Overview of Host Defense Lecture Sep 30

Question 1

What are the two methods the body uses to distinguish self from non-self?

Answer 1

1. Evolution of recognition molecules to identify molecular patterns associated with parasites (the innate immunity with macrophages and complement)
2. Adaptive methods where cels of the immune system are educated to identify agents that do not belong in the body while ignoring tissues that belong in the body (adaptive immunity)

Question 2

Since there are only 20,000 protein-coding genes in the genome and billions of different parasitic threats tot he body, the ability of the body to create specific antibodies for all those things exceeds the coding capacity of the genome. THerefore, genes cannot encode all the antibodies that are necessary. So how does the body do it?

Answer 2

THe immune response is anticipatory in that it creates B cells that are capable of recognizing virtually every possible protein sequence and structure.

Question 3

What is a vaccine?

Answer 3

an exogenous agent that induces specific immunity following a challenge

Question 4

What is an antigen and how can an antigen differ from an immunogen?

Answer 4

An antigen is the exogenous agent (given during a vaccine)

An antigen will not ammount an immune response unless the body has an antibody for it. THis is what makes antigens different from immunogens - immunogens are antigens that induce immunity because they are recognized by the immune system

Question 5

What is the primary antibody response?

Why is there a lag time before it happens?

Answer 5

There is a lag time because the adaptive immune response cannot create antibodies against an antigen until the inflammatory (innate) response occurs and presents the antigen to the adaptive response.

The primary antibody response is the formation of IgM immunoglobulins, which will initiate complement action against the antigen and trigger the B cell to proliferate and develop into plasma cells to manufacture immense quantifies of immunoglobulin. THe immunoglobulins produced by the plasma cells will be IgG antibodies which are more specific to the antigen than the initial IgM.

Depending on where you are in the body, this could also be IgA and IgE

Question 6

What is the secondary antibody response?

Answer 6

After the primary infection, IgG immunoglobulins will persist in circulation that have specificity for the antigen..

If there is a second infection, the IgG present in the body will mount a bigger and faster reponse to knock out the new infection.

This is because the adaptive immune response will retain a memory of the previous infections - we’re not quite sure about how the memory develops since plasma cells and antibodies don’t live forever, but memory is what’s observed

Question 7

How can the levels of IgM and IgG antibodies help in determining timing of infection?

Answer 7

Someone who has high concentrations of IgM has been infected recenctly - within the past couple weeks

Someone who has high IgG has been infected a while ago and might be harbouring a latent infection

Question 8

What type of infections can withstand the adaptive immune response?

Answer 8

latent infections that hide within cells (the antibodies can’t get at them)

Question 9

How are innate and adaptive immunity different?

Answer 9

Innate immunity is genetically hardwired, adaptive immunities arises from genetic recombination.

The innate immunity has a rapid response and adaptive immunity has a lag time.

Innate immunity has a limited repertoire and adaptive immunity has an immense repertroie.

Question 10

What does innate immunity use to label non-self?

What does adaptive immunity use to label non-self?

Answer 10

innate = complement

adaptive = antibody

Question 11

Describe the negative selection process of the adaptive immunity?

Answer 11

The immune system is anticipatory meaning it will create naive T cells and B cells that are specific for virtually aything that they could ever encounter.

Negative selection has to occur because those T cell and B cells might be specific for a self protein (about 99.8% of them are!)

Negative selection occurs when the T cells and B cells are in the thymus and bone marrow respectively. If they interact with a nurse cell (an eithelial cell that displays basically EVERY protein motif that’ sin the body), it is automatically destroyed.

Question 12

What benefit comes from the anticipatory characteristic of adaptive immunity? What detriment?

Answer 12

It increases the repertoire of the adaptive immune response, but can lead to autoimmunity

Question 13

What is the benefit and detriment of the lag time in the adaptive immunity?

Answer 13

It allows for refinement of the response, but the infection will proceed and worsen while the “education” part is going on.

Question 14

B cells that express the antigen specific antibody theat the innate response wants to use will be stimulated to do what two things?

Answer 14

1. stimulated to perform somatic hypermutation (greatly enhances the affinity of the antibody, but can lead to recognition fo totally different antigens)
2. Class switching (changing from IgM production to IgG/IgA/IgE)

Question 15

A lymphochyte repsonse to an antigen must be triggered by signals from what?

Answer 15

the innate immune response (via antigen presentation on MHC class 2 on the dentridtes)

Question 16

With the development of the adaptive immune response, there are 4 general ways to get it: 2 are natrual and 2 are artificial. WHat are they?

Answer 16

NATURAL

• Passive: receiving antibodies through breast milk
• Active: developing one’s own antibodies through a primary infection

ARTIFICIAL

1. Passive: Injecting preformed antibodies to treat an infection
2. Active: Giving a vaccine that makes the body develop its own antibodies

Question 17

Which will confer memory? Passive or Active methods of developing an immune response?

