Immune System Components & Complement System Flashcards
Innate vs Adaptive Intro, ROS, TLR, DAMPS, PAMPS, Phagocytes, Macs, Monocytes (95 cards)
1
Q
What are the two lines of defense in the immune system
A
Innate and adaptive immunity
2
Q
Innate vs Adaptive
A
Innate Immunity
• Ag-independent
• Used immediately /within hours of attack
• Possesses no immunological memory
Adaptive Immunity
• Ag-dependent
• Ag-specific
• Lag time between exposure and maximal response
• Immunological memory
– rapid and efficient IR upon re-exposure
3
Q
Innate immunity functions
A
- Recruit immune cells to site of infection and inflammation
- Occurs via production of Cytokines
- Cytokines production - Release of proteins, glycoproteins and Abs for activation of Complement
- Promotes clearance of dead cells or Ab complexes; removes foreign entities
- Activates adaptive immune system – Antigen presentation
4
Q
Cells involved in the innate immune system
A
Macrophage, dendritic cell, mast cell, basophil, eosinophil, neutrophil, natural killer cell, complement protein, gamma delta T cell, natural killer T cell
5
Q
Main types of phagocytes in innate immunity
A
Macs (MΦ) and Neutrophils
6
Q
Neutrophils are long-lived vs short-lived Macs (T/F)
A
False; Neutrophils are short-lived vs long-lived Macs
7
Q
Macs are not an APC (T/F)
A
False
8
Q
Neutrophils have granules that assist in elimination
of pathogenic microbes (T/F)
A
True
9
Q
DCs and Eosinophils also phagocytise (T/F)
A
True
10
Q
Most abundant granulocyte
A
Neutrophil
11
Q
Multi lobed nuclei
A
Neutrophil
12
Q
Possess granules which aid their functions
A
Neutrophils, Basophils, Eosinophils
13
Q
Aids in inflammatory response in allergy and
asthma
A
Basophils – along with Mast cells
14
Q
Destruction of parasites too large to be phagocytosed; also involved in allergy and asthma
A
Eosinophils
15
Q
Natural killer cells are also called ?
A
Large Granular Lymphocytes (LGLs)
16
Q
NK cells - function
A
NK cells can eliminate a variety of abnormal or stressed cells without prior sensitization, and even preferentially kill stem-like cells or cancer stem cells
17
Q
How do NK cells distinguish healthy cells from cancer cells?
A
Most normal healthy cells express MHC I receptors which mark these cells as ‘self’. Inhibitory receptors on the surface of the NK cell recognise MHC I, and this ‘switches off’ the NK cell, preventing it from killing.
18
Q
NK cells lyse cells, how does this occur?
A
NK cell releases cytotoxic granules containing perforin and granzymes, which leads to lysis/apoptosis of the target cell.
19
Q
How do perforins lyse cells?
A
Perforin inserts itself into the target cell’s plasma membrane, forms a pore and facilitates endocytosis of itself and granzyme proteases.
20
Q
List protective barriers of the body
A
Anatomic: Skin, mucous membrane
Physiologic: Temperature, low pH, chemical mediators,
Phagocytic: Specialized cells for endocytosis
Inflammatory: Tissue damage
21
Q
Anatomic barriers - name 1st type and explain
A
- Mechanical barrier - retards entry of microbes
* Acidic environment (pH 3-5) - retards growth of microbes
22
Q
Anatomic barriers - name 2nd type and explain
A
- Normal flora compete with microbes for attachment sites
- Mucous entraps foreign microbes
- Cilia propel microbes out of body
23
Q
Physiologic barriers - name 1st type and explain
A
• Body temperature/fever response inhibits growth of some pathogens
24
Q
Physiologic barriers - name 2nd type and explain
A
• Acidic pH of stomach kills most undigested microbes
25
Physiologic barriers - name 3rd type and explain
Chemical mediators
• Lysozyme cleaves bacterial cell wall
• Interferon induces antiviral defenses in uninfected cells
• Complement lyses microbes or facilitates phagocytosis
26
Phagocytic barriers -
• Various cells internalize (endocytosis) and break down foreign macromolecules
• Specialized cells (blood monocytes, neutrophils, tissue macrophages) internalize (phagocytose), kill
and digest whole organisms
27
Inflammatory barriers
• Tissue damage and infection induce
-- leakage of vascular fluid containing serum protein with
antibacterial activity,
-- leading to influx of phagocytic cells into the affected area
28
Type I interferons (IFNs) - define and function
- - Cytokines produced locally in response to infection
| - - Directly inhibit the growth of pathogens
29
Collectins,
- - Constitutively produced proteins
| - - Bind onto pathogens
30
Collectins are made of?
