Week 12 Flashcards
(149 cards)
1
Q
What is the purpose of acute inflammation?
A
Eliminate the initial cause of cell injury
Clear out necrotic cells and tissue damaged from original insult and inflammatory process
Initiate tissue repair
2
Q
Too little inflammation can lead to…
Too much inflammation can lead to….
A
Progressive tissue destruction and compromise the survival of the organism
A host of diseases such as cardiovascular disease, cancer, Alzheimer’s, neurological diseases, arthritis, autoimmune diseases, diabetes 2, pulmonary diseases
3
Q
What is the goal of antiinflammatory therapy?
A
Decrease inflammation
Decrease pain
Arrest tissue destruction
Preserve function
4
Q
True or false.. chronic inflammation involves an ongoing stimulus, lasts weeks, and is absent in any cardinal signs, and the fundamental cells ar lymphocytes, macrophages, and fibroblasts (whereas acute is neutrophils and macrophages)
A
True
5
Q
NSAIDs inhibit ____
A
Cyclooxygenase enzymes (COX enzymes)
This decreases pain and inflammation through inhibiton of prostaglandin synthesis.
6
Q
Glucocorticoids inhibit ____
A
Phospholipase A2
7
Q
What are DMARDs? What are the two types?
A
Disease modifying anti-rheumatic drugs
Traditional (non-biologic) DMARDs
Biologic DMARDs
8
Q
What are eicosanoids?
A
Oxygenation products of poly-unsaturated long-chain fatty acids
Act in autocrine/paracrine fashions
Includes prostanoids
9
Q
What are prostanoids?
A
Subclassification of eicosanoids including…
Prostaglandins -mediators of inflammatory response
Thromboxanes - mediators of vasoconstriction
Prostacyclin - active in the resolution of inflammation
10
Q
Prostanoids have major biological effects on what 5 things?
A
Smooth muscle
Platelets and blood cells
Nerve terminals
Endocrine organs
Adipose tissue
11
Q
COX2 selective inhibitors have reduced ___ adverse effects but ma increase risk of thrombosis, stroke, or kidney failure.
These drugs do not inhibit ___ or cause ____
A
GI
Platelet aggregation
GI upset/ulceration
(Note that this means that COX1 is responsible for GI upset, so COX2 selective inhibitors do not have these effects)
12
Q
The NSAID Aspirin (AKA acetylsalicylic acid) inhibits _____. It is the only NSAID to inhibit both COXs in an ____ manner. This drug is valued primarily for its _____ effects when used regularly.
A
COX1 and COX nonselectively
Irreversible
Anti-platelet aggregation
13
Q
True or false… aspirin is regularly used as an anti-inflammatory medication
A
False… it is mostly just used for its antitrhrombotic effects
14
Q
What are aspirin’s contraindications?
A
Avoid in children with viral-induced illness (reye syndrome)
Avoid in patients with NSAID allergies, renal insufficiency, gout, bleeding disorders,
15
Q
Ibuprofen is an NSAID derived from ____. Ibuprofen should not be taken with ____ because ibuprofen interferes with the ____ effect of low-dose ____, making it less effective for MI and stroke prevention.
A
Propionic acid
Aspirin
Antiplatelet
Aspirin
16
Q
What is naproxen?
A
Similar in pharmacological profile as other NSAIDs but available in slow-release formulation
17
Q
Name some adverse effects common to all NSAIDS
A
GI issues: abdominal pain, dysplasia, nausea, vomiting, ulcers
Reye syndrome: in children taking salicylates after viral induced illness. Potentially fatal
CNS
Skin
Renal
Hematological
18
Q
Name three NSAIDs
A
Aspirin
Ibuprofen
Naproxen
19
Q
What is celecoxib? What is it used to treat?
A
It is a cox-2 selective inhibitor (it is 10-20x more selective for cox-2 than cox-1)
Used to treat osteoarthritis, rheumatoid arthritis, ankylosing, and painful menstration
No effect on platelet aggregation
20
Q
What is acetaminophen? What is its mechanism?
