adaptive immune system B cells

Question 1

what is the Innate immune system?

Answer 1

→Rapid response
→Non-specific (generic anti-bacterial or anti-viral mechanisms)
→Most often fails to completely eliminate the infection

Question 2

what is the Adaptive immune system?

Answer 2

→Delayed response 
→Highly specific 
→Usually eliminates infection 
→Memory 
→Long term immunity, but specific to that particular pathogen

Question 3

what are the branches of adaptive immunity and what are they regulated by?

Answer 3

Humoral immunity
→Mediated by B-lymphocytes

Cellular immunity
→Mediated by CD8+ cytotoxic T- lymphocytes

→Both branches regulated by CD4+ helper T-lymphocytes (T-helper cells)

Question 4

what is Humoral immunity?

Answer 4

→Humor = fluid
→Following an infection
→Plasma contains substances- “antibody (Ab)”
→which neutralise that specific infectious agent
→Demonstrate in vitro Or in vivo, e.g. treatment of rabies by infusion of antibody “adoptive immunotherapy”

Question 5

what is an antibody?

Answer 5

→Protein- “immunoglobulin (Ig)”
→Migrates in the γ-globulin fraction on serum electrophoresis
→Each antibody binds to a specific antigen (most often a protein) on the infectious agent
→But plasma contains many different Abs

Question 6

what is the structure of an antibody?

Answer 6

→Immunoglobulin protein
→Y-shaped
→Tetrameric
→2 identical heavy chains
→2 identical light chains
→Held together by non-covalent interactions
→and by –S-S- crosslinks between cysteine a.a. residues

→Each Ig molecule has two antigen binding sites
→flexible hinge region

Question 7

describe light chains

Answer 7

→There are two types of light chain Kappa (κ) and lambda (λ)
→But any B-cell will only make one type
→Any Ig molecule will contain either kappa or lambda, never both.
→This phenomenon is called “light chain restriction”

Question 8

how many regions do antibodies have and describe them

Answer 8

variable region
→Amino acid sequence varies from one Ig molecule to another
→Binds antigen

→constant region
→Responsible for effector functions E.g. activating complement, binding to phagocytes

Question 9

what is Ig?

Answer 9

Ig is a glycoprotein (Carbohydrate added in the Golgi)

Question 10

what happens if you treat Ig with protease?

Answer 10

→Cuts molecule at hinge region
→Fab- fraction Antigen binding
→Fc- fraction crystallisable

Question 11

what are the three ways in which antibodies fight infection?

Answer 11

COATING AND NEUTRALIZING
→if a virus is coated with Ab it cannot bind to its receptors

ACTIVATING THE COMPLEMENT
→which can blow holes in a bacterial cell membrane

OPSONIZATION
phagocytes have Fc receptors on their cell membrane
→bind to pathogens coated in Ab and phagocytose them

Question 12

How does an Ab bind to an antigen?

Answer 12

→Non-covalent interactions 
→Electrostatic
→hydrophobic
→van der Waals forces
→hydrogen bonds 

→ Depends on the antibody binding site being exactly complementary, sterically and chemically, with a site on the surface of the antigen

→ The binding site on the antigen for one specific Ab is called an epitope

Question 13

what are different types of B cells?

Answer 13

→The body generates over 100,000,000 different B-cells each making a different “random” Ig
→Each B-cell only makes one specific Ig
→These naïve B-cells sit around in lymph nodes doing not very much

Question 14

what happens to the B cells in lymph nodes during an infection?

Answer 14

→During an infection, a small number of B-cells will, by chance, be making an Ig that binds one of the foreign antigens
→These B-cells are activated and begin to multiply- “clonal selection”

Question 15

why are B cells called clones?

Answer 15

→Descendants of the original activated B-cell make the same Ig
→therefore they are a clone

Question 16

how does Lymphocyte Development happen in the Bone Marrow?

