Immuno for Exam 5 Flashcards
(176 cards)
1
Q
obligate parasites
A
viruses capable of reproducing only within a living host cells
2
Q
Universal features of all viruses
A
- one or more viral genome segments (RNA or DNA)
- capsid
3
Q
capsomeres
A
each face of virus has a triad of identically placed proteins
larger viruses simply have more subunits
various rotational symmetries
most economical way of buildoing a shell - change volume!
4
Q
Baltimore Classification scheme
A
classification based on how protein is made and how virus generates mRNA.
how do you get to RNA?
has to be readable my machinery
5
Q
Group I - dsDNA
A
make mRNA from cell machinery
papovavirus, papillomaviruses, herpesviruses, adenoviruses
6
Q
Group II - + ssDNA
A
make second strand of DNA and then make a lot of RNA
7
Q
Group III - dsRNA
A
make single strand mRNA
has own RNA pol which copies negative strand to make a lot of positive strand that gets translated and packaged
once in a new capsid, positive strand is copied to make a negative strand and make dsRNA
8
Q
Group IV - ssRNA +
A
i.e. polio
can be read by ribosomes - usually make neg strand to make more pos strand
make template of self and then make more and more
Most positive-strand viruses (Group IV) often make a negative strand copy of themselves: this serves as (a) the template for making more viral genomes and (b) a way to make MORE copies of the positive strand to be translated into proteins.
the RNA is ‘infectious’ in the experimental sense because if introduced directly into a cell without any viral proteins being present it can be translated into the replication proteins including an RNA-dependent RNA polymerase and amplification will follow….
9
Q
Group V - ss RNA -
A
i.e. flu
have to make + strand to make mRNA
10
Q
Group VI - ssRNA +
A
i.e. HIV
use RT to make ssRNA into dsDNA
then make mRNA
11
Q
Group VII ds DNA
A
make ssRNA then rt to make ds DNA
dsDNA-RT virus
12
Q
+ RNA
A
can make peptide right from the strand
13
Q
RNA-dep RNA polymerase
A
used to make negative (antisense) RNA into positive (sense) RNA so it can be translated
cells don’t have, viruses bring it
often an amplifying step to make more RNA/protein
14
Q
positive strand ssRNA
A
no RNA-dep RNA pol, translate immediately, infectious
in reality - makes a lot of negative sense ssRNA too as a template to make more + ssRNA - some to be packaged and some to be translated
15
Q
negative strand ssRNA
A
RNA-dep polymerase, transcription first, non-infectious
16
Q
dsRNA
A
RNA-dep pol
transcription first, non infectious
17
Q
structural proteins
A
components of capsid and envelope
protection btwn cells - some stable, some sensitive
18
Q
virion-associated enzymes
A
polyemerase, integraze, enzymes needed to integate into chromosomes
19
Q
budding
A
how enveloped viruses are releaesd
20
Q
cell lysis
A
how non-enveloped viruses are released
21
Q
zoonosis
A
jump from animals to humans
i.e. ebola
from wild and domesticated animals creates a changing landscape of viral disease
22
Q
virus sensing system
A
virus has things that activate it
TLRs - rec RNA and DNA
RLRs - rec viral RNA
CDRs- rec viral DNA
stim production of IFN alpha and beta
secete to nearby cells
23
Q
IFN a/b signaling
A
bind to IFNAR (same cell or new cell)
TYK2/JAK
STAT/STAT/IRF
stim ISGs - IFN stim genes
24
Q
PAMPS
A
general indicators of viruses and ther pathogens
dsRNA
cytDNA
nakedDNA (no chromatin)
viral genome replication intermediates
capsid proteins/env glycoproteins
25
PRRs
TLRs - endosomes and PM
RIG-I (RLRs) - cytoplasm (mt anchored)
NOD-like Receptors (NLRs) - cytoplasm
CDRs - cytoplasmic DNA receptors
C-type lectin receptors - plasma membrane
26
TLRs
in plasma membrane, rec PAMPs
either send signal to transcribe pro-inflammatory cytokines OR endoctyosed and then signal to transcribe Type I IFNs