A
It is a non-aspirin pain reliever (tylenol)
Relieves fever, headaches , mild pains.
Not anti-inflmmatory (not an NSAID)!!!
Mechanism - centrally acting effect on hypothalamus to cause vasodilation and sweating (reduces fever), also elevates the pain threshold.
Overdose can result in hepatotoxicity
21
Q
What are glucocorticoids? What is its mechanism? Their anti-inflammatory effect results from…
A
Steroid hormones
Prevents conversion of membrane phospholipids to arachidonic acid by inhibiting the phospholipase A2 enzyme (which is a critical step in the formation of inflammatory mediators)
Inhibiton of phospholipase
Alteration in lymphocytes
Inhibition of cytokine expression
Stabilization of the cellular membrane
22
Q
What are some adverse effects of glucocorticoids?
A
Cardiovascular risk Cataracts Skin thinning Gastric ulcer CNS problems Osteonecrosis/porosis Myopathy Infections
23
Q
Name three short to medium acting glucocorticoids
A
Hydrocortisone
Cortisone
Prednisone
24
Q
Name one long-acting glucocorticoid.
A
Dexamethasone
25
Prednisone is an immunosuppressant drug once converted to its active metabolite ___ via ___ metabolism. Describe its mechanism of action
Prednisolone
Hepatic metabolism
Blocks phospholipase A2, thus shuts down immune responses
26
True or false... DMARDs can actually suppress the progression of the disease through their actions against the underlying immunological abnormalities.
True
27
What DMARD is the first line for rheumatoid arthritis?
Methotrexate
28
What is the mechanism of methotrexate?
Inhibits transformylase and thymidylate synthetase enzymes (leading to the inhibiton of pro-inflammatory cytokines and inhibiton and apoptosis of immune inflammatory cells)
29
Name two DMARDs
Methotrexate
Azathioprine
30
True or false... methotrexate may be taken in pregnancy
False. It is contraindicated in pregnancy
Also... there is a risk of serious life-threatening adverse effects if taken with NSAIDs
31
What is the mechanism, clinical use, and adverse effects of azathioprine?
Mechanism - prodrug that acts through its main metabolite 6-thioguanine to strongly suppress DNA synthesis in and production of rapidly proliferating immune cells
Clinical uses - approved for RA and kidney transplant rejection prophylaxis
Adverse effects - bone marrow suprression, GI upset
32
What are biologic DMARDs? Give some examples
Proteins produced by recombinant DNA technology
T-cell modulators and TNF-alpha blocking agents, and others
33
What is the mechanism, clinical use, and adverse effects of abatacept?
Mechanism - acts as a fusion protein to prevent activation of T cells
Clinical use - treatment of RA in patients whom have failed to respond to anti TNF-alpha therapy
Adverse effects - increased risk of lymphomas, infections, congestive heart failure
Very expensive drug!
34
True or false... there are 5 different TNF-alpha inhibition biologic dMARDs clinically available
True
35
What is the mechanism, clinical use, and adverse effects of adalimumab?
Mechanism - Prevents ligand from binding to TNF-alpha receptor.
Clinical uses - rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease
Adverse effects - increased risk of lymphomas, infections, congestive heart failure
36
True or false... plasma cells have the potential to differentiate into memory B cells
False
37
The chemokines ___ attracts immature B cells to HEV, then ___ and ___ attract the B cell into the lymph node. Then the chemokines __ attracts the B cells into the primary follicle of the lymph node
CCL21
CCL21 and CCL19
CXCL13
38
In the primary follicle, ___ is released form the B cell which binds to a receptor on a _____. Then, this cell releases ____to activate the B cell
Lymphotoxin
FDC (follicular dendritic cell)
BAFF (B cell activating factor)
39
What are follicular dendritic cells?
They are not really dendritic cells. They are more like stromal cells involved in B cell development
Accumulate antigens via complement receptors
No phagocytosis activity
40
Where are B cells presented antigen?
