cells

109
Q

What is released by binding of IgE to basophils or mast cells

A

Histamine

allergic response, also IgE associated with defence against parasitic infections

110
Q

What Ig contains a central carbohydrate unit (Fc’)

A

IgE

111
Q

What are cytokines?

A

Proteins secreted by immune and non-immune cells

112
Q

Give 4 examples of cytokines

A

Interferons (IFN)
Interleukins (IL)
Colony Stimulating Factors (CSF)
Tumour Necrosis Factors (TNF alpha and beta)

113
Q

What is role of interferons (cytokine)

A

Induce a state of antiviral resistance in uninfected cells and limit the spread of viral infection

114
Q

What cells produce IFN alpha and beta (interferons)

A

Virus infected cells

115
Q

What cells produce IFN gamma

A

Released by activated Th1 cells

116
Q

What are interleukins (IL)

A 
Any of a class of glycoproteins produced by leukocytes for regulating immune responses.
(produced by many cells (>30))
117
Q

What is difference between IL1 and IL-10

A 
IL-1 = Pro-inflammatory interleukin
IL-10 = Anti-inflammatory interleukin
118
Q

What is role of interleukins

A

Can cause cells to divide, differentiate and to secrete factors

119
Q

What is role of colony stimulating factors

A

Involved in directing the division and differentiation on bone marrow stem cells - precursors of leukocytes

120
Q

What is role of tumour necrosis factors (alpha and beta)?

A

Mediate inflammation and cytotoxic reactions

121
Q

What are chemokines?

A

Chemotactic cytokines
Group of approx 40 proteins that direct movement of leukocytes (and other cells) from the blood stream into the tissue or lymph organs by binding to specific receptors on cells

122
Q

What is role of chemokine?

A

Attract leukocytes to sites of infection/inflammation

123
Q

Give examples of Chemokines and the leukocytes they attract

A

CXCL - mainly neutrophils (also T and B lymphocytes)
CCL - monocytes, lymphocytes, eosinophils, basophils
CX3CL - mainly T lymphocytes and NK cells
XCL - Mainly T lymphocytes

124
Q

What chemokine attracts eosinophils

A

CCL

125
Q

What chemokine mainly attracts neutrophils

A

CXCL

126
Q

Which chemokines mainly attract T-lymphocytes?

A

XCL and CX3CL (and CXCL and CCL)

127
Q

What chemokine attracts NK cells

A

CX3CL

128
Q

What cells do CCL chemokines attract?

A

Monocytes
Lymphocytes
Eosinophils
Basophils

129
Q

Give differences between Innate and Adaptive immune responses

A 
Innate: Non-specific
1st line of defence
Provides barrier to antigen
Present from birth
(no long lasting memory)

Adaptive: Specifc
Response specific to antigen
Memory to specific antigen
Quicker Response

(both integrate with each other)

130
Q

Examples of innate immunity

A 
Physical and Chemical Barriers (skin - dermis and epidermis, intact skin preventing prevention or growth (low pH) and sebum - skin secretions pH 3-5)
Phagocytic cells (neutrophils, macrophages)
Serum proteins (Complement, acute phase)
131
Q

Examples of Physical Barriers (Innate immunity)

A

Skin (Physical carrier, fatty acids, commensals)
Bronchi (Mucus, cilia)
Gut (acid, rapid pH change)

Also:
Lysozyme in tears and other secretions
Commensals in digestive system
Removal of particles by rapid passage of air over turbinate bones
Flushing of urinary tract
Low pH and commensals of vagina
132
Q

Examples of Mucous membranes (innate immunity)

A 
Saliva
Tears
Mucous secretions
Mucous -entrapment
Cilia - elating removes microbes
Commensal colonies - attachment and nutrients
133
Q

Physiological barriers (innate immunity)

A 
Temperature (pyrexia)
Fever response (inhibits micro-organism growth)
pH
Gastric acidity (Helicobacter pylori)
Oxygen tension - aerobes/anaerobes
134
Q

Define Inflammation

A

A series of reactions that brings cells and molecules of the immune system to sites of infection or damage

135
Q

What cells sense microbes in blood

A

Monocytes

Neutrophils

136
Q

What cells sense microbes in tissues

A

Macrophages

Dendritic cells

137
Q

What are PRRs and PAMPs and where are they found

A

PRR - Pattern Recognition Receptors (on cells) e.g. TLRs

PAMP - Pathogen Associated Molecular Patterns (on microbe)

138
Q

How do TLRs (toll-like receptors) sense microbes?