27
OAS
oligoadenylate synthase
activated by viral dsRNA and makes a 2'-5' linked oligoadenylates from ATP
that activates RNAse L dimers which degrades RNA
inhibits viral propagation and induces apoptosis
28
cGAS
activated by cytoplasmic dsDNA
produces cGMP from ATP and GTP which can travel and alert nearby cells OR
bind to STING receptor which leads to a cascade that results in cytokine expression
29
Type I IFN
a/b
front line defense from cells that contact a lot of pathogens! fibroblasts, epithelial cells, macrophages, monocytes pDCs
mostly viruses, some microbial products
30
Type II IFN
ifn gamma
T cells and NK cells
immune activation stimulates them
31
Type III IFN
IFN-lamda
pDCs, endothelial cells
mostly viruses
32
IFN signaling
bind IFNAR (Type I) or IFNGR (type II)
kinases attract JAK/TYK2 and activate and P STAT
STAT 1/2 bind when P and usually bind to IRF9
goes into nucleus, binds to promoter, transcription of ISGs
33
IRF9
binds to STAT complex for TF function
34
herpes simplex Us11
how HSV evades immune system
OAS responds to viral dsRNA
Us11 binds to OAS 11 so it can't activate RNAse L so viral replication can happen and RNA isn't degraded!
35
herpes simplex virus ICP34.5
PRK detects viral dsRNA and when activated it P on EIF2A so it turns off protein synthesis
ICP is a phosphatase that removes the P so protein synthesis and viral replication can happen
36
Aicardi-Goutieres syndrome (AGS
clinical features mimic in utero acquired infections/systemic lupus
linked to 7 mutations
inhereted mutations lead to inappropriate accumulation of self-derived nucleic acids that induce a sustained Type I IFN response
37
systemic lupus erythematosus (SLE)
pDCs produce IFN-a in a sustained faschion
stimulate autoreactive B cells to differentiate into plasma cells and produce autoabs, stim autoreactive t cells
DNA and RNA containing immune complexes further activate pDCs, loop!
38
Defensins
cationic, amphipathic effector peptides of the innate immune system with broad antimicrobial activity
active against enveloped and non-enveloped viruses
alpha-defensins - neutrophils, epithelial cells in the gut
beta-defensins - epithelial cells of skin and mucosal surfaces
don't understand how they work
39
secondary immune response
40
memory B and T cell formation
41
primary response abs
IgM, IgG, IgA, IgE
tiny fraction respond to given ag
low affinity, low somatic hypermutation
42
secondary response abs
IgG, IgA, IgE (no M)
many more abs
high affinity, high somatic hypermutations
43
immuno memory points
resluts from ag exposure
follows primary immune response
more rapid, greater, more effective
innate respoinses help direct memory resoinse
duration of memory varies
44
how do vaccines induce immunity?
inject into muscle
inflammation - cells to area, acquire ag, exposed to adjuvent
cells migrate to LN, present ag - T cells and maybe B cells -- immune response
45
live attenuated vaccine
organism is alive and can replicate but mutated so can't cause serious illness
46
killed vaccine
chemical treatment to kill pathogen so it can't replicate
47
subunit vaccine
most antigenic part of vaccine
purified in vector - 1 proein expressed, covalently coupled to carrier
purified secreted protein - toxin
48
polysaccharide conjugates
immunogenic in infant
polysaccharides bring in T cell help so b cells make better abs against ag
use T cell help for higher affinity abs and longer lived memory
can prevent mucosal colonization - not just disease
49
adjuvants
stimulate APCs through innate immune receptors
induce:
DC maturation (increase MHC II and costim molecule expression)
dendritic cytokine secreteion to direct differentiation of stim cells
LA vaccines don't need - still have PAMPS!