Lymph nodes
41
B cell activation drives...
Clonal expansion
Class switching
Somatic hypermutation
42
In the lymph node, antigen is presented to B cells from FDCs and subcapsular sinus macrophages by ___
Cr2
43
What is the role of Cd3 in the activation of B cells?
Cd3 targets the antigens so the macrophages and follicular dendritic cells can hold onto it.
44
What are the two different types of antigen that can activate a B cell?
Thymus-dependent antigen
Thymus independent antigen
45
What antigen type is typically protein? What type is non-protein? What type of antigen presentation is most common?
Thymus-dependent antigen is typically protein
Thymus-independent is typically non-protein antigen.
Thymus-dependent is most common
46
What three signals are involved in thymus-dependent antigen?
Antibody crosslinking - activation
Co-receptor signals - survival and proliferation
Cytokines - differentiation, class switching, somatic hypermutation
47
What signals are involved in thymus-independent antigen presentation?
PRR-detected antigen
Complement bound to co-receptor
48
True or false... in thymus-dependent antigen presentation, a TFH cell (T follicular helper cell) is required
True
49
Describe the process of antibody crosslinking signaling
B-cell receptors bind antigen, resulting in clustering of the receptors.
Clustering of antigen receptors allows receptor-associated kinases to phosphorylate the ITAMs leading to activating signals. (Igalpha and Igbeta signaling)
50
What is the purpose of the co-receptor signals in the activation of B cells?
Ensures the target is pathogenic (as opposed to self)
Prevents the B cell from becoming anergic
Initiates clonal expansion
51
What are some things that coreceptors in B cells can bind?
Complement
PRRs (bind many different things)
CD40 receptors
52
What co-receptor complex binds C3d (complement)
CR2 bound to CD19 and CD81
This receptor complex must be activated in close timing and proximity to the antibody receptors in order to induce synergistic activation signals
53
____ cells are the most common source of cytokines during B cell activation. ____ cytokines can provide signals in the absence of T cell-mediated activation .
TFH
Local
54
What are the four roles of cytokine signaling in B cell activation?
Survival and proliferation
Class switching (same epitope binding, different heavy chain)
Somatic hypermutation (increases antibody specificity)
Differentiation (produces plasma cells and memory B cells)
55
B and t cells come together to form ____ at the follicle boundary. Describe how these form.
Cognate pairs
Naive B cells search for specific antigen displayed by FDCs in the B cell area. Meanwhile, naive T cells search for specific antigen displayed by dendritic cells in the T cell area.
Antigen activated T cells proliferate/differentiate. Antigen-activated B cells move to the boundary region
Antigen-activated B cells present antigen to effector TFH cells, forming cognate pairs.
56
True or false... if a B cell has an receptor for a lipid antigen, it will not form a cognate pair
True, because it will undergo thymus-independent antigen activation
57
True or false... TFH cells drive B cell activation, proliferation, enhanced specificity, and differentiation into plasma and memory cells
True
58
True or false.. thymus independent activation typically yields a larger population of plasma and memory cells
False... Thymus dependent activation (TFH) activation typically does
59
Describe how TFH cells aid in B cell activation
B cell is first activated by antigen binding
B cell the presents antigen to TFH cells
CD40 is a receptor on B cells that is stimulated by a CD40 ligand on T cell. This will induce survival and proliferation of B cells
Cytokines: differentiate and/or isotype switch
60
B cells form plasma cells in two stages and places. What are they?
Cognate pairs first move to the primary focus (medullary cords)
Cognate pairs then move to the secondary focus (located in the primary follicle) and form germinal centers
Note that the cognate pairs must cross the T-cell area in order to get from medullary cords to primary follicle
61
What occurs in the primary focus (medullary cords) in regards to the formation of plasma cells?
Production of IgM expressing plasma cells for several days
No class-switching or somatic hypermutation
62
Where is the boundary region in lymph nodes?
