Immunology Basics Quiz

Innate and Adaptive Immune Response (III)

• B cell activation is crucial for humoral immunity
• T-independent activation occurs without T helper cells
  • Polysaccharides bind to BCRs (surface IgD & IgM) on B cells
  • Complement receptors (CD21, CD35) are involved
  • Clinical example: Capsular polysaccharide of Haemophilus influenzae B
• T-dependent activation requires T helper cells
  • B cells bind to antigens using B cell receptors (surface IgD & IgM)
  • The B cell presents the antigen with MHC II complex to activate CD4 T cells
  • CD80/86 on B cells bind to CD28 on T helper 2 cells
  • CD40 on B cells bind to CD40L on T helper 2 cells
• T helper 2 cells release IL-4, IL-5, IL-6, and IL-13
  • This leads to B cell proliferation and differentiation into B memory cells and plasma cells
  • Plasma cells produce and secrete IgM (primary immune response)
• Memory B cells rapidly respond to re-exposure
  • They differentiate into plasma cells producing more IgM, IgG, and IgA (secondary immune response)
• Primary vs. Secondary Immune Response

  Feature	Primary	Secondary
  Exposure	First time	Second, third, or more
  Antigen dose	High	Low
  Antibody type	Primarily IgM	IgM, IgG, IgA
  Onset	Delayed	Rapid
  Duration	Short	Long

Immunoglobulins (Antibodies) (Ig)

• Immunoglobulins (Ig) are glycoproteins
• Mediate humoral immunity
• Produced by plasma cells
• Two forms: membrane-bound (IgM & BCRs) and secreted
• Five classes: three major (IgG, IgM, IgA) and two minor (IgD and IgE)
• Basic structure
  • Four polypeptide chains (two identical heavy chains, two identical light chains) held together by disulfide bonds in a Y-shape
  • Antibody carries one type of light chain (kappa or lambda)
  • Light chains have one variable (VL) and one constant (CL) domain
  • Heavy chains have one variable (VH) and three or four constant (CH) domains
• Functions of different Ig isotypes
  • Block binding of microbes or toxins to cells
  • Opsonization and phagocytosis
  • Antibody-dependent cellular cytotoxicity (ADCC)
  • Activation of the classical complement pathway by IgG and IgM

Complement System

• Circulating and membrane-associated proteins that function in both innate and adaptive immune responses
• Synthesized in the liver and present in inactive forms in serum
• Components include C1 to C9 and factors B, D, and P
• Complement Pathways
  • Classical pathway (adaptive): activated by antigen-antibody complexes (IgM & IgG)
  • Mannan-binding lectin pathway (innate): MBL binds to mannose residues on microbes, activating MBL-activated serine proteases (MASP1 & MASP2)
  • Alternative pathway (innate): bacterial endotoxin (LPS) directly produces spontaneous breakdown of C3 (C3a & C3b)
• Functions of the Complement system
  • Complement-mediated lysis: the membrane attack complex (MAC) induces osmotic lysis of target cells
  • Opsonization and phagocytosis: (C3b or C4b) enhancing phagocytosis of microbes by binding to them.
  • Mediators of inflammation and chemo-attractants to phagocytes: (C3a, C4a, C5a)

Study Questions

• Classical Pathway initiation
  • Antigen-antibody complexes (IgM and IgG)
• Alternative Pathway initiation
  • Lipopolysaccharides (LPS) of gram-negative bacteria

Cytokines

• Cytokines have various clinical uses (e.g., treatment of thrombocytopenia, bone marrow recovery, anemia with renal failure)