50
immunodeficiency
impaired immune response resulting in increased susceptibility to infections with obligate and opportunistic pathogens
51
primary immunodeficiencies
resulting from specific genetic defects in a component of the immune system
manifest in infancy or childhood
52
secondary immunodeficiencies
acquired as a result of disease, treatment, infection
53
physological immunodeficiencies
newborn/elderly
newborn (low IgG between maternal and own IgG)
54
glucocorticoids
cause immunosuppression
inhibition of T cells
inhibition of macrophages
apoptosis of immune cells
inhibition of TF needed to activate cells
55
cyclosporin A
immunosuppressive drug
organ transplant/autoimmune
T cell - rec ag ----\> Ca 2+ --\> calcineurin --\> deP NFAT --\> TF activates cytokines
cyclosporin A inhibits calcineurin
56
metabolic disorders
diabetes, kidney failure
hyperglycemia - suppress immune function and leukocyte igration (vasculopathy)
57
malnutrition
insufficient uptake of protein --\> decreased production of immune cells - need to constantly replenish
zinc = cofactor
decreased number and funcition of T cells and ab roduction by B cells
58
SCID
T cell defect - from mutations in genes that inhibit lymphocyte development
"bubble boy"
B and T cell defect, impaired ab production
frequent infection with obligate and opportunistic pathogens
candidiasis
failure to thrive
59
ADA
mutation - build up of nt - toxic
T, B, NK cells
60
RAG1/2
mutation for scid, no vdj, no b or t cells
61
AK2
mutation for scid
no b, t, nk - in becoming lymphoid stem cell
62
IL-2R gamma chain
SCID
no T or NK cellspart of ck receptor for IL7
most common cause of SCID
gene therapy: select CD34+ Stem cells, gene transfer IL2R gamma chain, expand, infuse stem cells
leukemia in 2/9 patients
63
Omenn syndrome
mutations in Rag 1/2
impaired but not completely absent VDJ
T cell numbers are normal but very restricted and autoreactive
no B cells - decreased IgG
opportunistic infection
looks like GVHD
64
SCID therapy
avoid infections (bubble boy)
abx
IVIG
bone marrow transplant
somatic gene therapy - IL-2R gamma chain gene transfer
65
66
DiGeorge Syndrome
no thymus
reduced number of T cells
increased infection
deletion in part of Ch 22
heart problems
67
Wiskott-Aldrich Syndrome
mutations in the gene for WAS protein - defects in actin polyerzation and signal transduction in T cells
severe eczema
bleeding (abnormal platelets)
bacterial infections (defect in T cell function)
68
Agammaglobulinemia
X-linked
no antibodies at all
No B cells
mutations in B cell tyrosine kinase - no signaling
many bacterial infections
69
hyper IgM Syndrome
B ell numbers are normal but imapired class switching
1. B cell intrinsic - AID and UNG - class switch and somatic hypermutation
2. mutation in CD40L so T cells can't signal to B cells to class switch
lots of IgM but no others
70
CVID
most common, mostly young adults
antibody deficiency but normal B cell numbers
usually genes important for terminal B cell diffeentation into plasma cells
71
IgA defieicency
infections with encapsulated bacteria!
can develop into CVID with time
72
neutropenias
chronic severe infections with pyogenic pacteria
mutations in neutrophil elastase (ELA2) required for neutrophil maturation
73
LADI, II, III
impaired neutrophil migration from blood to sites of infection
chronic serious infections (innate)
74
Macrophage defects
mutations in IL-12/IFN-g axis which is required for macrophage and T cell cooperation
increased susceptibility to mycobacterial infections
75
how do you know it's a T cell defect?
viruses, fungi, and parasites
76
how do you know its a neutrophil disorder?
pyogenic bacteria
77
How do you know it's a B cell disorder?