Consist of a Collagen domain fused to a lectin domain
31
Type I IFN -- IFN-alpha and IFN-beta
- produced in response to?
- name functions
- Antiviral effects = most potent
- Produced in response to pathogens
- Inhibits viral replication
- Promotes Th1 development
- Activates NK cells
32
Virally infected cells produce Type I IFN at front line (T/F)
True
33
Activated NK cells lyse infected cells (T/F)
True
34
pDCs stand for
pDCs - Plasmacytoid Dendritic Cells
35
pDCs produce _______ and are responsible for
pDCs produce Type I IFNs
| - antiviral response, autoimmune disease
36
What does PRMs stand for
PRMs - Pattern Recognition Molecules
37
Collectins are PRMs (T/F)
True
38
Collectins cannot bind to PAMPS (Pathogen Associated Molecular Patterns) (T/F)
False; They can bind to PAMPS (Pathogen Associated Molecular Patterns) and ensure clearance and aid in elimination of the pathogen.
39
Lectin binds to carbs from pathogen - list scenarios that occur as a result of the binding
* Complement activation
* Inducing uptake via phagocytosis
* Agglutination
* Stimulate leucocytes of phagocytise apoptotic cells
40
What role does DAMPS (Damage Associated Molecular Patterns) play in immune system?
If the collectin sees the DAMPS that means the cell has been damaged and has to be destroyed
41
Complement and C Reactive Protein (CRP)
CRP - An acute phase protein
Complement activation by CRP is restricted to C1, C4, C2 and C3 with little consumption of C5-9.
42
CRP binds to microbial polysaccharides and to ligands exposed on damaged cells (T/F)
True
43
What does the binding of CRP cause?
Binding of CRP to these substrates activates the classical complement pathway leading to their uptake by phagocytic cells.
44
The concentration of CRP does not increase or decrease in response to inflammation (T/F)
--- Conc'n >'s or
45
Concentration of CRP increases in response to what?
• Increases in response to cytokines secretion including IL-6 by Macs and T cells
46
Functions of CRP
* Control of inflammation
* Stimulation of clearance of damaged cell and tissue components
* Initiation of repair functions
* Activation of complement via C1q
47
What inhibits production of CRP
INF-α inhibits the production of CRP by the liver
48
Complement system is?
Complex system composed of proteins
| - Acts in a sequential cascade
49
Regulation is crucial since complement acts non-specifically (always turned on) (T/F)
True
50
What pathways activate Complement system?
Classical
Lectin
Alternative
51
Classical Pathway is triggered by immune complexes of __ and __.
Classical Pathway is triggered by immune complexes of Ab and Ag.
52
What is Fc in the Classical Pathway?
Fc receptor is a protein found on the surface of certain cells
Note:
In IgG, IgA and IgD antibody isotypes, the Fc region is composed of two identical protein fragments, derived from the second and third constant domains of the antibody's two heavy chains; IgM and IgE Fc regions contain three heavy chain constant domains
53
What is the initiating protein recognizing Fc portion of Ig in Classical Pathway?
C1 is the initiating protein recognizing Fc portion of Ig
54
What occurs when C1 recognizes Fc?
Activation of C2 and C4 leading to C3 activation.
55
What activates C1 complex?
Triggered by immune complex - antibody binding with antigen
56
Where does the antigen come from in the antibody antigen complex?
Antibodies Ig are complexed with antigens.
57
What are other ways the Classical pathway can be triggered?
NK cells - adaptive immmunity here (antibodies are produced by B cells which are part of adaptive system)
Binding to C-reactive protein
58
What Igs activate Classical pathway?
• Activated by IgG– (IgG1, IgG2, and IgG3 but not IgG4) or IgM–containing immune complexes through binding by C1q.
