Immune System 2

Question 1

What does TLR4 detect ?

Answer 1

• Detects LPS in bacteria

Question 2

Where is TLR4 expressed ?

Answer 2

-Expressed in macrophages and dendritic cells (where the signal transduction process stimulates their maturation)

Question 3

What happens when TLR4 detects LPS?

Answer 3

• Bacterium binding to the receptor stimulates a
  signal transduction pathway
• activates transcription of genes encoding for pro-
  inflammatory cytokines
  (e.g. TNF)

Question 4

What does TLR7 detect ?

Answer 4

• detects single-stranded RNA (ssRNA) from viruses.

Question 5

What happens when TLR7 detects ssRNA ?

Answer 5

• signal to activate signalling transduction inside the cell
  •This leads to the production of IFNα and
  IFNβ
  •IFNα and IFNβ have anti-viral properties

Question 6

What are the 3 key outcomes of the interferon (IFN-α, IFN-β) response during a viral infection?

Answer 6

• Inducing resistance to viral replication in all cells.
• Increasing expression of ligands for receptors on natural killer (NK) cells.
• Activating NK cells to kill virus-infected cells.

Question 7

What are the functions of natural killer cells ?

Answer 7

• Activated by cytokines IFNαand IFNβ(Interferon)
• Kill cells infected by viruses (and some cancer cells)
• Can contain viral infections whilst adaptive/specific response kicks in
• NK cells can produce IFNγ (immunostimulatory,
immunomodulatory and effects on viral replication)
• Deficiency -> persistent viral infections and increased risk of herpes (rare)

Question 8

How are NK cells activated and how do they affect cells ?

Answer 8

• IFN binds to IFN receptors expressed by NK cells, activating them
• NK cells proliferate and differentiate in effector NK cells
• Effector NK cells kill virus-infected cells by inducing apoptosis

Question 9

What are antibodies ?

Answer 9

• Antibodies are the secreted form of the BCR
• The BCR and the antibodies are more generally known as immunoglobulins (Ig)
  •

Question 10

Structure of antibody ?

Answer 10

• Y-like shape
• Basic 4-polypetide chain structure
• 2 identical heavy chains & 2 identical light chains, held together by covalent and non-covalent bonds
• Each chain has a variable (V) region and constant (C)
regions
• Antigen-binding sites (variable region) consist of VH and VL and are part of the Fab (Fragment Antigen Binding)
• One Ig can bind 2 antigens
• CH regions interact with effector cells and complement and are part of the Fc region

Question 11

what is the variable region of an antibody?

Answer 11

• specific to each antibody

Question 12

what is the Fab region ?

Answer 12

• antigen binding
• top part of antibody
• made up of VH and VL

Question 13

what is the Fc region ?

Answer 13

• constant region of heavy chains CH
• bottom half (only heavy chains)
• activates complement

Question 14

How do the hypervariable regions in the VH and VL contribute to antigen binding in an antibody?

Answer 14

• 3 in VH and 3 in VL
• so 6 hypervariable loops when paired together forming a hypervariable surface
• this surface creates the antigen binding site

Question 15

What are Complementarity-Determining Regions (CDRs) and how do they contribute to antibody-antigen interactions?

Answer 15

• CDR’s are the hypervariable regions in the VH and VL
• difference in CDRs between antibodies create the specificity and diversity of the antigen-binding sites.
• both the heavy and light chains contribute to the formation of the antibody’s antigen-binding site, enabling specific antibody-antigen interaction

Question 16

what are the anti-bacterial specific functions of antibodies ?

Answer 16

• protect against extracellular bacteria through
• neutralisation
• opsonisation
• complement activation

Question 17

How do antibodies protect against viruses?

Answer 17

• Neutralization: Antibodies bind to free viruses, preventing them from entering cells and spreading.
• e.g.= Influenza virus binds on cell surfaces through a protein called hemagglutinin.
• Neutralising antibodies coat the virus, inhibit its attachment and prevent
  infection
  Opsonization: increasing its recognition and phagocytosis
• Complement Activation: leading to the lysis of enveloped viruses

Question 18

What are the key functions of antibodies in the immune response?

Answer 18

• Neutralization (direct response to antigens)= Bacteria, Virus, Allergens
• Activation of complement (when antibody dependent)
• Opsonisation
• Activation of effector cells = Cells with Fc receptors
  (NK cells, macrophages, neutrophils etc.)
  Antibody –All functions

Question 19

what are the 5 classes of antibodies ?

Answer 19

• IgG
• IgD
• IgA have 3CH domains,
• while IgM and IgE have 4CH

Question 20

function of IgM ?

Answer 20

• First antibody to be produced
• Give the primary response
• Defense of tissues and prevention of septicemia (blood infection)

Question 21

function of IgG ?

Answer 21

• Give the **secondary response **(more specific and stronger)
• Defense of tissues and prevention of septicaemia

Question 22

function of IgA ?

Answer 22

• Prevents septicaemia
• Protects surfaces of the mucosal epithelium
• Present in maternal milk to give protection to infants

Question 23

function of IgE ?

Answer 23

* Defense against parasite infections
* Important in allergies

Question 24

function of monoclonal antibodies ?

Answer 24

• Immunosuppressive
• To prevent transplantation rejection
• To treat autoimmune disease
• To reduce immune response
• Produced in mice

Question 25

How do depleting monoclonal antibodies work ?

Answer 25

* monoclonal IgG antibodies bind to target cells and direcnt them to immune cells (macrophages and NK cells) which have Fc receptors * Target cells are killed by phagocytosis or Antibody Dependent Cell mediated Toxicity (ADCC)

Question 26

How do nonndepleting antibodies work ?

Answer 26

* Block the function of target proteins without killing the cell that bears it

Question 27

what is the problem with humanisation of monoclonal antibodies + what is the solution ?

Answer 27

* humans may develop an antibody response against non-human antibodies * leads to allergic reactions * solution = make antibodies not recognised as foreign by immune system

Question 28

what are chimeric antibodies ?

Answer 28

* The V regions from the mouse are spliced onto human antibody constant regions * Some regions of the remaining mouse sequence could trigger an immune response

Question 29

what are humanised antibodies ?

Answer 29

* The murine hypervariable regions (mouse) are spliced into a human antibody

Question 30

what are fully human anitbodies ?

Answer 30

* Entirely derived from human sequences and produced from cell lines