Immunity Flashcards
1
Q
3 examples of type 1 mediated reactions
A
asthma
hives
allergic rhinitis
2
Q
Ig__ in type 1
A
Ige
3
Q
most important cells in Type 1
A
mast cells, eosinophils
4
Q
primary reaction in Type 1 is from
A
preformed mediators
5
Q
secondary reaction in Type 1 is from
A
synthesized mediators
6
Q
type II is
A
direct attack on cell/tissues by antibodies
7
Q
6 examples of type II
A
hemolytic anemia erythroblastosis fetalis Goodpasture syndrome Myesthenia Gravis Rheumatic Fever Grave's Disease
8
Q
Type II involves
A
complements
9
Q
type 3 is
A
damage secondary to deposition of immune complexes (igg-ag)
10
Q
4 examples of type III
A
glomerulonephritis
serum sickness
polyarteritis nodosa
Arthus reaction
11
Q
type III also involves
A
complements
neutrophils!
12
Q
type IV is
A
t cell and macrophage mediated
delayed type hypersensitivity
13
Q
most important cells of type IV
A
cytotoxic T cells
macrophages
14
Q
hyperacute rejection
A
few minutes–>hour
throbmobosis and vessel attack
15
Q
acute reject
A
days–>weeks
host becomes sensitized to donor tissue
cellular and antibody mediated
vasculitis, parenchymal attack and damage
16
Q
chronic rejection
A
mixed mechanism with many macrophages, T cells and plasma cells
–extensive and longstanding damage and FIBROSIS to graft
17
Q
anaphylatoxins
A
C3a, C5a
18
Q
Type I mechanism
A
antigen–>DC processing–>DC stimulates TH2 cell–>helper T cell stimulates B cell–> can turn into plasma cell that makes IgE –> bind to FcRe on Mast cells
19
Q
IL involved in Hay fever
A
IL4
20
Q
cross linking
A
when Ag brings 2 IgEs close together, stimulating a signal across the mast cell membrane
21
Q
two phases of anaphylactic rxns
A
immediate/initial response (5 min-1 hr)
delayed/secondary response (2hrs - days)
22
Q
immediate response involves
A
IGe binding to mast cell and releasing preformed mediators
23
Q
4 tissue events in immediate/initial responses
A
- vasodilation & vascular congestion (histamine mediated)
- vascular leakage= edema
- smooth muscle contraction
- glandular secretion
24
Q
clinical response to secondary response
A
coughing
chest tightness
mucous after original exposure
25
3 tissue events due to secondary response
- tissue infiltraton by eosinophils, basophils, neutrophils, some T cells
- tissue injury
- mucosal damage and remodeling
26
primary mediators of secondary response
- leukotrienes
- prostaglandins
- platelet activating factor (PAF)
- cytokines
27
eosinophilic contribution
PAF acether--> LTC4 & 15 HETE
- mucous secretion & epithelial desquamation
Cationic/Neutrotoxic Protein-->Peroxidase & Arylsulphatase
- Major basic protein--> Mast cell degranulation & epithelial desquamation
28
3Localized Type 1 rxns
1) severe urticaria- massive degranulation in response to cold or heat
2) atopic keratoconjunctivitis- eye will become puffy and get corneal edema that extends into slclera
3) asthma
29
pathogenesis of asthma
1) epithelial cells killed off and have to be replaced--> myofibroblasts thicken basement membrane
2) smooth muscle cells hypertrophy
==> tissue damage and matrix remodeling
30
hemolysis through mismatched blood transfusion
type 2 rxns
31
2 mechanisms of hemolytic transfusion rxns
1) acute- premade antibodies--cells lyse due to complement very rapidly
2) delayed- no preexisting Abs- made as transfused Abs degrade by natural causes-- attacking remaining live cells
32
Mac complex
attaches to cell surface and creates pores in it
33
c3b
opsonin for Macrophages that phago the fragmented RBC
34
best Ig for hemolytic RBC
iGM (because relies on complement)
35
Good Pasture's Disease
auto-antibody against collagen Type IV in basement membrane in glomeruli (not tubule) and alveolar walls
clinical- hemoptysis and renal failure
36
where does rheumatic fever come from?
Group A beta hemolytic streptococcal infection (Ab that clear infection start attacking self-antigen)
37
subsets of rheumatic fever
endocarditis
| myocarditis
38
endocarditis
vegetations form on valves with fibrin/platelet aggregates
39
myocarditis
Aschoff bodies (areas of inflammation within heart CT that become granulomatous when fully developed)
40
Grave's Disease
anti-receptor antibodies can cause autoimmune overstimulation or receptor blockade
(TSH on TSH R)
41
Myasthenia Gravis
AchR antibody binds and destroys receptor
| --weakness in muscles as day progresses
42
Local Type III rxns
```
arthus rxn
vasculitis
glomerulonephritis
arthritis
pneumonitis
```
43
systemic type III rxns
serum sickness
SLE
drug rxns
44
key damage cell in Type III
neutrophil!
