MODULE 5 - 9 Flashcards
1
Q
4 main attributes of cytokines
A
pleiotrophy, redundancy, synergy, antagonism
2
Q
Pleiotrophy
A
a single cytokine can produce multiple effects
3
Q
Example of Pleiotrophy
A
Il-4 stimulates multiple effects on B-cells
4
Q
Redundancy
A
Cytokines can target the same cell and elicit the same effect
5
Q
Example of redundancy
A
IL-2, IL-4, and IL-5 can stimulate B-cells to undergo proliferation
6
Q
Synergy
A
the combined effect is greater than the added effect of them seperately
7
Q
Example of synergy
A
IL-4 and IL-5 together can more effectively stimulate B-cells to induce class switching to IgE
8
Q
Antagonism
A
cytokines can act on other cuytokines to impact their effects
9
Q
Example of antagonism
A
IL-4 functions to induce B-cell class switching, but IFN-gamma can act to block the effects of IL-4
10
Q
5 Cytokine receptor classes
A
Ig Superfamily Receptors, Class I Receptors, Class II Receptors, TNF Receptor Family, Chemokine Receptor Family
11
Q
Ig Superfamily Receptors
A
has the same domain structure found on MHCs and Igs
12
Q
Ig Superfamily Receptors Ligand
A
IL-1: induces fever through hypothalamus stimulation
13
Q
Class I Receptors
A
have Trp-Ser-X-Trp-Ser (WSXWS) amino acid motif
14
Q
Class I Receptors Ligand
A
IL-2, IL-3, pIL-4, IL-5, IL-6, IL-7, IL-12, IL-13
15
Q
Class II Receptors
A
similar to Class I but don’t have WSXWS motif; has cys disulfide bonds
16
Q
Class II Receptors Ligand
A
INF-alpha, INF-beta, INF-gamma, IL-10
17
Q
TNF Receptor Family
A
have cys-rich domains
18
Q
TNF Receptor Family Ligands
A
TNF-alpha, TNF-beta, CD40L, FAS
19
Q
Chemokine Receptor Family
A
belong to G-protein coupled receptors; have 7 transmembrane domains
20
Q
Chemokine Receptor Family Ligands
A
CCR5 and CXCR4: co-receptors for HIV
21
Q
Th1 cells secrete
A
IFN-gamma: promotes TH1 differentiation, inhibits TH2 proliferation
22
Q
Effector functions of Th1 cells
A
play role in the cell-mediated immune response
23
Q
Th2 cells secrete
A
IL-4, IL-5, and a little IL-10: promotes Th2 differentiation, inhibits Th1 activation
24
Q
Effector functions of Th2 cells
A
plays a role in the humoral immune response
25
Bacterial septic shock
gram-negative cell wall endotoxins stimulate the patients macrophages to over-produce IL-1 and TNF-alpha, leading to the secretion of additional pro-inflammatory cytokines (IL-6 and IL-8)
26
Symptoms of bactrial septic-shock
Macrophages secrete lipid mediators and reactive O2/N species, causing fever, diarrhea, organ dysfunction, and widespread clotting
27
Primary immune response on B-cells
activation and differentiation of naive B-cells into anti-body secreting plasma cells
28
Secondary immune response on B-cells
antigen-specific memory B-cells are preferentially activated, resulting in quick response
29
Primary immune response on Ig production
produces equal amounts of IgM and IgG over 4-7 days
30
Secondary immune response on Ig production
produces primarily IgG rapidly over 1-3 days and has an overall longer period of antibody concentration
31
T-cell dependent B-cell activation
When a helper T-cell recognizes an antigen:MHC class II complex on a B-cell, the T-cell becomes activated, which activates the B-cell
32
3 signals in T-cell Dependent B-cell Activation
TCR-MHC class II complex binding, costimulatory molecule signalling, cytokine signalling
33
TCR-MHC Class II Complex Binding
1. Antigens are processed and presented to T-cells
2. BCR binds its specific antigen resulting in internalization of the Ig-antigen complex by receptor-mediated endocytosis
3. Antigen is then processed by the endocytic antigen processing pathway and is displayed on MHC class II molecules on cell surface
4. TCR of the helper T-cell recognizes the processed Ag:MHC complex presented by the B-cell
