Antibodies

Question 1

What cells are antibodies produced by?

Answer 1

• B cells
• plasma cells - form of differentiated B cell

Question 2

What are the 2 main types of B lymphocyte responses?

Answer 2

• B-1B cells - produce antibodies but more innate-immune system-like in function
• B-2 B cells - conventional B cells with ability to have memory and huge diversity

Question 3

Describe B-2 B cells

Answer 3

• vast majority of B cells and produce vast majority of antibodies present in bloodstream
• proliferate when activated
• T cell dependent activation - require CD4+ T cells
• present antigen to T cell via MHC class II
• class switching - common in active response

Question 4

Describe the vast antibody repertoire of B-2 B cells

Answer 4

• directed against huge range of antigens
• protein based
• high-affinity antibodies - somatic hypermutation
• significant role in memory responses

Question 5

Describe where B-2 B cells are present

Answer 5

• in all mammals
• mainly located in blood, secondary lymphoid tissues, lymph nodes
• referred to as follicular B cell as present in follicles of secondary lymphoid tissues when not circulating

Question 6

Describe antibodies

Answer 6

• epitope binds to antigen binding site
• naïve B cells differ in this part of the protein due to changes at genomic level
• parts of DNA removed at light and heavy chains

Question 7

Describe antibody formation

Answer 7

• each pre-b cell has the same light and heavy chains
• heavy chain locus multiple variable, diversity and junction segments
• light chain locus only multiple V and J segments
• gene rearrangement on V, D and J segments created diversity
• DNA cut by recombinase RAG1 and RAG2

Question 8

Describe how DNA is cut by recombinase RAG1 and RAG2

Answer 8

• removes non-selected segments
• when re-joined, a few additional nucleotides added randomly to heavy chain gene
• base deletion also possible
• introduces more diversity

Question 9

How do many B cells have the same BCR/antibodies?

Answer 9

• via proliferation of mature B cells

Question 10

Describe antibody function

Answer 10

• function after secretion from B cell or plasma cell
• alternative splicing leads to either trans-membrane antibodies (BCR) attached to cell surface or secreted antibodies

Question 11

Describe where antibodies function

Answer 11

• attached to an immune cell bound to Fc receptors via Fc region
• work unbound freely in bloodstream, mucosal surfaces, lymph nodes, tissue fluid

Question 12

What are the 4 ways antibodies affect pathogens?

Answer 12

• neutralization
• opsonization
• activation of complement
• antibody-dependent cell-mediated cytoxicity

Question 13

Describe how antibodies neutralize pathogens

Answer 13

• bind to pathogens that prevents interaction with host cell receptors
• high affinity neutralizing antibodies can block viruses and bacteria from binding receptor by which they enter the host cell
• stop toxins binding to cell receptors

Question 14

Describe how neutralizing antibodies can block viruses and bacteria from the binding receptor

Answer 14

• virus binds to receptors on cell surface
• receptor-mediated endocytosis of virus
• acidification of endosome after endocytosis triggers fusion of virus with cell and entry of viral DNA
• antibody blocks binding to virus receptor and can also block fusion event

Question 15

Describe opsonization

Answer 15

• bacterium coated with complement and IgG antibody
• when C3b binds to CR1 and antibody binds to Fc receptor - bacteria phagocytosed
• macrophage membranes fuse - creates membrane-enclosed vesicle
• lysosomes fuse with these vesicles, delivering enzymes that degrade the bacteria

Question 16

Describe antibody-dependent cell-mediated cytotoxicity

Answer 16

• ADCC
• antibodies bind to non self antigens on host cell
• Fc receptors on immune cells bind to these antibodies
• signals to neutrophil, macrophage, eosinophil, NK cells
• cross-linking of Fc receptors key to apoptosis/release of perforins

Question 17

Describe the activation of complement

Answer 17

• antibodies are only 1 way to activate cascade
• complement is a series of proteins in serum, part of innate response
• 3 pathways of activation: classical, lectin, alternative

Question 18

Describe the classical activation of complement

Answer 18

• adaptive immune system
• antibody-antigen complexes and some non-specific reactivity
• initiated by C1q
• binds antibodies or pathogen surfaces

Question 19

Describe the lectin activation of complement

Answer 19

• innate immune system
• PRR molecules binding to pathogen surfaces
• initiated by mannose-binding lectin or ficolin
• mannose PAMPs on salmonella, fungi

Question 20

Describe the alternative pathway of complement activation

Answer 20

• innate
• spontaneous reactivity at pathogen surfaces
• initiated by C3
• blocked on host cells by multiple proteins including CD59

Question 21

Describe complement cascade

Answer 21

• more than 19 small plasma proteins involved, major ones C1-C9
• 3 functions: destruction, opsonization, inflammation

Question 22

Describe destruction in the complement cascade

Answer 22

• polymerization of terminal proteins (esp C9) to form membrane attack complexes
• MACS form pres in cell membranes
• can cause cell lysis

Question 23

Describe complement cascade opsonization

Answer 23

• C3b and C5a proteins increase phagocytosis
• bacterium coated with C3b
• when only C3b binds to CR1 - bacteria not phagocytosed
• C5a can activate macrophages to phagocytose via CR1

Question 24

Describe inflammation in the complement cascade

Answer 24

• C3a, C4a and C5a induce inflammation by acting on blood vessels to increase vascular permeability and cell-adhesion molecules
• specifically chemotaxis for phagocytes, activation of endothelia