45
deposited complexes form
- complement cascade
| - platelet activation (Hageman factor)
46
platelet activation results in
- microthrombi formation-->occlude small vessels-->potential ischemia if extensive
- hageman factor (f XII of coagulation cascade)-->activation of kinins-->vasodilation and edema
47
glomerulonephritis caused by
different streptococcus from that causing rheumatic fever
48
why do streps localize to glomeruli
charge- complexes have specific charge that allows them to cross the vascular membranes and enter blood vessel lumen
49
serum sickness
following diptheria horse antitoxin, pts develop arthritis, skin rash, and fever
formation of anti-horse Ig antibodies then form complexes that get stuck places
50
main types of cells in type IV
t cells
macrophages
APC
51
types of type Iv HS
1) Delayed type- CD4+
2) T cell mediated- CD8+
3) Rejection of transplanted organ- CD4/8/ antibodies
52
what almost always results in DTH
virally induced inflammation
53
detrimental cell products in type IV
```
TNFa/b
IL1
superoxides
NO
hydroxyl radicals
neuron toxins
```
54
beneficial cell products
TGFb
Growth & Trophic Factors
GM-CSF
55
prototype DTH
TB granuloma
56
what type of cells participate in allograph rejection
CD4 and CD8
57
hyperacute rejection
moments-48 hrs
Ab rxn at endothelium
- rapid thrombosis of vessels and organ death
58
acute rejection does NOT mean___ and is mediated by
neutrophils
| - t cells
59
2 types of acute rejection
acute cellular- CD4/CD8, lymphocytes, macrophages
acute humoral-
anti-graft antibodies
60
chronic rejection
months to years
chronic vasculitis, intimal fibrosis, obliteration of lumen-->organ ischemia, interstitial mononuclear cell infiltrates-->organ atrophy
61
2 mechanisms to initiate rejection
- cellular: Tc attack cells with foreign MHCI
| - humoral- Th cells recognize foreign MHCII and stim Tc and B cells-->B cells make plasma cells to make Ab
62
direct vs indirect antigen presentation
direct- APC from donor in graft
| Indirect- APC is dead and host cell presents
63
acute kidney rejection
congested
swollen
hyperemic
64
chronic rejection
shrunken
scarred
severely damaged kidney
65
graft atherosclerosis
chronic graft rejection secondary toe xtensive damage to endothelium and artery wall
66
acute GVH
initially limited to endothelium of skin, GI tract, and liver
67
chronic GVJ
multiple organs show significant damage
68
positive selection
thymocyte must recognize through the TCR an MHC/peptide above a certain affinity threshold
69
negative selection
deletion happens when affinity is too high
70
3 mechanism of peripheral tolerance
1) anergy- shut off t cells via CTLA4
2) Tregs
3) clonal deletion by activation-induced cell death
71
main mechanism that shapes repertoire
negative selection
72
5 mechanisms of autoimmunty
1) molecular mimicry
2) escape of autoreactive clones
3) release of sequestered antigen
4) epitope spreading- more and more antigen released by more and more tissue damage
5) polyclonal B activation
73
PTPN22
most freq implicated
-Rheumatoid arthritis, T1DM
encodes a protein tyrosine phosphatase
-defective copy- out of control tyrosine kinases in lymphocytes-->lnger phos & activation of proteins
74
NOD2
Crohn's disease
encodes a cytoplasmic sensor of microbes
-defective copy-->poor at sensing microbes-->increase in tissue invasion by microbes-->chronic inflammation
75
cytokine receptor genes
IL2Ra (CD25) and IL7Ra
associated w/ MS
may control maintenance or dev. of tregs
76
2 mechanisms of environmental triggers of autoimmune flare ups
adjuvant effect
| molecular mimicry
77
polyclonal b cell activation
increase production of autoantibodies (EBV, HIV)
78
t regs are
CD4+ CD25+
79
CD25
low affinity IL2 Receptor (alpha)
aka Tac antgien
--expression rapidly increases upon T cell activation
tends to be overexpressed in autoimmunity
80
how are CD4CD25 cells generated
- from thymus )high avidity)
- from regular t cells in periphery
**regulated by FoxP3
81
IPEX
x linked disease that is due to defect in FoxP3
| --characterized by neonatal DM, enteropathy, endocrinopathy
82
what cytokines are req for tregs to suppress other cells
IL10, TGFb
83
general features of autoimmune disease
progressive- sporadic relapses/remissions
epitope spreading (tissue damage releases self antigens and exposes previously hidden epitopes)
84
TH1 autoimmune disorder contains
macrophage rich inflammation
85
TH17 autoimmune disorder contains
neutrophil rich
86
type 1 diabetes mellitus