encapsulated bacteria (also for complement disorder)
78
elimination
developing tumor is recognized and destroyed by immune system - immune system is looking
79
equilibrium
tumor dormancy by immune system - not eradicated but kept in check
80
editing and escape
tumors are no longer recognized by immune system and develop immune suppressive enviromnent
response shapes what kind of cancer can escape
81
checkpoint blockade drugs
CTLA-4, PD-1
82
neoantigens
novel proteins due to tumor specific mutations
ag never seen in that person! foreign
i.e. lung and melanoma because of mutational burden --\> clinical efficacy
toxins and mutagens
83
CARs
1 molecule that rec ag like a B cell (no MHC) but activated/signals like a T cell
giving signal 2 = breakthrough
84
CD19
expressed on all B cells except plasma cells
CD19 CARs that rec CD19 for myeloma
possibly Breg with CD19 and suppress T cells
85
HP SC transplant
high dose therapy with HP stem cell rescue
only established SC therapy
immunotherapy of cancer (GVT)
personalized/precision med
adoptive cell therapy
86
autogenic
self - harvest marrow, gie high dose therapy, use own marrow as rescue
87
allogenic
someone else
gvt
88
GVT
T cells in allograft rec ags of host origin on tumor cells and kill
lower relapse if there is GVHD
89
GVHD
immune cells from allo transplant recognize host body cells as foreign and attack
certain organs more
none in heart or kidney
APCs in host may be activated by innate pways - start to show allo-ag rec by donor T cells, activate Tcells in graft to mediate GVHD
90
top cause of death after BMTP
1. primary disease
2. GVHD
3. Infection
91
92
infections following BMT
first - decrease t cell count, bacterial --\> sepsis immediately
later - parasites and viruses, opportunistic, slow rebound of T cells, like AIDS
93
CD34 T Cell BMT
less GVHD
BUT
no T cells (decreased GVHD and GVT)
many more infections
94
95
Prep for BMT
decrease tumor loads as much as possible wiht chemo
2nd therapy to increase tolerance to host
96
haplotransfer
from father or mother
share one set of chromosomes 50% - dangerous because GVHD
give chemo at peak alloactivation - GVHD is relatively low
97
BMT and microbiota
decreased diversity after transplant - turn into a monoculture - really bad!
decreased survival with decreased diversity of microbiota
fecal transplant
98
Type I Hypersensitivity
Allergies, anaphylaxis, atopic asthma
IgE antibodies and mast cells
immediate (minutes)
99
Type II Hypersensitivity
autoimmune disease
transfsion and drug rxns
IgG antibodies binding to:
cells --\> cytotoxicity
extracellular matrix --\> inflammation
100
Type III Hypersensitivity
serum sickness
arthus rxn
HS pneumonitis
autoimmune disease (SLE)
IgG form immune complexes with soluble ags
101
Type IV Hypersensitivity
contact dermitits
autoimmunity
transplant rejection
Delayed (2-3 days)
CD4 and CD8 T cells
102
Type I Hypersensitivity phases
1. sensitization
2. immediate response
3. late phase reponse
103
Sensitization
Type I hypersensitivity
allergen uptake and presentation by APCs, activate CD4+ T cells and diff to TH2, activate B cells to make IgE, bind mast cells, 2nd exposure
104
Th2
produce IL-4, become TH2 due to IL-4
105
IL-4
T cells
B cell class switching to IgE plasma cells
106
IL-5
TH2 make
eosinophil maturation/activation (phase 3)
107
TH2 bias
CD4 cells turn into TH2 in response to allergic stimuli
IL-4
108
Mast Cells
IgE (b cells) bind to FcE receptors on mast cells
filled with antimicrobial
binding of antigen causes mast cell activation and degranulation in seconds
109
atopy
exaggerated tendency to mount IgE responses to allergens
elevaed serum IgE and eosinphils
genetic, pollution, hygeine
110
Hygiene hypothesis
because no infections in early childhood, TH1 response is not used so TH2 predominates
111
Type I Immediate response
phase 2
primary and secondary mediators released
112
Type I Primary mediators
histamine
proteases
vasodilation/permeability
smooth muscle spasm
tissue damage
mucus secretion
113
Type I Secondary Mediators
hours: RNA --\> protein
IL-4, 1, 5, TNFa
IgE production, chemotaxis of eosinophils, macrophages
15 min-hours:
leukotrienes, prostaglandins, PAF (from PPL --\> arachadonic acid)
vasodilation and permeability
smooth muscle spasm
chemotaxis of neutro-baso-eosinophils
114
Type I late response
eosinophils n blood recruited to inflamation
by eotaxin, leukotriene B4 (mast cells)
115
eosinophils
Type I
Late phase
release granules with inflammatory mediators, proteins that destroy epithelial cells
activated by IL-5 (TH2 and mast cells)