Located between the primary follicle and T cell area. This is where cognate pairs are first formed
63
Describe what occur in the secondary focus in regards to the production of plasma cells
Cognate pair moves to the secondary focus in which a germinal center is formed and the following occurs...
Enormous proliferation and plasma/memory cell production
Class switching and somatic hypermutation
Selection of most specific plasma cells
64
B cells hypermutate and class switch in ____
Germinal centers
65
Cognate pairs form germinal centers in the ___ zone. What cells are found here?
Follicular
TFH cells
Follicular dendritic cells
Centroblasts
Centrocytes
66
What are centroblasts?
Form the germinal center dark zone
Proliferating source of new B cells
Do not express surface immunoglobulin
Somatic hypermutation occurs
Class switching occurs
Centroblasts form centrocytes
67
True or false.. centroblasts directly form plasma and memory cells
False... centrocytes form plasma cells and memory cells
68
What are centrocytes?
Form the light zone
Divide slowly
Express surface immunoglobulin
Cannot class switch or hypermutate
Interact with and selected by FDCs
Programmed to die
69
True or false... class switching and somatic hypermutation improve antibody specificity
True
70
In order for class switching to occur, ___ proteins are reactivated which will cause a change in the ____ ___ region of the antibodies produced. Class switching is ___ induced.
RAG
Heavy chain Fc
Cytokine
71
True or false... different cytokines yield different isotypes to be produced.
True
72
True or false... different classes of antibodies dictate effector functions
True
73
What is somatic hypermutation?
Directed hypervariable region mutations by single nucleotide insertions and substitutions yielding new epitope binding regions increasing antibody affinity.
Somatic hypermutation is paired with selection processes.
74
True or false.. as centroblasts divide, less mutations (somatic hypermutation) are produced
False... more mutations are produced
75
True or false... since centrocytes have undergone the first round of somatic hypermutation, they produce a new antibody that is different than the cognate B cell antibody
True
76
Only centrocytes that bind FDCs can bind to ___
TFH cells
77
What happens when FDC-bound centrocytes are bound by TFH cells? (5 things)
Limited TFH cell population in the germinal center
Survival signal
Selection of centrocytes with the highest antibody affinity
Further proliferation
Differentiation into plasma cells or memory B cells
78
Name some differences between naive B cells and plasma cells
Naive B cells produce surface Ig, have a surface MHC class 2, can undergo isotype switching, can grow, can undergo somatic hyper mutation
Plasma cells have a high ig secretion
79
True or false... all plasma cells will be found within the lymph nodes
False... some go to the site of infection
80
Antibodies have four broad effector functions. What are they?
Virus/toxin neutralization
Opsonization
Complement fixation/activation
Antibody-dependent cell-mediated immunity (targeting self infected cells)
81
What antibodies will you find in internal tissues?
IgM
IgA
IgG
82
What antibodies are found at mucosal surfaces?
IgA
83
What antibody is used for parasite immunity?
IgE
84
What antibody is a B cell receptor?
IgD
85
Fc receptors can be monomeric or dimeric, but often involve ____ for activation
Dimerization
86
There are Fc receptors for what classes of antibodies?
IgE
IgA
IgG
87
Fc receptors can have stimulatory or inhibitory signaling when bound to an antibody. What things may happen?
Phagocytosis
Degranulation
Targeted killing
Cytokine production/release
88
Name two functions of Fc receptors
To enhance innate immunity by stimulating or inhibiting signals
Involved in Ig transport
89
Explain how Fc receptors facilitate IgG transport into tissues
Cytokines upregulate Fc receptors on the endothelial cells of blood vessels. The receptors bind antibody and bring in the antibody (acidic pH in the vesicle causes an interaction with Fc receptor to protect the antibody from proteolytic). Then the antibody is released into the inflamed tissue by exocytosis
90
Explain how transcytosis of IgA protects mucosal surfaces.
