Immunology: principles and primary immune disease Flashcards
(90 cards)
0
Q
What is an antibody?
A
A protein produced in response to an antigen and has the property of binding specifically to that antigen
1
Q
What are the components of the innate immune system?
A
Complement Acute phase proteins Phagocytes Eosinophils Basophils and mast cells
2
Q
What is an antigen?
A
Any substance which can stimulate the adaptive immune system
3
Q
What are antibodies produced by?
A
B lymphocytes
4
Q
What do antibodies provide defence against?
A
Most bacteria
Viruses
5
Q
What are cytokines?
A
A diverse collection of small proteins and peptides which are produced in response to antigens, inflammation and tissue damage
6
Q
What do cytokines do?
A
They play a key role in coordinating the immune system - they modulate the behaviour of cells by binding to specific cytokine receptors on target cells
7
Q
Where are compliment proteins produced?
A
Liver
8
Q
What are acute phase proteins?
A
Produced in the liver in response to inflammatory signals
Basically - inflammatory markers
9
Q
What are the functions of acute phase proteins?
A
Modulate immune responses to micro organisms
Tissue repair and healing
10
Q
Where does the development of leukocytes occur?
A
Primary lymphoid tissue - bone marrow, thymus
11
Q
Where are mast cells found?
A
Resident in tissues e.g. Mucosal tissues
12
Q
Where are basophils found?
A
Blood
13
Q
What is characteristic of mast cells and basophils?
A
Highly granular cells
14
Q
What is released by mast cells and basophils when activated?
A
Pathogens/allergens
Histamine
Toxic substances
Cytokines
15
Q
What immune response are mast cells and basophils important in?
A
Responses to parasites e.g. worms
16
Q
Which immune cells play a role in allergic disease?
A
Eosinophils
17
Q
What is the function of eosinophils?
A
Defence against large pathogens that cannot be dealt with by phagocytes
18
Q
What are the phagocytes present in blood?
A
Neutrophils
Monocytes
19
Q
What are the phagocytes present in tissues?
A
Macrophages
Dendritic cells
20
Q
What are neutrophils?
A
Also known as polymorphonuclear cells
Most common circulating leukocyte
First immune cells recruited for damage, inflammation, infection
21
Q
What are monocytes?
A
Precursors of tissue-resident macrophages
22
Q
What is the purpose of monocytes and macrophages?
A
Detection, phagocytosis and destruction of pathogens and dead cells
Antigen presentation
Cytokine production
23
Q
What are dendritic cells?
A
Antigen presenting cells - they capture and process antigens and present them to T cells to induce adaptive immune responses
24
Which lymphocytes are involved in the innate immune system?
Natural killers cells
25
Which lymphocytes are involved in the adaptive immune system?
T cells
| B cells
26
What is the major function of natural killer cells
Detection and targeted killing of abnormal body cells e.g. cancerous cells, viral infections
27
What is the function of B cells?
Production of antigen-specific antibodies
28
What pathogens do T cells have a key role in defence against?
Viruses
Fungi
Mycobacteria
29
What are the two major T cell types?
CD4+ (T helper cells)
| CD8+ (cytotoxic T cells)
30
What is inflammation?
Tissue response to injury of infection - promotes tissue healing and repair and disposes of cell debris and pathogens
31
What is lysozyme?
Anti-bacterial enzyme that digests bacterial cell walls
32
How is the classical complement activation pathway initiated?
Binding of the C1 complex to antibody-antigen immune complexes
33
What is the C3 convertase in complement activation pathways?
C4b2a
34
How is the lectin pathway of complement activation initiated?
Lectins bind to carbohydrates in the cell wall of microorganisms
35
How is the alternative pathway of complement activation initiated?
Spontaneous hydrolysis of C3
36
What is the alternative C3 convertase involved in the alternative pathway?
C3bBb
37
Which bacteria is the alternative pathway of complement activation vital against?
Meningococcus
38
In complement activation, what happens after the hydrolysis of C3?
Splitting of C5
| Aggregation of other compliment proteins to form the membrane attack complex
39
What are the functions of complement?
```
Membrane attack complex
Opsonisation
Chemotaxis
Clearance of immune complexes
Inflammation
```
40
What is complement mediated opsonisation?
Coating of micro organisms by immune proteins e.g. C3b, antibodies, CRP
41
Where do phagocytes express their receptors for opsonins?
On their cell surface - this facilitates the uptake of microorganisms
42
What dissolves the immune complexes that trigger the classical complement activation pathway?
C3b binding
43
Which complement protein binds to the surface of pathogens to initiate the membrane attack complex?
C5b
44
How does the membrane attack complex work?
Inserts into target cell walls, putting a hole in the membrane causing osmotic cell lysis of the pathogen
45
What complement proteins are anaphylatoxins?
C3a and C5a
46
How do anaphylatoxins work?
Bind to receptors on mast cells & basophils, causing degranulation
Vasoactive substances and chemotactic factors cause the recruitment of phagocytes to the site of infection
47
What ensures that the complement system is kept under tight control at all times?
Only cleaved components are active
Have very short half life
Complement inhibitors - C1 inhibitor, factor I, factor H, C4 binding protein
48
What infection might deficiency of the complement pathway be associated with?
Recurrent meningococcal infection
49
Which structures on the pathogen are recognised by innate leukocytes?
PAMPS
50
What are toll-like receptors?
Receptors which specifically bind different pathogen components e.g. dsRNA, DNA, extra cellular proteins and sugars
51
At sites of inflammation, endothelial cells become activated. What do they express to recruit leukocytes?