5. TCR and CD4 bind to the Ag:MHC class II complex, resulting in activation of the helper T-cell
34
Costimulatory molecule signalling
1. Upon TCR recognition of the antigen, CD40L expression is induced on the surface of helper T-cell through TCR-mediated inositol lipid hydrolysis
2. CD40L interacts with expressed CD40 on B-cell, CD40L-CD40 interaction activates cytokine receptor expression on cell surface of B-cell and T-cell
3. MHC Class II mediated cAMP activation results in increased expression of B7 on the cell surface
4. B7 binds CD28 expressed by T-cell and provides necessary costimulatory signal to activate the helper T-cell
35
Cytokine signalling
1. B7-CD28 interaction induces the MAPK cascade in helper T-cell
2. This cascade activates cJUN and cFos which form AP-1 transcription factor that activates IL-2 gene
3. Cytokines bind their receptors on the B-cells and T-cells, initating proliferation and differentation
36
Type I T-cell independent antigens
polyclonal B-cell activators: capable of activating B-cell regardless of their antigenic specifity
37
Type 2 T-cell independent antigens
expressed on the surface of pathogens in an organized and highly repetitive form; can activate B-cells by cross-linking the membrane bound iG in a multivalent fashion
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Type 2 T-cell independent antigens example
polymeric proteins or bacterial cell wall polysaccarides with repeating polysaccaride units
39
Effector cells
cells that have a biological effect rather
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Effector cells in non-specific response
macrophages and NK cells
41
Results of non-specific response
increased IFN-alpha and IFN-beta, activate Th1 cell
42
Effector cells in specific response
Cytotoxic T-cells
43
Antigen-nonspecific response
Macrophages + NK cells can recognize pathogens, but are not specific to a particular antigen
44
Antigen-specific response
Th1 cells activate cytotoxic T-cells which are specific for a processed pathogen antigen in complex with MHC class I
45
The NK cell response is activated by:
IFN-alpha, IFN-beta, IL-2
46
4 characteristics of the NK cell response:
1) These are large granular lymphocyte-like cells that lack antigen-specific receptors
2) They're capable of Fas-mediating killing
3) They control infection during the period required for generation of specific cell-mediated effector cells
4) They're involved in antibody-dependent cell mediated cytotoxicity
47
Receptors on NK cells:
Killer inhibitory receptors (KIRs) recognize self MHC class I
48
How do KIRs work
All normal cells have MHC class I molecules, but virally infected cells have downregulating expression of MHC class I molecules, so KIRs are not engaged and NK cells then kill the cell
49
Antibody opsonization in ADCC
infected target cells express antigens, which are then marked to be phagocytosed
50
Fc-gamma-RIII in ADCC
Receptors on NK cells recognized and bind the Fc portion of antibodies; once bound to an antibody:target cell, the NK cell is activated
51
Activated NK cells in ADCC
activated NK cells bound to a target release the content of their cytolytic granules by directly killing the target cell or inducing FasL/Fas-mediated apoptosis
52
Cytotoxic T-cell killing adhesion
LFA-1 and ICAM-1 interaction
53
Cytotoxic T-cell killing antigen recognition
TCR:peptide/MHC complex binding
54
Cytotoxic T-cell killing movement of granules
reorientation of cytoskeleton and cytoplasmic components
55
Cytotoxic T-cell killing of target cell
"lethal hit," pore formation, cell apoptosis
56
3 complement pathways
Classical, alternative, lectin
57
Classical pathway is activated by
immune complexes (Ag-Ab) involving human Igs IgM, IgG1, IgG2, and IgG3
58
Alternative pathway is activated by:
Non-Ab substances such as lipopolysaccarides, polymers or venom factors
