Immunology Flashcards

1
Q

What do all blood cells derive from?

A

Multipotential haematopoietic stem cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What do common myeloid progenitors specialise into?

A

Megakaryocytes
Erythrocytes
Mast cells
Myeloblasts

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What do megakaryocytes specialise into?

A

Platelets

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What do myeloblasts specialise into?

A

Basophils
Neutrophils
Eosinophils
Monocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What do monocytes specialise into?

A

Macrophages and dendritic cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What do common lymphoid progenitors specialise into?

A

NK cells and small lymphocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What do small lymphocytes specialise into?

A

T and B lymphocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the innate immune system?

A

The initial rapid and non-specific response to antigenic material with no immunological memory

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What do haematopoietic stem cells specialise into?

A

Lymphoid and myeloid progenitors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What causes acute lymphocytic leukaemia (ALL)?

A

Lymphoid progenitors causing increased amounts of immature lymphocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What cells does chronic lymphocytic leukaemia affect (CLL)?

A

Naïve (not exposed to antigen) mature B cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What cells do lymphomas affect?

A

Mature naïve T cells and B cells in germinal centres

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is multiple myeloma?

A

Cancer of plasma cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is acute myeloid leukaemia (AML)?

A

Cancer of myeloid progenitors causing a decrease in their downstream cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Give some examples of myeloproliferative disorders

A

Chronic myeloid leukaemia

Proliferation of granulocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are the primary lymphoid organs?

A

Bone marrow and thymus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Where do all immune cells originate from?

A

Bone marrow

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Where do B cells mature?

A

Bone marrow

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Where do T cells mature?

A

Thymus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What are the secondary lymphoid organs?

A

Lymph nodes and spleen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What happens within the lymph nodes?

A

Site of B and T cell interaction. They also interact with dendritic cells that are delivering the antigen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What happens within the spleen?

A

Site of removal of RBCs and Ab-coated bacteria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What are the tertiary lymphoid organs?

A

Transient formation of germinal centres, usually pathology related

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What is the role of secondary lymphoid tissues?

A

(Lymph nodes) provide the stage to allow foreign antigen to interact with lymphocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What are tertiary lymphoid organs?

A

Lymph node like ectopic structures that form during chronic inflammation such as in chronic infection, transplant graft rejection and autoimmunity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Give an example of a condition where tertiary lymphoid organs are involved.

A

In multiple sclerosis focal TLOs form in the brain which produces anti-myelin antibody leading to the demyelinating pathology

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What happens to dendritic cells once they enter the lymph nodes?

A

DC enter with Ag in afferent lymphatics and interact with naïve CD4+ cells to activate them in the paracortex. T cell either become effector cells or memory cells.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What are lymphoid follicles?

A

Germinal centres which are the site of somatic hypermutation (this achieves a higher affinity Fab and class switching)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What is the role of the red pulp of the spleen?

A

Mechanical filtration of RBCs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What is the role of the white pulp in the spleen?

A

Active immune responses through humoral and cell-mediated immunity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What makes up the white pulp of the spleen?

A

Primary follicles
Marginal zone
Periarteriolar lymphoid sheath (PALS)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

What is found within the periarteriolar lymphoid sheath (PALS) of the spleen?

A

Rich in T cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

What is found within the lymphoid follicles of the spleen?

A

Rich in B cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

What is the role of the spleen only in the foetus?

A

Production of RBCs up to the 5th month of gestation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

What is the role of the spleen in people with thalassaemia?

A

Results in haemolytic anaemia so the spleen produces RBCs once more

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

What is thalassaemia?

A

Decreased Hb

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

What does the spleen store?

A

RBCs, lymphocytes, platelets and other elements

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

What percentage of lymphocytes are stored in the spleen?

A

~25%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

What percentage of RBCs are stored in the spleen?

A

~30%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

When are the RBCs stored in the spleen released?

A

In hypovolaemia and hypoxia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

What does the spleen clear from circulation?

A

Old platelets

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

Describe the receptors of the innate immune system.

A

Primitive and broad

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

Describe the receptors of the adaptive immune system.

A

Highly specific (T and B cell receptors)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

Describe the kinetics of the innate immune system.

A

Fast (hours-days)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

Describe the kinetics of the adaptive immune system.

A

Slow (days-weeks)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

What type of immunity is highly regulated?

A

Adaptive immunity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

What type of immunity can be amplified?

A

Adaptive immunity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

What type of immunity can self-discriminate?

A

Adaptive immunity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

Describe the duration of the innate immune response.

A

Short (days)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

Describe the duration of the adaptive immune response.

A

Long (months/years)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

What type of immunity has an aspect of memory?

A

Adaptive immunity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

Which WBC is most abundant in the blood?

A

Neutrophils

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

What percentage of WBC in the blood is neutrophils?

A

70%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

Describe the lifespan of neutrophils.

A

Short lived

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

Where do neutrophils travel to?

A

Rapidly egress into tissues during acute infection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

What type of cell is a neutrophil (other than being a WBC)

A

Phagocytic and bactericidal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

Describe the nucleus of a neutrophil.

A

Polymorphonuclear cells (multilobed)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

What are pathogens detected by in phagocytosis?

A

Pattern recognition receptors of innate phagocytic cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

What is the principal cell of acute inflammation?

A

Neutrophils

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q

How do neutrophils carry out phagocytosis?

A

They kill by internalising bacteria and degranulating their contents into a phagolysosome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

What are the major components found within a phagolysosome?

A

Alpha-defensins and lactoferrin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
62
Q

Other than phagocytosis, how else can neutrophils kill bacteria?

A

Respiratory burst

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
63
Q

What is the first stage of the respiratory burst carried out by neutrophils?

A

Electrons are pumped into the phagolysosome by NADPH oxidase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
64
Q

What happens after electrons have been pumped into the phagolysosome during the respiratory burst carried out by neutrophils?

A

The electrons combine with molecular oxygen to produce superoxide ions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
65
Q

What happens after the formation of superoxide ions during the respiratory burst carried out by neutrophils?

A

These ions combine with protons present in the granules to produce peroxide which is bactericidal in itself

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
66
Q

What happens after the formation of peroxide during the respiratory burst carried out by neutrophils?

A

Myeloperoxidase can then chlorinate the peroxide to produce a hypohalous acid which is also bactericidal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
67
Q

What is the first stage in the movement of neutrophils out of capillaries in acute inflammation?

A

E-selectin is activated by IL-1 and TNF-α from damaged cells, and binds to the glycoprotein CD15 on neutrophils in blood

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
68
Q

What is E-selectin?

