14.3 Immunology: Innate & Adaptive Immunity, the Immune Response, Antibodies, Complement, Cytokines & MHC

Why this area matters

The TOS lists "innate and acquired immunity (functions of immune system, events in the immune response, humoral versus cell-mediated immunity, antigen and antibody interaction), role of cytokines, MHC class I and II". These basics explain how vaccines work, why newborns rely on maternal IgG and breast milk IgA, what serologic tests mean (dengue IgM, HBsAg, anti-HBs) and how immunodeficiencies present.

Innate and adaptive immunity

NK cells kill virus-infected and tumor cells that have lost MHC class I (the "missing self" mechanism) and cells coated with IgG (antibody-dependent cellular cytotoxicity).

Events in an immune response

1. Recognition and capture: dendritic cells take up antigen at the site of entry and carry it to the lymph nodes.
2. Presentation: peptides are displayed on MHC molecules to naive T cells.
3. Activation: this needs two signals: the T-cell receptor binding peptide-MHC (signal 1) plus co-stimulation by CD28 binding B7 (CD80/86) (signal 2). Without signal 2, the T cell becomes anergic.
4. Clonal expansion and differentiation: IL-2 drives proliferation. CD4 cells differentiate into Th1, Th2, Th17 or follicular helper cells, and CD8 cells into cytotoxic cells.
5. Effector phase:
   • Humoral: B cells, helped by T follicular helper cells through CD40L-CD40, undergo class switching and affinity maturation in germinal centers and become plasma cells.
   • Cell-mediated: cytotoxic T cells kill infected cells with perforin, granzymes and Fas ligand, and Th1 cells activate macrophages.
6. Contraction and memory: most effector cells die, and memory B and T cells remain.

Antibodies and antigen-antibody interactions

An antibody has two identical heavy and two identical light chains (kappa or lambda). The Fab fragment binds antigen through the variable regions, which contain the hypervariable regions or CDRs. The Fc fragment determines class functions: complement binding and Fc receptor binding.

Antigen-antibody reactions are non-covalent: hydrogen bonds, electrostatic, van der Waals and hydrophobic forces. Their strength is affinity for a single site and avidity overall. Laboratory uses include:

• agglutination (blood typing, Widal test);
• precipitation;
• ELISA;
• immunofluorescence;
• lateral-flow rapid tests;
• the Coombs test for antibody-coated red cells.

The complement system

All three converge on C3 convertase. C3b is an opsonin. C3a and C5a are anaphylatoxins, and C5a is also a neutrophil chemoattractant. C5b-9 forms the membrane attack complex.

Regulators: C1 esterase inhibitor (its deficiency causes hereditary angioedema), and decay-accelerating factor and CD59 (their loss causes paroxysmal nocturnal hemoglobinuria).

Deficiencies: early classical components (C1, C2, C4) predispose to SLE; C3 deficiency to severe pyogenic infections; and C5 to C9 deficiency to recurrent Neisseria infections.

Cytokines

MHC (HLA) molecules

MHC genes on chromosome 6 are highly polymorphic, which matters for transplant matching. Some disease associations are HLA-B27 (ankylosing spondylitis), HLA-DR3 and DR4 (type 1 diabetes) and HLA-DQ2 and DQ8 (celiac disease).

Immunity and vaccines

• Active immunity comes from infection or vaccination. It is slow to develop but long-lasting, with memory.
• Passive immunity comes from maternal IgG, breast-milk IgA, or immune globulins (rabies, tetanus and hepatitis B immune globulin, antivenom). It is immediate but temporary.
• Live attenuated vaccines (MMR, BCG, oral polio, varicella) induce strong cellular immunity but are generally avoided in pregnancy and severe immunodeficiency.
• Inactivated, subunit, toxoid and conjugate vaccines need boosters.
• Conjugating a polysaccharide to a protein carrier (Hib, pneumococcal conjugate) converts a T-independent response into a T-dependent one that works in infants under 2 years.