Introduction to Immunology

Question 1

3 layers of the immune system:

Answer 1

• Physical barriers
• Innate immune system
• Adaptive immune system

Question 2

First line of defense? examples?

Answer 2

Physical and biochemical barriers = epithelial layers

E.g skin, and the linings of our gut and airway.

Question 3

Epithelial barriers to infection x 3?

Answer 3

Mechanical
Chemical
Microbiological

Question 4

Mechanical epithelial barriers to infection?

Answer 4

Epithelial cells joined together by tight gap junctions to prevent entry (skin, gut, lungs, eyes/nose/oral cavity).
Mechanical mechanisms sweep microbes away, such as tears or saliva flushing microbes into our gut or the cilia beating in our airway.
Preventing pathogens from crossing epithelial barrier and colonizing tissues to establish infection.

Question 5

Chemical epithelial barriers?

Answer 5

• Acidity and enzymes in the gut- low pH
• Anti microbial chemicals and enzymes that can degrade microbes.
• Mucus provides a barrier containing mucin glycoproteins preventing bacterial adhesion to epithelia and is removed by the beating of cilia.
• Saliva contributes to both the physical barrier by acting as a flushing agent and also the chemical barrier as it is a vehicle for the delivery of chemical defences such as lysozyme and antimicrobial peptides (Histatins, defensins, cathelcidin).

Question 6

Microbiological barrier of epithelial cells

Answer 6

The microbiological barrier is provided by our healthy commensal microflora, generating competition for space and nutrients.

Question 7

What is a lysozyme?

Answer 7

• Lysozyme is a glycosidase enzyme, it attacks the peptidoglycan component of the bacterial cell wall.

Question 8

What is Peptidoglycan? Action of lysozymes?

Answer 8

• Peptidoglycan is a polymer of two sugars N-acetylglucosamine and N-acetylmuramic acid and lysozyme cleaves the bonds linking these two sugars.
• Lysozyme is most effective against gram positive bacteria e.g. strep mutans, because they don’t have the outer lipid membrane to prevent access to the peptidoglycan.
• The action of lysozyme exposes the phospholipid bilayer of the bacterial cell membrane.

Question 9

How are anti-microbial peptides present in the oral cavity?

Answer 9

In the form of zymogens or inactive forms of the enzyme

Question 10

3 main classes of antimicrobial peptides?

Answer 10

The Defensins, Cathelicidins and Histatins.

Question 11

Defensins?

Answer 11

Amphipathic- has both hydrophilic and hydrophobic domains.

• Presence of both domains allows it to be inserted into the lipid bilayer.
• After insertion, can alter the arrangement to form pores = disrupts integrity + allows contents to escape/ enter, killing the bacteria.

Question 12

Cathelicidins

Answer 12

Cathelicidins are primarily released from neutrophils, they are also amphipathic and cause membrane disruption.

Question 13

Histatins- Produced where? Named after? Active against?

Answer 13

Histatins are produced by the parotid, sublingual, submandibular glands. They are named due to the fact that their polypeptide sequence is rich in histadine amino acids. Histatins provide important activity against fungal pathogens.

Question 14

Innate arm of immunity

Answer 14

• Response speed= mins/ hour, always present
• Recognition (determine self from non-self)= limited range, remain unchanged during response, genome encoded receptors
• Lasting protection/ memory=none

Question 15

Adapive arm of immunity:

Answer 15

Response speed= days/ weeks, usually silent response has to be raised.
Recognition (determine self from non-self)= vast range, receptor recognition improves during the response. Receptors not genome encoded.
Lasting protection/ memory= years

Question 16

Innate vs. adaptive ; Role and response speed.

Answer 16

Innate
- Provides initial defences, limiting pathogen proliferation and spread.
- Can control less virulent pathogens.
- Important role in inducing the adaptive immune response.
Adaptive response.
- More potent activity to control more virulent pathogens
- Takes time to raise population of cells specific for pathogen

Question 17

Innate vs. adaptive ; diversity of recognition
How do host cells detect microbes?
How does this relate to the innate and adaptive immunity?

Answer 17

Host cells with defensive functions will use receptor molecules expressed on their cell surfaces (or sometimes inside the cells) to detect microbes and damaged cells.

• Innate immune effector cells have a limited range of types of these receptors and they recognise structures that are shared by various classes of microbes.
• The adaptive immune system provides a massive array of receptors that can recognise unique structures that are not common to lots of types of microbes. As a new adaptive immune cell matures it will have it’s own unique receptor that will specifically recognise a unique foreign structure.

Question 17

Innate vs. adaptive ; diversity of recognition
How do host cells detect microbes?
How does this relate to the innate and adaptive immunity?

Answer 17

Host cells with defensive functions will use receptor molecules expressed on their cell surfaces (or sometimes inside the cells) to detect microbes and damaged cells.

• Innate immune effector cells have a limited range of types of these receptors and they recognise structures that are shared by various classes of microbes.
• The adaptive immune system provides a massive array of receptors that can recognise unique structures that are not common to lots of types of microbes. As a new adaptive immune cell matures it will have it’s own unique receptor that will specifically recognise a unique foreign structure.

