Immunology 6

Question 1

Describe antigen-dependent B cell activation and differentiation

Answer 1

Specific antigen + co-stimulation activates resting B cells

Activated B cells:

Enter cell cycle/mitosis leading to clonal expansion

Cells then differentiate into memory B cells and plasma cells (effector B cells), which produce antibodies

Question 2

Structure of lymph node interior?

Answer 2

B cell zone - inc. stromal cells with opsonin receptors for opsonins on antigen, like C3b

B cells also have PRRs to recognise PAMPs

B cells produce low affinity, antigen-specific antibodies (no memory cells), like IgM Same mechanism can occur, with stromal cells, with additional T cell help to produce a germinal centre, leading to memory B cell production and antibody production

Question 3

Difference between production of antibodies by B cells?

Answer 3

B cells alone - produce low affinity, antigen-specific antibodies (no memory cells); in other words, IgM only

B cells + T cell help - high affinity, antigen-specific antibodies (+ memory cells); in other words, IgM initially and then IgG, IgA, IgE and IgD

Question 4

Describe IgG

Answer 4

Most abundant Ig in PLASMA, and is actively transported across PLACENTA

4 sub-types - IgG_1-4

Question 5

Describe IgA

Answer 5

2nd most abundant Ig type

Monomeric form - blood

Dimeric form - BREAST MILK (passive transfer of pre-formed, protective anitbodies from mother to baby), saliva, tears, mucosal secretions

Question 6

Describe IgM

Answer 6

As a surface bound monomer is BCR (B cell receptor antigen) and is only antibody produced in response to nucleic acids

PRIMARY RESPONSE:

1st Ig type produce during an immune response (present only in plasma/secretions - pentameric so efficiently binds to antigens on pathogens)

Question 7

Describe IgD

Answer 7

Extremely low levels in blood

When surface bound act as BCR

Uncertain function

Question 8

Describe IgE

Answer 8

Extremely low levels normally but are produced in response to PARASITIC infection and ALLERGIC responses

Question 9

Dual biological function of antibodies?

Answer 9

Have variable and constant regions:

Variable regions have RECOGNITION function - binding to antigen mediated by variable region sites

Constant regions (Fc) have EFFECTOR function - clearance mechanisms mediated interaction by Fc region with effector molecules, like COMPLEMENT and Fc receptors

Question 10

Function of high affinity, neutralising antibodies binding to antigens?

Answer 10

Protective

Prevent viruses from infecting host cells using AGGLUTINATION (of virus particles by antibodies) - this is IMMUNE COMPLEX FORMATION

Also, to prevent microbial toxins from disrupting normal cell function, like diphtheria toxin and tetanus toxin - the antibody blocks the binding to the toxin to a cellular receptor

Question 11

Effector functions of antibodies?

Answer 11

Can activate classical complement pathway

Can function as opsonins

Can help stimulate NK cells

Can trigger allergic responses, like asthma, allergy, anaphylaxis

Question 12

How can antibodies help stimulate NK cells?

Answer 12

Results in Antibody-Dependent Cell-Mediated Cytotoxicity

Antibody binds antigens, on surface of target cell Fc receptors, on NK cell recognise bound antibody

Cross-linking of Fc receptors signals NK cells to kill the target cell

Target cell dies by apoptosis

Question 13

What are opsonins and how do antibodies function as them?

Answer 13

Coating of micro-organisms by immune proteins (opsonins), like C3b, CRP and antibodies

Phagocytes express Fc receptors that bind to the constant regions of Igs - opsonisation enhances phagocytosis, especially encapsulated bacteria

Question 14

How can antibodies trigger allergic responses?

Answer 14

IgE binds to allergen and IgE also binds to Fc receptor on mast cell, which degranulates A

Question 15

Effector functions of different antibody classes?

Answer 15

Question 16

Functions of antigen activated T cells?

