Soluble mediators of the immune system Flashcards

1
Q

4 main sources of BRMs by (mononuclear leukocytes)

Biological response mediators (BRMs)

A

-B lymphocytes: secrete specific Abs
-T lymphocytes: secrete soluble mediators (IL-2, other-ILs, GM-CSF, TNF-β, IFY-γ)
-Monocytes and macrophages: secrete (IL-1, other ILs, GM-CSF, TNF-α, M-CSF, IFN-α)
–NK lymphocytes: secrete IFN-α

^modulate individual’s own immune response

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2
Q

Classes of BRM immunotherapy

A

-Active— use of microbial or chemical immunomodulators (adjuvants) in a specific or non-specific form
-Adoptive— use of soluble mediators, such as ILs, to regulate components of the immune systems
-Passive— Transfer of preformed antibodies to tumorous recipients, such as monoclonal antibodies
-Restorative— application of soluble substances, such as interferons, for a wide range of diseases

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3
Q

What are Cytokines, what do they do?

A

-A polypeptide product of activated cells (lymphocytes or macrophages) that control a variety of cellular responses & thereby regulates the immune system
-Most cytokines have multiple activities & act on numerous cell types
-synthesized and secreted by cells of the innate/adoptive immunity in response to microbial & other Ag exposures (variety of host defense)
-Very potent; act on neighboring cells by binding to their surface cytokine receptors
-effect limited to local area; BUT CAN HAVE systemic effects

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4
Q

What are Lymphokines vs Interleukins
(separate?)

A

-Lymphokines— cytokines produced by activated lymphocytes
-Interleukins— cytokines produced by leukocytes that act on other leukocytes

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5
Q

Describe the role of cytokines in innate immunity

A

-mediate early inflammatory reactions to microbial products
-stimulate adaptive immune response

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6
Q

Cytokines in adaptive immunity

A

-stimulate proliferation/ differentiation of Ag-stimulated lymphocytes
-activate specialized effector cells (e.g macrophages)

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7
Q

What actions do the different cytokines share?

A

They differ in molecular structure but share the following
-secrete cytokines in rapid bursts (keep? in response to cellular activation)
-bind to specific receptors on target cells
-regulate receptor expression in T/B cells, for positive amplification or negative feedback
-excite the same functional effects w/ multiple cytokine (redundancy)
-act close to site of synthesis/ same cell or (different) neighboring cell
-influence the synthesis & actions of other cytokines

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8
Q

What’s a Cytokine storm

A

-Severe immune reaction characterized by
the rapid release of a high concentration
of cytokines into peripheral blood
circulation
-biological concepts not completely understood
-associated w/ covid-19
-termed in 2005 w/ h1n1 bird flu
-important factor— the kinetics of cytokines & chemokine gene expression

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9
Q

What chemokines make the cytokine storm? Think broad categories. Not asking for specifics like IL-1 or TNF-alpha

A

-ILs, CSFs, TNFs, IFNs, chemokines
-severe damage can occur b/c body attacks own cells/tissues rather than fighting virus (acute lung injury is common)
-SARS chemokines => strong pro-inflammatory response => pulmonary fibrosis

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10
Q

Interleukins (ILs)

A

-cytokines produced by leukocytes that affect the inflammatory process thru increase in soluble factors (or cells)
-modulate inflammation (IL-1)
-Modulate immunity by regulating growth, mobility, & differentiation of lymphoid cells
-many different individual families/superfamilies of ILs have been identified w/ overlapping functions

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11
Q

Interferons (IFNs)

A

-cytokines produced by T lymphocytes & other cells that inhibit viral synthesis or act as immunes suppressors
-natural defensive responses to foreign components (microbes, tumors, Ags)

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12
Q

Type I IFNs

A

-mediate in early innate immune response to viral infections
-consist of IFN-α and IFN-β
^structurally different; bind to same cell surface receptor; similar biological functions

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13
Q

IFN-γ

A

-Principal macrophage-activating cytokine
-critical for innate immunity & specific cell-mediated immunity
-Stimulates expression of MHC class I and MHC II
-costimulates APCs
-Promotes the differentiation of naïve CD4+ T cells to the TH1 subset
-Inhibits the proliferation of TH2 cells

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14
Q

Tumor necrosis factor (TNF)

A
  • Principal physiologic functions is to stimulate the recruitment of neutrophils & monocytes to sites of infection (to eradicate microbes)
  • principal mediator of acute inflammatory response to gram negative bacteria (other microbes)
  • responsible for many systemic complications of severe infections
  • TNF receptor family stimulate gene transcription or induces apoptosis in a variety of cells
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15
Q

Stem cell factor (c-kit ligand)

A

-Cytokine interacts w/ tyrosine kinase membrane receptor (the protein product of the cellular oncogene c-kit)
-Acts on immature stem cells
-Needed to make bone marrow stem cells responsive to other CSFs (Does not cause colony formation itself)
-May play role in sustaining, viability & proliferative capacity of immature T cells in the thymus & mast cells in mucosal tissues

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16
Q

Colony stimulating factors (CSF)

A

-Variety of CSFs (like G-CSF and GM-CSF) are made by T cells -Provide a link between lymphoid and hematopoietic systems
-G-CSF and GM-CSF regulate the production of granulocytes and monocytes—allows T cell system to promote inflammatory response
-necessary for survival, proliferation, & differentiation in precursor cells of the immune system
-Increases circulating leukocytes in patients w/ AIDS, chemo patients, bone marrow transplants (important in treatment of disease)

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17
Q

Transforming growth factors (TGFs)

A

-products of virally transformed cells
-induce phenotypic transformation in nonneoplastic cells

