Prep For Exam Flashcards
1
Q
Define: PAMPs
A
Recognized by innate immune system; Shared characteristics of many pathogens (including LPS, CpG DNA, mannose, flagellum, dsRNA)
2
Q
What does the complement system do?
A
Lyses the pathogen cell; opsonizes pathogen; recruits phagocytes
3
Q
What are the 3 types of phagocytes?
A
Macrophages; neutrophils; dendritic cells
4
Q
What are the components of the innate immune system?
A
Complement cascade; phagocytes; natural killers
5
Q
Where do T cells develop?
A
They are derived from pluripotent stem cells that are located in the bone marrow and then they develop in the thymus
6
Q
How long does T cell development take?
A
3 weeks
7
Q
What are the parts of the thymus?
A
Peripheral cortex (densely populated w/ lymphoid cells) and central medulla (less lymphocyte rich, contains DCs and macrophages)
8
Q
What are the 3 stages of T cell development?
A
Double negative (CD4-/8-); double positive (CD4+/8+); single positive (express CD4 or CD8 only) NOTE: DN thymocytes are not committed to T cell lineage (can become B or NK cells)
9
Q
Define: Alpha Beta T Cells
A
Surface TCR composed of alpha and beta chains; most abundant; responsible for adaptive immune response
10
Q
Define: Gamma-delta T Cells
A
Surface TCR composed of gamma and delta T cells; minor population; recognizes lipid antigens in the gut
11
Q
How do T cells decide whether they should become gamma-delta or alpha-beta?
A
DN T cells rearrange their beta, gamma, and delta; if beta chain successfully rearranges, then it becomes a pre-TCR; if gamma and delta chains rearrange, then they commit to gamma-delta lineage; NOTCH signaling can also influence choice
12
Q
How many rounds of recombination does TCRbeta chain go through?
A
2, due to the two D-J clusters and C domains;
If unsuccessful, then the cell dies;
If successful, then the TCRbeta is expressed with pre-TCRalpha on the cell surface
13
Q
What do B cells in the mucosa express?
A
IgA
14
Q
What makes a pentameter?
A
IgM
15
Q
What segments does the light chain have? The heavy?
A
LC = V, J; HC = V, D, J
16
Q
What activates complement?
A
IgM; IgG
17
Q
What opsonizes?
A
IgG
18
Q
What participates in mast cell sensitization?
A
IgE
19
Q
What is responsible for adding non-germline encoded nucleotides at VDJ junctions?
A
TdT
20
Q
What kind of immunoglobulins do B cells express?
A
IgG, IgA, and IgE
21
Q
Which immunoglobulin dimerizes?
A
IgA
22
Q
What immunoglobulins do naive B cells express?
A
IgM, IgD
23
Q
Which cells perform cell-mediated cytotoxicity?
A
Natural Killer Cells (NK Cells)
24
Q
Where is MHC Class I found?
A
Any nucleated cell
25
What is the length of peptide bound by MHC I?
9 AAs
26
What kind of MHC Class are HLA-DR, HLA-DQ, and HLA-DP?
MHC Class II
27
What kind of MHC Class are HLA-A, HLA-B, and HLA-C?
MHC Class I
28
What is the length of the peptide bound by MHC Class II?
Variable
29
Where are MHC Class II molecules found?
APCs and B cells
30
What is a pre-TCR receptor?
TCR beta chain plus the invariable pre-TCRa chain; associates with CD3 signaling complex
31
What does a pre-TCR do?
Blocks further rearrangement of the beta chain; induces proliferation and generates a pool of cells w/ the same beta chain that will subsequently rearrange TCR alpha; induces differentiation into DP
32
What occurs in TCRa rearrangement?
V and J segments rearrange, allowing multiple rounds or recombinations; deletes TCR delta; NOTE: TCRa rearrangement does not immediately block continued recombination
33
When does TCRa rearrangement stop?
TCRa recombination is blocked by recognition of self-MHC complexes during positive selection
34
Define: Positive T cell Selection
The process of rescue from cell death and maturation to SP CD4 or SP CD8 cells upon recognition of MHC-self peptides; occurs in the cortex
35
Define: Negative T cell Selection
TCR receptors that respond too strongly to self-peptide are eliminated (too self-reactive)
36
How does a T cell decide whether to be CD4 or CD8?
If it interacts via TCR w/ an epithelial cell expressing MHC Class I vs. MHC Class II; if it doesn't react with either, then alpha rearranges and the TCR tries again
37
What do macrophages secrete?
Pro-inflammatory cytokines including IL-6, TNFa, IL-1b, CXCL8, and IL-12
38
What does IL-6 do?
Activate lymphocytes
39
What does CXCL8 do?
Recruits PMN
40
What are the 2 main cytokine families are their components?