Answer 16

→ Haematopoietic stem cells differentiate into either
→common myeloid progenitor (neutrophils,red cells, platelets)
→ common lymphoid progenitor ( either pre-T or pre-B)

Question 17

what are Primary and Secondary Lymphoid Organs?

Answer 17

→ HSC into Pre-B
→ imm B-cells
→ Imm B-cells into follicles containing resting B-cells

→ (secondary lymphoid organs, lymph nodes, spleen, gut etc)

Question 18

how are B cells activated?

Answer 18

→Functional Ig is first expressed as IgM on the cell surface (sIgM)

→this acts as a “B-cell receptor” in a similar way to a growth factor receptor.

→The IgM does not have intrinsic tyrosine kinase activity, but associates with other tyrosine kinases

→Binding of antigen to IgM activates the tyrosine kinases and their signal transduction pathways

Question 19

what does B cell activation require?

Answer 19

→Antigen binding to the B-cell receptor (sIgM), resulting in stimulation of signal transduction pathways
→Co-stimulation by T-cells
→The activated B-cell begins to secrete soluble IgM

Question 20

what happens to activated B cells?

Answer 20

→B cells activated
→Multiply rapidly
→Differentiate to become Ig secreting cells
→First make IgM
→Then undergo class switching to make Igs with the same Ag specificity but different heavy chain constant regions

Question 21

what do memory B-cells do?

Answer 21

→Memory B-cells allow a very rapid response to a second exposure
→Immediate production of IgG rather than IgM

Question 22

why are natural immune responses described as polyclonal?

Answer 22

→More than one clone of B-cells is generated
→More than one Ig is synthesised
→ Multiple antigens on organism
→Multiple epitopes on each antigen
→More than one Ig may recognise the same epitope

Question 23

what is class (or isotype) Switching?

Answer 23

→The body can make different classes of Ig IgG, IgM, IgA, IgD, IgE differ slightly in heavy chain constant region amino acid sequence

→Have different functions note: there are actually 4 types of IgG (subclass IgG1 – IgG4) 
→And 2 types of IgA (subclass IgA1 and IgA2)

Question 24

what are the heavy chain isotypes?

Answer 24

γ = IgG 
μ = IgM 
α = IgA 
δ = IgD 
ε = IgE

Question 25

properties of IgM

Answer 25

→Always the first class of Ig made by B-cells during the primary response
→First made as a membrane bound protein on B-cell surface
→Activates B-cell by signal transduction
→ Later made in secreted form
→Activates complement
→Acts as opsonin

Question 26

what does presence of IgM and IgG mean?

Answer 26

→Presence of specific IgM antibodies to an antigen indicates a recent primary response to that antigen

→Implies a current primary infection

→Presence of IgG antibodies may be due to past exposure to antigen

Question 27

what is IgM structure?

Answer 27

→Membrane bound IgM is formed of a single Ig tetramer

→In secreted IgM five molecules of the basic Ig tetramer polymerise to form a pentamer

Question 28

what is IgG and what does it do?

Answer 28

→Major class of Ig in the circulation
→Very good at activating complement system
→Good as an opsonin
→Formed of a single Ig tetramer

Question 29

what is IgA?

Answer 29

→Most abundant class in external secretions Milk, sweat, tears, gut secretions 
→Protects mucosal surfaces 
→Does not activate complement 
→Does bind Fc receptors triggering
- Phagocytosis 
-Inflammatory reactions

Question 30

what is IgA structure?

Answer 30

→In serum, occurs as a single Ig molecule In secretions, →most IgA is present as a dimer of two whole Ig molecules (+ accessory proteins)

Question 31

what does IgE do?

Answer 31

→Physiological role in protection against parasitic worms →Binds to Fc receptors on mast cells and basophils →Triggers release of histamine BUT also involved in allergies!
→IgE produced in response to allergens (pollen, peanuts etc)
→Release of histamine causes symptoms of allergies Over response can cause anaphylactic shock

Question 32

where is IgD found ?

Answer 32

→Extremely low concentration in circulation
→Also found on B-cell membrane
→Role is unknown