immune system ppt1

8/3/2019 Immune System Ppt1

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Extra credit opportunity see Bi1 website


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The Immune System

A complex system that is responsible for

distinguishing us from everything foreign to us,and for protecting us against infections andforeign substances. The immune system works toseek and kill invaders.

www.als.net/als101/glossary.asp


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Which, in this list, is not a part of the immunesystem?

1) Mucous

2) Skin

3) Thymus

4) All of above are parts of the immune system.5) None of the above are parts of the immune system.

Clicker question


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Clicker question

Which of the following disordersresult from immune systemmalfunctions?

1) Allergies2) Diabetes3) Arthritis

4) Multiple sclerosis5) All of the above6) None of the above


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Overview of your immune system

First line of defense: Physical barriers that viruses, bacteria mustcross

skin covers ~2 m2 Mucous membranes that line digestive, respiratory, reproductive tracts

cover ~400 m2

Second line of defense: Innate immune system (germline-encodedreceptors -- no adaptation to specific pathogens) Macrophages (Greek for big eater), neutrophils, natural killer (NK) cells Cytokines -- hormone-like proteins that mediate inflammation,

Complement proteins

Third line of defense (vertebrates only): Adaptive immune system

(adapts to defend against specific pathogens using variablereceptors) B cells make antibodies that vary -- can make an antibody specific for

any new antigen T cells mediate cellular responses using variable receptors (T cell

receptors; TCRs)


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Immune cells and other blood cells made in bone marrow --all are descendents of self-renewing stem cells

p. 4 How the Immune System Works by Lauren Sompayrac

Make variable antibodies

Membrane-bound variable T cell receptors

Kill cells that are missing self proteins

Phagocyte

Phagocyte

Note these are adultstem cells, NOT

embryonic stem cells.


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Innate Immune System

Second line of defense -- worksagainst invaders that breach physical

barriers of skin and mucosa

Innate because shared by all

animals (vertebrates andinvertebrates)


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Figure 2-1Three phases of an initial immune response

First two phases rely on recognition by germline-encoded receptors of theinnate immune system.Third phase uses variable antigen-specific receptors produced as a resultof gene segment rearrangements (not germline encoded).


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The innate immune system responds morequickly than adaptive immune system.Why is a quick response important?

Starting with one bacterium that doubles every

thirty minutes --> 100 x 1012 bacteria in one day 100 x 1012 bacteria equivalent to ~100 liters of a

dense culture Total volume of blood in human ~5 liters

VERY important to check a bacterial infectionquickly!


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Clicker question

Fruit flies can be infected by _____.They use ______ immune responsesto clear infections.

1) Bacteria and viruses; innate and adaptive2) Bacteria; innate3) Viruses; innate and adaptive

4) Viruses; adaptive5) Bacteria and viruses; innate6) Bacteria and viruses; adaptive


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Three components of the innateimmune system

Phagocytes (cells) (e.g., macrophages) Complement proteins Natural killer (NK) cells

Innate immune receptors recognize features common to manypathogens. Receptors are employed by all cells of a given celltype. Response does not lead to immunological memory.

Adaptive immune receptors are antigen specific. Antigenreceptors of adaptive immune system are clonallydistributed on individual lymphocytes. Response can lead toimmunological memory.


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Macrophages can engulf and digest bacteria

p. 4 How the Immune System Works by Lauren Sompayrac

Macrophageabout to eata bacterium

http://www.biochemweb.org/neutrophil.shtml


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Clicker question

Which component of bacteria servesas a very potent stimulant of theinnate immune system?

1) Ribosomes2) Proteins

3) Carbohydrates4) DNA5) RNA6) Plasmids


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Clicker question

Carbohydrates on viruses stronglyactivate the innate immune system.

1) True2) False


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Complement system Ancient system (found in invertebrates such as

sea urchins) ~20 different proteins that work together to

destroy invaders and recruit immune cells Activated three different ways

Classical pathway: by antibodies bound to pathogen(vertebrates only) Alternative pathway: by bacterial surfaces Lectin activation pathway: by binding of mannose-binding

lectin (MBL) to yeast, bacteria, parasites or viruses (e.g.,HIV)

Activation of complement system is tightlyregulated because end results can be dangerous


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Figure 2-18The three pathways of complement activation converge

Combination of adaptive and

innate immune responses Innate immunity Innate immunity


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Figure 2-11

Binding of mannose-bindinglectin, a plasma protein,

initiates lectin pathway ofcomplement activation.

MBL discriminates selfcarbohydrates fromnon-self carbohydrates byrecognition of a particularpattern of sugar residues


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Figure 2-35 part 3 of 3One of the end results of complement activation -- themembrane attack complex kills a cellElectron micrographs of ~100 diameter membrane attack complex channels


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Laboratory uses of complement:isolate one population of cells by

killing off another populationExample:

Have mixture CD4 T-cells and CD8 T-cells

Want only CD8 T-cells

Add anti-CD4 antibody to mixture of T cells. It binds.Now add complement, and CD4 T-cells will be killed,

leaving you with CD8 T-cells only.