A

An adhesion molecule on the capillary endothelium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
69
Q

What happens in the movement of neutrophils out of capillaries in acute inflammation after the neutrophils have bound to E-selectin?

A

This causes neutrophils in the blood to slow down and roll along the endothelium lining

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
70
Q

What happens in the movement of neutrophils out of capillaries in acute inflammation after neutrophils have rolled along the endothelium lining?

A

ICAM-1 on endothelium (induced by LPS, IL-1, TNF-α) binds to integrin on neutrophil; the neutrophil stops

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
71
Q

What happens in the movement of neutrophils out of capillaries in acute inflammation after neutrophils have stopped rolling?

A

Diapedesis: neutrophil squeezes through endothelium (holes caused by C3a, C5a, chemokines, histamines, prostaglandins, leukotrienes (causing smooth muscle contractions in the bronchioles))

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
72
Q

What is the role of macrophages?

A

Phagocytosis, antigen presentation and cytokine secretion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
73
Q

What cytokines do macrophages secrete?

A

TNFα, IL-1, IL-6, IL-8, and IL-12

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
74
Q

Describe the nuclei of macrophages.

A

Round single nuclei often with a small indentation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
75
Q

What do macrophages derive from?

A

Blood monocytes or as tissue resident macrophages

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
76
Q

How do macrophages detect pathogens?

A

Detect pathogens and damage markers by pattern recognition receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
77
Q

In what type of inflammation are macrophages one of the principal cells?

A

Chronic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
78
Q

Where do tissue resident macrophages derive from?

A

Tissue resident macrophages are derived from the yolk sac and foetal liver during development

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
79
Q

Where are tissue resident macrophages found?

A

Persist in tissues via self renewal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
80
Q

What are M1 macrophages?

A

M1 is considered pro-inflammatory due to its ability to metabolise arginine to nitric oxide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
81
Q

What are M2 macrophages?

A

M2 are considered anti-inflammatory due to their ability to metabolise arginine to the repair molecule ornithine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
82
Q

What do pattern recognition receptors (PRRs) on macrophages detect?

A

Pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
83
Q

What is the role of TLR4?

A

Found on macrophages and detects LPS on g-ve bacteria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
84
Q

Where do antibodies bind to pathogens?

A

By their Fab regions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
85
Q

How do macrophages use receptors and antibodies to phagocytose bacteria?

A

Macrophages have Fc receptors that bind antibody and in turn phagocytoses the bacteria the antibody has bound

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
86
Q

What do macrophages do when antibodies bind to pathogens?

A

Complement then binds antibody Fc regions forming a complex. Macrophages have complement receptors that recognise this complex

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
87
Q

When do basophils release histamine?

A

Upon IgE crosslinking Fcε receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
88
Q

What do basophils release?

A

Histamine, serotonin and heparin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
89
Q

In what conditions are basophils important?

A

Asthma, anaphylaxis, atopic dermatitis, and hay fever

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
90
Q

What cells can basophils be compared to?

A

Circulating mast cells - they do not egress into tissues and become mast cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
91
Q

What type of infection are eosinophils important in?

A

Parasitic infections

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
92
Q

What do eosinophils release?

A

Release cationic granules such as major basic protein, ROS, eicosanoids, leukotrienes, elastase etc.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
93
Q

What cells are classed as granulocytes?

A

BEN: basophils, eosinophils and neutrophils

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
94
Q

What is the role of mast cells?

A

Important in parasitic infection and allergic reactions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
95
Q

Where are mast cells found?

A

At mucosal surfaces

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
96
Q

What is important for the development of mast cells?

A

Stem cell factor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
97
Q

What cell is the main source of histamine?

A

Mast cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
98
Q

How are mast cells activated?

A

By immune complex IgE cross-linking FcεR1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
99
Q

What do mast cells secrete?

A

Histamine, cytokines (IL-4, IL-13 and TNFα) and lipid mediators (leukotrienes and prostaglandins)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
100
Q

What does histamine do?

A

Increases vascular permeability and causes smooth muscle contraction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
101
Q

What does IL-4 do?

A

Promotes Th2 differentiation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
102
Q

What does IL-13 do?

A

Promotes IgE production

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
103
Q

What does TNFα do?

A

Promotes tissue inflammation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
104
Q

What do lipid mediators such as leukotrienes and prostaglandins do?

A

Increase vascular permeability
Cause smooth muscle contraction
Stimulate mucus secretion
Chemoattractants for T cells, eosinophils, mast cells and basophils

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
105
Q

What happens when IgE binds to an allergen?

A

Activates mast cells via Fc receptor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
106
Q

Where are NK cells found?

A

In blood and tissues

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
107
Q

What receptors do macrophages have?

A

CD14+ and CD40+

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
108
Q

What receptors do NK cells have?

A

CD16+

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
109
Q

What process do NK cells use to kill pathogens?

A

Antibody-dependent cellular cytotoxicity (ADCC) - not phagocytic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
110
Q

How do NK cells kill pathogens?

A

Release lytic granules that kill virus infected cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
111
Q

How do NK cells recognise self and non-self?

A

NK cell’s inhibitory receptors detect levels of MHC-I on cell surfaces

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
112
Q

What molecule does ADCC not require?

A

Complement

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
113
Q

How many cell types does ADCC use?

A

1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
114
Q

What is the first stage of ADCC?

A

IgG will bind surface antigens on the pathogen-infected cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
115
Q

What happens during ADCC once IgG is bound to antigens?

A

NK cells have Fc receptors (CD16) that recognise the antibody Fc region

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
116
Q

What happens during ADCC once NK cells have bound to the antibody?

A

This cross-linking triggers degranulation and cell apoptosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
117
Q

How do viruses become antibody targets?

A

Viral proteins are expressed on the surface of cells during viral replication

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
118
Q

What do the lytic granules of NK cells contain?

A

Perforin and granzymes that induce apoptosis and cell lysis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
119
Q

What is the effect of cancer on NK cells?

A

Cancers tend to downregulate MHC-I mediated antigen presentation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
120
Q

What happens if there is not enough MHC-1 on the cell surface due to cancer?

A

NK cells will activate and try to kill the cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
121
Q

What is the purpose of MHC-!?

A

Cells that have MHC-I activate the inhibitory receptor and therefore does not elicit a response from NK cells.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
122
Q

When do cytotoxic T cells act on tumour cells?

A

In response to NK cell cytokine production

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
123
Q

What are the professional antigen presenting cells?

A

Macrophages
B cells
Dendritic cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
124
Q

What do the professional antigen presenting cells present?

