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87 Cards in this Set

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What are 3 of 5 differences between systemic and mucosal immunity?
anatomy: immunogen from epithelium
nonspecific factors: for gut only
Ab is sIgA major and sIgM minor
What are two differences between systemic and mucosal immunity?
T cells: mucosal specific immunity
Homing system: selective homing to diffuse lymph tissue
Where is diffuse lymphoid tissue located?
mucosal lamina propria
What are the three main locations of GALT?
Peyer's patches - t and b cells
Lamina propria - many IgA producing B cells
Intraepithelial lymphocytes - lymphocytes between epithelial and under tight junctions
What are M cells?
specialized flattened epithelial cells that pinocytose material from the overlying lumen and transport it to the epithelial cells
What are nonspecific factors operating with mucosal immunity?
Mechanical, chemical and mirobiological
What transmembrane proteins form tight junctions?
claudin and occludin
What is the most abundant mucosal Ig?
IgA - subclass 1 dominates in serum and subclass 2 dominates in secretions
sIgA is resistant to proteolysis
How is sIgA antiinflammatory?
does not activate compliment by either classic or alternate pathways
Binding to neutrophils and phagocytes inhibits phagocytosis
NET EFFECT: prevent colonization by pathgens without inducing inflammation
How do Tcells regulate IgA synthesis?
1 Activated Tcells interact with IgM expressing Bcells
2 TGF beta and tcell interactions with bcells induce class switching to IgA
what cytokines cause production of sIgA?
TGF beta causes class switching
Similar to IL-10 as an anti-inflammatory
How does sIgA get across epothelium?
Part of the poly Ig receptor remains bound to sIgA and this part helps it cross as well as stay stuck to the membrane
What is transcytosis?
movement of macromolecules from one side of a cell tothe other via receptors
What is immune exclusion?
restricts immune responses to mucosal immunogens to the mucosal lyphoid system
sIgA deficiencies show what?
increased abs of macromolecules and high levels of immune responses following ingestion of immunogens
IgM in the mucosal immune system?
can replace IgA in individuals with Ig deficiency
IgG in the mucosal immune system?
not effectively transported across epithelium
Synthesized in large amounts in distal respiratory tract
IMPORTANT for pulmonary secretions
Describe mucosal homing
lymphocytes activated in mucosal follicles AFFERENT move to EFFERENT areas like diffuse lymphoid tissues
Mechanism of mucosal homing for lymphocytes
integrin alpha4beta7 binds MadCAM-1 on endothelial cells
Mucosal homing for intraepithelial lymphocytes
integrin alphaEbeta7 binds epithelial cadherins
What is oral tolerance?
it is the suppression of immune cell responses to Ag introduced from the oral route
Failure: crohn's disease or ulcerative colitis
what are the mechanisms of oral tolerance?
regulatory Tcells Treg secrete TGF beta
Induction of tcell anergy and deletion of autoreactive Tcells
what Ig is in mother's milk?
sIgA is a passively transferred immunity
What are immune factors in mother's milk?
lysozymes, lactoferrin, Activated leukocytes
Lactadhedrin protects against rotavirus
MUCIN-1 protects against ecoli
Where is cell mediated immunity most important?
facultative intracellular infect
obligate intracell infect
cellular Ag
usually intracellular
Where is Ab mediated immunity most important?
molecular Ag
Extracellular infections
usually extracellular
What are the major products of Tcells?
cytokines - not specific
effector t cell is specific for antigen
What surface molecules are expressed on all t cells?
TCRs and CD3
what enzyme helps construct t cell receptor genes?
VDJ recombinase
What are the major locations of t cell development?
stem cells = bone marrow
thymocytes - thymus
peripheral tcells in lymphoid tissue
What is positive selection of Tcells?
promotes survival of tcells that recognize peptides complexed to self-mhc
do not recognize self mhc - do not survive
what is negative selection of Tcells?
deletion of thymocytes whose tcrs recognize peptides derived from self-proteins
what are double negative thymocytes?
cells that express neither cd4 or cd8
what are double positive t cells?
cells that express both cd4 and cd8
Describe the first phase of tcell development
double negative thymocytes undergo stimulation to double positive thymocytes
2nd phase of tcell development
double positive thymocytes express cd3 and undergo positive selection
leads to single positive tcells
3rd phase of tcell development
double positive thymocytes undergo negative seletion for self reactivity
then leave thymus and enter blood
What are similarities between tcell receptors and antibodies
amino terminal variable region
variable and constant in each chain
Differences between antibodies and t cell receptors
monovalent vs. divalent
Ag vs. Ag/MHC recognition
tcr - 55000mw
Ab - 150-190000mw
What are gamma delta tcells
major pop of intraepithelial lymphocytes
Doesn't need MHC!
cytotoxic esp to tumor cells
Do tcr genes undergo somatic hypermutation?
no
alpha chain - VJ
beta chain - VDJ
main role of th1 cells
Th1 - activate tissue macrophages to eat and kill extracellular pathogens
secrete cytokines
main role of Th2 cells
stimulating b cells to make Ab which bind to extracellular bacteria and virus particles
What is a super Ag?
certain bacterial toxins that bind MHC class II and TCR without Ag processing
Where do super ag's bind
outside the peptide binding region of class 2 and to the variable beta side of TCR
process of super ag destruction
profound immune stimulation without costimulation
profound immune suppression from anergy or apoptosis
mechanism of toxic shock
massive t cell activation and the resulting cytokine release contributes to the pathology of TSS
what is the result of stimulation of the tcell without costimulation
anergy - absent or decreased response to an immunogen
can be persistent
mechanism of peripheral tolerance to self
Which cytokine is responsible for clonal expansion of tcell in 1' response and who produces it?
