Infection and microbiology

Question 1

Where are the variable domains located on an antibody

Answer 1

On the N terminal end of the Ig chains.

Question 2

What is the role of N-glycans in antibody structure

Answer 2

Large molecule which holds immunoglobulins apart, exposing complement binding sites. Also provides rigidity depending on number of N-glycans present.

Question 3

How do Mature B cells switch to different Ig classes.

Answer 3

Somatic recombination of DNA, where DNA forms a loop and intervening DNA (dna not needed for new Ig class) is excised to create a gene which only codes for the required constant heavy chain.

Question 4

Definition of clonal selection

Answer 4

Following infection, individual clones are selected by antigen, the result is pathogen specific lymphocytes are selected from pools of B and T cells.

Question 5

Definition of clonal expansion

Answer 5

Clones from clonal selection undergo rapid mitosis and differentiation to form many B / T cells which are specific to the pathogen.

Question 6

what are the 3 main features of the Structure of viruses

Answer 6

Nucleic acid, Protein coat, Viral envolope

Question 7

What is the name of the nucleic acid + capsid in a virus

Answer 7

Nucleocapsid.

Question 8

What are VAPs on viruses and where are they found

Answer 8

Viral attatchment proteins, found on the envolope or capsid depending on whether or not a virus has an envolope.

Question 9

What are the two types of genes found in viruses.

Answer 9

Structural and non structural.

Question 10

Give examples of uses of non structural genes in a virus

Answer 10

DNA Polymerase, RNA polymerase
Pathogenesis
Transformation
Modulation of host defences.

Question 11

What are the segments that make up the capsid in a virus called?

Answer 11

Capsomeres

Question 12

What shape do some viral capsids form, how many faces, vertices and edges does it have.

Why do some viruses create this shape?

Answer 12

Regular icosahedron, 20 faces, 30 edges, 12 vertices.

Permits the greatest number of capsomeres to be packed in a regular stable figure.

Question 13

What are the different types of capsid symmetry

Answer 13

Icosahedral
Helical
Complex

Question 14

What does the mucus layer consist of on the surface of epithelial cells

Answer 14

Mucins and glycoproteins

Question 15

Describe the general structure of defensins

Answer 15

Small positively charged antimicrobial peptides, which have hydrophobic or amphipathic helical domains.

Question 16

Describe the two possible mechanisms of defensin action.

Answer 16

Hydrophobic domains or amphipathic helices may enter into the core of the lipid membrane of the pathogen and estabilise it, leading to cell lysis

Following membrane disruption, the positive charges may interact with negatively-charged nucleic acids in the pathogen.

Question 17

How do defensins lyse pathogens but not our own epithelial surfaces.

Answer 17

They are much more active on cell membranes that do not contain cholersterol.

Question 18

What are PAMPs

Answer 18

Pathogen associated molecular patterns, which are common to many pathogens but essentially absent in the host, which are used to recognise pathogenic molecules.

Question 19

Give 6 examples of PAMPs that are recognised by human cells.

Answer 19

N-Formylmethionine (fMet) is used for becterial translation initiation. Proteins containing fMet also attract neutrophils.

Peptidoglyhcans from bacterial cell walls

Bacterial flagellae

Lipopolysaccharides (LPS) from Gram-Negative bacteria

Mannans, Glucans and chitin from fungi.

CpG motifs in bacterial or viral DNA.

Question 20

How are PAMPs detected in the blood and by cellular receptors.

Answer 20

Blood: Peptidoglycans, mannans, glucans, chitin.

Soluble receptors in the blood, members of the complement system.

Cell receptors: Lipopolysaccharides, ‘CpG’ motifs, Flagellae.

Toll-like receptors (membrane bound)

Question 21

What occurs when a PAMP is detected by a cell receptor.

Answer 21

Alarm system.

Question 22

What occurs when a PAMP is detected by the complement system

Answer 22

Direct killing and aid in phagocytosis.

Question 23

Describe the process of complement activation to target pathogens for lysis.