A

Exogenous Ag on cell surface in the context of MHC-II

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
125
Q

Which type of cell is the most potent antigen presenting cell?

A

Dendritic cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
126
Q

Where do dendritic cells travel to?

A

Egress to secondary organs to aid the adaptive response

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
127
Q

Which cells are capable of MHC-I presentation?

A

All nucleated cells (although thrombocytes are anucleate and still have MHC-I molecules but RBCs do not)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
128
Q

Which chromosome codes for MHC molecules?

A

Chromosome 6

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
129
Q

Where is exogenous antigen processed in antigen presenting cells?

A

ER

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
130
Q

Give some examples of endogenous proteins that might be present in the cytosol of an antigen presenting cell.

A

Viral proteins

Cancer-related proteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
131
Q

Where are endogenous proteins processed in antigen-presenting cells?

A

Endosomes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
132
Q

How are endogenous proteins presented on antigen-presenting cells?

A

In the context of MHC-I

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
133
Q

Which cells are capable of cross-presentation?

A

Dendritic cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
134
Q

How do dendritic cells carry out cross-presentation?

A

They can present exogenous Ag in the context of MHC-I in order to activate Tc cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
135
Q

What can dendritic cells be thought of as?

A

The bridge between the innate and adaptive immune responses in secondary lymphoid organs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
136
Q

What happens when immune cells come together?

A

They form an immune synapse

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
137
Q

What must happen for a response to occur upon formation of an immune synapse?

A

Binding of primary receptors e.g. TCR to MHC-II
Binding of co-stimulatory molecules e.g. CD28/CTLA4 to CD80/CD86
A robust release of the appropriate cytokines

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
138
Q

What happens if there is MHC binding without other stimulation?

A

Anergy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
139
Q

What is anergy?

A

T cell anergy is a tolerance mechanism in which the lymphocyte is intrinsically functionally inactivated following an antigen encounter

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
140
Q

What happens to T cells during initial encounter with a novel antigen?

A

T cell will differentiate into either memory or effector T cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
141
Q

What is the common T cell marker?

A

CD3 - the identifying co-stimulating molecule for all T cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
142
Q

What are the 2 different T cells following maturation?

A

CD4 or CD8

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
143
Q

What receptors do T cells have?

A

CD3
CD4/CD8
T cell receptor - TCR
CD25

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
144
Q

What is the main function of the CD3 molecule?

A

Intracellular signalling that activates the T cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
145
Q

What is the structure of the CD3 molecule?

A

It is a protein complex comprised of one gamma, one theta, and two epsilon polypeptide chains.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
146
Q

What do T cells start off as?

A

In the bone marrow as HSCs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
147
Q

What do T cells differentiate into from HSCs?

A

Differentiate through the lymphoid pathway into immature T cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
148
Q

What are naïve T cells?

A

Not encountered the antigen yet. How immature T cells start as.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
149
Q

Do naïve T cells present CD4 or CD8?

A

Both - they are double positive cells.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
150
Q

What happens to naïve T cells during maturation?

A

They undergo thymic education to retain either CD4 or CD8, and they undergo VDJ recombination in the thymus to determine the antigen epitope that their TCR will recognise

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
151
Q

How do T cells recognise antigens?

A

T-cells must recognise antigen in the context of MHC molecules using their T-cell receptors (except for superantigens)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
152
Q

What do superantigens do?

A

Superantigens bind the beta chain of TCR regardless of TCR

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
153
Q

How are naïve T cells identified?

A

Naïve T cells are identified by being CD45RA+

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
154
Q

How are memory T cells identified?

A

Memory T cells are identified by being CD45RO+

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
155
Q

What receptors do cytotoxic T cells present?

A

CD8

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
156
Q

What do cytotoxic T cells release?

A

Perforins and granzymes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
157
Q

How do cytotoxic T cells recognise Ag?

A

In the context of MHC-I

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
158
Q

What do cytotoxic T cells become?

A

Effector or memory cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
159
Q

How can cytotoxic T cells kill pathogens?

A

Perforin and granzymes

Expression of Fas ligand

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
160
Q

How do cytotoxic T cells use perforin to kill pathogens?

A

Allows salt and water to enter cells and causing them to lyse

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
161
Q

How do cytotoxic T cells use granzymes to kill pathogens?

A

They cleave a caspase protein (CPP-32) which will activate a nuclease (CAD) which initiations DNA degradation and apoptosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
162
Q

What are granzymes?

A

Group of serine proteases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
163
Q

What is perforin?

A

Pore forming cytolytic protein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
164
Q

How do T cells use the Fas ligand to kill pathogens?

A

CD8 T cells also express the Fas ligand, this binds Fas on target cells which activates the caspase cascade and therefore apoptosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
165
Q

What type of immunity are Th1 cells involved in?

A

Cell-mediated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
166
Q

What do Th1 cells do?

A

Activate/regulate macrophages, monocytes, cytotoxic T cells and NK cells
Elimination of cellular antigens (viruses, intracellular bacteria, tumour cells)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
167
Q

What type of immunity are Th2 cells involved in?

A

Humoral

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
168
Q

What do Th2 cells do?

A

Stimulation of B cells
Boost in the synthesis of IgE, IgG1 and IgG3 antibodies
Regulate eosinophils, basophils and mast cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
169
Q

What are Treg cells the principle cell in?

A

Peripheral immune tolerance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
170
Q

What is the key cytokine of Treg cells?

A

IL-10

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
171
Q

What is the role of IL-10?

A

Mass anti-inflammatory action

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
172
Q

Where are Th17 cells important?

A

Mucosal membranes

173
Q

What is the principle cytokine of Th17 cells?

A

IL-17

174
Q

What does IL-17 do?

A

Affects innate immune cells to produce IL-8

175
Q

What is the relationship between Treg and Th17 cells?

A

They are antagonistic

176
Q

How are Treg and Th17 cells antagonistic?

A

Transcription factors and cytokines produced by Th17 cells suppressive T reg cells and vice versa

177
Q

What is the purpose of IL-8?

A

The most important cytokine in neutrophil production and recruitment

178
Q

What is the purpose of IL-23?

A

IL-23 maintains Th17 populations and is a target for biologics

179
Q

What receptors do B cells have?

A

BCR - B cell receptor
CD19
CD20
(CD15)

180
Q

What is the CD19 receptor?

A

Co-stimulatory molecule of mature B cells

181
Q

What is the CD20 receptor?

A

Mature B cell marker

182
Q

Where does B cell activation take place?

A

Secondary lymphoid organs (lymph nodes)

183
Q

What 2 processes are aided by dendritic and T cells?