A

TLRs recognise Pathogen-Associated Molecular Patterns expressed by microbes

139
Q 
What PAMPs (pathogen associated molecular patterns) are detected by each of these PRRs?
TLR2
TLR3
TLR4
TLR7
TLR9
A

TLR2 = Peptidoglycan

TLR3 = Double stranded RNA

TLR4 = Lipopolysaccharide (LPS)

TLR7 = Single stranded RNA

TLR9= Double stranded DNA or CpG DNA

140
Q

What PRRs are expressed by plasmacytoid dendritic cell

A

TLR7, TLR9

141
Q

Which TLRs/PRRs detect viruses

A

TLR3, TLR7, TLR9

142
Q

What pathogen is detected by TLR2?

A

Gram Positive bacteria

143
Q

What pathogen is detected by TLR4?

A

Gram Negative bacteria

144
Q

What is detected by TLR5

A

Flagellin

145
Q

What are 3 functions of complements (C’)?

A
  • Lyse microbes directly via Membrane Attack Complex
  • Increase chemotaxis (C3a and C5a)
  • Opsonisation (C3b)
146
Q

*What is meant by opsonisation?

A

Targeting particles such as bacteria for destruction by a phagocyte

147
Q

What are 2 killing pathways present in polymorphs and macrophages?

A

O2 - dependent

O2 - independent

148
Q

Describe O2 dependent pathways of killing

A

Reactive Oxygen Intermediates (ROI):

  • Superoxides (O2 ^-) converted to H2O2 then .OH (free radical)
  • Nitric Oxide (NO) - vasodilation increases extravasation but also directly anti-mircobial
149
Q

Describe the O2 independent mechanism of killing

A 
Enzymes
Defensins (insert into membranes), lysozyme, pH, TNF
150
Q

Give examples of accessory molecules

A

Acute phase proteins (that are present in blood and increase during infection):
C reactive protein
Mannose binding lectin (MBL)
Surfactant protein-A (SP-A)

151
Q

What is C reactive protein and what is it’s function

A 
Serum protein produced by liver
Binds to some bacterial cell walls (pneumococci)
Promotes opsonisation
Binds to C1q
Activates C' (complement)
152
Q

What is function of Mannose Binding Lectin (MBL)

A

Binds to lectin on microbes
Promotes Opsonisation (via MBLR)
Activates C’

153
Q

What is the function of Surfactant Protein-A

A

Binds haemagglutinin in influenza

Reduces ability of virus to infect cells

154
Q

What is Cell-Mediated Immunity

A

Immune response that does not involve antibodies, but evolves the activation of phagocytes, antigen-specific cytotoxic T-lymphocytes an release of cytokines in response to antigen

155
Q

Do T-cells respond to soluble antigens?

A

NO

They only respond to intracellular antigens (presented antigens)

156
Q

Where are t-cells that recognise ‘self’ eliminated

A

T cells that recognise ‘self’ are killed in the foetal thymus as they mature (called T cell selection)

157
Q

Describe structure of TCR (T cell receptor)

A

Similar to Fab Ig’s

Heterodimers are 90% alpha/beta, 10% gamma/delta

158
Q

What does MHC stain for

A

Major Histocompatibility Complex

159
Q

What is function of MHC

A

Display peptides from self or non-self proteins (e.g. degraded microbial proteins) on the cell surface
Invasion alert

160
Q

What genes code for MHC 1 and 2 in humans

A

Human Leukocyte Antigen (HLA) genes
MHC I coded by HLA (A, B and C genes)
MHC II coded by HLA (DP, DQ and DR)

161
Q

What does MHC III code for

A

Secreted proteins (complement)

162
Q

*What T-cells display MHC class I

A

MHC I = all cells -> CD8 T cells

163
Q

What T-cells display MHC class II

A

MHC II = APC only -> CD4 T helper

164
Q

What antigens are detected by MHC I

A

Intrinsic/Intracellular antigens e.g. virus

165
Q

What antigens are detected by MHC II

A

Extrinsic/Extracellular antigens (phagocytosis)

166
Q

What antigens are detected by MHC II

A

Extrinsic/Extracellular antigens (phagocytosis)

167
Q

What is the function of MHC II and their APC

A

Help B cells make Abs to extracellular pathogens

Can help directly kill these pathogens

168
Q

Describe the structure of Class I and II MHCs

A

Class I:
8-10 aa peptide on receptor of 3 alpha units and a beta2m unit
Class II:
13-24 aa peptide on receptor of 2 alpha and 2 beta subunits on APC

169
Q

Upon activation, what is secreted by pDCs (plamsacytoid dendritic cell) in large quantities

A

IFN alpha

potent antiviral and pro inflammatory cytokine

170
Q

How does a mature dendritic cell activate naive T cells?

