the basics of immunology presentation (updated)

8/2/2019 The Basics of Immunology Presentation (Updated)

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Aya Musbahi and Sidrah Jabbar


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Components of the immune systemLymphoid organs or tissues Primary lymphoid organs (bone marrow,

thymus)

Secondary lymphoid organs (spleen, lymphnodes, other peripheral lymphoid tissues e.g.

Peyers patches, MALT, SALT)


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The major elements of the innate and adaptive immunesystemsAdaptive immune systemInnate immune systemCharacter/

element

* Resistanceimproved byrepeated infection

* acts as the second line of

defense.

* Resistancenot improved byrepeatedinfection

* acts as the first line of defense against

infection.

Action

Antibody, Lymphocyte

derived cytokines

Lysozyme, complement, acute phase

proteins e.g. CRP, Macrophage-derivedcytokines, e.g.-, - and -interferons,tumor necrosis factor

Soluble

factors ormediators

lymphocytesPhagocytes (neutrophil polymorphs,

monocytes and macrophages)

Natural killer (NK) cells

Cells

Cutaneous and mucous

immune systems, antibody in

mucosal secretions

Skin, mucous membranesPhysio-

chemical

barriers

SpecificNon specificSpecificity


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Its defence mechanisms are:

i- Always present (prior to exposure to infectiousmicrobes)

ii- Ready to recognize and eliminate microbes

iii- Defense mechanisms include physicalbarriers,

phagocytic cells, eosinophils in the blood andtissues,

natural killer cells and various blood-bornemolecules.

iv- This system is considered the first line ofdefense against infections.


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Anatomical

1. Mechanical

2. Chemical

3. Biological Humoral

1. Complement

Cellular

1. Neutrophils

2. Macrophages

3. Phagocytosis

4. NK cells


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Anatomical1. Mechanical

2. Chemical

3. Biological

Humoral1. Complement

Cellular

1. Neutrophils

2. Macrophages3. Phagocytosis4. NK cells


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Skin- squamous epithelium. Itis both a PHYSICAL barrier and

desquamationMucous membranes e.g.peristalsis in GI tract,

mucociliary escalator in therespiratory tract


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Sweat Sebaceous glands in the skin, associated with the

hair follicles.

Produce sebum (oily secretion)= consist of lactic

acid and fatty acids, PH 3-5, that inhibits growthof microorganisms.

Tears- lysozyme

HCl- stomach acid

Saliva

Defensins

Surfactant


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2. Chemical

3. Biological


Cellular

1. Neutrophils



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Normal flora competes with pathogenic florafor nutrients and colonisation e.g. Straphaureus, Strep. epidermidis. Etc.


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2. Chemical

3. Biological


Cellular

1. Neutrophils



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Complement can be tricky to understand Everybody panics about complement, but

theres no need to!

Unless you are studying immunology indepth, there is no need to know the intricatedetails of all the pathways.

The handouts explains the details of

complement. The next slide is all you need to know for

complement.


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Complement is a cascade system of many proteins that hasmany roles including:

1. Opsonisation (enhances phagocytosis)

2. Clearance of immune complexes

3. Clearance of apoptotic cells4. Regulation of antibody responses

It has 3 pathways- called the Classical, Lectin andAlternative Pathway.

Ultimately, all the pathways lead to the formation of a

membrane attack complex (MAC) which punches a hole inthe pathogen cell wall, causing lysis.

In addition to MAC, complement causes release of by-products which can act as opsonins and help clear antigen-antibody complexes.


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In the handout Ive described the threepathways using the analogy of recipes to helpyou learn!

Classical Pathway recipe- doing it the oldfashioned way

Alternative Pathway recipe- the cop out

Lectin Pathway- exotic recipe!

Look at the notes to understand more aboutthe intricate details of the complementsystem!


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Ingredients:C1 complex- which has three bits stuck onto

each other- q, r, s

C2

C3

C4

A good bacterial/pathogen surface with bound

antibodies for the cooking to take place on.


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1. Add some C1 complex into the hot pan (bacterial cellwall). This will cause the complex to become

activated.2. Then throw in some C4 with the C1. The C1 will

cleave the C4 into C4a, C4b. Remove the C4a fromthe pan and discard. Notice that the C4b will bind tothe wall.

