12: Effector responses: Antibody- and cell-mediated immunity

Question 1

Antibody-mediated effector functions

Answer 1

Response depends on antigen specificity and isotype (heavy-chain class or subclass) of Ab’s.

• Can it activate complement?
• Which Fc receptor(s) does it bind?
• Can it be transported across certain tissue layers?

Neutralizing pathogens/toxins
- Blocks the ability of pathogens to infect

Agglutinate pathogens
- Cross-linking of pathogens

Opsonize pathogens or altered cells
- Coating of pathogens so that they are recognized and phagocytosed

Activate complement
- Binding complement to pathogen

Antibody-dependent cell-mediated cytotoxicity (ADCC)
- Directing other cells of innate immune system to kill infected cells.

Ab’s can trigger degranulation

Question 2

Effector functions of different Ab’s

Answer 2

Several subclasses induce apoptosis

IgM and IgG:
- Fix complement

IgG:
- Mediate antibody-dependent cell-mediated cytotoxicity (ADCC)

IgE:
- Induce the release of inflammatory molecules from granulocytes to kill parasites.

IgA:
- Bodily secretions that block entry of bacteria and toxins to the tissues.

IgD:
- Stimulate release of protective molecules from basophils in the respiratory tract.

Question 3

Fc receptors (FcR)

Answer 3

Bind specific immunoglobulin classes/subclasses.
Generate signals when bound to Ab-Ag complexes.

Activating: associates with ITAM motif
Inhibiting: associates with ITIM motif

Question 4

Cell-mediated effector responses

Answer 4

Recognize and attack any cell that exhibits “nonself” or “altered-self” characteristics.

• Pathogen infection
• Tumor cells
• Cells that have been stressed by extreme temperatures or trauma

Question 5

Cell-mediated effector responses

Answer 5

Recognize and attack any cell that exhibits “nonself” or “altered-self” characteristics.

• Pathogen infection
• Tumor cells
• Cells that have been stressed by extreme temperatures or trauma

Question 6

How CTLs kill cells

Answer 6

CTLs are easily activated, express high levels of cell-adhesion molecules, exhibit different trafficking patterns (than naïve T cells), and produce soluble and membrane bound effector molecules.

1. Directional release of granule contents or
2. Fas-FasL membrane signaling interaction.

Does not induce cell lysis, but apoptosis.

Events:

• Binding to target cell via MHC class I => cell-cell conjugate
• Ca2+ dependent, energy requiring step => apoptosis
• Disssociation, binding to another cell

1. Granzyme/perforin-mediated cytolysis
   - Perforin is a 65 kDa pore-forming protein
   - Granzymes are serine proteases
   - Both taken up by endocytic processes,
   - Perforin punch holes in the membranes and release Granzyme B
   - Granzymes activates apoptotic pathways that lead to
   fragmentation of target cell DNA
   => Induce apoptosis from the inside out
2. Fas/FasL pathways
   - Crosslinks Fas (CD95) on target => delivers a death signal

Question 7

Natural killer cells, NK

Answer 7

Induce apoptisis by similar mechanisms ad CTLs, but regulated by different receptors.

Regulated by a balance of positive signals generated by the engagement of activating NK receptors ad negative signals from inhibitory NK receptors.

Structural groups of NK receptors based on extracellular regions:

• Lectin-like
• Ig-like

Intracellular regions decide if activating or inhibiting:

• ITAM
• ITIM (often binds MHC I)

Can kill via Ab-dependent cell-mediated cytotoxicity (ADCC)

Have memory responses

Question 8

Natural killer T cells, NKT

Answer 8

Characteristics common to T lymphocytes and NK cells.
Many express invariant TCR that recognizes lipid Ag’s bound to DC1 proteins, as well as markers common to NKT cells.
Exhibit both helper and cytotoxic activity and kills predominantly via FasL-Fas interactions.