IgA binds to an pIgR ((poly-Ig receptor) IgA Fc receptor) on basolateral side of epithelial cell. Receptor mediated endocytosis of antibody occurs and transports the IgA to apical side of cell. Receptor is cleaved, but IgA remains bound to mucus through the secretory piece
91
Which classes of antibodies are capable of neutralizing antibodies to prevent pathogen establishment? Explain how it works
IgA and IgG
Antibody binding to viruses will prevent the viruses ability to infect/penetrate cells
Antibody binding to strep. Pyogenes will prevent bacteria from attaching to surfaces
92
Explain how erythrocytes clear agglutinized antigens
Antibody complexes form within blood which bind antigen. Complement binds to antibody complex. Erythrocytes binds to complement -antigen-antibody complex. This erythrocytes carries this complex to liver or spleen where macrophages take up the immune complex
93
Explain how IgE makes mast cells, basophils, and eosinophils competent
IgE binds to these cells to become these cells' receptors. Mast cells, for example remained in a fixed location and accumulate many different types of of IgE. Then when one of these receptors are stimulated, they degranulate. This is important in allergic responses
94
True or false... IgM and IgG initiate the complement cascade.
True. IgM is typically better at initiation
95
Describe how antibody-dependent cellular cytotoxicity works
Anti CD20 antibody binds to CD20 on the surface of abnormal self cells (cancer) Fc receptors on NK cells recognize anti-CD20 antibody and degranulate
96
Antibodies provide passive immunity during development. ... ____ during gestation. ____ protects infant mucosal surfaces (from breast feeding) In these ways, the mothers immunity is passed on to the child
IgG
IgA
97
What are two roles of NK cells?
Destroy diseased and dysfunctional self-cells
Interface between adaptive and innate immune system
98
NK cells are developmentally similar to ___ cells
T cells
99
True or false... NK cells may form memory cells
True
100
Positive and negative signal balance determines NK cell killing. Describe the three cell states that regulate NK cell targeting.
Protection - healthy cells express low amounts of stimulatory ligand but also MHC-1 which. Inhibitory signal from MHC-1 overrides stress signal
Missing self - unhealthy cells reduce MHC-1 expression so that the stimulatory signal of the stress ligands override the inhibitory signal. This will result in NK cells killing the target cell
Induced self - unhealthy cells increase stress ligand expression. This causes the stimulatory signal to override the inhibitory signal, leading to death of the target cell
101
True or false.. all NK cells detect all MHC1 receptors or stress ligands
False
102
NK cells have activating and inhibitory receptors. Name two activating receptors and two inhibitory receptors
Activating:
NKG2D (preferentially binds MIC)
CD16 (Fc receptor) (this binds to MIC proteins)
Inhibitory:
NKG2A (preferentially binds MHC)
KIR family
103
True or false... all NK cells in the body have the same combinations of receptors
False.. NK cells express diverse combinations of receptors
104
What are the three major receptor families for NK cells?
CD16: low affinity IgG Fc receptor; activating receptor
NKG family
KIR family (Killer-cell immunoglobulin-like receptors) - bind MHC1, inhibits NK cell activation, detects healthy self tissue
105
True or false... NK cells usually express NKG2A and KIR receptors at the same time
False. Typically one or the other
106
What is the significance of having multiple isotypes of MHC1?
Each isotype has variance, which allows the MHC1s to bind to lots of different antigen.
107
Describe NK cell education
MHC1 exposure during development
NK cells detect that specific MHC1 isotype
NK cells must detect that MHC1
NK cells only detect that MHC1
108
HLA-E is recognized by....
CD94:NKG2A
109
What detects the following...
HLA-A, B, C
HLA-E, G
HLA-F
HLA-A, B, C - T cell and NK cell receptors
HLA-E, G - NK cell receptors
HLA-F, - Intracellular chaperone
110
What three things activate NK cells?
Target cell interaction (down regulated MHC1, Stress ligands, CD16)
Leukocyte interaction (antigen presenting cells, Th cells, NKT cells)
Cytokines (IFNs, IL-12, proliferation , receptor expression, cytokines, granule production)
111
What are the effector functions of NK cells?
