Test 1, deck 1 Flashcards
(99 cards)
1
Q
specific characteristics of innate immunity
A
- inherited in the genome
- expressed by all cells of a particular type (e.g. macrophages)
- triggers immediate response
- recognizes broad classes of pathogens (NOT SPECIFIC)
- no memory
- interacts with a range of molecular structures
- modified epigenetically
2
Q
specific characteristics of acquired immunity
A
- encoded in multiple gene segments
- requires gene rearrangement
- lag between exposure and response
- clonal expansion of immune cells for efficient response
- able to discriminate between closely related molecular structures (SPECIFIC)
- immunologic memory
- modified epigenetically
3
Q
key advantage of innate system? disadvantage?
A
- adv: activated instantaneously
- disadv: lack of ability to precisely target pathogens and limit collateral damage
4
Q
key advantage of adaptive system? disadvantage?
A
- adv: memory & precise specificity
- disadv: takes more than a week to become fully operational
5
Q
what are 2 initial barriers to infection, what mechanisms do they employ, and where are they found?
A
- mucosa (gut, lungs, eyes/nose) & skin
- mechanical, chemical, microbiological
6
Q
how does the innate immune system recognize danger?
A
- patterns called PAMPs and DAMPs which activate receptors on the innate cells called TLRs (“on” switch for immune response)
7
Q
2 pathways innate immunity uses to neutralize threat
A
1) soluble proteins made in liver (mannose-triggered phagocytosis)
2) immune effector cells
8
Q
what are cytokines? fundamental concepts?
A
- small messenger peptides
- two peptide chains encoded by separate genes
- develop as families, exhibit redundancy
- are expressed by immune and non-immune cells
- mediate communication between humoral and cellular immunity
- regulate the intensity of immune response; act as yin and yang
9
Q
cells of adaptive (acquired) system
A
1) macrophages and dendritic cells given new functions
2) small lymphocyte (B (antibodies) and T (killer,helper) cells)
10
Q
4 features that determine immunogenicity of acquired immune system
A
1) recognizes antigens with very specific receptors
2) can distinguish between self and non-self
3) can clonally expand antigen specific cells after their activation
4) can remember specific encounters
11
Q
what are the effector molecules of the adaptive system?
A
- cytokines
- recognition molecules (antibodies, complement system)
12
Q
what are HSCs?
A
hematopoietic stem cells- multi-potent, self-renewing sources of WBCs, RBCs & platelets
13
Q
where are the HSC niches in bone marrow? what is their purpose?
A
- osteoblasts and sinusoidal endothelial cells
- Even though stem cells have the ability to self-renew, they must be
surrounded by this niche in order to do so. This is because the niches supply growth factors and other regulatory molecules that support HSC self-renewal.
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14
Q
what are stromal cells and where are they found?
A
- found in niches; provide factors needed for HSC maintenance
- can push HSCs to differentiate into peripheral blood progenitors
- importance for replenishing of peripheral blood
15
Q
T/F HSCs are found in the peripheral circulation
A
T- may return to circulation in circadian manner, but chemical signals encourage them to go home (to the bone marrow)
16
Q
HSCs differentiate into ____; what growth factors/cytokines (ILs) induce these changes?
A
common myeloid (IL-3 and GM-CSF) & lymphoid (IL-7) progenitors
17
Q
common myeloid progenitors differentiate into ____
A
RBCs (thrombocytes), mast cells (granulocytes) and
- N (G-CSF)
- M (GM-CSF, M-CSF)
- E (IL5)
- B (IL4)
- dendritic cells- Flt3L
18
Q
common lymphoids differentiate into _____
A
NK cells & lymphocytes (b cells (IL3 and IL7) & t cells (IL2 & 7))
19
Q
where are the lymphoid organs?
A
1- lymph nodes
2- mucosal tissue- intestines
3- spleen
4- tonsils and adenoids
20
Q
5 types of leukocytes
A
neutrophils lymphocytes (Bs and Ts) monocytes eosinophils basophils
21
Q
general route of the immune response
A
naive lymphocytes travel in blood to lymph nodes where they may run into dendritic cells presenting matching pathogen; activated lymphocyte then goes back into blood via thoracic duct & left subclavian vein; is called to site of injury by cytokines
22
Q
which cells are most important front line defense of the innate immune system? where are they normally found?
A
- neutrophils- have LOTS
- normally found circulating, not in tissue
23
Q
what is pus?
A
dead neutrophils
24
Q
3 neutrophil killing mechanisms
A
phagocytosis, degraulation, neutrophil extracellular traps (NETs)
25
what is the distinction between macrophages and monocytes?
monocytes are in blood, macrophages are in tissue
26
what is sepsis a result of?
bystander effects of macrophage recruitment
27
2 ways dendritic cells take up an antigen
1- phagocytosis
| 2- macropinocytosis
28
which type of WBCs are known to be able to sustain allergic reactions?
eosinophils
29
what is the function of mast cells?