A

Mature DC provides 3 major signals:

  • Presentation of the peptide fragments from the pathogen bound to surface HLA molecules
  • Co-stimulation through CD80 and CD86 interacting with CD28 on T-cells
  • Secretion of cytokines - e.g. IL-12
  • T-cell also secretes IL-2 which binds to IL-2R on T-cells (autocrine) to activate them

Activated T-cell leads to division, differentiation, effector functions, memory

171
Q

What 2 types of T cells can naive alpha/beta T-cells differentiate into?

A

CD4 or CD8

CD8 can kill intracellular pathogens directly

172
Q

What 2 cells can CD4 cells mature into and what cytokine determines this

A

Th1 or Th2 (T-helper)
IL-12
High IL-12 leads to Th1 where as low IL-12 leads to Th2

173
Q

What cytokines are released from Th2 cells and what is the cell’s general function?

A

IL-4,5,10

Ab production

174
Q

What cytokines are released from Th1 cells?

A

IL-2

IFN gamma

175
Q

What is function of IFN gamma

A

Helps kill intracellular pathogens by activating macrophages

176
Q

What is required to form a cytotoxic t cell (CTL or Tc)

A

CD8 and MHC I and TCR (t cell receptor)

177
Q

What chemicals released from Cytotoxic T cells lead to apoptosis or pathogen killing?

A

CTL forms proteolytic granules and releases perforins (apoptosis) and granulysin (killing of pathogen)

178
Q

**Describe Th1 (CD4) activation

A
  • APC presents Ag with MHC II to a naïve CD4 T cell
  • Stimulation with high levels of IL-12 activate naïve cells to CD4 Th1 cells
  • Th1 cells travel to secondary lymphoid tissue (spleen, lymph nodes)
  • Activated CD4 Th1 cells proliferate (clonal expansion)
  • Th1 cell recognises Ag on infected cells (with MHC II) via TCR (CD4)
  • Th1 secretes INFγ – stop virus spread (apoptosis)
179
Q

Which of the following statements regarding B cells is false:
*B cells express membrane bound Ig (IgM or IgD
monomer)
*Each B cell can only make one Ab that will only bind
one epitope on one Antigen
*We are born with more than 10^9 immature B cells
*B cells that recognise self are killed in spleen

A

B cells that recognise self are killed in the bone marrow

We ARE born with over 10^9 immature B cells

180
Q

Where are B cells that recognise self killed?

A

Bone Marrow

181
Q

What Membrane bound Igs are expressed on B cells

A

IgM or IgD monomer

mIgM

182
Q

Describe process of B cells presenting Ag to T cells via MHC II

A

-mIgM (or mIgD) binds Ag
-Phagocytosis
-Peptide displayed on surface with MHC II
-TCR of naive Th (CD4) binds to MHC II
(Lots of other co-stimulatory molecules required)

183
Q

Describe process of forming plasma or memory cells from the APC engulfing the Ag (extrinsic) and presenting it

A

-APC eats Ag (extrinsic) and presents it to naïve CD4+ T cells (via MHC II)
-These turn into primed Th2 cells
-Th2 cells bind to B cells that are presenting Ag (via MHC II). This Ag
has been captured using the mIgR on cell surface.
-Th2 cell secretes cytokines (IL-4, IL-5, IL-10 and IL-13)
-These cause B cells to divide by CLONAL EXPANSION and differentiate into Plasma cells (AFC) and Memory B cells (Bm)

184
Q

What is an AFC?

A

Antibody Forming Cell

185
Q

What are primary lymphoid organs of body?

A

Thymus

Bone marrow

186
Q

What are secondary lymphoid organs of body?