recruited by leukotriene B4 (mast cells), eotaxin (lung, fibroblasts, smooth muscle)
116
acute uticaria
wheel and flare
ag uptae through skin or systemic
mast cell activation in upper dermis
local - vascular permability, edema, inflammation
117
angioedema
ag uptake through mucosal surfaces/sytemic
mast cell activation in dermis/mucosa
edema and inflammation
118
allergic asthma
type I hypersensitivity
elevated IgE, eosinophil
mast cell activation in lung
triggered by specific allergens
(like immdiate phase of type I)
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120
anaphylaxis
systemic allergen uptake (iv, oral)
acute
shock - systemic vasodilation, slow hearth
121
anaphylaxis treatments
epinephrine - cardio
b2 receptor agonist, methylprednisone - bronchospasm
antihistimine - hives
122
damange from Type II Hypersensitivity
1. phagocytosis/lysis of ab coated cells
2. recruitment of neutrophils causing inflammation
123
abs for type II hypersensitivity
IgG
124
Transfusion reactions
Type II Hypersensitivity
donor is O, give to A, abs attack RBCs --\> anemia
125
erythroblastosis fetalis
Type II hypersensitivity
transplacental tranfer of maternal anti-RBC abs from mom to fetus
lysis of fetal red blood cells
during pregnancy - circulating abs from mom
126
drug allergies
type II hypersensitivity
some drugs alter cell surface molecules that can be targets for ab responses
127
acutre rheumatic fever
autoimmune
type II hypersensitivity
strep abs bind to cardiac glycoproteins
128
Complement and Type II Hypersensitivity
abs bind to membrane protein --? complememnt activated --\> C5a recruits neutrophils --\> release reactive oxygen and enzymes to degrade ECM proteins
129
goodpasture syndrome
ab to collagen of basement membrane --\> complememnt
130
immune complexes
Type III hypersensitivity
between soluble ag and IgG abs
ICs are deposited in the wall of blood vessels --\> vasculitis (inflammation)
131
Phases of Type III Hypersensitivity
1. IgG production (about 1 wk after infection)
2. IC form and deposit
3. IC mediated inflammation
132
serum sickness
IV application of protein (serum components)
drugs
systemic IC disease
rashes (IC in skin)
arthritis (IC in joints)
glomerulonephritis (IC in kidney)
delayed onset after first ag exposure
133
arthus rxn
type III hpersensitivity
local IC vasculitis
subcutaneously deposited ag diffuses into walls of blood vessels and forms large ICs with preformed abs
edema, swelling
hours after injection
134
Farmer's Lung
Type III hypersensitivity
not infection - immune response
bacteria causes ab response
abs and bacteria form immune complex in lungs
135
Stages of Type IV Hypersensitivity
1. memory TH1 cells rec ag on apc
2. T cell releases cks
3. recruitment and activation of macrophages 48-72h - tissue damage by macrophages
136
cytokines in Type IV hypersensitivity
IFNg - activates macrophages
TNFa - local tissue destruction
IL-8 - recruit macrophages
137
Poison Ivy
Type IV hypersensitivity
urushol in skin
modify intracellular (CD8), modify extracellular (CD4)
138
contact dermatitis
type 4 hypersensitivity
nickel, poison ivy
139
Autoimmune adrenalitis
most common cause of adrenocortial insufficiency
destruction of steroidogenic cells that generate glucocorticoids 0 abs against it
isolated or part of APECED
140
negative selection
in bone marrowor thymus
clonal deletion of all self reactive T and B cells
141
AIRE
transcriptional regulator
tissue specific in thymus
proteins from body
T cells see self ag expressed by aire - preview of peripheray
negative selection
142
APECED
disease due to mutation in AIRE
autoimmune against peripheral things
143
immune privileged sites
no lymphocyte access to some sites
bloo, eye, testes
limited lymph drainage
low MHC I
inhibit complement
Fas ligan - apoptosis in Fas-expressing lymphoid cells
144
Treg
suppression of autoimmune
kill auto effector T
145
IPEX
no Treg - peripheral tolerance
146
anergy
lymphocyte is unresponsive bc insufficient stimulation
147
Fas
CTLs have contraction phase - cells all kill each other
Fas/FasL all stim each other for cell death
get rid so don't damage
148
ALPS
mutation in Fas expression on CD8 T cells - can't get rid of them after infection
149
C1q
complement, required for clearance of IC
if mutated --\> SLE
150
T1D + HLA
mutation in specific HLA
failure of autoantigen presentation in thymus and lack of negative selection of autoreactive T cell clonse
151
inducing costimulation
APCs have self ag and are triggered to activate by bacteria
able to give costimulation to auto CD4 T cell - rec self ag in person
effector T - only need 1 signal!