59
Steps in Classical Pathway
1. C1 qrs meets with C2 and C4
2. C1qrs cleaves C2 and C4 giving C4b and 2a come together to form C3 convertase
3. C3 convertase cleaves C3 to give c3a and c3b
c3b and c4b2a form c4a2a3b/C5 convertase
4. C5 convertase cleaves/breaks apart C5 to give C5a and C5b
5. C5 b attracts C6 which attracts C7 -- brings in C8 --- C9 (C5b, C6, C7, C8, C9 form the MAC and this forms a pore in pathogen leading to lysis)
60
Regulatory factors of Classical Pathway
• MCP – membrane co-factor protein
• DAF – decay accelerating factor
• CD59 – Prevents C9 from completing
MAC
61
What happens when lectin recognizes carbs? (Lectin Pathway)
Lectin recognizes carbs
- ficolin = collection of lectins
Causes cleavage of C2 and C4 - this causes c2a and c4b to find to get c4bc2a which is c3 convertase which cleaves c3.
62
Diff between classical and lectin pathway
Same as classical - diff is lectin binds to carb along with help from MASPs leading to cleavage of C2 and C4.
63
MASP stands for
MASP – MBL - associated serine proteases
64
How are the MASPs activated?
MBL binds to mannose residues which activates MASP1 & MASP2
65
C3 is main component in each pathway (T/F)
True
66
Alternative pathway steps
1. C3 is hydrolysed - in the presence of factor B and factor D and forms a hydrolysed C3 and Bb and this cleaves C3 into C3a and C3b.
(doesn't use C2 and C4 - goes straight to C3)
2. This then gives C5 convertase (C3bBbP or C3Bb2P)
3. C5 convertase cleaves C to form C5a and C5b, C5b attracts C6, C7, C8, C9 to form MAC
Role of factor D : Assists in formation of C3 convertase (C3(H2O)Bb)
Role of factor B: C3 needs the b element from Factor b to form C3 convertase
Role of properdin: Joins with C3 convertase and C3b to form C5 convertase
67
Factor D - role
Factor D - helps in formation of C3 convertase b part of factor B - helps as well
Properdin also
68
Roles of C3a, C4a and C5a also known as Anaphylatoxins
| And activation cycle
1. Smooth muscle contractions and capillary leakage push the WBCs to the site of infection - action of anaphylatoxins C3a, C4a, C5a
(Capillary leakage = endothelial cells of tissues change the tight junctions so they are no longer tight allowing passage of antibodies or more complement proteins in the form of fluid - edema)
2. C3a, C5a - chemoattractants/chemotaxis - attracting immune cells to come to site of infection
Neutrophils (phagocytosis) and monocytes (differentiate into macrophage/DCs) have receptors for anaphylatoxins
3. Increase leukocyte adhesion: ensures that the leukocytes aren't just flowing with the blood but are more likely to stick to the BV walls facilitating their entry into the site of infection
4. Stimulates phagocytosis and degranulation -- Mast cells have receptors which are recognized by cleaved complement components for e.g. C5a, they bind and produce histamine which causes increased vascular permeability, vasodilation and inflammation
Macrophages - when bound to anaphylatoxin e.g. C5a, causes more production of CR1 (- complement receptor that can bind C3b's that are fixed to surface of pathogens) -- Improved functioning of Macrophages via CR1 production
Cycle
1. Complement components are inactive until cleaved (C3, C4, C5)
2. Component is cleaved by upstream molecule (can vary depending on the complement pathway)
3. Large fragment of component acquires enzyme activity and acts in complement pathway
4. Small fragment active as anaphylatoxin - until blocked by inhibitor on cell surface
69
What activates Alternative pathway?
Initiated constantly by spontaneous hydrolysis of C3, leading to the formation of C3(H2O)Bb, which cleaves C3 into C3a and C3b.
70
Activation of alternative pathway
Amplification of this pathway is on the basis of the covalent binding of C3b to activating surfaces (e.g., bacterial surface) followed by cleavage of factor B (FB).
