Immunology basics

Immunoglobulins

B-lymphocytes when fully differentiated turn into plasma cells which produces antibodies.

Antibodies are present in plasma proteins.

Plasma proteins are negatively charged at body pH.

Globulins are heavy molecular weight molecules of plasma protein which move towards the negative pole in electrophoresis

Albumins are lightest molecular weight molecules (70 KD) of plasma protein which move towards the positive poles in electrophoresis.

Plasma proteins are in globulins. They are part of gammaglobulins

Antibodies = immunoglobulin = gamma globulin

Antibodies are protein molecules which react readily and specifically to antigens that stimulated their synthesis.

Antibodies are glycoproteins. They have a tetrapeptide structure. 2 heavy chains and 2 light chains, both held together by disulfide bonds.

Hypervariable regions are present within the variable regions and impart more specific ab-ag and precision.

Forces that bind: electrostatic and Vanderwaal forces.

Complement system

Complement pathways: classical, alternative, and lectin.

Classical pathway C1 (C1q, r, s), C2, C3, and C5

These are a series of proteins in plasma that augment the function of antibodies. They are a whole series of complementary proteins that complement the immune system and complement the inflammatory reaction.

Complement proteins are produced in the liver and distributed in blood and tissues.

They are proenzymes and are circulated in inactive state. They get activated only in case of immune activity.

Many complements are also elaborated by macrophages.

C1 is mainly produced by GI mucosa.

How does it work?

When a bacterial antigen activates the humoral response IgM, IgG are the only immunoglobulins that activate complement system. A single molecule of IgM or a double molecule of IgG activate complement.

Macrophage takes up the antigen and presents to Th (helper) cells > B cells >>turn into>> plasma cells. Plasma cells secretes antibodies. When ab react with ag there is a change in the tail of ab. The Fc portion of ab has a special loop that becomes available when ab binds to ag. When ab-binds to ag, it undergos a transformational change and exposes special domains in the loop that bind and activate the complementary cascade. In normal state these domains are not exposed and so they do not bind and activate the complement.

IgG or IgM >> bound at Fc portion by C1q > C1 + (C4bC2b = a.k.a C3 convertase) + C3b (a.k.a C5 convertase) >>late events>>C5b+C6+C7+C8+C9

C1 = C1q, C1r, C1s (3 peptides of C1)

C1 does not fragment in C1b and C1a after binding to the Fc portion of Ig.

C3 is the central complement.

C4bC2b is C3 convertase > C3b

C4bC2bC3b is C5 covertase > C5b.

IgG, IgG2, IgG3 can activate complement cascade.

IgG4 cannot activate complement.

C5b binds to C6, C7, then to C7, C8, C9. All of them combined are called MAC (membrane attack complex) which causes a pentameric hole in the bacterial membrane.

Early events in activation of complement: C4b, C2b, C3b.

Terminal events (late) in activation of complement: C5b, C7, C8, C9.

MAC is more effective on gram negative bacteria as they have a thin peptoglycan layer and lipid membrane. It is less effective on gram positive bacteria.

Hypocomplementemia makes a person susceptible to gram negative bacteria like Nesseria gonococci and meningococci. These are more prevalent in patients with terminal hypocomplement deficiency.