L9. Humoral and Cell-Mediated Immunity 1

Question 1

What is the overall role of antibodies?

Answer 1

Antibodies Label pathogens –> elimination/ destruction

Question 2

What does 1) Affinity 2) Avidity mean?

Answer 2

1) Affinity= binding of one Fab arm to antigen

2) Avidity= whole Antibody binding to a pathogen (if more than one arm)

Question 3

What are 5 roles of the Fab arms of an antibody, and how does it do each, and which antibody heavy chain class does each?

Answer 3

1) Immobilise pathogens (IgM)
>Bind to flagella and stop movement.

2) Agglutinate particles e.g. bacteria (IgM, IgA)
>More easy to remove clumps from the body

3) Form “immune complexes” with soluble antigen
>Cross linking

4) Block binding of pathogens to host cells (IgG, IgA)
>IgG and IgA go through affinity maturation so bind with high affinity.
>e.g. antibodies to bacterial adhesins or viral receptors

5) Neutralize toxins e.g. tetanus, diphtheria, cholera (IgG, IgA)
>IgG and IgA bind with high affinity to toxins, stopping them causing damage

Question 4

What is the role of the Fc section of an antibody?

Answer 4

Invoke destruction of labelled pathogens

Question 4

What are 2 ways the Fc region of an antibody Invokes destruction of labelled pathogens?

Answer 4

1) Activate complement (IgM, IgG)

2) Bind Fc receptors on leukocyte surfaces (IgG, IgA, IgE)

Question 4

What is required for the activation of complement from the classical pathway?

Answer 4

Requires Antigen/Antibody, C1, C2 and C4

Question 5

What 3 factors about infection will determine the effector mechanism which act on it?

Answer 5

1) Site of infection (e.g. in secretions or gut will be IgA)

2) Type of infection (if is parasite will be IgE)

3) Stage of the immune response (primary or secondary uses different classes for flexible response)

Question 6

What makes up C1 in complement?

Answer 6

> C1 is made up of 3 proteins, linked together

> C1 = C1q +C1r + C1s

> C1s and C1r are serine proteases when activated (cleave proteins).

Question 7

What interaction must occur to trigger the start of complement activation by the classical pathway?

Answer 7

C1q must interact with 2 Fc regions (of IgG or IgM) for activation of complement by classical pathway to occur

Question 8

What is the structure of C1q?

Answer 8

6 globular heads joined together by collagen stalk, 2 of these heads must bind to Fc antibody for stable binding

Question 9

Why is valency important in the binding of C1q to Fc regions?

Answer 9

Down to valency as needs interaction with 2 heads (of C1q) to get stable binding.

Question 10

What antibody is most efficient at activating complement by the classical pathway and why?

Answer 10

> IgM is the best at activating complement

> As would require two IgG molecules at the perfect distance between to interact while IgM is a pentamer so has 2 adjacent IgM

Question 11

How does IgM not constantly activate complement in the blood (as two Fc regions are adjacent before binding)?

Answer 11

IgM doesn’t bind complement in blood due to its confirmation blocking binding to Fc regions

Question 12

How can complement bind to IgM once bound to antigen, and what allows this?

Answer 12

Before binding to antigen Fc region is not accessible by C1q to bind but once bound the Fc region extends out for binding to complement due to flexible functional hinge region (forms crab like shape)

Question 13

What IgG type is best at activating complement and which is the worst?

Answer 13

IgG3 > IgG1 > IgG2 > IgG4

IgG4 doesn’t activate complement at all but IgG3 is the best out of IgG.

Question 14

Describe the classical pathway of activation for complement in 5 steps

Answer 14

1. When antibodies bind to antigen, can interact with C1q causing conformational change associated with the serine proteases C1r and C1s
2. When C1r is activated, it cleaves a bit of C1s, acting C1s
3. C1s is now a protease, acts on C4 and C2 (cleaves)
4. This generates the C3 convertase which cleaves C3 into C3a/ C3b
5. This generates the C5 convertase which can cleave C5 into C5a and C5b leading to formation of membrane attack complex on bacterial cell.

Question 15

What are the roles of complement?