A 
Waldeyers ring (tonsils and adenoids)
Bronchus associated lymphoid tissue
Lymphoid nodules
Peyers Patch
Urogenital Lymphoid tissue
187
Q

Give examples of lymphatic vessels important

A

Thoracic Duct

188
Q

What type of antibody is generally secreted by plasma cells

A

IgM

of same specificity of plasma cells, but later these turn into IgG (still keeping same specificity)

189
Q

What is conversion of IgM to IgG called (B cell activation)

A

Class switching

190
Q

What are 3 functions of antibody

A
  • Neutralise toxin by binding to it
  • Increase opsonisation - phagocytosis
  • Activate complement
191
Q

Very briefly describe vaccination

A

(inactive) Toxoid injected to trigger primary antibody response and produce memory B cells.
Then in natural infection secondary antibody response triggered which is much quicker and bigger and destroy toxins and invading organisms.
(Acquired immunity)

192
Q

What 3 layers are formed from centrifuging a blood sample and what is found at each of these layers?

A

Upper layer:
Plasma - straw coloured liquid
-90% water, also electrolytes, proteins, lipids, sugars etc

Middle Layer: (Thin)
Buffy Coat of White Blood cells
-leukocytes

Lower Layer: (approx 45% of blood)
-Erythrocytes, platelets (Haematocrit)

193
Q

What is serum?

A

Plasma without fibrinogen and other clotting factors

194
Q

What is source and role of cytokine IL-1

A

Source - Macrophages, Endothelial and Epithelial cells

Role - Induces inflammation, fever, activation of leukocytes

195
Q

What is source and role of cytokine IL-2

A

Source - Tcells

Role - Stimulates T, B and NK cell growth

196
Q

What is source and role of cytokine IL-4

A

Source - Th2 cells; mast cells

Role - induces IgE production; promotes Th2 differentiation (autocrine)

197
Q

What is source and role of cytokine IL-8

A

Source - macrophages, endothelium, fibroblasts, keratinocytes
Role - Induces neutrophil chemotaxis

198
Q

What is source and role of cytokine IL-10

A

Source - monocytes, Th2 cells

Role - Down-regulates Th1 cytokines, MHC II expression

199
Q

What is source and role of cytokine Interferon gamma

A

Source - Th1 cells, NK cells

Role - Activates macrophages and NK cells; increases MHC II expression

200
Q

What is source and role of cytokine Tumour Necrosis Factor - alpha (TNF - alpha)

A

Source - T cells, macrophage, NK cells

Role - Activates neutrophils, endothelial cells; induces cachexia (wasting away of muscle and body fat)

201
Q

What is cachexia

A

Loss/Wasting of muscle and body fat

202
Q

What are 3 subgroups of T helper cells and how do they differ?

A

Th1, Th2, TREG cells

Differ in the types of cytokines they make

203
Q

What cytokines are produced by Th1 cells?

A

IL-2
Interferon-gamma
TNF-beta

204
Q

What cytokines are produced by Th2 cells?

A 
IL-4
IL-5
IL-6
IL-10 (also TREG cells)
IL-13
205
Q

What cytokines are produced by TREG cells?

A

IL-10
TGF-beta
(down regulates other T-cell subsets)

206
Q

What are functions of Th2 cells?

A

Activate eosinophils and mast cells
Induce B cells to make IgE - promotes release of inflammatory mediators e.g. histamine from mast cells
Releases IL-4 and IL-13 important in helminth infections and allergy

207
Q

*What are functions of Th1 cells?

A

Activate macrophages to cause inflammation
Promotes production of cytotoxic T cells
Important in intracellular infections
Induce B cells to make IgG antibodies

208
Q

How does the Fab region of antibody protect against infection?

A 
Specific binding/multivalency:
Neutralise e.g. toxins (IgG, IgA)
Immobilise motile microbes (IgM)
Prevent binding to and infection of host cells
Form complexes
209
Q

How does Fc region of antibody protect against infection?

A 
Enhance Innate Mechanisms:
Activate complement (IgG, IgM)
Bind Fc receptors
210
Q

What cells have Fc receptors and which antibodies are each associated to?