Question 18

The innate vs. adaptive ; memory

Answer 18

• The innate immune system responds in essentially the same way to repeated encounters with a particular microbe.
• An adaptive response leaves behind long lived effector cells with the improved recognition of that particular pathogen. These memory cells can respond much more efficiently on subsequent occasions when we might encounter (be challenged) with the same pathogen.

Question 19

When did the adaptive and innate immune system evolve?

Answer 19

The adaptive system has evolved more recently than the innate immune system.
The innate immune system is ancient.
Many organisms that evolved prior to the formation of the adaptive immune system only have the innate immune system.

Question 20

The complement system functions and consists of?

Answer 20

Functions are

1) facilitates recognition of bacteria by phagocytes
2) can directly lyse bacteria
3) Can be quick and effective compared to de novo as the proteins are already circulating and just need to be activated.

Consists of 30 different types of plasma proteins and takes place as a zymogen activation cascade.

Question 21

Complement system part 1:

initial components

Answer 21

• Initial components act as recognition system, recognition activates them and in turn they activate multiple copies of the components of the next step. This is replicated over multiple steps and becomes therefore an amplifying cascade.
• Many of the molecules are proteases, meaning they can cleave proteins and activate downstream molecules in the chain.
• Results in the detection of small number of pathogens producing a rapid amplified response

Question 22

3 Pathways activating the complement system:

Answer 22

• Classical pathway
• Lectin Pathway
• Alternative pathway

Question 23

Complement system Classical pathway:

Answer 23

It is initiated when the C1 component binds either directly to the pathogen surface or binds to antibody that has already bound to pathogen surface. This binding activates the C1 molecule and triggers a cascade of reactions.
(Example of how the adaptive and innate arms of immunity act synergistically as antibody is a product of adaptive immunity.)

Question 24

Complement system Lectin Pathway:

Answer 24

The Lectin pathway is activated when a carbohydrate binding protein that circulates in our plasma called mannose-binding lectin (MBL) binds to mannose that is part of glycoproteins on the surface of microbes.

Question 25

Complement system Alternative Pathway

Answer 25

Low level of spontaneous activation of C3 that occurs. Activated C3 can bind to cells. If this C3 binds to a host cell there are inhibitory modules on the cells that deactivated this deposited activated C3. But microbes don’t have these inhibitory molecules meaning that this deposited C3 can build up. This is the alternative pathway of activation.

Question 26

Where do all the complement activation pathways lead?

Answer 26

All these activation pathways generate enzymes complexes which are C3 convertases meaning they will convert the precursor C3 molecules into 2 products C3a and C3b.

Question 27

Role of C3b

Answer 27

C3b initiates the late steps of complement activation, which can then result in 3 functional outcomes.

Question 28

3 functional outcomes of the complement system:

Answer 28

3 potential effector functions

• Opsonisation
• Anaphlatoxin production
• Formation of Membrane Attack Complex

Question 29

Formation of Membrane Attack Complex

Answer 29

• The generation of active C3b triggers a cascade that culminates in the formation of a multiprotein complex called the membrane attack complex (MAC).
• C6, C7 and C8 complement components insert into the membrane of the pathogen, this triggers to C9 to insert and polymerise in the membrane assembling into the MAC, a pore like structure which is a transmembrane channel causes lysis of thin-walled microbes.

Question 30

Anaphlatoxin production

Answer 30

Peptide by-products released during complement activation are the anaphlatoxins C3a and C5a which induce inflammation, they act as chemoattractants that recruit innate immune-system cells to the site of infection.

Question 31

Opsonisation

Answer 31

• C3b bound to a pathogen acts as an opsonin which is recognised by receptors on innate immune cells that then phagocytose (engulf) microbes in order to destroy them.
• The opsonin acts like a label, highlighting the microbe for destruction, so the complement-coated bacteria is recognised more easily by host innate immune cells that express complement receptor 1 (CR1). Binding to CR1 tethers the microbe to the cell and then send signals triggering the engulfing of the microbe.

Question 32

What are all cells of the blood derived from?

Answer 32

pluripotent haematopoietic stem cells.

- Pluripotent = gives rise to many cell types

Question 33

pluripotent haematopoietic stem cells give rise to:

Answer 33

Either a common lymphoid progenitor or common myeloid progenitor.

Question 34

A common lymphoid progenitor cell can give rise to:

Answer 34

• B cells (antibody producing),
• T cells (cell mediated immunity),
• NK cells (Natural killers),

Question 35

The common myeloid progenitor cell can give rise to:

Answer 35

• Granulocytes (granular cytoplasm also called
• Polymorphonuclear leukocytes due to irregular nuclei,)
• Mast cells
• Monocytes that mature into macrophages

Question 36

Roles of the myeloid and lymphoid lineages:

Answer 36

The myeloid lineage granulocyte groups are effector cell groups of the innate system. While the T cell lymphocytes and B cell lymphocytes of lymphoid origin make up the majority of the adaptive immune cells.
However Natural Killer lymphocytes (NK cells) are of lymphoid origin and are considered part of the innate system.
Dendritic cells are considered innate immune cells and although majority of dendritic cells are derived from the myeloid lineage but there is also a population of lymphoid derived DCs.