71
Properdin purpose in alternative pathway
Properdin promotes association between
C3b and FB, thus stabilizing the alternative
pathway C3 convertase (C3bBb)
72
Complement inhibitors: types
C1 inhibitor - soluble protein prevents C1-activating C4 and C2
- inhibits proteases of the complement system (C1r, C1s, MASP2)
Series of soluble + membrane bound inhibitors - prevents C3 activation (esp in alternative pathway)
Membrane bound inhibitors - prevents action of MAC (Membrane Attack Complex)
73
Phagocytosis functions
Main function
- clearing of small extracellular pathogens and cellular debris
Secondary function
- production of cytokines and cell-surface molecules for alerting the adaptive immune system
74
Endocytosis vs Phagocytosis
| Opsonins
Endocytosis - process by which materials move into cell
Phagocytosis - type of endocytosis - cell plasma membrane surrounds extracellular entitity and forms phagosome.
Phagosome fuses with lysosome - hydrolytic enzymes digest entity.
Opsonin - when opsonins are attached to molecule e.g. complement C3a, when C3a binds to surface of pathogen, the macrophage has a receptor for opsonin so the C3a can easily bind and pathogen can be brought into cell = makes it easier for pathogen to be brought into cell and more easily recognizable
Another e.g. of opsonin is antibodies
75
Phagocytes - Neutrophils - characteristics
* Numbers in the blood vary – during infection production
* Migrate rapidly to sites of infection to kill pathogens
* Crucial role in early defense against bacterial infections
76
.Life cycle lasts for days for Neutrophils (T/F)
False; Life cycle is a few hours for Neutrophils
77
Pus is largely composed of dead neutrophils (T/F)
True
78
Monocytes - define
Monocytes in the blood are immature cells migrating to site of activity in tissues where they mature into Macrophages
79
Specialized Macs - name them
* Tissue macs e.g. Histiocytes in BM and LN
* Macs undergo further maturation at chronic inflammation into Giant cells or Epithelioid cells
* Kupffer cells – Macs in the liver
* Alveolar macrophages – Macs in the lung
* Glial cells – Macs in the nervous system
* Osteoclasts – Macs in bone
80
Phagocytes survive in tissues for only a few days (T/F)
False; Phagocytes survive in tissues for months or years
81
Phagocytes use numerous receptors for chemokines, cytokines, pathogen-associated molecular patterns (PAMPs) and damageassociated molecular patterns (DAMPs) (T/F)
True
82
PAMPs – cell-derived – initiate and perpetuate immunity in response to trauma, ischemia and tissue damage (T/F)
False; PAMPs – derived from microbes- recognized by pattern recognition receptors (PRR)
83
DAMPs – derived from microbes- recognized by pattern recognition receptors (PRR) (T/F)
False; DAMPs – cell-derived – initiate and perpetuate immunity in response to trauma, ischemia and tissue damage
84
Ischemia - define
Restriction of blood supply to tissue due to BV issues; can cause tissue damage
85
Toll-like receptor- define and list roles
It is an e.g. of pattern recognition receptor - recognize particular patterns associated with particular pathogens
- can differentiate btw virus and fungi and bacteria
- knows what method of immune response to put forth - adaptive response
86
Pattern Recognition receptor - function
To recognize particular patterns associated with particular pathogens
87
Diff TLRs recognize diff molelcules (T/F)
True; E.g. TLR-3 expressed on DCs and epithelial cells -- associated pathogen is viruses
88
TLR-2 expressed on _____ and associated pathogen _____ ______ ___ ________
Widespread, wide range of bacteria
89
TLR-4 expressed on ____ and associated pathogen _______ ______ ________
Macs, Gram-neg bacteria
90
TLR-5 expressed on ____ and associated pathogen ____ ____ __ _______ ________
Macs, wide range of motile bacteria
91
TLR-7 expressed on ___ and associated pathogen _______
DCs, viruses
92
TLR-9 expressed on ____, ____ and associated pathogen _______
DCs, B cells, Bacteria
93
Reactive oxygen species - define
A type of unstable molecule that contains oxygen and that easily reacts with other molecules in a cell.
Toxic metabolites – used to damage pathogenic structures
Controlled by inactivating enzymes
94
ROS inhibitors
Inhibitors
• Glutathione peroxidase
• Glutathione reductase
• Glucose-6-Phosphate Dehydrogenase (G6PD)
95
ROS activators
Superoxide dismutase
| Myeloperoxidase