Four-helix bundle family of interleukins (IL-2, IL-4, etc AND IFNs) - signal through JAK-STAT; TNF (TNFa, FasL, CD40L AND IL-33) - these signal through the NFkB or Caspase pathway;
NOTE: IL-1, IL-17, and TGFb are NOT part of these families
41
Define: chemokines
Very small secreted proteins that bind ligand-specific G-protein coupled receptors; chemotaxis and chemoattraction is most important; work with integrins to promote cell-specific adhesion
42
What are the 2 families of chemokines?
Homeostatic chemokines (important for creating immune structures; the CCRs; CXCR5); inflammatory chemokines (important for recruiting leukocyte a in response to an immune challenge; pretty much all of the other CXCLs and CXCRs)
43
What is "the troika" of sepsis?
IL-1B, IL-6, and TNFa activation, resulting in activation of complement opsonization, PMN phagocytosis, increased immune response
44
How does Hepcidin affect the immune system?
Hepcidin turns off ferroportin leading to Fe sequestration - elevated Hepcidin can cause Anemia of Chronic Disease! This is b/c both the infection and host want iron for life cycle - battle it out
45
What does CRP do?
Opsonizes bacteria; can be measured clinically as an inflammatory marker
46
What are the 4 types of hypersensitivity?
Type I: Immediate - IgE mediated; Type II: Cytotoxic - Ab mediated; Type III: Immune complex mediated; Type IV: delayed-type, T cell mediated
47
Define: Hapten
Chemical moiety too small to elicit a T cell response alone, but capable of tight association with self proteins; this "conjugation" creates a new (foreign) target
48
What is sensitization? (As in hypersensitivity)
Low-dose allergen exposure often via mucous membranes, resulting in IgE production
49
What is the process of Type I Hypersensitivity?
Sensitization; Elicitation (Re-exposure; pre-formed IgE triggers mast cell activation)
50
Define: Mast Cell
Subepithelial tissue sentinel of myeloid lineage - major express or of high-affinity receptor for IgE; preformed granules contain histamine
51
What is involved in sensitization response?
IgE
Basophils
Mast cells (plasma cell)
52
What is the early phase of sensitization?
IgE cross links w/ antigen, releasing preformed mediators (resulting in histamine release, vasodilation, smooth muscle constriction, GI motility, mucous secretion, sensory nerve activation) followed by rapid production of arachnids ice acid products (leukotrienes, prostaglandins)
53
What occurs in the late phase of sensitization?
Gene activation and new cytokine production (TNFa recruits inflammatory cells, IL3 and IL5 stimulate eosinophil production, IL4 and IL13 propagate Th2 response)
54
How does immune complex hypersensitivity cause damage?
Ag-Ab complexes deposit in local blood vessel walls, fix complement and generate C5a; bind Fc receptors on neutrophils (releasing free radicals and proteases) and platelets (causing aggregation, thrombosis, necrosis)
55
What are the symptoms of serum sickness?
Fever; lymphadenopathy; hives; joint pain; proteinuria
These occur about 2 weeks following introduction of long-lived antigen in a naive receptor (like injection of horse serum)
56
What is Delayed-Type Hypersensitivity?
Group of T-cell mediated responses to antigen - requires sensitization like Type I, but on re-exposure the reactions occur over 1-3 days; example: poison ivy
57
What do effector T cells produce?
Interferon-gamma, chemokines; they recruit macrophages (which produce TNFa)
58
Where is the Hapten taken up if it modifies extracellular proteins?
Cutaneous macrophages
59
What is the pathophysiology of atopic dermatitis?
Th2 response is increased, decreasing levels of IFN-g, IL2 and increasing IL4 and IL5; IgE, mast cells, and eosinophils are increased
60
What are the major criteria for atopic dermatitis?
Must have 3+: pruritis (itching), personal or family history of autopsy, chronic or chronically relapsing dermatitis, typical morphology and distribution
61
What is allergic contact dermatitis?
Immune mediated response that requires sensitization, not dose dependent
62
What is irritant contact dermatitis?
Not an immune mediated reaction; local, toxic effect on cells that elicits an inflammatory response - can be acute, corrosive, phototoxicity
63
What does IL-1 do?
Fever, macrophage activation, activation of vascular endothelium, PMN mobilization
64
What does IL-2 do?
T cell proliferation
65
What does IL-3 do?
Hematopoietic growth factor for multiplier WBC lineages
66
What does IL-4 do?
B cell activation, IgE CSR, Th2 polarization
67
What does IL-5 do?
Eosinophil hematopoiesis, chemotaxis, and activation
68
What does IL-6 do?
Fever, Th17 differentiation, acute phase reactant induction
69
What does IL-7 do?
Proliferation of pre-B and pre-T cells
70
What does IL-10 do?
Suppresses APC MHCII and B7 expression
71
What does IL-12 do?
Activates NK cells, promotes IFN-g production by macrophages, promotes Th1 polarization
72
What does IL-13 do?
B cell proliferation, inhibits macrophage inflammatory cytokine production
73
What does IL-17 do?
PMN recruitment and activation
74
What does IL-23 do?
Promotes Th17 differentiation
75
What does IFNa do?
Proteasome induction, increased MHC I expression
76
What does INFb do?