t cells reacting to beta cells in islets
often preceeded by dev of anti-insulin antibodies
major targets include insulin and GAD
87
clinical manifestations of lupus
Malar Rash
Libman Sacks
Retinal Damage (vasculitis-->arterial occusion)
88
Malar Rash
liquefactive degeneration of the basal layer of the epidermis and edema at the dermo-epidermal junction
igg deposits
89
Libman Sacks
sterile, inflmmation-free valve vegtations associated with SLE
90
immunological pathology of SLE
failed self tolerance-cant eliminate b cells, CD4 cells
| abnormal rxn of TLr to self DNA/RNA rather than viral RNA (mediated by IFN1)
91
environmental factors that influence sLe
UV exposure
sex hormones (esp during reproductive years)
drugs
92
rheumatoid arthritis
chronic systemic inflammatory disease affecting many organs but main target is joint (non-suppurative proliferative/inflam synovitis)
93
microscopic of RA
synovial hypertrophy with formation of villi
subsynovial tissue containg dense lymphoid aggregate
94
environmental associatins with RA
infectious agents, but one agent has not been specifically implicated
citrullinated proteins (arginine-->citruline)- can be seen in lung of smokers
95
immunological factors of RA
CD4+ t cells with TH17 and TH1 appear early
96
80% of patients with RA have
rheumatoid factor-typically igm
autoanitbodies to Fc portion of IgG
NOT cause of disease but marker of disease
97
anti-CCP
antibody to citrullinated peptides
produced at sites of inflammation
98
clinical success with RA and
TNFa antagonists
99
primary vs secondary ids
primary-genetically determined
| secondary-acquired
100
xlinked primary iDs
xla
hyper igm
scids
wiskott-aldrich syndrome
101
autosomal primary ids
dominant -
C1 inhibitor deficiency
recessive-
digeorge syndrome
scids
102
molecular primary ids
isolated iga deficiency
| common variable immunodeficinecy
103
secondary ids
iatrogenic
| hiv
104
humoral deficiencies
- XLA
- common variable immunodeficinecy
- isolated iga deficiency
- hyper igm syndorme
105
XLA
failure of b cell precursors to develop into mature b cells--> decrease to absent b cells-->deficiency of igg
t cells are still intact so increase risk of autoimmune
106
what are pts with xla susceptible to?
```
bacterial infection
-- haemophilus, strept, staph
enteroviral
--echovirus, poliovirus, coxsackie
severe intenstinal giardiasis (parasite normally resisted by iga)
--giardia lamblia
```
107
etiology of xla
mutation on Btk gene on x chrome-->req for signal transduction necessary for ig light-chain rearrangement and b cell maturation-->mutation removes maturation signal
108
treatment xla
ivig
109
common variable immunodef
- hypogammaglobulinemia
| - normal number of b cells, but cant turn into plasma
110
differentiating brutons and CVI
- CVI affects both geneders equally
| - CVI has later onset
111
isolated iga def
low levels iga-->increase risk resp and gi and uti
112
hyper igm syndrome
defect in Th cells ability to deliver activiating signals to b cells for class switching
most are xlinked with mutation in gene encoding CD40L (CD154)
113
cellular deficiencies
digeorge syndrome
114
digeorge syndrome
- failure of 3rd and 4th pharyngeal pouches to develop during embryogenesis (no thymus, no pth)
- loss of t cell mediated immunity
115
clinical manifestations digeorge
tetany (no PTH-->noCa2+), congenital heart defects, abnormal facia appearance
116
genetic manifestation of digeorge
22q11 deletion
117
infections associated with t cell defects
bacterial sepsis
viruses- cmv, epistein-barr, severe varicella, chronic respiratory and intestina infection
fungi/parasites- candida
118
overlap syndromes
SCID
Wiskott-Aldrich Syndrome
Complement Deficiencies
119
SCID cellualr level
- lymphopenia (low absent T/B cells)
| - hypogammaglobulinemia
120
etiology of scid is
```
variable!
cytokine recepto def: impacts t cell dev (x linked)
ADA def (autosomal recessive) -- cant remove excess purines (accum of toxic derivatives)
```
121
WAS genetics
x linked recessive mutation of XP11.23 Was protein
| --from a family of membrane receptor signal proteins
122
WAS presentation
thrombocytopenia (dec platelets)
eczema
immune defiency
123
WAS at cellular level
- low igm, normal igg, high iga & ige
- do not make antibodies to polysacch antigens and poor antibodies to protein antigens
- progressive t lymph depeletion
124
Rx WAS
- bone marrow transplant to cure
| - platelet transfusion support before that
125
compliment deficiencies
C2 def.
