Immune-3 Flashcards
1
Q
what is immunotherapy
A
any approach that manipulates the immune system of a patient for therapeutic benefit
2
Q
what is the goal for immunotherapy
A
selectively reduce unwanted immune response but retain the other protective immune response
3
Q
what are 2 types of effector t cells
A
CD8+ and CD4+
4
Q
what do t regulatory cells do to CD4 cells
A
inhibits
5
Q
what is the difference between effector t cells vs t regulatory cells with inflammation
A
effector T cells promote inflammation, regulatory T cells serve to control it
6
Q
what are 3 examples of chronic inflammatory disorders
A
- rheumatoid arthritis
- multiple sclerosis
- allergies: asthma
7
Q
what is rheumatoid arthritis (what kind of disease)
A
multisystemic autoimmune disease
8
Q
what is the etiopathogenesis of rheumatoid arthritis
A
unknown
9
Q
what 2 things characterize rheumatoid arthritis
A
- joint inflammation
- bone destruction
10
Q
what systems does rheumatoid arthritis affect
A
joints, lung, eyes, skin, nervous system
11
Q
what characterizes rheumatoid arthritis
A
inflammatory disease of the synovial membrane that lines surface of joints
12
Q
what happens to the synovial membrane in rheumatoid arthritis
A
it is invaded by T and B cells and chronic inflammatory cells
13
Q
what do osteoclases do in rheumatoid arthritis
A
osteoclasts eat the bone
14
Q
what is the etiology and pathogenesis of rheumatoid arthritis
A
unsolved, but many genetic
15
Q
what could be the genetic link for rheumatoid arthritis
A
MHC class 2
16
Q
what can happen with circulating antibodies in rheumatoid arthritis
A
some have circulating autoantibodies
17
Q
what are the autoantibodies that some rheumatoid arthritis patients have
A
rheumatoid factor (antibody) against Fc region of other antibodies
18
Q
what happens with the synovial membrane in rheumatoid arthritis
A
it becomes infiltrated with various inflammatory cells
19
Q
what activates T cells in rheumatoid arthritis
A
DCs
20
Q
what do T cells stimulate in rheumatoid arthritis
A
macrophages
21
Q
what is important for TNFalpha secretion in rheumatoid arthritis
A
T cell-macrophage contact
22
Q
how do synovial fibroblasts and osteoclasts cause damage in rheumatoid arthritis
A
through secretion of MMPs
23
Q
what kinds of things cause joint damage in rheumatoid arthritis
A
synovial fibroblasts, osteoclasts, cytokines
24
Q
what stimulates B cells in rheumatoid arthritis
A
T cells
25
what are 3 things that B cells do in rheumatoid arthritis
- secrete cytokines
- act as APCs that maintain T cell activation
- secrete antibodies
26
what kind of cascade leads to rheumatoid arthritis
cytokine cascade
27
what are 2 successful treatment strategies for rheumatoid arthritis
- one or more disease modifying anti-rheumatic drugs (DMARDs)
- NSAIDS or corticosteroids
28
what are DMARDs
agents that impede both the inflammatory and destructive processes of RA
29
what do DMARDs do
reduce pain and swelling and reduce the progression of destruction
30
what are 2 examples of DMARD subtypes
small molecule and biologics
31
what is multiple sclerosis
a chronic inflammatory and neurogenerative demyelinating disease of the CNS
32
when does multiple sclerosis onset usually happen
in young adulthood
33
what is the eiology of multiple sclerosis
multifactorial, involves interaction of genetic and environmental factors in a complex manner
34
what characterizes multiple sclerosis
autoimmune reaction against myelin
35
what kind of cells attack the myelin sheath and neurons with multiple sclerosis
T cells B cells and macrophages
36
what are the 3 main subtypes of multiple sclerosis
- relapsing form
- primary progressive
- progressive relapsing
37
what % of patients have relapsing forms of MS
85%
38
what are the 2 types of relapsing forms of MS
- relapsing remitting
| - secondary progressive
39
what % of patients have primary progressive of MS
10%
40
what % of patients have progressive relapsing of MS
5%
41
what % of patients with relapsing remitting MS becomes secondary progressive MS
80%
42
what are 3 cell types involved in the multicellular pathophysiology of MS
- infiltrating peripheral adaptive and innate immune cells
| - CNS resident innate cells with inflammatory capacity
43
what are the 2 CNS cells that are often involved with MS
Mostly astrocytes and microglia (macrophage in CNS)
44
what part of the body has the first MS symptoms
the periphery
45
what happens in the periphery in MS
dysregulation of immune effector-suppressor cell interactions
46
what are 2 things that abnormal DC activation results in MS
- increased production of pro-inflammatory cytokines
| - aberrant activation of adaptive immune effectors
47
what kind of cells infiltrate and damage the CNS in MS
autoreactive adaptive imune cells
48
what kind of cells express surface molecules to penetrate the BBB in MS
activated immune effects (TH1 cells, CD8 cells and B cells)
49
what do activated immune effects (TH1 cells, CD8 cells and B cells) do in MS
express surface molecules to penetrate the BBB
50
what do autoreactive immune effectors and abnormally activated CNS astrocytes and microglia cause (4)
- increased production of reactive species
- excitotoxicity
- antibody production
- direct cytotoxicity
51
where do peripheral innate and adaptive immune cells accumulate with MS
in perivascular space and enter the CNS parenchyma
52
how do the immune cells promote demyelination
through direct cell contact-dependent mechanisms and through the action of soluble inflammatory and neurotoxic mediators
53
what do cytokines do to t cells with MS at the BBB
they slow them down
54
how do t cells attach to the endothelium