A

Phagocytes (IgG or IgA) - enhance phagocytosis

Mast Cells (IgE) - release inflammatory mediators

NK cells (IgG) - enhanced killing of infected cells

211
Q

Research, Diagnostics, Therapy:

What is specificity and indication for product OKT3

A

CD3

Transplant Rejection

212
Q

Research, Diagnostics, Therapy:

What is specificity and indication for product Campath

A

CD52

Chronic lymphocytic leukemia

213
Q

Research, Diagnostics, Therapy:

What is specificity and indication for product Herceptin

A

Her-2

Breast cancer

214
Q

Research, Diagnostics, Therapy:

What is specificity and indication for product Remicade

A

TNF-alpha

Crohn’s disease, rheumatoid arthritis

215
Q

Research, Diagnostics, Therapy:

What is specificity and indication for product CroFab

A

Snake venom

Rattle snake antidote

216
Q

Research, Diagnostics, Therapy:

What is specificity and indication for product Synagis

A

RSV

Respiratory syncytial virus

217
Q

What ligands are recognised by TLR 1/2

A

Gram positive lipopeptides (exogenous)

218
Q

What ligands are recognised by TLR 3

A

Double-stranded RNA (exogenous)

mRNA (endogenous)

219
Q

What ligands are recognised by TLR 4

A

LPS, pneumolysin, viral proteins (exogenous)

Heat shock proteins, HMGB1, hyaluronan, fibrinogen (endogenous)

220
Q

What ligands are recognised by TLR 5

A

Flagellin (exogenous)

221
Q

What ligands are recognised by TLR 2/6

A

Gram POSITIVE lipopeptides

Gram negative also noticed by TLR 2

222
Q

What ligands are recognised by TLR 7 or 8

A

Single-stranded RNA (exogenous)

223
Q

What ligands are recognised by TLR 9

A 
CpG DNA (exogenous)
DNA, mitochondrial DNA? (endogenous)
224
Q

What are NLRs

A

Nod-Like Receptors
(Best known are NOD1, NOD2, NLRP3)
Detect intracellular microbial pathogens

225
Q

What is function of NOD2

A

Recognises MDP (muramyl dipeptide), a breakdown product of peptidoglycan.
Activates inflammatory signalling pathways.
Can also activate anti-viral signalling

226
Q

What disease can result from non-functioning NOD2 mutation?

A

Crohn’s disease

227
Q

What disease can result from a hyper-functioning NOD2 mutation?

A 
Blau syndrome
(Rare; Chronic granulomatous inflammation of skin, eyes and joints)
228
Q

What are RLRs

A

PRR type
Best known are RIG-1 and MDA5 - roles to detect intracellular dsRNA and DNA - viral.
They couple effectively to activate interferon production, enabling an antiviral response.

229
Q

What are 2 groups of PRRs

A

Secreted and circulating PRRs

Cell-associated PRRs

230
Q

Give example fo secreted/circulating PRRs

A

Antimicrobial peptides secreted in lining fluids, from epithelial and phagocytes e.g. Defensins and Cathelicidin

Lectins and Collectins:
Carbohdrate-containing proteins that bind carbs or lipids in microbe walls. Activate complement and improve phagocytosis.

Pentraxins:
Can react with C protein of pneumococci, activate complement and promote phagocytosis

231
Q

Give examples of cell-associated PRRs

A

Receptors present on cell membrane or in the cytosol of cells
Recognise a broad range of molecular patterns
e.g. TLRs

232
Q

Describe importance of TLR4

and result of its activation

A 
Recognises LPS (lipopolysaccharide), a component present in many Gram-negative bacteria and some Gram-positive.
Activation of TLR4 leads to intracellular signalling pathway NF-κB and inflammatory cytokine production responsible for activating the innate immune system.
233
Q

What is NF-κB?

A

Nuclear factor kappa-light-chain-enhancer of activated B cells

Protein complex that controls transcription of DNA, cytokine production and cell survival.

Involved in cellular responses to stimuli such as stress, cytokines, free radicals, UV irradiation, oxidised LDL and bacterial/viral antigens.

Key role in regulating immune response to infection. Incorrect regulation linked to cancer, autoimmunity, viral infection, septic shock and improper immune development.