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Clicker questionIf you sequenced the receptors and proteins

of the innate immune system from identicaltwins, they would be identical, regardless ofdifferences in immunological experience.

If you sequenced the receptors and proteinsof the adaptive immune system from identicaltwins, they would be identical, regardless ofdifferences in immunological experience.

1) True, True2) False, False3) True, False

4) False, True


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Clicker questionWhich type of pathogen is easier for the innateimmune system to deal with: bacteria or viruses?

1) Bacteria2) Viruses


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So far, weve talked only about activerecognition of features of pathogens

But pathogens have also developed ways to remove some of thecells critical proteins, often so that they can escape detectionby the immune system.

For example, in the adaptive immune system, T lymphocytes(T cells) recognize viral fragments (peptides) bound to MHCproteins.

Its hard for a virus to hide out in a cell if the cell surface MHC

proteins contain viral fragments that can be recognized by Tcells.

Whats a virus to do?

Get rid of the host MHC proteins!


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For every strategy a virus comes up with,the immune system (usually) has an answer

Natural killer cells recognize cells thatdo not express adequate levels of MHC

proteins on their surface.

They respond to missing self.


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How could you design a system that respondsto the absence of a critical surface protein?A trick used by many viruses is to down-regulate MHC proteins -- MHC proteins normally

alert the immune system to the presence of a virus.

1) Create a receptor that activates a killer cell if itcant find its target protein.

2) Create a killer cell with two receptors: oneinhibitory (binds to MHC protein) and oneactivating. Inhibitory signal overrides activatingsignal, so killer cell does nothing unless it finds acell with no MHC proteins.

Clicker question

N t l kill (NK) ll


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Natural killer (NK) cells

Can kill tumor cells, virus-infected cells, bacteria, parasites,

fungi in tissues

Identify targets based on missing self Two types of NK receptors: inhibitory and activating If inhibitory receptor recognizes a self protein (a class I MHC

molecule) on a target cell, the NK cell is turned OFF even if activatingreceptor binds a ligand on the same target cell

If activating receptor binds a ligand, but inhibitory receptor does not(target cell has down-regulated class I MHC proteins), NK cells kill

Many virally-infected cells and tumor cells down-regulate expression ofclass I MHC molecules (NK cells important for preventing cancers)


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Extra slides

Not discussed in lecture


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Figure 2-19

Overview f c mplement activati n


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Overview of complement activation C3 proteins cleaved into C3a and C3b. C3b reacts with amino (NH3) or

hydroxyl (OH) groups oftenfound on surfaces of invaders.

Activated C3b neutralized by H2Oif doesnt react with NH3 or OH groupwithin ~60 sec. (Important for regulation!)

Complement protein B binds tocell surface-bound C3b, thenprotein D cleaves B to yield C3bBb.

C3bBb (a convertase) cleaves otherC3 proteins to C3b to increase number ofC3b molecules bound to the invader.

C3bBb also cleaves C5. C5b combineswith C6, C7, C8 and C9 to make amembrane attack complex (MAC).

C9 forms a channel that opens a holein invader membrane to lyse it. Many of the a fragments (e.g., C5a)

are peptide mediators of inflammation.


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The immune cells were talking about arecalled white blood cells.

This means they are in the ____.

How do they get to a site of infection?

N t hils l th bl d d mi t t sit s f i f ti


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Figure 2-44Inactive neutrophils are swept alongby blood at ~1000 m/sec. Activatedmacrophages produce alarmcytokines (IL-1 and TNF; interleukin-1 and tumor necrosis factor) thatturn on selectins (sugar-bindingproteins) on endothelial cells.Now neutrophils roll alongendothelium, making and breakingcontacts with endothelial cells onwalls of veins.

Upon activation by inflammatorysignals (e.g., complement proteinC5a -- more later), bindingproteins on the neutrophil(integrin) and on endothelial cells(ICAM) are induced, resulting intighter binding, arrested rolling,and squeezing of neutrophilthrough endothelium to the site ofinfection.

Neutrophils leave the blood and migrate to sites of infection

Neutr phils leave the bl d and mi rate t sites f infecti n


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Figure 2-44Watch The Inner Life of the Cell(link on Bi1 website)

Main points:If nothing is wrong, neutrophils travel

at high speed through the blood.If there is an infection somewhere,macrophages produce alarm moleculesthat cause proteins on the endothelialcells* to be expressed.

These new proteins bind weakly tosugars on the neutrophils, causing theneutrophils to slow down, but not stop(they roll along the endothelialsurface). By moving slowly, they have achance to find the infection site.When the neutrophil comes to a sitenear the infection, it stops becauseinflammatory signals at the infection

site induce proteins on it and thenearby endothelial cells that bindtightly to each other. The neutrophilnow squeezes through the endotheliumto get to the site of infection.*endothelial cells: cells lining blood vessels

Neutrophils leave the blood and migrate to sites of infection

Leukocyte rolling and migration through blood vessel walls


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Leukocyte rolling and migration through blood vessel walls

immune system ppt1

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