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18
Q

TGF-β

A

-group of 5 cytokines released by cells (Macrophages & platelets)
-potent inhibitor of IL-1-induced T cell proliferation/ differentiation
-inhibits proliferation/activation of lymphocytes (T-cell p/d) & leukocytes (activation of macrophages)

19
Q

Chemokines

A

Large family of structurally homologous
cytokines that:
-Move leukocyte from the blood to site of infection
-Regulate/maintain migration of PMNs & mononuclear (immune cells) to lymphoid organs/ specialized cells

3 families Largest, second, third families

other functions:
-increase the affinity of leukocyte integrins to their endothelial ligands
-regulate traffic of lymphocytes (& other leukocytes) thru peripheral lymphoid tissues

20
Q

CC chemokine

A

Part of large family - attract mononuclear cells to sites of chronic inflammation

21
Q

CXC chemokine

A

Part of second family - attracts PMNs to acute inflammation; activates monocytes; direct WBC to vascular lesions

22
Q

CXC3 chemokine

A

Part of third family - forms a cell adhesion receptor capable of arresting cells under physiologic flow conditions (WBC slowing down & crossing blood vessel)

23
Q

what are Acute phase proteins / reactants?
(APPs)

what triggers them?

A

-a group of glycoproteins associated w/ acute phase response
-various protein rise to various rate/ lvls in response to injury
-increased synthesis starts shortly after trauma (initiated/sustained by pro-inflamm-cytokines)
- >20 APPs have role in inflammation

24
Q

clinically useful acute phase proteins (APPs)

A

-CRP binds to membranes of microbes & activates complement
-Inflammatory mediators C3/C4 of complement
-fibrinogen
-transport protein => haptoglobin
-inhibitors => α1- antitrypsin
-α1-acid glycoprotein

25
Q

synthesis and catabolism of acute phase proteins (APPs)

A

-acute phase proteins have different kinetics & various degrees of increase
-rate of change & peak concentrations vary w/ component & clinical situation
—acute inflammation: CRP & α1-antichymotrypsin increase w/ 12hrs
—C3, C4 & ceruloplasmin don’t rise for several days
-Acute phase proteins don’t always change in parallel

Increase
-tissue injury/ damage rapidly produces APP
-strenuous exercise triggers inflammation response similar to sepsis
-indices; Leukocytosis, release of inflammtory mediators & acute phase reactants, priming of WBCs, production of free radicals, complement activation, coagulation & fibrinolytic cascades

Decrease
-Negative acute phase proteins (fibrinogen /DIC)
—most have half-life of 2-4 days, CRP 5-7hrs (CRP falls more rapidly back to normal)

26
Q

C-reactive protein (CRP)

A

-used for monitoring infections, autoimmune disorders, healing after heart attack
-lvls of CRP are parallel with inflammatory course
-lvls rise with tissue injury or surgery (CRP peak at 2 days post surgery. Back to normal in 7-10 days —uncomplicated Sx)
-fastest/most sensitive indicator of inflammation
-increase faster w/ ESR
-CRP can signal infection hrs before culture (useful when WBCs counts don’t shoot up)

27
Q

What diseases can CRPs be elevated in?

A

-meningitis in neonates
-Myocardial infractions (MIs)
-burns complicated by infections
-malignant tumors
-Serious post-op infections
-infections in immunosuppressed patients
-septicemia
-Rheumatic diseases

28
Q

True or False
CRP can help differentiate b/w bacterial & viral infections

A

TRUE - CRPs will be extremely high in bacterial infections compared to viral infections

29
Q

True or False
CRP can be used as a definitive diagnostic tool

A

FALSE - CRP lack specificity

30
Q

True or False
CRP can be used in serial measurements

A

TRUE - can monitor; effect of treatment, post-op complications, or recurrent infections

31
Q

True or False
CRP can be used as a reliable indicator for SLE, ulcerative colitis, & dermatomyositis

A

TRUE

32
Q

True or False
CRP can used to evaluate risk of cardiovascular disease

A

TRUE - used with low density lipoprotein (LDL) to evaluate cardio disease

33
Q

True or False
Procalcitonin (PCT) is NOT a good marker for sepsis

A

False - PCT has greater specificity than other proinflammatory markers

34
Q

True or False
Procalcitonin (PCT) can be used to diagnose bacterial infections

A

TRUE

35
Q

True or False
α1-Antitrypsin decreases with acute inflammatory reactions

A

False - it increases with acute inflammatory reactions

36
Q

True or False
α1-Antitrypsin decreases with generalized vasculitis

A

TRUE

37
Q

True or False
Ceruloplasmin is measured as serum copper

A

TRUE

38
Q

True or False
Ceruloplasmin is NOT used for Hodgkin disease

A

FALSE - it can indicate relapse

39
Q

True or False
C3, C4 components decrease with immune complex diseases & gram-negative bacteremia

A

True - components decrease with complement activation because they get used up

40
Q

True or False
C3, C4 components are slightly elevated with acute inflammation

A

True

41
Q

True or False
Inflammation does not follow acute tissue damage

A

False - Damage->inflammation

42
Q

Lab tests for early acute inflammation

A

-total WBC count (segs/bands/ neutrophils)
-Acute-phase proteins
-ESR (erythrocyte sedimentation rate)
-CRPs

43
Q

Erythrocyte sedimentation rate (ESR)

A

-most common ordered lab test
-non-specific indicator of disease
-increase in acute & chronic inflammation, malignancies

44
Q

Diagnostic categories for APP include

A

-bacterial causes
-non-bacterial causes: trauma, chronic inflammation, viral disease