Answer 23

1. Early complement components (proenzymes) activate the next member of complement system by cleavage, resulting in an amplified proteolytic (splitting of protein) cascade.
2. Pivotal proteolysis is the cleavage of C3 into C3a and C3b.
3. C3a calls for help, attracting phagocytes and lymphocytes, stimulating inflammation.
4. C3b binds covantly to the pathogens plasma mebrane.
5. Pathogen-bound C3b stimulates a local cascade of reactions (C5-C8) at the marked membrane.
6. C9 is inserted into the membrane
7. A C9 pore breaches the membrane (C9 multimers form a membrane-attack complex)
8. Pathogen lysis occurs as fluids can flow through the C9 pore.

Question 24

How do toll like receptors aid in pathogen defence.

Answer 24

TLRs bind to PAMPs, sending signals to the nucleus resulting in the transcription of hundreds of genes, especially those that promote inflammation.

Question 25

Where are lymphocytes initially developed

Answer 25

Primary lymphoid organs: Bone marrow, thymus

Question 26

Where to lymphocytes migrate after initial development.

Answer 26

Peripheral/secondary lymphoid organs.
- Adenoids
- Tonsils
- Lymph nodes
- Spleen
- Peyer’s patches
- Appendix
- Skin
- Respiratory tract

Question 27

How do dendritic cells contribute to the adaptive immune response.

Answer 27

Display a wide variety of TLRs and other pattern receptors.

DC activated by binding of pathogen to any of these TLRs

Activated dendritic cells phagocytose and degrade invading microorganisms.

Peptides from the degraded organism are displayed on the cell surface of the dendritic cell.

They then migrate to a nearby lymphoid organ such as a lymph node where they activate adaptive immune responses.

Question 28

How do DC mature into an antigen presenting cell (APC)

Answer 28

Innate immune responses activate DC, which engulfs its prey.

They digest the pathogen into peptides whilst migrating to a nearby lymphoid organ,

Mature during this process to an APC that displays peptides from the pathogen on the cell surface

These peptides are presented to T cells.

Question 29

How do T cells develop.

Answer 29

Develop in the thymus tissue (T for thymus) from thymocytes derived from common lymphoid progenitor cells, which are themselves derived from haemopoietic stem cells originating in the liver (foetuses) or bone marrow (adults).

Question 30

How do dendritic cells activate T cells.

Answer 30

DC presents peptides to T cells in the lymphoid organ.

T cell TCR recognises ‘self’ antigen, no action taken

T cell TCR recognises no antigen: no action taken

T cell recognises ‘non self’ antigen: activation, mitosis and clonal expansion of SPECIFIC T cells (specific to the pathogen they need to provide immunity to)

Question 31

Why do APCs only present to T cells?

Answer 31

Co stimulatory molecules on APC ‘dock’ with T-cell specific co-stimulatory molecules.

Peptide is held in the groove of an APC presenting protein and is scanned by the TCR on the T-cell

No recognition: no action, cells undock

Recognition: T cell activated.

Question 32

What are the three classes of T cell

Answer 32

Regulatory (Treg)
Cytotoxic (Tc)
Helper (TH)

Question 33

What is the function of Helper T cells

Answer 33

Activate macrophages, dendritic cells, B cells and maintain cytotoxic T cell activity by secreting a variety of Cytokines.

Question 34

What is the function of Regulatory T cells

Answer 34

Inhibit the function of helper T cells, cytotoxic T cells and dendritic cells.

Question 35

What is the function of cytotoxic T cells

Answer 35

Kill infected host cells by persuading them to commit suicide apoptotically.

Question 36

How do cytotoxic T cells kill.

Answer 36

Tc Cell recognises the antigens that were used to activate it on the target cell membrane, so it binds specifically to a target cell. The contact points form an immunological synapse.

Tc Cell secretes perforins which assemble and form a channel in the target cell wall.

T cell than secretes specific proteases which enters the target cell and activated caspases, the effector proteins of apoptosis

Can also bind receptors on the target cell which sends a signal that activates caspases, causing apoptosis.

In summary:

Binds specifically to the target cell, causing caspases to be activated which causes apoptosis of target cells.

Question 37

Definition of viral tropism

Answer 37

Specificity of a virus to a specific host.