integrin/ vascular cell adhesion molecule 1 (VCAM 1)
55
how do lymphocytes enter the CNS
via diapedesis
56
what are the 3 steps for lymphocytes to enter CNS
- slow down cause cytokines
- integrin/VCAM 1: attach to endothelium
- enter through diapedesis
57
what is a late event that occurs in MS + why
immune cell infiltration decreases because adaptive immune cell exhaustion from chronic antigen exposure
58
what 3 things continue chronic CNS instrinsic inflammation and neurogeneration
- previously infiltrating adaptive immune cells
- CNS resident innate cells
- meningeal lymphoid like structures (SPMS)
59
what do astrocytes do with late MS
- produce chemokines which lead to further microglial recruitment and activation
- inhibit progenitor cells from developing into mature ODCs
60
where can clonally expanded B cells be found in late MS
in the meninges, parenchyma and CSF
61
what is the mechanism of B cell activation, selection and maturation in MS (WHERE)
unclear, maybe in periphery
62
what do B cells produce in MS and what is the big deal
produce antibodies that are detectable in CSF and are of daignostic value
63
where can you detect b cell antibodies for MS
in the CSF
64
where can antigen experienced B cells mature before transmigration into the CNS + what does this imply
in the cervical lymph nodes
| this implies a therapeutic potential for the peripheral modulation of specific B cell subtypes
65
what on the B cell in MS is a target for therapy
CD20
66
what is immediate hypersensitivity type 1 responsible for
many types of allergies, like dermatitis, rhinitis, asthma, food
67
what mediates immediate hypersensitivity type 1
IgE-FcR complex on mast cells
68
what activates IgE sensitized APCs
allergens
69
what do APCs promote with immediate hypersensitivity type 1
IgE production by B cells to replenish IgE consumed in the allergic reaction
70
what are the 3 phases for immediate hypersensitivity type 1
sensitization, early and late effector phase
71
what happens in the sensitization phase for immediate hypersensitivity type 1
- antigen induces formation of IgE
| - IgE binds by its Fc to receptors on basophils and mast cells
72
what does IgE in sensitization phase for immediate hypersensitivity type 1
IgE binds by its Fc to receptors on basophils and mast cells
73
what happens in the early effector phase for immediate hypersensitivity type 1
- cross linking of cell bound IgE
- degranulation and release of mediates
- happens quick (mins) after reexposure
74
what happens in the late effector phase for immediate hypersensitivity type 1
- recruitment and activation of inflammatory cells at sites sensitive to allergens
- peaks hours later
75
how can allergens be sampled by DCs
in the airway lumen or through disrupted epithelium or epithelial tight cell junctions
76
how can allergens enter tissues
through disrupted epithelium
77
where does IgE bind
to high affinity receptor for IGE on mast cells
78
where do IgE diffuse
locally and enters the lymphatic vessels
79
what happens once IgE enters the lymphatic vessels
it subsequently enters the blood and is then distributed systemically
80
what is a way to induce IgE production
TH2 activate B cells to produce it
81
where do activated DCs mature and migrate to
regional lymph nodes or local mucosa where they activate naive T cells to TH2
82
what do mast cells release once activated
cytokines, chemokines and growth factors
83
what part of the reaction do mast cells contribute to
initial and the transition to late phase reaction
84
what happens when the receptor recognizes the particular antigen
it activates mast cells to secrete preformed mediators
85
what are the symptoms of the mediates
bronchoconstriction, vasodilation, vascular permeability, mucus production
86
when does asthma occur
hours after allergen challenge
87
what is asthma (inflammation, time line with immediate hypersensitivity type 1 )
late phase of inflammation, common features with early reactions
88
what are 2 things involved in asthma
- innate and adaptive immune cells recruited from the circulation
- secretion of inflammatory mediators by tissue resident cells
89
what causes the chronic stage of inflammation in asthma
repetitive of persistent exposure to allergens
90
what kind of immune cells take up residence in tissues in asthma
innate and adaptive immune cells
91
which kind of cells develop in tissue in asthma
more mast cells
92
what is something that lots of mast cells display
large amounts of IgE bound to FCERI (IgE receptor)
93
what is AIDS caused by
consequence of chronic retroviral infection with HIV
94
how does AIDS virus work
uses host cell machinery for transcription of HIV gene products and viral replication
95
what is the main thing affected in HIV
life threatening dysfunction of CD4+ T helper lymphocytes
96
what happens to CD4 levels with AIDS
chronic decline, inverses CD4/CD8 ratio
97
what 2 things are impaired with B lymphocytes and AIDS
- marked hypergammaglobulinemia (lots of antibodies)
| - impaired specific antibody responses
98
what plays an important role in the pathogenesis of HIV
chemokines
99
what determines the cell/tissue tropism of each viral strain (like macrophages, T cells
chemokine co receptor
100
which kind of people are highly resistant to HIV
those with nonfunctional CCR5
101
what is required for virion entry and cellular infection
binding to two co-receptors on targets
102
what do all HIV strains express
gp120 that binds to CD4 molecules
103
what determines the cell tropism of each viral strain
chemokine co receptor
104
what are 2 things that are required for virion entry and cellular infection
CCR5 and CD4
