IHO Week 1 Diebel Flashcards
1
Q
Major Functions of Innate Immunity
A
- Complement activation 2. Inflammation 3. Cell activation (cytokine and chemokine production, phagocytosis and other killing microbes) 4. priming of the adaptive immune response
2
Q
3 Things Recognized by the Innate Immune System
A
- Foreign molecular structures called PAMPs 2. stress or damage indicators aka DAMPs 3. absence of certain ‘self’ MHC1marker molecules by NK cells
3
Q
PRRs
A
pattern recognition receptors; 13 TLRs are included in this
4
Q
PRRs that recognize PAMPs do not activate phagocytosis and do trigger cell signaling leading to gene transcription events to foreign material
A
TLRs
5
Q
C-Type Lectin Receptors
A
Mannose, Dectin 1, DC-SIGN
6
Q
Scavenger Receptors
A
SR-A and SR-B
7
Q
Steps Phagocytosis
A
- bacterium attaches to membrane and evaginations called pseudopodia 2. ingested to form phagosome 3. fuses with lysosome 4. bacterium is killed and digested by lysosomal enzymes 5. digestion products released from cell
8
Q
Phagocytosis Oxidative Attack from:
A
Reactive Oxygen Species (O2, OH, H2O2, HClO) and Reactive Nitrogen Species (NO, NO2, ONOO-)
9
Q
Alternative Pathway to activate the complement system
A
innate immune defense strategy which results in opsonization and facilitated uptake of the coated microorganism by phagocytosis
10
Q
Classical Pathway to Activated by
A
Antibodies or mannose binding lectin
11
Q
Complement activation is a cascade reaction leads to:
A
opsonization, chemotaxis of phagocytes, increased blood flow, increased permeability, damage to plasma membranes on cells, G(-) bacteria, enveloped viruses, and other organisms, release of inflammatory mediators from mast cells
12
Q
Classical Pathway (Adaptive Immunity) direct destruction
A
- C1q binds to antigen: antibody complex; cleaves and activates downstream complement components 2. C5b binds to the membrane associated with the antigen:antibody complex which leads to the formation of the membrane attack complex
13
Q
Lectin Pathway (Innate Immunity) direct destruction
A
- Mannose binding protein bound to bacterial carbohydrates mimics C1q -> cleavage and activation of downstream complement components 2. C5b binds to the membrane to form attack complex
14
Q
Alternative Pathway (Innate Immunity)
A
C3 is spontaneously cleaved or cleaved by C3b by serum proteases activated by bacteria; C3b binds to bacterial and yeast cell walls and viral envelopes; bound C3b leads to the downstream activation of the complement components
15
Q
A Components-C3a, C4a and C5a action
A
-chemotactic factors that direct migration of/degranulation of PMNs and macrophages and degranulate mast cells and basophils to large amounts of histamine
16
Q
Potency of A Complement Components
A
C5a»C3a»C4a
17
Q
What complement deposits on any surface with an exposed amine or hydroxyl ie bacteria cell
A
C3b and C4b
18
Q
What complement acts as opsonins and further cleaves C3 to ramp up signaling at the surface
A
C3b and C4b
19
Q
What are inactivated when bound to host cells by decay accelerating factor
A
C3b and C4b
20
Q
What complement binds to microorganisms or host body cells
A
C5b
21
Q
What complement acts as a focal point for the deposition of the membrane attack complex?