A

Somatic hypermutation and affinity selection

184
Q

What can activated B cells become?

A

Short lived plasma cells (IgM+) or long-lived plasma cells (IgG, E, or A+)

185
Q

How are B cells activated in the absence of T cell help?

A

Directly by antigen

186
Q

Describe the response when B cells are activated directly by the antigen.

A

Rapid but short lived response

Less affinity and IgM releasing

187
Q

How are B cells activated?

A

When they internalise antigen and present it to T cells in the context of MHC II

188
Q

What happens to B cells after activation?

A

They migrate to newly formed germinal centres to undergo somatic hypermutation

189
Q

What is somatic hypermutation?

A

When RAG enzymes (activation-induced cysteine deaminase - AID) introduce random mutations in the variable region of the antibody gene

190
Q

What is the role of dendritic cells within the germinal centres?

A

They will present the same antigen to the B cell to test if the avidity of its antibodies has increased (affinity selection)

191
Q

What is affinity selection?

A

B cells with less avidity will be negatively selected and those with greater avidity will be positively selected and undergo class switching and clonal proliferation

192
Q

What type of cell appears in Hodgkin lymphoma?

A

Reed-Sternberg cells

193
Q

What are Reed-Sternberg cells?

A

These are B-cell derived giant cells that are distinctive of Hodgkin lymphoma

194
Q

What is the distinctive marker of Reed-Sternberg cells?

A

CD15

195
Q

What do Reed-Sternberg cells look like?

A

They have prominenteosinophilicinclusion-likenucleoli(thus resembling an “owl’s eye” appearance) under microscopy

196
Q

What B cell receptor is targeted by rituximab?

A

CD20

197
Q

Which part of the lymph node is the B cell region?

A

Cortex

198
Q

Which part of the lymph node is the T cell region?

A

Paracortex

199
Q

Which part of the lymph node is the plasma cell region?

A

Medulla

200
Q

What happens when memory B cells encounter their specific antigen?

A

They become activated and undergo clonal proliferation and begin secreting IgG

201
Q

What does the constant region of antibodies do?

A

Determines antibody type and therefore effector function

202
Q

What does the Fab (antigen-binding fragment) region of antibodies do?

A

Binds epitopes of antigen

203
Q

How are Fab regions determined?

A

Initially determined by a process called VDJ recombination during maturation in the bone marrow

204
Q

When does the avidity of an antibody for its antigen increase?

A

During infection through somatic hypermutation in the germinal centres of secondary organs

205
Q

What is the Fc (fragment crystallisation) region of antibodies?

A

The area that binds Fc receptors on immune cell surfaces

206
Q

What does the Fc region of antibodies do?

A

Binds complement to aid in opsonisation of pathogens for phagocytosis

207
Q

What are the functions of antibodies?

A

Neutralisation of toxins, opsonisation of pathogens, complement activation via the classical pathway

208
Q

Where is IgA found and what as?

A

The mucosal Ab as a dimer

209
Q

What fluid is IgA found in?

A

Present in colostrum and coats neonate gut

210
Q

What does IgM look like?

A

Pentameric

211
Q

What are the features of IgM?

A

Not entirely specific to antigen

Highest capacity to activate complement

212
Q

What antibody is most abundant in the blood?

A

IgG

213
Q

How many subclasses of IgG are there?

A

4

214
Q

Which antibody can cross the placenta?

A

IgG

215
Q

What are the features of IgG?

A

Highly specific

Important during secondary responses (second infection - levels spike most of all antibodies)

216
Q

What antibody is least abundant in the blood?

A

IgE

217
Q

What is IgE bound to?

A

Mast cells and basophils by FcεR

218
Q

What is IgE important in?

A

Allergy and helminth infection

219
Q

What are the features of IgD?

A

Not that important. Function is debated in the literature

220
Q

What does IL-5 promote?

A

IgA class switching

221
Q

What does IL-4 promote?

A

IgE class switching

222
Q

What does colostrum contain?

A

IgA, IgM, and IgG where IgA is the principle antibody

223
Q

What is type I hypersensitivity?

A

Anaphylactic

224
Q

What is type II hypersensitivity?

A

Cell bound

225
Q

What is type III hypersensitivity?

A

Immune complex

226
Q

What is type IV hypersensitivity?

A

Delayed hypersensitivity

227
Q

What is the mechanism of type I hypersensitivity?

A

Antigen reacts with IgE bound to mast cells

228
Q

Give some examples of type I hypersensitivity.

A

Anaphylaxis


Atopy (e.g.asthma, eczema andhayfever)

229
Q

What is the mechanism of type II hypersensitivity?

A

IgG or IgM binds to antigen on cell surface

230
Q

Give some examples of type II hypersensitivity.

A

Autoimmune haemolytic anaemia
Goodpasture’s syndrome
Pernicious anaemia
Rheumatic fever

231
Q

What is the mechanism of type III hypersensitivity?

A

Free antigen and antibody (IgG, IgA) combine

232
Q

Give some examples of type III hypersensitivity.

A

Systemic lupus erythematosus

Post-streptococcal glomerulonephritis

233
Q

What is the mechanism of type IV hypersensitivity?

A

T-cell mediated (Th1)

234
Q

Give some examples of type IV hypersensitivity.

A

Tuberculosis/tuberculin skin reaction
Graft versus host disease
Multiple sclerosis
Guillain-Barre syndrome

235
Q

Describe the rate of type I hypersensitivity reactions.

A

Fast reaction occurring in minutes

236
Q

What happens in a type I hypersensitivity reaction?

A

Cross-linking of antigen to IgE on mast cells and basophils causes massive degranulation and therefore massive release of histamine

237
Q

What happens in a type II hypersensitivity reaction?

A

IgM or IgG binds to self antigen leading to cell destruction by the membrane attack complex and cellular mechanisms

238
Q

What is the first stage of a type III hypersensitivity reaction?

A

IgG binds soluble antigen forming a circulating immune complex

239
Q

What happens after IgG has bound soluble antigen in a type III hypersensitivity reaction?

A

These deposit in vessel walls especially in the kidneys

240
Q

What happens after the circulating immune complexes have deposited in vessel walls in a type III hypersensitivity reaction?

A

Here they kick off an inflammatory response causing complement deposition, opsonisation, phagocytosis etc

241
Q

What happens after the inflammatory response in a type III hypersensitivity reaction?

A

RBCs carrying the complement receptor 1 bind complement coated immune complexes and transport them to the liver and spleen for phagocytosis

242
Q

What is the first stage of a type IV hypersensitivity reaction?