3. Chuck in some C2 now. C1 will also cleave C2 intoC2a and C2b. Remove the C2b from the mixture anddiscard. Notice that C2a will bind to the C4b.

4. You have now made C3 convertase, an enzyme!However, we're not done cooking just yet. Add insome C3 to complete the recipe and add in some

extra flavour. C3 will split into C3a and C3b. Removethe C3a from the mixture and discard. C3b will jointo C1, C2a and the C4b.

5. You have now successfully made C5 convertase!


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For advanced chefs! To make this dish into amichelin star masterpiece follow the recipefor Lytic Attack Pathway! Note! Don't waste the C2b and the C3a andC4a, these can be used to make opsonins,chemoattractants and prokinin. If you find

you've put in too much C1 into the recipe,don't panic! C1INH can be added to inhibitC1.


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Ingredients: C3

Factor B

a good bacterial/pathogen surface withbound antibodies for the cooking to takeplace on

Factor P- just to stabilise the mixture and for

seasoning


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Chuck some C3 into the pan with water. TheC3 will form C3a and C3b. Add in some factorB which binds the C3b. Add in some more C3,which will cleave into C3b and a. The

C3bBC3b is now C5 covertase! You have now successfully made C5

convertase!

Add Factor P to taste!

For advanced chefs! To make this dish into amichelin star masterpiece follow the recipe forLytic Attack Pathway!


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Ingredients: MBL-mannose binding lectin MASP1 MASP2 C4 C2 a good bacterial/pathogen surface with bound

antibodies for the cooking to take place on, makesure the pan is coated with mannose.

(most bacteria has mannose which is a sugar onthe surface)


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Add in some MBL, ensure this sticks to the mannose on thesurface. Add in some MASP1 and MASP2. Ensure they stick on to the MBL.

This now acts just like C1 of the classical pathway. Add in C4 and watch the MASP1/2/MBL complex cleave it into

C4b which sticks to the pan and C4a which you can discard fromthe pan. Add in C2 and watch it be cleaved into C2a and C2b(which you can discard). C2a sticks to C4b.

Add in C3 which gets cleaved into C3a (discard) and C3b whichcan bind to C4b and C2a. This is now C5 convertase!

You have now successfully made C5 convertase!

For advanced chefs! To make this dish into a michelin starmasterpiece follow the recipe for Lytic Attack Pathway!Note! Don't waste the C2b and the C3a and C4a, these can be usedto make opsonins, chemoattractants and prokinin.


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Ingredients: C5, C6, C7, C8, C9

a good bacterial/pathogen surface with boundantibodies for the cooking to take place on,

METHOD: Using the C5 convertase that you made with any

of the 3 above recipes, add in some C5. Watch itbeing cleaved into C5a and C5b. Discard the C5a.Use the C5b to bind to the pan. Add in C6, C7,

C8 and lots and lots of C9. Assemble themixture to form a transmembrane protein porei.e. MAC.


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Complement: function of C3a versus C3bC3a: Activates Acute

[inflammation].C3b:Bonds Bacteria [tomacrophages--easier digestion].

If wish to know more than just C3:C3a,C4a, C5aactivate acute.C3b, C4b bind bacteria.


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C- Cascade O- Opsonisation e.g. C3a, C2b

M- MAC

P- Phagocytosis

L- Lysis of pathogens results

E- Enzymes cleave components to form the cascade

M- Mannose binding lectin, alternative and classicalpathways

E- Everything is regulated tightly e.g. DAF, factor B,factor P

N- Non specific to pathogen/No memory i.e. INNATE

T- Titration of immune complexes


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2. Chemical

3. Biological


Cellular

1. Neutrophils



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Phagocytes: Neutrophils and Monocytes/Macrophages Bone marrow deliver blood monocytes which when

traveled into tissues called macrophages(monocytes/macrophage series).

Macrophage in tissues include alveolar macrophages,

splenic and lymph nodes resident and recirculatingmacrophages. Resident macrophages are found in theconnective tissues and in every organ in the body.