152
molecular mimicry
cross activation of autoreactive T or B cells by structurally similar peptides from infective pathogens
153
rheumatic fever
molecular mimicry
abs to strep proeins cross react with glycoprotein ags of heart and joints
154
MS
Type IV hypersensitivity and autoimmune
demyelinating CNS inflammation
CD4T cells in CNS --\> rec myelin --\> secrete inflam cks --\> recruit macrophages --\> destroy myelin sheath --\> neuro disease with motor and sensory deficits
155
T1D
type IV hypersensitivity
T cell mediated autoimmune destruction of pancreatic beta cells - absolute insulin deficiency
CD4 - activate macrophages (cks from T cells and macrophages induce apoptosis)
CD8 - directly kill beta cells
156
autoimmune hemolytic anemia
type II hypersensitivity
abs to RBCs, platelets
157
goodpasture syndrome
type II hypersensitivity
autoabs to type IV collagen in basement membrane of kidney and lung
activate compliment and neutrophils - severe tissue injury
158
graves disease
type II hypersensitivity
abs activate TSH receptor - make a lot of hormormoes without ligand
hyperthyroidism
159
mysthenia gravis
type II hypersensitivity
abs to Ach receptors - inhibit receptor, compliment fixation and injury
defect in neuromuscular transmission
muscle weakness
160
Type III hypersensitivity autoimmune
immune complexes of soluble DNA and anti-DNA abs - deposited in small blood vessels --\> vasculitis
161
SLE
Type III hypersensitivity
systemic lupus erythematosus
multiorgan disease
mylar rash and many other criteria
IC deposition
genetic + environmental --\> IgG ab productin --\> IC formation --\> clinical symptoms
162
epitope spreading
SLE
tissue damage --\> more cells die --\> more free proteins --\> more complexes
perpetuates autimmune response
self ag can't be cleared by immune! ubiquitous
163
ANA
antinuclear antibodies
directed against ubiquitous intracellular ags
DNA, histones, RNOs
anti-dsDNA and anti-Sm abs are diagnostic for SLE
164
sjogrens
immune mediated destruction of lacrimal and salivary glands
dry eye and dry mouth
ANAs
165
systemic sclerosis (scleroderma)
chronic disease of unknown etiology characterised by fibrossi of the skin and mutliple organs
ANA
166
Tumor intrinsic factors
ag/MHC loss
secretion of immunosuppressive cks
cell surface markers like PD-L1
167
tumor extrinsic factors
geographic barriers
suppressive/reg immune cells
Tregs, MDSCs, TAMs
168
checkpoint blockade proteins
CTLA-4
PD-1
PD-L1
169
CD28
costim molecule - has positive impact on T cell activation
170
CTLA-4
inhibits T cell response
binds instead of CD28 costim
171
ipilimumab
human mab
IgG
abs block CTLA-4, attenuate neg feedback for T cells, results in more sustained T cell activation
survival benefits
toxicity: autoimmune (colitis)
delayed response (may get worse before better)
172
PD-1
from inflammation in tissue
dont regulated expereinced T cell (later than CTLA-4)
173
Nivolumab
ab to PD-1
better results than ipi!
PD-L1+ had better response, but both had better than control
174
abscopal effect
systemic response to localized inflammation
175
combined nivolumab and ipilumumab
much better overall response but also more toxicity
176
PD-L1
on tumor cells
binds PD-1 on T cells