A

Th1 are activated by antigen presenting cells

243
Q

What happens after Th1 cells are activated in a type IV hypersensitivity reaction?

A

Memory T cells are formed

244
Q

What happens after memory T cells are formed in a type IV hypersensitivity reaction?

A

When the memory T cells encounter the antigen again they will activate macrophages leading to tissue damage

245
Q

What happens in a type V hypersensitivity reaction?

A

IgM or IgG bind cell surface receptors and either stimulating or blocks endogenous ligand binding

246
Q

Give some examples of type V hypersensitivity reactions.

A

Grave’s disease and myasthenia gravis

247
Q

What happens during anaphylaxis?

A

IgE binds antigen which then cross-links FcεRI on mast cells and basophils leading to massive degranulation and histamine release

248
Q

What is the first thing to administer to an anaphylactic patient?

A

IM adrenaline is 1st line

249
Q

What is given to an anaphylactic patient after adrenaline?

A

Chlorphenamine (antihistamine) and hydrocortisone (cortisol)

250
Q

What do you check if you suspect a patient is anaphylactic?

A
Airway
Breathing
Circulation
Disability
Exposure
251
Q

What do you look for to confirm a patient is anaphylactic?

A

Acute onset of illness
Life threatening airway and/or breathing and/or circulation problems
Skin changes

252
Q

What are some life-threatening airway problems?

A

Swelling, hoarseness, stridor

253
Q

What are some life-threatening breathing problems?

A

Rapid breathing, wheeze, fatigue, cyanosis, SpO2<92%, confusion

254
Q

What are some life-threatening circulation problems?

A

Pale, clammy, low blood pressure, faintness, drowsy/coma

255
Q

How does autoimmunity develop?

A

Thymic education
Tregs
CD4 activation against autoantigen

256
Q

What are the features of autoimmunity?

A

Often relapsing-remitting
Organ-specific vs systemic
Damage to or destruction of tissues
Altered organ growth/function

257
Q

What is central tolerance?

A

When TCRs and BCRs are tested against self antigen

258
Q

Where are B cells tested in central tolerance?

A

Bone marrow

259
Q

What happens to B cells in central tolerance?

A

BCRs that recognise self antigen either leads to clonal deletion (apoptosis), receptor editing, or anergy

260
Q

What is positive selection?

A

T-cells that recognise MHC molecules

261
Q

What happens if T cells can’t recognise MHC molecules in positive selection

A

They don’t receive survival signals

262
Q

How is CD4 or CD8 lineage determined?

A

Positive selection

263
Q

Where does positive and negative selection of T cells take place?

A

Thymus

264
Q

What happens in negative selection?

A

This tests the T cell’s affinity to self

265
Q

What happens if the T cell binds to self antigens in negative selection?

A

They receive signals to apoptose

266
Q

What happens to T cells that pass both positive and negative selection?

A

They move to secondary organs as mature naïve T cells

267
Q

What is peripheral tolerance?

A

Low affinity self reactive T cells can escape the thymus to the periphery

268
Q

What happens in secondary lymphoid organs in peripheral tolerance?

A

T cells are presented self antigen again by dendritic cells and if they recognise they either are clonally deleted or converted to Treg

269
Q

How is autoimmunity treated?

A

Tx involve reducing inflammation and suppressing the immune system. This usually relieves symptoms but do not typically cure.

270
Q

What is the most common CNS immune mediated condition?

A

MS

271
Q

What type of condition is MS?

A

Demyelinating

272
Q

What causes MS?

A

Failure of central and peripheral tolerance to eliminate self reactive T cells. These T cells are reactive to myelin proteins such myelin basic protein.

273
Q

What forms in the brain in MS patients?

A

Tertiary Lymphoid organs form in the brain of MS allowing T and B cell interactions and the generation of autoantibodies

274
Q

What are the different types of MS?

A
Relapsing-remitting (RRMS)
Primary progressive (PPMS)
Secondary progressive (SPMS)
275
Q

What is RRMS?

A

Where there are periods of disease activity and no activity. Often incomplete recovery will occur > disability. Some will progress to secondary progressive

276
Q

What is PPMS?

A

Worsening neurological function from onset of symptoms with no early relapses or remissions

277
Q

What is SPMS?

A

Progressive worsening of neurological function over time. There will be periods of active disease with progression of the disease as well as periods of non-active disease where it still progresses

278
Q

How is MS diagnosed?

A

Spinal tap; demonstrating MS associated autoantibodies
MRI; Highlights brain lesions.
Evoked potential tests,which record the electrical signals produced by your nervous system in response to stimuli

279
Q

How are acute MS attacks managed?

A

IV methylprednisolone

280
Q

How is RRMS managed?

A

Immunomodulators > Interferon beta 1a, or 1b, or peginterferon beta 1a

281
Q

How is SPMS managed?

A

Siponimod or methylprednisolone

282
Q

How is PPMS managed?

A

Ocrelizumab and anti CD20 MAb similar to rituximab

283
Q

What is primary immunodeficiency?

A

Those born with intrinsic defects in their immune system

284
Q

How common is primary immunodeficiency?

A

Rare and mostly genetic disorders

285
Q

Give an example of primary immunodeficiency.

A

SCID - severe combined immunodeficiency

286
Q

What is SCID?

A

Severe combined immunodeficiency (bubble boy disease) = Where both B and T cells lose functionality. The most severe primary immunodeficiency with various genetic causes and subtypes

287
Q

What is the main hallmark of AIDS?

A

Profound immunodeficiency

288
Q

Give some examples of secondary immunodeficiencies.

A

Hypothyroidism, diabetes and hypoglycaemia

289
Q

What is secondary immunodeficiency?

A

These are acquired and are referred to generally as immunosuppression

290
Q

What drugs can induce secondary immunodeficiency?

A

Steroids, azathioprine, chemotherapy

291
Q

What diseases can induce secondary immunodeficiency?

A

Cancers of the bone marrow and blood cells (Leukaemia, Lymphoma, and Myeloma)
AIDS

292
Q

How do steroids cause immunodeficiency?

A

Suppress cell-mediated immunity by inhibiting NF-κB transcription factor which supresses IL-2 production which in turn reduced T cell proliferation

293
Q

How are steroids anti-inflammatory?

A

Steroids, specifically glucocorticoids, are anti-inflammatory by blocking eicosanoid production

294
Q

How does azathioprine cause immunodeficiency?

A

Azathioprine is an immunosuppressive drug that is a purine analogue that inhibits fast proliferating cells such as T cells

295
Q

How does HIV cause immunodeficiency?