Also bone marrow deliver directly phagocytic cells,e.g. brain microglial cells, liver kupffercells (line the

sinusoids along which blood flows), kidney mesangialphagocytic cells, synovial A cells (line the synovialcavity in joints).


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The two types of circulating phagocytes,neutrophils and monocytes when recruited to sitesof infection, they recognize and ingest microbesfor intracellular killing Neutrophils (also called thepolymorphonuclear leukocytes, PMNs) are

the most abundant leukocytes in the blood,numbering 4000 to 10,000 per mm3.

Monocytes are less abundant thanneutrophils, numbering 500 to 1000 per mm3of blood


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Never Let Monkeys Eat Bananas Neutrophils (most common)

Lymphocytes

Monocytes

Eosinophils

Basophils (least common)


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Characteristic Nucleus Cytoplasm has granules

Primary granules: contain lyzozyme,

defensins, MPO, elastase cationicproteins

Secondary granules: contain lysozyme,

NADPH oxidase, lactoferrin


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Macrophages are similar, but contain lessgranules and a kidney shaped nucleus.


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Phagocyte Response to Infection:

THE SOS Signals

These molecules send an SOS signal to the

phagocyte to alert them of an infection.These are:

1. N-formyl methionine containing peptides2. Clotting system peptides

3. Complement products4. Cytokines


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Phagocyte Response Once the phagocyte has been alerted, the

phagocyte responds by:1. Vascular adherence: it sticks to the endothelial

cells via adhesion molecules such as P selectin

and E-selectin.2. Diapedesis: phagocyte moves in between theendothelial cells

3. Chemotaxis: substances sent from the infectedtissue (chemoattractants) attract the phagocyte

into the tissue.4. Activation: the phagocyte becomes activated5. Phagocytosis and killing


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Attachment

Phagosome formation (pathogen contained inthe phagosome)

Granule/lysosome fusion

Phagolysosome formation


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NK cells are responsible for the non specifickilling of virus infected and malignant cells.

You dont need to know much more than this,however, the details of their activation and

function are in the handout.


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Imagine a small town (body) being attacked by forces from outside (pathogens). The firstline of defence for this town is the giant wall they have built around it. This immediately is abarrier for an any army attacking them. This huge wall represents the skin.

From the top of the wall, the defenders of the town can throw buckets of acid and boilingwater at the soldiers below them. This represents the HCl stomach acid and tears and salivathat contain antimicrobial substances used to destroy the pathogens and also bycomplement products.

At the same time, the inhabitants of this town are very clever, they employ soldiersmasquerading as enemy soldiers and use them to infiltrate the enemy and steal their gunsand armour from them. This represents the normal flora which competes with thepathogen for nutrients and colonisation.

The enemy is too strong and the battle continues ferociously. The inhabitants of the townare keen to keep the enemy soldiers outside and stop them infiltrating the wall. They usemore force. They decide to fire through panels in the wall, cannon shots at the enemy to

break up their ranks (phagocytes). Fighting continues and the enemy are closer and closer to the wall, eventually they manage

to break down the wooden door and infiltrate the town. What will the inhabitants do now?

Acquired Immunity!


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Adaptive ImmunityInnate Immunity

The myth


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What is the link betweenthe innate and adaptive

immunities?


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DENDRITIC CELL:Disguised in host tissue (but still have same function!)ECF ingestionNothing left to chance (ensures an immune response)Derived from bone marrowRegulates the immune responseInduces an immune response (makes it unique among antigen presentingcells)Transfers information from the ECF into the cellImmune tolerance (increases it)Co-ordinates the adaptive and innate immune systemsCaptures and processes antigen

Expresses lymphocyte costimulatory moleculesLong processes extend from cell (stellate shaped)Lives in lymphoid tissueSecretes cytokine to initiate immune response


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T-cells cant recognizenative antigen onlyprocessed fragments ofantigen

APCs pick up antigen,

process it and present iton MajorHistocompatibilityComplex (MHC) orHuman LeukocyteAntigen (HLA) proteins

MHC proteins werediscovered tragicallythrough failed tissuetransplantationoperations


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CD8

killer

T cell

CD4

helper

T cell

Intracellular pathogens

(i.e. Viruses)

Presents antigen to:

the basics of immunology presentation (updated)

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