A
C5b
22
Q
What complement associated with CD59 protectin and homologous restriction factor to prevent formation of membrane attack complex
A
C5b
23
Q
Phagocytosis-Opsonin Receptors: Collagen-domain receptor examples and ligands
A
examples: CD91/calreticulin
ligands: collectins SP-A, SP-D, MBL; L-ficolin; C1q
24
Q
Phagocytosis-Opsonin Receptors: Complement Receptors examples and ligands
A
ex: CR1, CR3, CR4, CRig, C1qRp
ligands: complement components and fragments
25
Phagocytosis-Opsonin Receptors: immunoglobulin Fc receptors
ex: FcalphaR and FcgammaRs
ligands: specific IgA or IgG antibodies bound to antigen and CRP
26
Hallmarks of Inflammation
-edema, hyperthermia, local hypoxia, extravasation (influx of WBC via IL-8)
27
What increases vascular permeability besides Leukotriene D4
histamine-complement C5a stimulation of basophil and mast cell degranulation
28
What causes vasodilation and increased vascular permeability
prostaglandin E2-complement C5a stimulation of basophil and mast cell degranulation
29
What causes neutrophil chemotaxis, increased vascular permability
Leukotriene-complement C5a stimulation of basophil and mast cell degranulation
30
What besides histamine increased vascular permeabillity
Leukotriene D4-complement C5a stimulation of basophil and mast cell degranulation
31
Macrophages Triggers of Inflammation: 3
TNF, IL-1 and IL-8
32
can cause a fever, stimulates expression of E-selectin
TNF
33
induction of local inflammation; activates endothelial cells to express adhesion molecules; induces the production of chemokines to recruit leukocytes and role in fever
IL-1
34
chemotaxis
IL-8
35
activation of phagocytic cells and NK cells in trigger of inflammation
IFNgamma
36
Name 3 changes in tissue during acute inflammation
1. increased blood supply 2. increased capillary permeability 3. increased leukocyte migration
37
Cells in acute inflammation
more neutrophils and activated helper T cells
38
Cells in chronic inflammation
more macrophages, cytotoxic T cells and B cells
39
Important Inflammatory Cytokines (3)
TNFalpha, IL-1 and IFNgamma
40
More migration in high shear or low shear
low shear
41
3 Step Model of Leukocyte Adhesion
1. Tethering with CD15 and E-selectin 2. Triggering with direct signal and chemokines 3. Adhesion-activation of integrins and CR3/LFA-1, ICAM-1
42
histamine main source and action
mast/basophils: increased permeability, smooth muscle contraction, chemokinesis
43
5HT
platelets/mast cells: increased permeability, smooth muscle contraction
44
platelet activating factor main source and action
basophils/neutrophils/macrophages: mediator release from platelets, increased perm., smooth muscle contraction, neutrophil activation
45
IL-8 main source and action
mast/endothelium/monocytes and lymphocytes: polymorph and monocyte localization
46
C3a main source and action
C3: mast cell degranulation, smooth muscle contraction
47
C5a main source and action
C5: mast cell degran, neutrophil and macrophage chemotaxis, neutrophil activation, smooth muscle contraction, increased capillary perm
48
bradykinin main source and action
kinin system: vasodilation, smooth muscle contraction, increase capillary perm, pain
49
fibrinopeptides and fibrin breakdown products main source and action
clotting system: increased vasc perm, neutrophil and macrophage chemotaxis
50
PGE2 main source and action
cycolo-oxygenase pathway, mast cells: vasodilation, potentiates vasc. perm produced by histamine and bradykinin
51
leukotriene B4 main source and action
lipoxygenase pathway, mast cells: neutrophil chemotaxis, syngergizes with PGE2 in increasing vascular permeability
52
leukotriene D4 main source and action
lipoxygenase pathway: smooth muscle contraction, increasing vascular permeability
53
PMN signaling differentiation
(IL3+GMCSF)->(IL-3 + GMCSF +GMCSF)
54
have Fc receptors to bind antibodies which makes them able to kill by antibody-dependent cellular cytotoxicity
PMN
55
Eosinphils signaling
(IL3 +GMCSF)->(IL3+GMCSF +IL5)
56
what activates C5a and C3a to degranulate
Eosinophils and Basophils
57
Basophils signaling
(IL3+GMCSF)->(IL3 + GMCSF + IL4)
58
Macrophages signaling
(IL3 + GMCSF)-> (IL3 + GMCSF +MCSF)-> (GMCSF +MCSF)
59
Cytokines and lymphokines produced by macrophages
IFNalpha, IL1beta, IL6, TNFalpha, IL8, IL12
60
Dendritic Cell Signaling
from myeloid: (IL3 +GMCSF)-> (IL3 +GMCSF+MCSF)-> (GMCSF+ IL4)
61
process and present foreign protein antigens to T cells
Classical dendritic cells
62
passively present foreign antigen in the form of immune complexes to B cells in lymphoid follicles
Follicular dendritic cells
63
NK signaling for differentiation
(IL-7)->(IL-2)
64
2 markers of NK cells
CD16 (FcyRIII) and CD56 (NCAM)
65
What activates NK cells to secrete cytokine INFgamma
IL-12 and TNFalpha
66
signal transduction element of T cell; Th and Tc
CD3
67
adhesion molecule that binds to class II MHC molecules; signal transduction; Th
CD4
68
low affinity receptor for Fc region of IgG; NKcell
CD16(FcyRIII)
69
signal transduction; CD21 co-receptor; Bcell
CD19
70
receptor for complement (C3d and EBV); B cell
CD21 (CR2)
71
receptor for costimulatory B7 molecule on APC; Th and Tc
CD28
72
receptor for Fc region of IgG
CD32 (FcgammaRII)
73
signal transduction; Bcell
CD40
74
adhesion molecule; NK cell
CD56
75
IgG
main antibody in blood and tissue fluids; neutralized toxins and blood borne viruses, binds bacteria and facilitates destruction via complement
76
How long for activation of B and T lymphocytes?