- have lots of histamine which causes vasodilation, allowing WBCs to enter the site of infection
- cause increased local blood flow & leaky vessels
30
what do NK cells do?
- go after cells that don't look right- virus infected & tumor cells
- can target viruses when slow adaptive response is gearing up
- induce apoptosis
31
What are the 2 key phagocytic cells in the innate system?
macrophages and neutrophils
32
What are the differences between the 2 key phagocytic cells in the innate system?
macrophages- mature, long lived, increase at sites of infection, 1st to encounter pathogen
neutrophils- abundant in circulation (not tissues), short lived, rapid responders
33
Two ways phagocytes counter threats
1) phagocytosis- use receptors to recognize PAMPs when sampling the environment
2) mediator production- release factors to activate other responses (cytokines, chemokines)
34
What are the four signs of inflammation?
redness, pain, heat, swelling
35
What are the 3 things inflammation does?
1) alters blood flow
2) increases permeability of vascular system
3) gives infiltration of WBCs
36
how is the inflammation response initiated?
- by recognizing PAMPs and DAMPs (pathogen associated molecular pattern) and activate an immune response best suited towards eliminating the infected organism; takes minutes from exposure
37
what are the 4 classes of pathogen recognition receptors (PRRs)?
- toll like
- c-type lectin
- Rig-I like receptor
- NOD-like receptor
38
Where are the two places PRRs can be expressed?
transmembrane (TLRs CTLRs) or soluble intracytoplasmic (Rig and NOD)
39
What does TLR-4 recognize?
LPS (on gram negative bacteria)
40
What is the TLR4 pathway?
receptor binds MyD88, binds IRAK, releases NFKB and initiates transcription
41
What happens if TLR is missing?
get unrestricted replication of bacteria
42
what are the critical cells in the innate response that interface with the adaptive system?
** dendritic cells
| NK cells
43
what are some key characteristics of dendritic cells?
1) roam freely in all tissues/organs
2) have lots of PRRs
3) interact with NK cells and GDTs (gamma delta t-cells)
44
how do NK cells interact with the adaptive system?
- bind to antibody coated cells and degradulate
| ADCC- antibody dependent cytotoxicity
45
what are 2 innate-like lymphocytes?
- NKT cells - subset of T cells with molecules found on NK cells ; recognize lipid antigens, provide immediate help for adaptive system
- GDTs- recognize phosphoantigens (metabolic intermediate produced by fungi & bacteria)
46
where are GDTs commonly found?
mucosal sites
47
which type of innate cells can establish memory phenotype?
GDTs, NKTs, ILCs
| - macrophages- epigenetic changes which train them for faster response
48
what is the sequence like at the N-terminal end of the light & heavy chains?
- it is the variable terminal, the sequence is very specific
49
what are the 5 antibody isotopes?
```
"MADGE"
IgM- mu
IgA- alpha
IdD- delta
IgG- gamma
IgE- epsilon
```
50
Which two antibodies have extra long heavy chains?
IgM and IgG
51
what is the predominant antibody induced in the secondary response?
IgG
52
what is the predominant antibody in external secretions?
IgA
53
What is the predominant antibody induced in the primary response?
IgM
54
Which antibody is found mainly on the surface of B cells?
IgD
55
Which antibody is involved in allergic hypersensitivities?
IgE
56
How are isotopes classified?
in the constant region of their heavy chain
57
What are the two types of light chains?
kappa (60) & lambda (40)
58
what kind of bond holds the heavy chains together? light chains?
both are disulfide
59
What are the two fragments above and below the disulfide bond called?
Fab (fragment antigen binding) &
| Fc (crystalizing fragment)
60
which is special about IgM
comes together as a pentamer in blood; is predominant antibody induced in the primary response; is 5x larger
61
what is special about IgA
found in blood as monomer & in mucosal secretions as dimer
62
what is the major Ig in blood?
IgG
63
what is the half-life of IgG?
21 days (3 weeks)
64
what do mast cells have receptor for?
Fc part of IgE (allergies) = FCeR
| Fc= crystalized fragment
65
3 functions of antibodies
1) neutralization (prevents bacterial adherence)
2) opsonization (promotes phagocytosis)
3) complement activation (complement enhances opsonization)
66
what is the IgE mediated allergy response?
have two IgEs bound to Fc receptor specific for IgE side by side; allergen binds to both IgEs, cross linking promotes degranulation of histamine packets
67
what is Fc receptor-mediated killing?
macrophages, neutrophils, NK cells, eosinophils, basophils and mast cells all have Fc receptors (FcR's) on their surface, and the cells can be triggered by cross linking of the receptors (phagocytosis or secretion)
68
when is the critical time for babies with regards to serum Igs?