IL-2 is produced by T helper cells
IL-2R are not on resting tcells
They appear on activation of tcell
name cytokines produced by Th0 cells
secrete interferon gamma and IL-4
depending on other cytokines, they will change into Th1 or Th2
cytokines produced by Th1 cells
stimulated by IL-12
make IL-2, interferon gamma, and TNFbeta
How do Th1 cells benefit macrophage response?
enhances intracell killing
induces isotype switch in b cells to IgG1 for which macrophages have a receptor (Fc gamma)
cytokines produced by Th2 cells
stimulated by IL-4
make IL-4, 5, 6, 10, 13
What do Th2 cells promote?
growth and differentiation of various inflammatory cells (mast cells, basophils, and eosinophils)
Class switch to IgE
what 2 cells mutually inhibit each other and the balance between 2 is specific
Th1 and Th2
What are Treg cells?
inhibitory for inflam response
secrete IL-10 and TGF beta
allergy - good for tolerance
cancer - bad because they turn off anti-tumor response
describe Th17 cells
promote inflam
make IL-17
hallmark of chronic inflammation
IL-23 promotes their development
How do CTL kill target cells?
lysis -- perforins released by CTL
apoptosis -- Fas-ligand on CTL activates FAS-receptor on Target cell
What cells are targeted by CTL?
virus infected cells, cells infected with other intracell pathogens, allografts
What accounts for most of the 2' characteristics of the Tcell response?
the increased number of antigen reactive cells that accounts for most of the characteristics of the 2' immune response
What is the most important NK cell receptor? describe the activation
Fcgamma receptors
ADCC - Antibody Dependent Cell mediated Cytotoxicity
2 receptors needed for crosslink activation
activation = lytic granule release
Describe NK cells
not immunogen specific and not MHC restricted
Generally inhibited by MHC class I
First line of defense
Define cytokines
cytokines are intercellular regulatory proteins produced by many different cells that ultimately control every aspect of the body's defenses
cytokine properties
low mw proteins
extremely potent
autocrine or paracrine, minor endocrine functions
pleitropic - different effects on different target cells
3 ways of coping with pleiotropy
1 only activated cell expresses receptor
2 limited ratius of effectiveness
3 short half life
Describe costimulation using CD28 and B7
CD28 is on tcell and binds to B7 on APC cell to cause costimulation
without costim, the T cell becomes anergic
describe IL-1 production and function
produced by APC's
stimulates T helper cells
similar to TNF alpha
Induces ICAM expression
chemotactic
IL-2 production and function
produced by Th1 cells
stimulates tcell proliferation and activation
enhances cytoxicity of NK cells and CTL
IL-3 production and function
produced by T cells and NK cells
stimulates growth factor for hematopoetic cells
IL-4 production and function
IL-5
produced by Th2 cells and mast cells
stimulates proliferation and differentiation of B cells
Induces IgG to IgE
promotes Th2 proliferation and mast cell growth
IL-6
produced by Th2 cells
aids in Bcell development
Proinflammatory
Wound healing
aids Th2 mediated events
IL-8
produced by macrophages
also known as CXCL8
chemoattractant for neutrophils and tcells
IL-10
Produced by Th2 and Treg cells
Anti-inflammatory similar to TGF beta
IL-17
produced by Th17 cells
proinflammatory
Interferon alpha and beta
produced by all cells
antiviral properties well known for induction of MHC class I on all somatic cells
Interferon Gamma
produced by Th1 cells, CTL, and NK cells
enhances macrophage activity and pushes production to IgG
TNF alpha
produced by macrophages, Th1, and mast cells as well as almost all other cells
stimulates acute phase of inflam
causes cytokine secretion by inflammatory cells
TNF alpha is similar to what interleukin and which cells have receptor for TNF alpha
Similar to IL-1
all nucleated cells have receptors for TNF alpha
TGF beta
produced by Treg cells
stimulates antiinflam response
similar to IL-10
CSF
colony stimulating factors
promote formation of colonies of myeloid lineage in bone marrow
how are chemokines different from cytokines
different from other cytokines due to
1 bind to vascular bed like adhesion molecules
2 may bind to one or several chemokine receptors
IL-12
produced by macrophage
stimulates T cells into Th1 cells
activates NK cells
CXC vs. CC
CXC have 2' structural motif
ELR+ -- acute inflam
ELR- -- chronic inflam
CC aka beta chemokines
Major families of cytokine receptors
Ig superRF
Hematopoietin RF
INF RF
TNF RF
Chemokine RF
IL-2 receptor
NK cells express beta-gamma - mid affinity
Tcells have gamma only
the alpha subunit is inducible
Th1 cells make what cytokines?
IL-2 INF gamma and TNFbeta
promote macrophage mediated response
Th2 cells make what cytokines
IL-4 IL-5 IL-6 IL-10
promote some allergic reactions and responses to some extracellular pathogens