7-10 days
77
T cell job versus B cell job
Tcell (cell mediated) survey surfaces of body's cells for parasites within or dangerous mutations and release lymphokines while Bcells (humoral) protect extracellular spaces of the body with antibodies
78
Residence of B and T cells
can be in blood or lymph nodes and spleen
79
Can mature B and T cells travel from one lymph node to another or to and from the spleen?
yes
80
Primary Lymphoid Organs
Thymus and Bone Marrow
81
Secondary Lymphoid Organs and Tissues
-waldeyer's ring (tonsils and adenoids), bronchus associated lymphoid tissue (lymph nodes, bone marrow, spleen), lymphoid nodules, peyer's patch, urogenital lymphoid tissue
82
anther name for epitopes
antigenic determinants
83
a cytokine made by a lymphocyte
lymphokine
84
What 2 things do all T cells express
CD3 and T cell receptors created through DNA arrangement
85
what couples with CD3 complex to make up the TCR
alpha beta peptides in alpha beta T cells
86
alpha beta T cells function by binding what
MHCI or MHCII molecules
87
gamma delta can function with binding what
MHC
88
Job of Type 1 Helper T cells; Th1 (CD4)
recognize antigen and make a lymphokine that attracts MACROPHAGES
89
job of Th17 Helper T cells; Th17 (CD4)
inflammation; more powerful than Th1; autoimmunity
90
job of Type 2 Helper T cells, Th2 (CD4)
alternatively activated macrophages, function in walling-off pathogens and promoting healing; usually after Th1; parasites
91
job of Follicular Helper T cells, Tfh (CD4)
stimulated via antigen and migrate from T cell areas of lymph nodes into the B cell follicles where they help B cells get activated to IgM/IgG/IgE/IgA
92
job of Regulatory T cells, Treg (CD4)
make cytokines that suppress the activation and function of Th1, Th17, and Th2 to keep immune response in check
93
job of cytotoxic or killer cells, CTL (CD8)
destroy body cell they id as bearing a foreign or abnormal antigen
94
what serves to increase affinity for antigen, activates Th and serves as tag for identification
CD4
95
Needed for adhesion
LFA-1 on T and ICAM-1/3
96
Needed for Ag Specific activation
CD2 to CD58, CD8/4 to MHCI/II
97
Needed for co-stimulation
CD28 to B7 (akaCD80/86)
98
Needed for cytokine signals
IL-1R to IL-1, CD25 to IL-2
99
2 ways of killing via Killer T cells
1. FAS-FAS ligand interaction (induces caspase to apoptosis) 2. secreting toxic agents as well (TNF or granzymes to apoptosis)
100
Where do T cells differentiate to CD4 or CD8?
Thymus
101
Positive versus Negative selection of T cell maturation
(+) self restricted, (-) tolerant to self-antigens
102
Most abundant immunoglobulin, 2 adjacent to activate complement
IgG
103
only antibody to pass from mother to fetus in humans; valence 2
IgG
104
secreted as a pentamer held together by the J chain with 4 constant domains; immunoglobulin; better at activating COMPLEMENT and first to appear in blood after new exposure; then replaced by IgG; valence 10
IgM
105
main form of antibody inserted into B cell membranes as their antigen receptor; sits on the membrane; valence 2
IgD
106
in secretions (saliva, tears, genitourinary and gi fluids, milk), associated with secretory component that acquires epithelial cells, first line defense in mucous membranes; secreted as dimer; valence 2, 4, 6, or 8
IgA
107
immunoglobulin to attach to mast cells in tissues to make PG, leukotrienes, and cytokines to inflammation (histamine); parasites; valence 2
IgE
108
4 was antibody as adapter molecules
1. immune complex (C1q) 2. immune complex/pathogen opsonization phagocytosis (FcR) 3. target cell/pathogen (recognition killing-FcR) 4. antigen (sensitization cell activation FcR)
109
If you change the heavy chain from mu to alpha does the light chain change from kappa or lambda or stay the same
stays the same
110
what two immunoglobulins when bind change the angle b/w Fab
IgG or IgM
111
Angle change with binding of Fab for 2 reasons
1. binding to phagocytic cells via Fc receptors for altered Fc of IgG 2. C1qto bind to 2 adjacent Fcs
112
If lots of IgG around what happens
forms a hexamer that allows CH2 landing pad for C1q to complement cascade
113
what is the trade off in IgG hexamer versus monomer
complement activation versus opsonization
114
Heavy chain chromosome
14; VDJ
115
What germline for VDJ chromosome 14
DNA to CH genes
116
what recognizes open sites in the DNA for VDJ recombination?
RAG1-RAG2 multimers
117
Stages of VDJ Recombination
1. synapsis: RAG synaptic complex 2. cleavage: RAG post-cleavage complex 3. joining: coding joint (imprecise junction) or signal joint (precise junction)