6-9 months
| passively protected by maternal IgG for first few months
69
half life of serum antibody titers?
tetanus- 11 years
| measles- 2014 years
70
what is a monoclonal antibody? when is this useful?
antibody from a clone of B cells (B-cells make antibody to 1 epitope); useful for targeting cancerous tumor; any drug that ends in MAB
71
what is a polyclonal antibody?
antibody from multiple close of B cells (IVIG treatment, immunizations)
72
what secrete immunoglobulins?
terminally differentiated B cells (plasma cells)
73
describe the specificity of antibodies produced by 1 B cell
all antibodies produced by same B cell have same variable heavy chain, and same variable light chain
74
describe DNA rearrangement for light chains
one of ~40 Vks is rearranged next to one of ~5 Jks; everything in between is deleted
75
describe RNA splicing for light chain
an intron after Jk is taken out to connect with Ck sequence
76
what three genes need to be rearranged together for a heavy chain? what is the order re-arrangement occurs in?
Vh, Dh, Jh
| - DJ rearranged first, then VDJ
77
what is allelic exclusion?
only one Vh and one Vl are rearranged per B cell (only one allele is rearranged (and thus expressed))
78
which CD represents HSCs?
CD34
79
where do mature B-cell precursors exist?
bone marrow
80
what two antibodies must a mature B cell have on the surface?
IgM & IgD
(MD!)
** remember the variable regions on these two Igs will be the same!!
81
in which B cell precursor does DJ (heavy chain) rearranging occur?
early pro B cell
| pro B cells are where there are IgH rearrangements and no light chain arrangements
82
in which B cell precursor does V-DJ (heavy chain) rearranging occur?
late pro B cell
| pro B cells are where there are IgH rearrangements and no light chain arrangements
83
what happens in pre-B cells?
there is a pre-B cell receptor composed of a surrogate light chain and mu heavy chain; this is transiently localized to surface, shuts of rearrangement of other allele OFF, then goes back intracellularly
(** pre-B cells have mu heavy chain)
84
in which B cell precursor does VJ (light chain) rearranging occur?
starts in small pre-B cell, completes by immature B cell
85
what happens to make immature B cells?
light chain is produced, associate with mu heavy chains, and IgM is expressed on cell surface; called immature b/c they don't proliferate/ differentiate in response to antigens (will always express the same variable region)
86
what two things is recombination mediated by?
RSS (sequence) and RAG1/2 (enzyme)
87
what is a BREC?
B-cell recombination excision circle= excised DNA= rings left over when excision occurs, look for them when trying to determine if making new B cells
88
what determines if an antibody will be secreted or left on the membrane?
alternative splicing of SC (1st) and MC (downstream) (C-terminal end of transcript)
89
how do you get co-expression of IgM and IgD on same B cell?
Vh is the same
| Cu and Cd are chosen based on alternative splicing (Cd is downstream (but close) to Cu)
90
what is an isotype switch? where and when does it occur?
changing the Ch of an antibody
occurs NOT in bone marrow
happens after the antibody has encountered an antigen
91
what are the equivalents of the RSS & RAG sequences for a class/antibody switch?
RSS= switch region
| RAG (enzyme)= AID
92
3 ways of generating antibody diversity in bone marrow
1) VDJ gene joining
2) N-Nucleotide addition by TdT (adding in random type and # of nucleotides between excision & rejoining)
3) combinatorial association of H & L chains (each have own variable region)
93
Way to generate antibody diversity not in bone marrow
4) somatic hypermutation (variable region mutates 1 in 1,000 bps)
94
what is a Tdt?
terminal deoxynucleotidyl transferase
| enzyme which adds in random NTs
95
what happens to VDJ rearrangements that shift the reading frame?
they die
96
what are the two things that happen to VDJ rearrangements that produce self-reactive antibodies
1) if the antigen is multivalent (have lots of sites for attachement), they undergo apoptosis
2) if the antigen is soluble, they become anergic (don't activate)
97
how can multivalent cells be rescued?
up-regulate RAG, get "receptor editing", where the cell choses new V & J sites for the light chain
98
how are T cell receptors (TCRs) analogues of B cell receptors (antibodies)?
- they are analogous to the FAB fragment
- instead of heavy and light chains, they have alpha and beta chains (or gamma delta)
- see allelic exclusion
- use RSS/RAG system to get TRECs
- have Valpha, Calpha, Vbeta, Cbeta
99
what genes are required for the alpha and beta chains?
alpha- V&J (&C)
| beta- VDJ (&C)