Answer 17

Passive will NOT be permanent because the antibodies given through either breast milk or injection will eventually die.

Active immunity IS permament because the body has to learn to make its own antibodies and will then have the memory of that antigen

Question 18

WHy did an immune response have to develop when we became more complex species?

Answer 18

Multicellular organisms requires stringent control of resource useage to survive. THerefore, an immune response was necessary to remove non[cooperative cells (which are essentially parasites and nonself)

Question 19

Recognition requires specificity which can arise through affinity and/or avidity. what is the difference between the two?

Answer 19

Affinity is how strongly the receptor holds onto its target and is determined by how many places of interaction occur within the small binding region

Avidity arises from several interactions that happen over a larger area - think zipper. High binding strenth arises when sevel low affinity sites work in cooperation to form a strong itneraction

Question 20

What is an alert signal and why are they so useful for the immune response.

What is the alert signal from outside sources?

What ist he alert signal from inside sources?

Answer 20

Alert signals are characteristics of non-self materials that are ESSENTIAL for the material. Endotoxin is an example for gram negative bacteria - it needs endotoxin for its wall. Thse therefore make excellent targets for the immune system because they’re characteristics of non-self material that will never change.

The alert signal for exogenous material is a PAMP (pathogen associated molecular pattern).

THe alert signal for endogenous “non-self material” is a DAMP (damage associated molecular patterns) - for cancer cells or virus-infected cells

Question 21

what branch of the immune mechanism recognizes the PAMPs and DAMPs

what does recognition initiate?

Answer 21

PAMPs and DAMPs are recognized by the innate immune mechanism and initiate inflammation

Question 22

What are some examples of DAMPs?

Answer 22

It’s either a damage signal or a danger signal that is recognized by the innate immune system

Examples include heat shock proteins, ATP and DNA (if they’re in the ECM because they shouldn’t be), uric acid crystals (grout), heparin sulfate, hyaluonan fragments, hyaluronan fragments, and S100 molecules

Question 23

What are some examples of PAMPs?

Answer 23

THey are molecular moieties that are absolutely required for pathogen/invader survival:

endotoxin

flaggelin

dsRNA

CpG DNA (bacterial DNA)

Peptidoglycan

Terminal mannose (that has been uncapped)

Question 24

What receptors will recognize PAMPs and DAMPs?

Where are they found?

Answer 24

Toll like Receptors (TLR)

There are 9 varieties so far

Three are found in the endosomal comparmtents of phagocytic cells like neutrophils, macrophages, dendritic cells and B-cells

Six are expressed on the cell surface as dimers (homodimers or heterodimers)

Question 25

What do the TLRs use to initiat “danger” signals when they bind PAMPs or DAMPs?

Answer 25

They use transcription factors like NF-kB to promote inflammation by releasing cytokines

and

IRF3 to promote viral response through interferon release and increase MHC class 1 expression

Interferons basically tell other cells that they need to present what they have inside on MHC 1 molecules on the surface. If they dont present an MHC 1, the immune cells will assume that there is an infection blocking MHC1 expression and kill the cell

Question 26

What is recognized by the TLR when endotoxin is present?

Answer 26

It’s actually not the endotoxin itself.

Specifically, the lipid A of the LPS endotoxin will bind to an LPS binding protein in the serum.

The TLR recognizes the bound LPS binding protein.

Question 27

What are the three immunological zones?

Answer 27

mucosal

interstitial

skin

Question 28

What types of infection will occur in the skin immunological zone?

What will be the response?

Answer 28

parasites, protozoans, helminthes, fungal, viral

Langerhand’s cells, mast cells, neutrophils, macrophages, eosinophils

Question 29

What types of infections will you have in the interstitial immunological zone?

What cells will be involved in the response?

Answer 29

virus and bacteria

cells will include macrophages, effector lymphocytes (Helper T cells, cytotoxic T cells, and NK cells)

(note that naive T cells will never be in the interstitial zone - they stay in circulation until they differentiate into effectors)

Question 30

What infections will you find in the mucosal immunological zone?

What percentage of the immune response is active here?

WHat cells will be involved in the response?

Answer 30

Bacterial and viral.

This zone requires constant vigilance and uses 70-80% of the immune system activity

Cells include Macrophages, Dendritic cells, gamma delta T cells (they have limite repertoire and are specific for bacterial carbohydrate groupins only, but they’re always active and don’t require a lag period), and B1 cells

Question 31

What is the epithelium’s line of defense?

What is the mesoderm’s line of defense?

What is the endoderm line of defense?

Answer 31

Epithelium: barrier to infection

mesoderm: cellular responses, flushing, lyses, trapping

Endoderm: cellular responses and flushing