A

HIV has a cell tropism for CD4+ T cells. In uncontrolled infection there is increasing destruction of CD4 cells

296
Q

What must the CD4 T cell count be to diagnose AIDS?

A

Once it drops below 200 cells/uL there is profound immunodeficiency and is defining aspect of the development of AIDS

297
Q

What is the negative phase?

A

A period after initial antigen exposure where ones immunity is actually lower than before encountering the antigen.

298
Q

How many doses are most vaccines?

A

A lot of vaccines have an initial “prime” dose followed by a “boost dose”

299
Q

What will an ideal vaccine do?

A

Induce both T and B memory cells

300
Q

What do adjuvants do?

A

Help boost the immune response

301
Q

What is often used to boost the immune response?

A

Viral vectors

302
Q

Where are monocytes found?

A

Bone marrow/blood

303
Q

Where are Kupffer cells found?

A

Liver

304
Q

Where are sinus histocytes found?

A

Lymph nodes

305
Q

Where are alveolar macrophages found?

A

Alveoli

306
Q

Where are tissue macrophages leading to giant cells found

A

Connective tissue

307
Q

Where are microglia found?

A

CNS

308
Q

Where are Hofbauer cells found?

A

Placenta

309
Q

Where are intraglomerular mesangial cells found?

A

Kidney

310
Q

Where are osteoclasts found?

A

Bone

311
Q

Where are epithelioid cells found?

A

Granulomas

312
Q

Where are sinusoidal lining cells found?

A

Red pulp of the spleen

313
Q

Where are Langerhans cells found?

A

Skin

314
Q

What is the main source of IL-1?

A

Macrophages

315
Q

What is the main source of IL-2?

A

Th1 cells

316
Q

What is the main source of IL-3?

A

Activated T helper cells

317
Q

What is the main source of IL-4?

A

Th2 cells

318
Q

What is the main source of IL-5?

A

Th2 cells

319
Q

What is the main source of IL-6?

A

Macrophages, Th2 cells

320
Q

What is the main source of IL-8?

A

Macrophages (can be released from any TLR bearing cell)

321
Q

What is the main source of IL-10?

A

Th2 cells

322
Q

What is the main source of IL-12?

A

Dendritic cells, macrophages and B cells

323
Q

What is the main source of tumour necrosis factor-α (TNF-α)

A

Macrophages

324
Q

What is the main source of interferon-γ?

A

Th1 cells

325
Q

What is the function of IL-1?

Pro/anti-inflammatory?

A

Acute inflammation
Induces fever
Pro-inflammatory

326
Q

What is the function of IL-2?

Pro/anti-inflammatory?

A

Stimulates growth and differentiation of T cell response

Pro-inflammatory

327
Q

What is the function of IL-3?

Pro/anti-inflammatory?

A

Stimulates differentiation and proliferation of myeloid progenitor cells
Pro-inflammatory

328
Q

What is the function of IL-4?

Pro/anti-inflammatory?

A

Stimulates proliferation and differentiation of B cells
Promotes class switching to IgE in B cells
Anti-inflammatory

329
Q

What is the function of IL-5?

Pro/anti-inflammatory?

A

Stimulate production of eosinophils

Pro-inflammatory

330
Q

What is the function of IL-6?

Pro/anti-inflammatory?

A

Stimulates differentiation of B cells
Induces fever
Pro-inflammatory

331
Q

What is the function of IL-8?

Pro/anti-inflammatory?

A

Neutrophil chemotaxis (can attract all granulocytes but neutrophils most)
Promotes phagocytosis
Pro-inflammatory

332
Q

What is the function of IL-10?

Pro/anti-inflammatory?

A

Inhibits Th1 cytokine production

Anti-inflammatory

333
Q

What is the function of IL-12?

Pro/anti-inflammatory?

A

Activates NK cellsandstimulates differentiation of naive T cells into Th1 cells
Pro-inflammatory

334
Q

What is the function of tumour necrosis factor-α (TNF-α)?

Pro/anti-inflammatory?

A

Induces fever
Neutrophil chemotaxis
Pro-inflammatory

335
Q

What is the function of interferon-γ?

Pro/anti-inflammatory?

A

Activates macrophages + NK cells

Pro-inflammatory

336
Q

What phenotype of macrophage does IL-4 promote?

A

Promotes M2 phenotype macrophages and therefore aids in wound healing

337
Q

What happens when IL-4 is released from T cells?

A

Positive feedback loop when released from T cells so Th2 is favoured and Th1 is suppressed

338
Q

What is IL-8 also known as?

A

CXCL9 and an angiogenesis promoter

339
Q

What are interferons?

A

Cytokines released by the body in response to viral infections and neoplasia

340
Q

What interferons bind to type 1 receptors?

A

IFN-alpha (all WBC) and IFN-beta (fibroblasts)

341
Q

What interferons bind to type 2 receptors?

A

IFN-gamma (NK and Th)

342
Q

Give some examples of immune based therapies.

A

Monoclonal antibodies
Immunosuppressive drugs
Cytokines and anticytokines
Intravenous immunoglobulin

343
Q

What is the mechanism of monoclonal antibodies as a therapy?

A

Very targeted. Do not carry antigenic segments. Designed to either deplete certain cell populations or functionally downregulate a population

344
Q

Give some examples of immunosuppressive drugs.

A

Glucocorticoids
Ciclosporin, tacrolimus and rapamycin
Purine analogues (most important is azathioprine)
Alkylating agents e.g. cyclophosphamide

345
Q

What is the mechanism of cytokines and anticytokines as therapies?

A

Either activate or block cytokine receptors to achieve immunomodulatory effects e.g. pegylated interferon

346
Q

What is the mechanism of intravenous immunoglobulin?

A

Replacing IgG in patients with immunodeficiencies. Can also be used in certain inflammatory conditions

347
Q

Give an example of monoclonal antibody therapy.

A

Anti-TNF therapy

348
Q

What is anti-TNF therapy used to treat?

A

Autoinflammatory conditions e.g. Crohn’s disease - Infliximab is a chimeric mAb used in CD often in acute infusions. Adalimumab is a humanised mAb that is a subcut injection that is patient administered and can be preferred when encouraging patient autonomy.

349
Q

Give some examples of glucocorticoids.

A

Hydrocortisone, prednisone

350
Q

What do glucocorticoids do when given as an immune based therapy?

A

They downregulate the monocyte production of IL-1 and TNF-alpha. They block the T-cell production of IL-2 and IFN-gamma and therefore humoral immunity. They also reduce the activation and migration of innate and adaptive cells in general

351
Q

What do ciclosporin, tacrolimus and rapamycin do when given as immune based therapies?