Answer 16

Help activate other immune cells - HELPER T CELLS/Th (CD4+ cells) become activated when presented with peptide antigens, which are presented using MHC Class II on antigen-presenting cells

Kill infected and cancer cells - CYTOTOXIC T CELLS/Tc/CTLs (CD8+ cells) become activated when presented with peptide antigen, which are presented using MHC Class I on all nucleated cells

Question 17

Types of T cells?

Answer 17

CD4+ is a resting T cell, when activated becomes a helper T cell

CD8+ is a resting T cell, when activated becomes a cytotoxic T cell

Question 18

Function of effector Th cells?

Answer 18

Key master regulators of immune system - can “help” STIMULATE OTHER IMMUNE CELLS, like CD8+ cells (to become cytotoxic cells), macrophages and B cells, using cytokines and direct cell contact

Question 19

How do effector Th cells help T cell responses?

Answer 19

CD4+ cell binds to peptide presented by dendritic cell, using T cell receptor (TCR)

CD8+ cell binds to peptide presented by dendritic cell, using TCR CD4+ cell activated a Th cell, which produced IL-2, stimulating production of multiple Th cells

IL-2 also stimulates CD8+ cells to activate into Tc cells

Question 20

How do effector Th cells help macrophages?

Answer 20

1. Effector Th cells migrate from lymph node into sites of infection/inflammation
2. Th cells are re-activated by macrophages in an antigen-specific manner
3. Th cells express co-stimulatory molecules and hyper-activate macrophages, using IFNγ, enhancing their killing activities and pro-inflammatory responses

Question 21

How do effector Th cells help B cells?

Answer 21

Help B cells respond effectively to PROTEIN ANTIGENS (provide signal 2)

1. Protein antigen bound to BCR is internalised by B cell Antigen is degraded and peptides are presented on the B cell surface complex with MHC-II
2. Effector Th cells move into B cell zone, of lymph node, where they are re-stimulated by B cells in an antigen-specific manner and start to express CD40L Re-activated effector Th cells stimulate B cell to proliferate and survive (via CD40L : CD40 interactions)
3. Effector Th cells secrete cytokines that further activate B cell and stimulate germinal centre response

Question 22

What does the germinal centre response involve?

Answer 22

B cell proliferation

Antibody heavy chain switching

Generation of high affinity antibodies

Differentiation into plasma cells and memory B cells

Question 23

What is antibody heavy chain switching (class switching)?

Answer 23

B cells switch antibody heavy chain constant region gene segment they use

Question 24

Describe generation of high affinity antibodies

Answer 24

AKA somatic hypermutation

Aim - produce antibodies that recognise the SAME ANTIGEN with INCREASED AFFINITY:

Point mutations made in heavy/light chain gene segments that encode for the variable antigen binding sites of antibodies

Question 25

Functions of cytotoxic T cells?

Answer 25

Fas ligand mediated killing

Kill infected host cells - effector cytotoxic T cells exit lymph node, migrate to sites of infection, recognise and kill infected tissue cells in an antigen-specific manner:

CTL recognises and binds virus-infected cell peptide, presented by MHC-I

CTL programs target for death, inducing DNA fragmentation

CTL migrates to new target

Target cell dies by apoptosis

Question 26

Proteins in lytic granules of cytotoxic T cell?

Answer 26

Perforin - polymerises to form a pore in target membrane

Granzymes - serine proteases, which acitvate apoptosis once in the cytoplasm of the target cell

Granulysin - induces apoptosis

Question 27

Describe immunological memory

Answer 27

Once adaptive immune system has recognised and responded to a specific antigen, it exhibits life-long immunity to this antigen

Question 28

Cells of immunological memory?

Answer 28

Memory Th cells

Memory Tc cells

Memory B cells

Long-lived plasma cells

Question 29

What are memory cells?

Answer 29

Memory cells are small, long-lived re-circulating antigen-specific cells that are primed and ready to respond upon re-encounter with same antigen

High numbers and have a lower threshold for activation

Memory B cells have already undergone class switching and somatic hypermutation