Adhesion molecules - selectins and ICAMs
| Chemokines
52
What do selectins allow the leukocyte to do?
Weakly bind to endothelial cells and roll along the cell surface
53
How do leukocytes bind firmly to endothelial cells?
Chemokines activate leukocytes
| Leukocytes bind strongly to endothelial cells via integrins (receptors on leukocyte) binding to ICAMs (endothelium)
54
What is the name given to the process of the leukocyte squeezing through the endothelial layer?
Diapedesis
| Transmigration
55
Once leukocytes are in tissues, how do they get to the site of inflammation?
Follow a chemokine gradient
56
What is oxidative killing?
Neutrophils and macrophages can phagocytose and destroy pathogens by generating lethal toxic oxygen and nitrogen free radicals
57
In which leukocyte - neutrophils or macrophages - is oxidative killing particularly important?
Neutrophils
58
What is the crucial enzyme in oxidative killing?
NADPH oxidase complex
59
What is a granuloma?
A collection of immune cells that walls off the mycobacteria, but does not eradicate them
60
What activates B cells?
Antigen engagement
| Requires a strong signal
61
Why do B cells need T cells?
To help respond to protein antigens
| To help B cells switch the antibody type
62
Where are T cells produced and where do they mature?
Bone marrow
| Mature in thymus
63
What is the structure of the T cell antigen receptor (TCR)?
A membrane bound heterodimer with alpha and beta chains
64
Which immune cells are involved in cell-mediated immunity?
T cells
65
What are T dependant antigens?
Large proteins that are able to activate both T and B cells
They produce several types on antibody - IgM, IgG, IgE, IgA
They stimulate immunological memory
66
What are T independent antigens?
Carbohydrates, lipids and nucleic acids that are only able to activate B cells and only produce IgM
67
B cell antigen receptors can bind directly to large, intact molecules. What must happen to protein antigens in order to be recognised by T cells?
Antigens must be processed and presented to their T cell antigen receptor in complex with major histocompatibility complex (MCH) molecules
69
What are major histocompatibility complex molecules?
The immune systems way of displaying peptide antigens to T cells
70
What are "SPUR" infections?
Serious infections
Persistent infections
Unusual infections
Recurrent infections
71
What are some of the clinical features of phagocyte deficiencies?
Recurrent infections - may affect common and unusual sites
| Normal bacteria, unusual bacteria, mycobacteria and fungi
72
What does the term "phagocyte deficiency" encompass?
Defects of phagocyte production, mobilisation and recruitment
73
What is Kostmann syndrome?
Rare autosomal recessive disorder where neutrophils are not effectively produced, resulting in low circulating neutrophil count
74
What is the clinical presentation of Kostmann syndrome?
```
Infections, usually within 2 weeks after birth:
Recurrent bacterial infection
Systemic or localised infection
Non specific features:
Fever
Irritability
Oral ulceration
Failure to thrive
```
75
Where is the defect in Kostmann syndrome?
In the neutrophil precursor
76
How is Kostmann syndrome managed?
Prophylactic antibiotics
Prophylactic antifungals
Granulocyte colony stimulating factor (G-CSF)
Stem cell transplant
77
What is leukocyte adhesion deficiency?
A rare primary immunodeficiency caused by genetic defect in leucocyte integrins (CD18)
Results in failure of neutrophil adhesion and migration
78
What is the clinical picture of leukocyte adhesion deficiency?
Marked leukocytosis and localized bacterial infections that are difficult to detect
High circulating neutrophil count
79
What receptors do phagocytes express that allow binding of antibody that is also bound to antigen?
Fc receptors
80
What defects might result in ineffective opsonisation and phagocytosis?
Complement receptor defects
| Antibody and complement production defects
81
What causes chronic granulomatous disease?
Failure of oxidative killing mechanisms
Inability to clear organisms and excessive inflammation
results in failure to degrade chemoattractants and antigens, persistent accumulation of neutrophils, activated macrophages and lymphocytes:
This results in granuloma formation
82
What is the clinical picture of chronic granulomatous disease?
```
Recurrent deep bacterial infections, especially Staphylococcus, Aspergillus, pseudomonas cepacia
Mycobacteria, atypical mycobacteria
Recurrent fungal infections
Failure to thrive
Lymphadenopathy and hepatosplenomegaly
Granuloma formation
```
83
How do you test for chronic granulomatous disease/assess whether neutrophils are capable of oxidative killing?
NBT (“nitroblue tetrazolium”) test
84
How is an NBT test carried out?
Feed patient neutrophils source of E coli
Add dye that is sensitive to H202
If hydrogen peroxide is produced by neutrophils, dye changes colour
85
How do CD8+ cytotoxic cells kill cells directly?
Production of pore-forming molecules: perforin
Triggering apoptosis of the target
Secrete cytokines e.g. IFNγ
86
What is reticular dysgenesis?
```
A rare genetic disorder of the bone marrow resulting in complete absence of granulocytes and decreased number of abnormal lymphocytes
Failure of production of:
Neutrophils
Lymphocytes
Monocyte/macrophages
Platelets
```
87
What is severe combined immunodeficiency?
Failure of production of lymphocytes
88
What is the classical presentation of severe combined immunodeficiency?
Unwell by 3 months of age
Persistent diarrhoea
Failure to thrive
Infections of all types
89
Why do diseases like SCID present roughly three months into life?
Maternal IgG protects neonate until then
90
What is the most common form of SCID?
X-linked SCID
| Genetic mutation in IL2 receptor