Cytokine release
Cytotoxicity
112
Explain NK activation via innate immune system
Multiple (2) signals are required
MHC surveillance
Stress ligands
113
Explain how the adaptive immune system may activate NK cells
On signal from antibodies are required. Fc binds to CD16 on NK cells to activate them
This signal is an override signal than will result in death of the target cells (covered in antibodies)
114
Describe Nk cell cytotoxicity (3 things)
Degranulation (perforins and granzymes)
Death-receptors (FasL, TRAIL)
Interferons and NO
115
What is the major role of gamma-delta T cells? Where are they prominently found?
Major role: remove diseased and malignant cells
Prominent in tissues and mucosal surfaces (as opposed to blood) - sit in epithelial layers. Intraepitheilal lymphocytes
116
What kind of antigens do gamma-delta T cells bind?
Lipids
Phospholipids
Phosphoantigens (phosphorylated proteins)
117
What are the effector functions of gamma delta T cells?
They have both CD8 and CD4 -like activity. Direct killing. Cytokine and chemokine release. NK, macrophage, and DC activation
Can be APCs and migrate to lymph nodes
Similar to NK cells in that they express stress-ligand receptors and they also detect the presence of MHC
Promote tissue repair
118
What is the role of CD1?
Expresses self and non-self lipids. Interacts with gamma delta T cells to discriminate self vs. nonself. Will drive activation, and potential targeting killing. Co signal dependent
119
True or false... because CD1-gamma delta T cell interactions are highly specific, they are co-signal dependent
True
120
What three things do gamma delta T cell receptors bind?
Phospholipid receptors
MHC1-related receptors
Stress ligands
121
Gamma delta T cells drive inflammation by...
Th17 and Th1 and NK cell activation (locally)
122
Gamma delta T cells are directly cytotoxic by releasing...
Perforin and granzyme
| CD16
123
How do delta gamma T cells drive the adaptive immune system?
They stimulate DC and macrophages
They are APCs
124
Delta gamma T cells have relatively rapid responses to local pathogens and disease. They react to ...
PAMPs
Stress ligands
125
Mucosal surfaces are widespread and prominent sites of infection. What is the number one world wide cause of death from mucosal surface infections?
Acute respiratory infections
126
What are the three tracts within the body that have mucosal surfaces?
Respiratory tract
Gastrointestinal tract
Urogenital tract
127
Intestinal lymphocytes are found in ___ tissues where immune responses are induced and ____ ____ the intestine, where they carry out effector functions
Organized
Scattered throughout
128
What are the three compartments of mucosal tissues?
Epithelium
Lamina propria
Mucosal associated lymphoid tissue (MALT)
129
True or false... the epithelium in the mouth and the gut are both single layered
False. The gut epithelium is single layered whereas the mouth is multilayered
130
What are the immune cells found within the epithelium of mucosal tissues?
Intraepithelial lymphocytes.. which include the following...
Delta gamma T cells
CD8 a:a T cells
Memory CD8 cells
131
What immune cells are found within the lamina propria of mucosal tissues?
Delta gamma T cells
CD8 T cells
CD4 T cells (Th1, Th17)
Plasma cells and memory b cells
Macrophages
Dendritic cells
132
In the oral mucosal system.. the tonsils and adenoids form a ring of lymphoid tissues called ____, around the entrance of the gut and airway
Waldeyer's ring
133
True or false... mucosal infections follow the traditional inflammatory pathway
False
134
Mucosal immunity often employs limited ____. In fact, most infections are often cleared ___ an inflammatory response. It has a ____ proactive and ____ reactive immunity. Both ____ and ___ cells respond. Neutrophils are only recruited if the infection is _____
Inflammation
Without
Strong
Limited
Local innate
Adaptive cells
Severe, persistent, and/or causes tissue damage
135
Mucosal surfaces have unique immune features. Name the unique anatomical, features, effector mechanisms, and immunoregulaory environment
Anatomical: intimate interactions between mucosal epithelia and lymphoid tissues. Specialized antigen uptake mechanisms (M cells)
Effector mechanisms: secretory IgA. Activated/memory T cells predominate even in absence of infection.