Answer 15

Complement activation can result in phagocyte recruitment, inflammation, opsonization and direct bacterial killing

Question 16

What receptor on phagocytes allows interaction with antibodies?

Answer 16

Fc receptor (FcR)

Question 17

What antibodies does Fc receptors (FcR) on phagocytes best recognise (opsonisation)?

Answer 17

> IgG (IgG1 and 3 are both good, IgG4 is okay but IgG2 cannot opsonize)

> Monomer IgA

Question 18

What are the 2 roles of Fc receptors on phagocytes?

Answer 18

1) This facilitates the uptake of immune complexes (soluble antigen + antibody), can be important for presenting processed antigen to T cells or just the destruction of pathogen.

2) OPSONIZATION - phagocytosis and destruction of antibody-coated pathogens

Question 19

What occurs if a pathogen cannot be phagocytosed?

Answer 19

Frustrated phagocytosis

Question 20

What is frustrated phagocytosis?

Answer 20

> If pathogen cannot be phagocytosed, frustrated phagocytosis occurs where it spits out lysosome contents onto surface of pathogen/ Release lysosomal contents (“frustrated phagocytosis”, for pathogens too big to phagocytose)

> As they would eb large pathogens, many leukocytes e.g. eosinophils surround it and release lysosomal contents (e.g. ROS).

Question 21

What is the role of Fc receptors on NK cells?

Answer 21

Mediate antibody-dependent cell-mediated cytotoxicity (ADCC)

Question 22

What are NK cells good at defending against?

Answer 22

NK cells good for dealing with intracellular infections

Question 23

What antibodies can mediate antibody-dependent cell-mediated cytotoxicity (ADCC)?

Answer 23

Only IgG1 and IgG3 in humans.

Question 24

Describe the process of antibody-dependent cell-mediated cytotoxicity (ADCC) in 4 steps

Answer 24

1) IgG1 and IgG3 binds antigen on surface of target cells.

2) Fc receptors on NK cells recognise bound IgG1 and IgG3

3) Cross-linking of Fc receptors signals the NK cell to kill the target cell.

4) NK cells release granzymes and perforin from cytoplasmic granules to cause apoptosis to host cell.

Question 25

What receptor does IgE bind to with high affinity and what cells are these found on?

Answer 25

IgE binds with high affinity to FcεR on mast cells and basophils

Question 26

What do FcεR on mast cells and basophils mediate?

Answer 26

> Mediate allergy/defence against large parasites

> Mast cells secrete inflammatory mediators and cytokines, Setting up strong inflammatory response.

Question 27

How does an allergy be formed?

Answer 27

1. Allergen which gets through tissue leads to IgE produced against this allergen and binds to mast cell tightly
2. If the allergen gets through tissue again, activates IgE (immediate hypersensitivity) where mast cells undergo degranulation releasing inflammatory mediators. (good for dealing with large parasite)

Question 28

What are “NUDE” mice?

Answer 28

Have no thymus and therefore no T cell responses

Question 29

Why were “NUDE” mice good to study on?

Answer 29

Still survived if kept in germ free environment as still have innate and some B cell responses, allows us to study immune responses without T cells.

Question 30

What is a common property of thymus independent antigen and give an example

Answer 30

> Lots of repeated epitopes (shapes) that B cells recognise which is enough to trigger B cell differentiation

> e.g. bacterial polysaccharides

Question 31

What response is produced from thymus independent antigens (e.g. bacterial polysaccharides)?

Answer 31

1. Induce a rapid response and production of IgM antibodies(agglutination and activating complement).
2. Memory cells are not generated, as no class switching or affinity maturation can occur.

Question 32

What usually is a thymus dependent antigen and why?

Answer 32

> Most proteins

> As these are processed into peptides and presented to T cells to recognise (only T cells can recognise peptide + MHC complex and has adaptor proteins CD3).

Question 33

Why are T cells required for a response against thymus dependent antigens?

Answer 33

Require T cells for differentiation of B cells into plasma cells.

Question 34

What response is produced from thymus dependent antigen?

Answer 34

1. Long-lived memory B cells may also be generated.
2. Responses can involve somatic hypermutation (allows for affinity maturation) and class switching.