Proteasome induction, increased MHC I expression
77
What does IFNg do?
Macrophage activation, increased expression of MHC I and II and antigen processing components, suppression of Th2 polarization
78
What does TNFa do?
Neutrophil mobilization, activation of vascular endothelium, increase in vascular leafiness, maturation of DCs, Fever, acute phase reactants
79
What does TGFb do?
Inhibits lymphocyte growth and macrophage activation, directs IgA class switch
80
What does GM-CSF do?
Hematopoietic growth factor for granulocytes and monocytes
81
What do TNF ligands do?
Promote receptor trimerization and NFkB (inflammatory gene expression) and Caspase (programmed cell death) expression
82
What is Autoimmune Lymphoproliferative Syndrome (ALPS)?
Rare, often somatic mutation of the FAS gene
| Associated profound lymphadenopathy with increased B cells and double negative T cells
83
Why are chemokines desirable drug targets?
They signal through G protein coupled receptors (GPCRs)
84
What is the path of a dendritic cell?
Antigen taken up by Langerhans cells in the skin, CCR7 increased; L cells go to the lymph system; Mature DC cells transfer antigen to resident DC cells; B7 positive DC stimulate naive T cells; T cells bind to DC through low-affinity LFA-1:ICAM-1 interactions, confirmational change
85
How is a T cell activated?
1. Interacts w/ DC that presents antigen; 2. ZAP-70 kinase; 3. Lots of kinases (NFkB, IP3, NFAT, AP-1); 4. Cell division, proliferation, and differentiation to effector T cells
86
What defines what kind of T cell it will become?
A cytokine - Singal #3 (TGFb is Treg; IL6 is TFH; TGFb is TH17, etc)
87
What is needed to activate memory cells?
MHC I or MHC II presentation
88
What are the 3 major signals of naive T cell activation?
1. Antigen presentation; 2. APC co-stimulating receptors like CD80/86 activate CD28; 3. Cytokines promote T-cell polarization
89
What are Th1 cells?
CD 4 cell that targets intracellular microbes - type I immunity; release IFNg
90
What are Th2 cells?
CD4 cells that target helminthes, activate Eos and mast cells; secretes IL-4
91
What is Th17 cell?
CD4 cell that targets extracellular microbes, release IL-17
92
What are TFH cells?
CD4 cells that are T-cell help for B cells (promoter affinity maturation and class switching)
93
What are Treg cells?
CD4 T cells that suppress T-cells directed against self or acquired antigens
94
Why does TB form granulomas?
Th1 cells (the "classical" activator of macrophages) surround and partial remove the M. Tuberculosis infected macrophages
95
Why do superantigens cause TSS?
Cytokine Storm/exuberant polyclonal T-cell activation; cross-link MHCII to T-cell receptors
96
What do TNF ligands do?
Promote receptor trimerization and NFkB (inflammatory gene expression) and Caspase (programmed cell death) expression
97
What is Autoimmune Lymphoproliferative Syndrome (ALPS)?
Rare, often somatic mutation of the FAS gene
| Associated profound lymphadenopathy with increased B cells and double negative T cells
98
Why are chemokines desirable drug targets?
They signal through G protein coupled receptors (GPCRs)
99
What is the path of a dendritic cell?
Antigen taken up by Langerhans cells in the skin, CCR7 increased; L cells go to the lymph system; Mature DC cells transfer antigen to resident DC cells; B7 positive DC stimulate naive T cells; T cells bind to DC through low-affinity LFA-1:ICAM-1 interactions, confirmational change
100
How is a T cell activated?
1. Interacts w/ DC that presents antigen; 2. ZAP-70 kinase; 3. Lots of kinases (NFkB, IP3, NFAT, AP-1); 4. Cell division, proliferation, and differentiation to effector T cells
101
What defines what kind of T cell it will become?
A cytokine - Singal #3 (TGFb is Treg; IL6 is TFH; TGFb is TH17, etc)
102
What is needed to activate memory cells?
MHC I or MHC II presentation
103
What are the 3 major signals of naive T cell activation?
1. Antigen presentation; 2. APC co-stimulating receptors like CD80/86 activate CD28; 3. Cytokines promote T-cell polarization
104
What are Th1 cells?
CD 4 cell that targets intracellular microbes - type I immunity; release IFNg
105
What are Th2 cells?
CD4 cells that target helminthes, activate Eos and mast cells; secretes IL-4
106
What is Th17 cell?
CD4 cell that targets extracellular microbes, release IL-17
107
What are TFH cells?
CD4 cells that are T-cell help for B cells (promoter affinity maturation and class switching)
108
What are Treg cells?
CD4 T cells that suppress T-cells directed against self or acquired antigens
109
Why does TB form granulomas?
Th1 cells (the "classical" activator of macrophages) surround and partial remove the M. Tuberculosis infected macrophages
110
Why do superantigens cause TSS?
Cytokine Storm/exuberant polyclonal T-cell activation; cross-link MHCII to T-cell receptors