C3 def.
C5-9 def.
C1 inhibitor
126
C2 def
does not result in an increased risk of infection (alternative C pathway compensates), but there is an increased risk of SLE like autoimmune disease
most common
127
C3 deficiency
- required for function both classic and alt pathways
| - increased risk of serious bacterial infection
128
C5- 9 Deficiency
cannot form MAC involved in lysis of organisms
| -increased suceptibility to Neisseria infection, as this bacteria's thin cell walls make it susceptible to MAC
129
C1 inhibitory deficiency
hereditary angioedema
- episodic edema of skin and mucosa surfaces due to stressor trauma
stressor trauma-->unregulated C1 Hageman factor, kallikrein and Plasmin-->mast cell degran and vasoactive peptide release
130
Iatrogenic disorders due to
Chemotherapy, immunosuppressive therapy
--bone marrow becomes less cellular and more fatty
underlying medical conditions
-cancer, diabetes, renal disease, infection
131
HIV structure
spherical and contains an electron-dense, cone-shaped core surrounded by a lipid envelope derived from the host cell membrane
132
virus core contains
1) major capsid protein p24
2) nucleocapid protein p7/p9
3) two copies of genomic RNA
4) three viral enzymes
133
three viral proteins of HIV
protease
reverse transcriptase
integrase
134
p24
most readily detected viral antigen and is target for antibodies that are used for the diagnosis of HIV infection in the widely used enzyme-linked immunosorbent assay
135
2 glycoproteins on viral envelope
gp120, gp41
| critical for hib infection of cells
136
HIV genome
RNA--> gag, pol, env
| -->translated into large precursor protein that are cleaved by viral protease--> mature proteins
137
targets of highly effective anti-hiv1 drugs
protease
inhibit formation of mature viral proteins-->not curative, but suppress viral load
138
primary infection of HIV
virus enters blood or mucosal tissues-->infects t cells, DC, and MO-->carry it to lymphoid tissue-->viremia
139
mechanism of infection of HIV
gp120 binds CD4 R and chemokine coreceptors on t cell, monocyte macrophage, or DC-->confirmational change in gp41 that allows fusion of virus with host cell-->viral core enters cytoplasm of host cell--> lipid envelope surrounds capsids derived from host membrane-->viral particles bud
140
mechanisms of ID in HIV
- direct, cytopathic effect of replicating virus
- colonization of lymphoid tissue leading to progress destruction
- chronic activation of uninfected cells leading to activation induced cell death
- klling of infected cells by cytotoxic t lymphocytes
141
3 phases of HIV infection
1) acute retroviral syndrome
2) middle, chronic phase
3) clinical AIDS
142
acute retroviral syndrome
- infection of CD4+ t cells (expresse CCR5)
- mucosal infection--> dissemination of virus & dev of host immune response
-CD8+ t cells- initial containment (kill Cd4) -->drop in viremia
==> end of acute phase reflects equil. between virus and host response (patient can be stable for several years)
143
middle chronic phase
asymptomatic--" clinical latency period"
- replicate and destroy cells in lymph nodes and spleen
- majority of circulating CD4+ t cells do not have disease, but since ones made in lymph nodes are being destroyed, level of t cells is steadily declining
144
clinical AIDs
- breakdown of host defense, dramatic increase in plasma virus, severe
- long-lasting fever, fatigue, weight loss, diarrhea
- after a period of time, opportunistic infections, secondary neoplasms, clinical neurologic disease emerge
145
when and how does HIV evade host immune system?
chronic phase
- virus has glycan shield -prevents antibody binding
- pt mutations, insertions, deletions-->alter position of sugars--> ever-changing disguise
146
when is seroconverstion first detected?
3-7 weeks post-exposure
147
considered to have aids when
<200 cells/ul
148
category B conditions
- oroopharyngeal candida (thrush)
- vulvovaginal candidiasis (yeast infecton)
- pelvic inflammatory disease
- hairy, leukoplakia, oral-cancer
- idiopathic thrombocytopenic purpura
- peripheral neuropathy
- herpes zoster (shingles)
149
category C indicator conditiosn
- active CMV in lungs
- mycobacterium avium-intracellulare infection of lymph nodes in
- toxoplasmosis of brain
- lung infection with pneumocystis carinii
- kaposi sarcoma lesion