59
Lectin-pathway is activated by
mannan, which is expressed only on bacteria and viruses
60
7 steps of classical pathway
1) Antibodies bind to multivalent antigen on the cell membrane of the target cell; the C1 complex (C1qr2s2) binds the FC region of the antibody bound to the target cell
2) C4 then binds to the C1q portion of the Ig:C1 complex; r2s2 enyme cleaves C4 into C4a and C4b
3) C4b covalently attaches to the cell membrane or antibody; C2 binds to C4b; C1qr2s2 cleaves C2 into C2a and C2b
4) C4b and C2a combine to form C3 convertase (C4bC2a)
5) C3 convertase binds and cleaves C3 into C3a and C3b
6) C3b binds C4bC2a to form C5 convertase (C4bC2aC3b); C3a is hydrolyzed or bonds with target cell surfaces
7) C5 convertase binds to C5 and cleaves it into C5b
61
8 step of lectin pathway
1) Serum mannose-binding lectin binds to mannose residues on glycoproteins or carbohydrates on surface of microbes; mannose-binding lectin is an acute phase protein produced during inflammation
2) Mannose-binding lectin-associated serine protease (MASP) binds to mannose-binding lectin (MBL)
3) The active MASP-MBL complex cleaves inactive C4 into active C4a and C4b
4) C4b can attach to pathogen cell via mannose binding; C2 binds C4b
5) C2 of the C4bC2 complex is cleaved by MASP to form C4bC2a (C3 convertase)
6) C3 convertase binds and cleave C3 into C3a and C3b
7) C3b binds to C4bC2a to form C5 convertase; C3a is hydrolyzed or bonds with target cell surfaces
8) C5 convertase binds to C5 and cleaves it into C5b
62
7 steps of alternative pathway
1) Continuous cleavage of C3 occurs in plasma, resulting in C3a and C3b
2) C3b binds to microbial surface via active thioester bonds; factor B binds C3b
3) Factor D cleaves Factor B (still bound to C3b)
4) Factor P stabilizes C3bBb, making it C3 convertase
5) Cleavage of another C3 by cell-associated C3bBb, giving C3a and C3b
6) C3b binds to the cell surface, forming C3bBbC3b complex (C5 convertase)
7) C5 convertase cleave C5 into C5b
63
Mnuemonic to remember Classical, Alternative, and Lectin Pathways
Classroom 142, Lecture 42, Focused on Classical or Developmental Biology
64
C1, C2, C4 Deficiency
Immune complex disease
65
C3, Factor D, Factor I Deficiency
Pyogenic infections
66
MBL deficiency
susceptible to reccurent infections and decrease lung function in cystic fibrosis patients
67
4 steps of complememnt cascade after C5 convertase formation
1) Cell-associated C5 convertase cleaves C5 into C5a and C5b; C5b remains bound to C5 convertase
2) C6 and C7 sequentially bind to C5b; C5bC6C7 complex becomes directly inserted into the lipid bilayer of the target cell membrane
3) C8 is bound to C7 to stabilize the complex
4) Up to 15 C9 molecules polymerize around the C5bC6C7C8 complex to form the membrane attack complex (MAC)
68
Type 1 Gell-Coombs Hypersensitivity Reactions
Specific antibody-mediated reaction that can develop into anaphylactic responses
69
Type 1 Gell-Coombs Hypersensitivity Reactions occur due to
IgE on mast cell binds an allergen, resulting in mast cell degranulation C3a, C4a, and C5a can also cause this reaction
70
4 typical Type 1 Gell-Coombs Hypersensitivity Reaction Allergens
Fel d1 and Fel4 (cats), Fra a1 (strawberries), hyaluronidase (honeybee venom), Der p1 (Dust mite feces)
71
Mechanism of Type 1 Gell-Coombs Hypersensitivity Reactions
Ag induces cross-linking of IgE mast cells with release of vasoactive mediators
72
Clinical manifestations of Type 1 Gell-Coombs Hypersensitivity Reactions
Atopy, asthma, laryngeal edema
73
Type 2 Gell-Coombs Hypersensitivity Reactions
mediated by an antibody directed against cell surface antigens
74
What results from Type 2 Gell-Coombs Hypersensitivity Reactions
Hemolytic anemia, bullous pemphigus, transfusion reactions, Rh disease
75
Type 3 Gell-Coombs Hypersensitivity Reactions