A

Are all calcineurin inhibits and inhibit Ca2+ dependent second messenger signals in T cells following TCR activation. This makes them potent T cell inhibitors

352
Q

What are purine analogues used for?

A

IBD and organ rejection

353
Q

What do purine analogues do when given as immune based therapies?

A

They incorporate into DNA resulting in chain termination. They are a potent antiproliferative in dividing adaptive immune cells

354
Q

What do alkylating agents do when given as immune based therapies?

A

Interfere with DNA synthesis and induce immunosuppression

355
Q

What do cytokines and anticytokines do when given as immune based therapies?

A

Cytokines are pleotropic and regulate the immune system so are attractive targets for therapy e.g. anakinra and pegylated interferon

356
Q

What does anakinra do?

A

IL-1 receptor antagonist which is beneficial in type 2 DM

357
Q

What does pegylated interferon do?

A

Used in chronic hepatitis C infection

358
Q

What is IV immunoglobulin?

A

A preparation of poly specific IgG pooled from a large number of healthy donors (>20k)

359
Q

What is IV immunoglobulin used for?

A

Patients with primary or secondary immunodeficiencies e.g. selective IgA deficiency
Recommended for a small number of other diseases such as immune-mediated thrombocytopenia, and Kawasaki’s

360
Q

What are the possible mechanisms of IV immunoglobulins?

A

Fc receptor blockade to prevent phagocytosis, inhibition of autoantibody synthesis, inhibition of complement activation, induction of T cell regulation

361
Q

What is complement?

A

An acute phase protein that are synthesised by the liver and circulate in an inactive form

362
Q

How is complement activated?

A

Complement proteins are cleaved by convertases into two components e.g. C3 becomes C3a and C3b

363
Q

What are complement components ending in ‘a’ involved in?

A

Inflammation and chemotaxis

364
Q

What are complement components ending in ‘b’ involved in?

A

Opsonisation of pathogens - the membrane attack complex inserts itself into pathogen membranes and causes lysis

365
Q

What do all complement pathways converge to?

A

Activate C3 convertase

366
Q

What is the complement classical pathway?

A

Initiated by antigen-antibody complexes (IgM/IgG) which bind complement and activate the cascade

367
Q

What is the complement alternative pathway?

A

The alternative pathway is activated when C3b (which is free and abundant in plasma) binds pathogens surfaces directly e.g. in G-ve bacteria

368
Q

What does the complement protein C3 do?

A

C3 has the ability to auto hydrolyse into C3a and C3b where C3b then goes on to activate the cascade

369
Q

What is the mannose binding lectin (MBL) pathway?

A

MBL binds mannose on pathogens’ surface. Mannose is not present on human cells. This activates MASP proteins (serine proteases) and cleave C2 and C4

370
Q

What markers are found on haematopoietic stem cells?

A

CD34

371
Q

What markers are found on helper T cells?

A

CD4, TCR, CD3, CD28

372
Q

What markers are found on cytotoxic T cells?

A

CD8, TCR, CD3, CD28

373
Q

What markers are found on regulatory T cells?

A

CD4, CD25, TCR, CD3, CD28

374
Q

What markers are found on B cells?

A

CD19, CD20, CD40, MHC II, B7

375
Q

What markers are found on macrophages?

A

CD14, CD40, MHC II, B7

376
Q

What markers are found on NK cells?

A

CD16, CD56

377
Q

What are CD1 molecules?

A

MHC molecule that presents lipid molecules

378
Q

What are CD2 molecules?

A

CD2Found on thymocytes, T cells, and some natural killer cells that acts as a ligand for CD58 and CD59 and is involved in signal transduction and cell adhesion

379
Q

What are CD3 molecules?

A

The signalling component of the T cell receptor (TCR) complex

380
Q

What are CD4 molecules?

A

Found on helper T cells. Co-receptor for MHC class II Used by HIV to enter T cells

381
Q

What are CD5 molecules?

A

Found in the majority of mantle cell lymphomas

382
Q

What are CD8 molecules?

A

Found on cytotoxic T cells. Co-receptor for MHC class I Found on a subset of myeloid dendritic cells

383
Q

What are CD14 molecules?

A

Cell surface marker for macrophages

384
Q

What are CD15 molecules?

A

Expressed on Reed-Sternberg cells (along with CD30)

385
Q

What are CD16 molecules?

A

Bind to the Fc portion of IgG antibodies

386
Q

What are CD21 molecules?

A

Receptor for Epstein-Barr virus

387
Q

What are CD28 molecules?

A

Interacts with B7 on antigen presenting cell as costimulation signal

388
Q

What are CD45 molecules?

A

Protein tyrosine phosphatase present on all leucocytes

389
Q

What are CD56 molecules?

A

Unique marker for natural killer cells

390
Q

What are CD95 molecules?

A

Acts as the FAS receptor, involved in apoptosis

391
Q

What is passive immunisation?

A

Transfer of performed antibodies to the circulation can be natural or artificial

392
Q

When does natural passive immunity occur?

A

This occurs naturally by the transfer of maternal antibodies across the placenta to the developing foetus

393
Q

What does natural passive immunity provide protection against?

A
  • Diptheria
  • Tetanus
  • Streptococcus
  • Rubella
  • Mumps
  • Polio virus
394
Q

When is artificial passive immunity used?

A
  • Those with agammaglobulinaemias - essentially B cell defects, these are
    treated with pooled normal human IgG
  • Exposure to a disease that could cause complications - like an
    immunocompromised patient who is exposed to measles for example
  • When there is no time for active immunisation to give protection i.e. a
    pathogen with a short incubation time e.g. rabies
395
Q

For what diseases is passive immunisation used?

A

Botulism, tetanus, diphtheria - given anti-toxin

Hepatitis, measles, rabies - used prophylactically to reduce the chance of establishing infection after exposure

396
Q

What are the drawbacks of passive immunisation?

A
  • Does not activate immunological memory
  • No long term protection
  • Possibility of reaction to antisera (due to the fact its non-self so if used second time will be immune to it itself and could result in anaphylaxis)
397
Q

What is active immunisation?

A
  • The production of high affinity protective antibodies against the immunogen
  • Protection that is produced by an individuals own immune system and is usually long- lasting
398
Q

What is the goal of active immunisation?

A

The goal of immunisation is to achieve initial exposure without the risks of an actual infection

399
Q

What are the aims of a perfect vaccine?