234
Q 
Which of the following is NOT an organ-specific auto-immune disease?
Type 1 diabetes mellitus
Ulcerative colitis
Graves disease
Hashimoto's thyroiditis
Sjorgen's syndrome
A

Ulcerative colitis

235
Q 
Which of the following is a classical PAMP
Interleukin 12
Heat shock protein 70
RIG-I
Lipopolysaccharide
Toll-like receptor 2
A

Lipopolysaccharide

236
Q

Which of the following answers is NOT true? Biological therapies for autoimmune diseases…:
are usually delivered with a low dose of the cytotoxic drug methotrexate
have no risk of bacterial infection, unlike conventional treatments
include adalimumab, tocilizumab and retuximab
are immunosuppressive and are always injected
are comparatively very expensive and only prescribed in the NHS once conventional therapies have failed

A

NOT true:

Biological therapies for autoimmune diseases have no risk of bacterial infection, unlike conventional treatments

237
Q

Which of the following are features of the adaptive immune response?
Its efficiency is not affected by prior contact with the pathogen
It would not work without B and T lymphocytes
It lacks specificity
It generally distinguishes self from non-self
Its effectiveness is enhanced by complement

A

It would not work without B and T lymphocytes

238
Q

Which of the following functions of T lymphocytes is true:
T lymphocytes mature in thyroid gland
All T cells secrete cytotoxic materials
T cells respond to proteins on surface of host cells
T cells secrete IgG when they are activated

A

T cells respond to proteins on surface of host cells

239
Q

What is Hashimoto’s thyroiditis

A

Autoimmune disease in which immune system attacks body’s thyroid
aka Chronic Lymphocytic Thyroiditis

240
Q

What is Graves disease

A

Thyroid autoimmune disease

Most common cause of hyperthyroidism and often results in enlarged thyroid

241
Q

What is Sjorgen’s syndrome

A

Autoimmune disease that affects the body’s moisture-producing glands

242
Q

What are primary symptoms of Sjorgen’s syndrome

A

Dry mouth and dry eyes

243
Q

Explain the distinction/difference between Fibrin and fibrous

A

Fibrin is deposited in BVs and tissues or on surfaces (e.g. in acute inflammation) as a result of the action of thrombin on fibrinogen.
Fibrous describes the texture of non-mineralised tissue of which the principal component is collagen (e.g. scar tissue)

244
Q

Explain the distinction/difference between Monocytes, macrophages and histocytes

A

Monocytes are newly formed cells of the mononuclear phagocyte system. After a few hours in the blood, they enter tissues and undergo further differentiation into macrophages.
Some macrophages in tissues have specific features and names (e.g. Kupffer cells), others are referred to as histiocytes

245
Q

*Explain the distinction/difference between Granuloma and Granulation tissue

A

Granuloma is an aggregate of epithelioid histiocytes and feature of some specific chronic inflammatory disorders.
Granulation tissue is an important component of healing and comprises small blood vessels in a connective tissue matrix with myofibroblasts.

246
Q

Explain the distinction/difference between Exudate and Transudate

A

Exudates hae a high protein content as they result from increased vascular permeability.
Transudates have a LOW protein content as the vessels have normal permeability characteristics.

247
Q

Explain the distinction/difference between Acute and chronic inflammation

A

in inflammation, acute and chronic denote both the dynamics and character of the process.
Acute inflammation has a relatively rapid onset and (usually) resolution. Neutrophil polymorphs are also the most abundant cell.
Chronic inflammation has a relatively insidious onset, prolonged course and slow resolution. Lymphocytes, plasma cells and macrophages (sometimes with granuloma formation) are the most abundant cells.

248
Q

**Causes of acute inflammation (easy exam q)

A
  • Microbial infections e.g pyogenic (pus causing) bacteria, viruses
  • Hypersensitivity reactions e.g parasites, tubercle bacilli
  • Physical agents e.g trauma, ionising radiation, heat, cold (frost-bite) - Chemicals e.g corrosives, acids, alkalis, reducing agents
  • Bacterial toxins
  • Tissue necrosis e.g. ischaemic infarction
249
Q

Essential macroscopic appearances of acute inflammation (and latin translation where appropriate)

A
  • Redness - rubor
  • Heat - calor
  • Swelling - tumor
  • Pain - dolor
  • Loss of function is also characteristic
250
Q

What is fibrinolytic system

A

Generating plasmin which causes fibrin dissolution

Starts with release of plasminogen activator (t-PA) from endothelial cells. t-PA convert plasminogen to plasmin

251
Q

Define scar

A

The connective tissue forming a scar and composed chiefly of fibroblasts in recent scars and largely of dense collagenous fibres in old scars.

Medicine Phase 2a (22 decks)

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