Lecture 19: B cells and Antibodies

Question 1

Innate cytokines?

Answer 1

Interferons - IFN - alpha, beta, gamma

• Inhibit viral infections by causing a change in other non-infected cells and cause them to go into a transient virus resistant phase.
• Also activate NK cells to recognise virally infected cells

IL-1, IL-6 and TNF-alpha

• Pro-inflammatory cytokines (esp. bacterial infections)
• For wound healing and tissue repair by stimulating fibroblast proliferation, bone resorption, PG and collagenase synthesis as well as neuroendocrine effects.

Question 2

Adaptive Cytokines?

Answer 2

IL-1:

• T cell activation and B cell activation

IFN-gamma:

• Antiviral, macrophage activation, NKC activation and MHC upregulation

​IL-2:

• T cell proliferation
• NK cell activation

IL-4,5,6:

• B cell differentiation
• Antibody class switching

(dont need to memorise, just know there is overlap)

Question 3

Other types of cytokines?

Answer 3

• Chemokines
• Haemopoetic cytokines (G-CSF, M-CSF, IL-3,5 adn 7)

Question 4

Antibody structure?

Answer 4

Question 5

Antibody classes?

Answer 5

Light chain isotopes: conserved regions in the light chains

• k (kappa)
• λ (lambda)

Heavy Chain Isotopes - What the Antibodies are named off (eg. IgM, IgG, IgE) and are conserved regions.

• ε (epsilon)
• μ (mu)
• γ (Gamma)
• δ (delta)
• α (alpha)

Question 6

Antibodies arounf birth?

Answer 6

In utero across the placenta IgG can cross the placenta and IgA is able to cross the gut wall from breastmilk.

Then:

• By 12months reaching 80% of IgG levels
• 6months before birth till 12 months 75% of IgM
• From about 2 months till 12 months you build up 20% of IgA

By 6 months you start to build a basis for a good immune system and it is at this point here that if there are to be issues you will notice them.

Question 7

Main Antibody effects?

Answer 7

Blocking and Neutralising

• Attachment and entry (virus, parasites etc.)
• Main protective effect of secretory IgA
• Toxins (tetanus, diptheria)
• Immonilising bacterial flagella

Agglutination (because of their two binding sites)

• Climping to assist phagocytosis (especially IgM)
• Can precipitate when AB:antigen is 1:1

Opsonisation

• Enhancing phagocytosis through exposure of their FC region for easy binding by neutrophils

Antibody-dependent Cellular Cytotoxicity

• Large granular leukocytes release toxins due to binding, killing the cell

Enhancing the complement cascade

• Classical pathway = early components(C1,4,2) binding to AB and enzymatically cleaving C3a and b from C3 causing chemotaxis and opsonisation.C5 is involved in chemotaxis. C6,7,8 and 9 (late components) lyse the bacterium.

Question 8

Alternative Pathway for complement cascade?

Answer 8

Doesn’t use antibodies

• Early components are still enzymatically cleaved but by C3 convertase into C3a (vasodilation, chemotaxis) and C3b(opsonisation)
• C3b also has a focus on late components assembly into membrane pores to lyse the bacterium

Question 9

What is IgM? what do ya know bout it?

Answer 9

• Largest antibody molecule (pentamer) with effectively 10 antigen binding sites.
• Virtually confined to circulatory pathwats
• About 10% of antibodies
• First primary antibody response and is a very effective agglutinator and efficient complement activator
• Important defense against blood-borne spread of infections arganisms such as bacteria

Question 10

How about IgG now? flex on me?

Answer 10

• Smaller monomer
• 70-75% of the Ig pool and diffuses into extravascular space
• Potent antitoxin antibody and effective barrier against virus infection
• Activelly transported across placenta and is a good complement activator
• Strongly bound by phagocytic cells
• Enhancement of phagocytosis (opsonisation)

Question 11

Almost done…IgA?

Answer 11

• 15-20% of human blood antibodies and is predominant class in sero-mucus secretions
• Main role is protection of external body surfaces
• Surface protection of gut, respiratory and genitourinary systems.

Question 12

IgD?

Answer 12

• Trace amounts in blood and other body fluids
• Found on the surface of antigen-sensitive, naive B cells
• Receptor for antigen binding to activate naive B cells

Question 13

IgE?

Answer 13

• Generally only in trace amounts in people’s blood
• Has a very high affinity for mast cells (differentiated basophils) and is important in the symptoms of allergic sensitivity
• Also plays historically a role in parasite infections
• Allergens binding to mast cell-associated IgE, activates processes that lead to symptoms of allergen or asthma.