A
  • To achieve long term protection (ideally from a small number of
    immunisations)
  • To stimulate both B cells and T cells
  • To induce MEMORY B cells and T cells
  • To stimulate protective high affinity IgG production (IgA too if possible (can migrate through mucosal barriers useful some pathogens infect primarily through mucous membranes))
  • The importance the memory B cell response depends on the nature of the pathogen
400
Q

What happens in active immunisation?

A

The first stage of any immunisation is to engage the INNATE IMMUNE SYSTEM:
• Elicit ‘danger’ signals that activate the immune system - triggers such as pathogen-associated molecular patterns (PAMPs) to engage the toll- like receptors on T cells
• Activate specialist antigen presenting cells - e.g follicular dendritic cells
• Lastly engage the ADAPTIVE IMMUNE SYSTEM - generate memory T and B cells and active T helper cells

401
Q

Which diseases use a live attenuated (not harmful) pathogen as a vaccine?

A

Tuberculosis:

  • Bacilus Calmette-Guerin (BCG)
  • Polio Sabin:
  • Polio virus grown on monkey kidney epithelial cells
  • Typhoid
  • Mumps
402
Q

What are the advantages of live attenuated vaccines?

A
  • Attenuated pathogens sets up a transient infection
  • Activation of full natural immune response
  • Prolonged contact with the immune system
  • Stimulation of a memory response in the T and B cell compartments
  • Often only a single immunisation is required - advantages in the third world
403
Q

What are the disadvantages of live attenuated vaccines?

A
  • Immunocompromised patients may become infected as a result of immunisation
  • Complications:
  • In live measles vaccine occasionally the attenuated
    organism can revert to its virulent form
  • Refrigeration and transport:
  • Typically live organisms need to be refrigerated for stable storage
  • Can be a issue in remote areas of the world
404
Q

Which diseases use a killed, inactivated pathogen as a vaccine?

A
  • Anthrax
  • Cholera
  • Hepatits A
405
Q

What are the advantages of killed, inactivated pathogens as vaccines?

A
  • No risk of infection

- Storage is less critical

406
Q

What are the disadvantages of killed, inactivated pathogens as vaccines?

A
  • Tend to just activate the humoral response
  • Lack of T cell involvement
  • Without transient infection the immune response can be quite weak
  • Repeated booster vaccines required - patient compliance can be an issue
407
Q

Which diseases use toxoids (inactivated exotoxins) as a vaccine?

A

Diptheria:
- This toxin is an inhibitor of translation resulting in necrosis of the heart and liver
Tetanus:
- Neurotoxin resulting in uncontrolled contraction of
voluntary muscles

408
Q

What are the advantages of toxoid vaccines?

A
  • Theoretically safer than handling live or inactivated pathogens
  • No risk of infection
  • Easier to store and preserve
409
Q

What are the disadvantages of toxoid vaccines?

A
  • Immune response is less powerful than to live attenuated vaccines
  • Repeat vaccinations required and adjuvants
410
Q

What are adjuvants?

A
  • Any substance that is added to a vaccine to stimulate the immune system
  • Ensures a powerful immune response
411
Q

What can be used as an adjuvant?

A
  • Whole killed organisms - trigger the immune system and send out ‘danger signals’
  • Toxoids - trigger the immune system and send out ‘danger signals’
  • Proteins
  • Chemicals:
  • Aluminium salts (extend the half life of immunogen in the site of the injection, resulting in a depot effect - the slow release of vaccine)
  • Paraffin oil
412
Q

What do DNA vaccines do?

A
  • Aim to transiently express genes from pathogens in host cells
  • Generates immune response similar to natural infection leading to T and B cell memory responses
413
Q

What are the advantages of DNA vaccines?

A
  • DNA vaccines do not require complex storage

- Delivery can be simple and adaptable to widespread programs - no refrigeration is necessary

414
Q

What are the disadvantages of DNA vaccines?

A
  • As with ‘killed’ vaccines and subunit vaccines there is no transient infection
  • DNA vaccination is likely to produce a mild immune response and will require subsequent boosting
415
Q

What is the aim of recombinant vector vaccines?

A

Aim is to imitate the effect of transient infection with pathogen but using a non-pathogenic organism

416
Q

How are recombinant vector vaccines used?

A

Genes for major pathogen antigens are introduced into a non- pathogenic or attenuated microorganism and introduced into the host

417
Q

What microbes do recombinant vector vaccines use?

A

Can be viral (e.g. attenuate poliovirus) or bacterial (e.g. attenuated strains of salmonella)

418
Q

What are the advantages of recombinant vector vaccines?

A
  • Produce immunological memory

- Safe - relative to live attenuated pathogen

419
Q

What are the disadvantages of recombinant vector vaccines?

A
  • Requires refrigeration for transport

- Immune response to virus in subject can negate effectiveness

420
Q

What does complement do when activated?

A
  • Lyse microbes directly (Membrane Attack Complex - when a group of complement proteins make a hole in a pathogen which causes an inrushing of fluids that results in lysis and thus the destruction of the pathogen)
  • Increase chemotaxis (C3a & C5a)
  • Enhance inflammation
  • Induce opsonisation (C3b) - process by which an antigen becomes coated with substances (i.e. complement) that make it more easily engulfed by phagocytic cells since macrophages have special receptors for specific complement proteins
421
Q

What is the purpose of the complement pathway?

A

The major purpose of the complement pathway is to remove or destroy antigen, either by direct lysis or by opsonisation

422
Q

What is an epitope?

A

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

423
Q

What is affinity in terms of antibodies?

A

A measure of binding strength between an epitope and an antibody binding site - the higher the affinity the better

424
Q

What are cytokines?

A

Soluble proteins secreted by lymphocytes or macrophages/monocytes that act as stimulatory or inhibitory signals between cells

425
Q

What is MHC I glycoprotein?

A
  • Intracellular i.e virus
  • Found on the surface of virtually all cells of the body except erythrocytes
  • Cytotoxic T cells (CD8) require an antigen to be associated with class I MHC proteins before they kill the cell containing the intracellular pathogen
426
Q

What is MHC II glycoprotein?

A
  • Extracellular i.e. phagocytosis
  • Found mainly on the surface of macrophages, B cells & dendritic cells (i.e antigen presenting cells)
  • Helper T cells (CD4) require class II MHC proteins before they help B cells to make antibodies to the extracellular pathogen
427
Q

What is atopy?

A

Inherited tendency for overproduction of IgE antibodies to common environmental antigens

428
Q

What is immunodeficiency?

A

Deficiency in the immune response, can either be acquired (HIV) or inherited (defects in T cell function)