Immunoregulatory enviornment: active downregulation of immune responses. Inhibitory macrophages and tolerance-inducing dendritic cells
136
Naive lymphocytes are activated in ____ to give rise to effector cells that will travel in the lymph and blood to gain access to the ____ of the mucosal tissue, or become ___
Peyer's patches
Lamina propria
Interepithelial lymphocytes
137
As you progress down the GI tract, you get more and more of what genus of bacteira?
Bacteroidetes
138
True or false... The oral microbiome is diverse and changes with disease. Diversity and richness increases with disease
True
139
How is the microbiome constantly shaped at mucosal surfaces?
Antigens are taken up in peyer's patches in lymphoid follicles
Local immune responses activate protective mechanisms that stabilize the epithelial barrier (release antimicrobial peptides and IgA)
CD4 Th17 are important
140
The mucosal microbiome affects the local cytokine environment and subsequently CD4 T cell differentiation. Describe this relationship.
TGF-beta with inflammatory cytokines will lead to Th17 cells (these cells drive inflammation by neutrophil recruitment, antimicrobial peptide production, and tissue repair)
TGF-beta without inflammatory cytokines will lead to TReg cells (these cells inhibit mucosal inflammation)
141
Th 17 cells play a critical role in mucosal and oral immunity. They protect barriers and induce inflammation when needed. What are the two interleukins they release? What do they do?
IL-17 and IL-22
Regulate tight junction protein expression (maintain barriers)
Induce antimicrobial peptide production (B-defensins, cathelicidins, lactoferrin)
Induce neutrophil chemotaxis
142
Impaired or excessive Th17 function is linked to oral disease. What are they linked to?
Impaired Th17 function -Chronic mucocutaneous candidiasis (persistent fungal infection, deficient IL-17 signaling. Caused by deficient IL-17 receptors, impaired TH17 differentiation or development)
Excessive Th17 function - periodontitis (chronic and excessive neutrophil recruitment, chronic inflammatory cytokine production, osteoclast activation)
143
What are 4 important roles that immunoglobulin secretion plays in mucosal membranes? What is the main Ig involved?
Neutralize pathogens/toxins
Bind/neutralize antigens in endosomes
Export toxins/pathogens from lamina propria to be secreted
Transported through M cells to a DC to shape microbiome
Predominantly IgA
144
Mucosal antigens are constantly browsed by what three mechanisms? What is the outcome?
Antigen capture by macrophage
Uptake by goblet cell
Capture by interepithelial dendritic cell
Impacts IgA and antimicrobial peptide production and release
Commensal bacteria repress immune response
Pathogenic bacteria trigger immune response
145
What are the three mechanisms in which mucosal antigens are constantly browsed by cells?
Nonspecific transport across epithelium (M cells)
FcRn-dependent transport
Apoptosis-dependent transfer
146
Mucosal epithelial cells are active immune components. How? (6 things)
Actively direct immune responses
Express TLR and NOD receptors
Form inflammasomes
Phagocytose mucosal bacteria
Express cytokines and antimicrobial peptides
Induces local immune respsone
147
Explain how epithelial damage can promote mucosal inflammation
Antibiotics kill commensal bacteria. Clostridium gains a foothold and produces toxins that causes mucosal injury.
Neutrophils and RBCs leak into gut between injured epithelial cells
This leads to pseudomembranous colitis
148
Established pathogens illicit inflammatory responses. After pathogen evades mucosal immunity, what happens?
Local macrophage and DCs are activated
Leads to neutrophil recruitment
Th17 and Th1 response
149
Gamma delta T cells are located in which layer of the mucosa?
Epithelial layer
