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Immuno Exam 1 > Lecture 6 > Flashcards

Lecture 6 Flashcards

1
Q

What are the Clinical symptoms of inflammation?

A

Redness
Dilatation of small blood vessels and increased blood flow

Heat
Dilatation of small blood vessels and increased blood flow

Swelling
Accumulation of fluid and inflammatory cells in the extravascular space

Pain
Stretching and distortion of tissues by inflammatory fluid

Release of pain-inducing inflammatory mediators

Loss of function
Swelling and pain inhibit movement

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2
Q

cytokines

A

A diverse collection of soluble proteins and peptides that modulate the behaviour of cells at nanomolar to picomolar concentrations

Act both locally and systemically

Have highly pleiotropic effects

The activities of cytokines and chemokines often overlap with other cytokines and chemokines

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3
Q

In the innate immune response the principal sources of cytokines are….

(slide 7)

A

macrophages, mast cells, and dendritic cells that have been activated by the recognition of microbes.

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4
Q

What are some thing that an activated macrophage will secrete?

A 
IL-1
IL-6
TNF-alpha
IL-8 (CXCL8)
IL-12
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5
Q

What pathway is up-regulated in an activated macrophage?

A

NF-kB pathway is activated leading to the production of these proinflammatory cytokines.

NF-kappa B
increase the amount of transcription of genere for :

IL-1
IL-6
TNF-alpha
IL-8 (CXCL8)
IL-12
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6
Q

The Major Proinflammatory Cytokines:

A

TNF, IL-1, and IL-6

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7
Q

The local effects of proinflammatory cytokines act to activate the local endothelium and subsequent recruitment of leukocytes. What are the steps?

A

Vasodilation- marginalization of leukocytes

Activation of endothelium- adhesion molecules make it sticky

Increased endothelial permeability- give space for leukocytes to traverse (diapedesis or extravasation)

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8
Q

Systemic Effects of Inflammatory Cytokines take place in which tissues?

A

LIver

Bone Marrow/Endothelium

Hypothalmus

Fat,Muscle

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9
Q

Pyrogens

A

IL-1 (MAIN!!)
IL-6
TNF-alpha

Pathogens (or pathogen products) that induce fever generally do so through inducing the production of these cytokines

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10
Q

endogenous pyrogens

A

Cytokines are called endogenous pyrogens because they originate inside of the body.

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11
Q

exogenous pyrogens

A

The bacterial products that induce fever are called exogenous pyrogens, because they originate outside of the body

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12
Q

wHY RAISE TEMP?

A

An elevated temperature slows pathogen growth. In addition, at higher temps. the body is thought to more actively sequester iron, which also limits bacterial growth.

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13
Q

iRON SEQUESTRATION (slide 11)

A

elevating temps in body will cause the body to store away iron. this is good bc it limits bacterial growth

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14
Q

IL-6 main role =

A

induce the production of Acute Phase proteins

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15
Q

Where are Acute Phase proteins secreted from?

A

LIver in response to inflammatroy cytokines

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16
Q

What are some key Acute Phase proteins?

A

Mannose-binding lectin (MBL): recognizes microbial carbohydrates, and can coat microbes for phagocytosis or activate the lectin complement pathway.

C-reactive protein: binds to phosphorylcholine on microbes and coats the microbes for phagocytosis by macrophages, which express a receptor for CRP. CRP can also trigger the classical complement pathway.

C-reactive protein= can check the level of this in the blood/serum to see if you are having inflame response

Acts as an Opsonin!!

17
Q

Why are Excessive amounts of inflammatory cytokines released systemically extremely dangerous?

(slide 13)

A

Septic Shock:
The early clinical and
pathologic manifestations of septic shock are caused by very high levels of TNFa produced in response to a systemic bacterial infection.

Gram (-) bacteria will cause Sepsis

dec blood volume, collapse of vessels, organ failure

18
Q

a major chemotactic factor for neutrophils

A

IL-8

IL-8 will signal the leukocytes to change the formation of their integrins and it will change from a low affinitiy state and then go to a HIGH AFFINITY CELLS- and this makes it go from rolling to firm adhesion, and then they will be able to go thru the endothelium (transmigration thru the tissue)

19
Q

IL-12

slide 17

A

made by activated- macrophages and dendritic cells

So important cytokine bc is a link between the innate and the adaptive immunity

Activates NK cells–which make Interferon gamma (IFN-GAMMA) which causes the macrophages hulk out

induces CD4 T cells to differentiate into Th1 cells

20
Q

The major innate cytokines produced in response to viral infection are ….

A

Type I Interferons (IFN)

21
Q

Type I Interferons (IFN) is made of…..

A

Interferon-alpha (IFN-α)

Interferon-beta (IFN-β)

22
Q

What is the function of IFN?

A

Secreted by virally infected cells and various leukocytes

Act to protect surrounding cells from becoming infected

23
Q

IFN-gamma

A

this is secreted by the NK cells once marcophage secrete IL-12

24
Q

what is the role of RIG-1 in a viral infection

slide 19

A

Important in the cytoplasm-

Host cells are alerted to the presence of a viral infection by the recognition of viral PAMPs (here dsRNA), by pattern recognition receptors, such as RIG-1.

Activate IRF

stimulate the production of type I interferons IFN-α and IFN-β

25
Q

Biologic actions of type I interferons

A

Type I interferons (IFN-α, IFN-β) are produced by virus-infected cells in response to intracellular TLR signaling and other sensors of viral RNA.

  • Type I interferons bind to receptors on neighboring uninfected cells and activate JAK-STAT signaling pathways, which induce expression of genes whose products interfere with viral replication. Type I interferons also bind to receptors on infected cells and induce expression of genes whose products enhance the cell’s susceptibility to CTL-mediated killing. PKR, double stranded RNA-activated protein kinase.
26
Q

Why are Type 1 IFN so ciritcal?

A

Increase MHC class I expression and antigen presentation by all cells

Activate dendritic cells and macrophages

Increase the cytotoxicity of NK cells and cytotoxic T cells

Induce chemokines to recruit more leukocytes

27
Q

Pneumococci

A

Resistance to phagocytosis

Capsular polysaccharide inhibits phagocytosis

28
Q

Staphylococci

A

Resistance to ROS

Production of catalase, breaks down ROS

29
Q

Neisseria meningitidis, Streptococci

(slide 25)

IMP

A

Resistance to alternative complement pathway

Expression of sialic acid inhibits C3 and C5 convertases; M protein blocks C3 function.

30
Q

Pseudomonas

A

Resistance to antimicrobial peptides

Synthesis of modified LPS that resists action of antimicrobial peptides

Immuno Exam 1 (10 decks)

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