mediated by an Ab-Ag immune complex deposited on the tissue
76
What results from Type 3 Gell-Coombs Hypersensitivity Reactions
Immune complexes activate complement and recruit innate cells to cause tissue damage
77
Mechanism of Type 3 Gell-Coombs Hypersensitivity Reactions
Ag-Ab complexes deposited in various tissues induce complement activation and an ensuing inflammatory response mediated by massive infiltration of neutrophils
78
Clinical presentation of Type 3 Gell-Coombs Hypersensitivity Reactions
Serum sickness, farmer's lung, rheumatoid arthritis
79
Type 4 Gell-Coombs Hypersensitivity Reactions
Involves a complex intervention of T-cells and monocytes/macrophages
80
Mechanism for Type 4 Gell-Coombs Hypersensitivity Reactions
Sensitized T-cells release inflammatory cytokines that activate macrophages which mediate direct cellular damage
81
Mechanism for Type 2 Gell-Coombs Hypersensitivity Reactions
Ab directed against cell surface antigens mediates cell destruction via complememnt activation or ADCC
82
Clinical presentation for Type 4 Gell-Coombs Hypersensitivity Reactions
conact dermatitis, tubercular lesion, gluten intolerance
83
Atopy
exaggerated IgE-mediated immune response to environmental allergen
84
Asthma
inflamation and obstructed airways that can be both atopic and non-atopic
85
Laryngeal edema
swelling of the larynx with high pitch breathing sound
86
Hemolytic anemia
condition where immune system recognizes own RBCs as foreign
87
Bullous pemphigus
autoimmune skin disease resulting in formation of blisters between epidermis and dermis
88
Transfusion reactions
Adverse reaction to allogenic RBCs following transfusion reaction
89
Rh disease
hemolytic condition where maternal and fetal blood are not compatible
90
Serum sickness
Reaction to proteins in antiserum derived from non-human animals
91
Farmer's lung
Hypersensitivity pneumonitis
92
Rheumatoid arthritis
long-term autoimmune disorder involving both Type 1 and Type 2 hypersensitivity
93
Contact dermatitis
a reactive chemical binds to skin proteins and presented to T-cells
94
Gluten intolerance
Reaction to giladen antigen causing atrophy in small bowel
95
Central tolerance
Mechanism where immune system learns to discriminate self vs non-self antigens
96
Peripheral tolerance
mechanism where the body prevents over-reactivity to environmental factors
97
Autoimmune disease have been linked to
certain MHC haplotypes - as they may fail to delete anti-self T-cells or B-cells
98
Sympathetic Uveitis
Inflammation that occurs following insult to the eye
99
Clinical presentation of sympathetic uveitis
mutton-fat keratic precipitates, choroidal infiltrations, Dalen-Fuchs nodules
100
Myathenia gravis
antibodies against nicotinic Ach receptors at neuromuscular joint prevent Ach from binding, preventing muscle contractions
101
Clinical presentation myathenia gravis
muscle weakness, drooping eyelids (ptosis)
102
Grave's disease
manifests as hyperthyroidism due to antibodies against TSH receptor
103
Clinical presentation of Grave's disease
goitre-swelling of neck from enlarged thyroid gland, bulging eyes
104
Organ-specific autoimmune disease
immune response against self antigen of a single organ
105
Systemic autoimmune disease
immune response against self-antigens throughout many tissues
106
Primary immunodeficiency
genetic defects result in absence of functioning immune system parts
107
Secondary immunodeficiency
environmental factors that compromise the immune system
108
4 factors of secondary immunedeficiency
malnutrition, medication, aging, disease
109
Malnutrition
protein deficiency leads to a decreased ability to fight infection
110
Medication
Cytotoxic agents target rapidly dividing cells which supress the immune system
111
Aging
Thymus shrinks, producing fewer T-cells
