Table 1.

The clinical outcome and the B and T cell memory responses after exposure to influenza viruses are summarized below.

	Influenza antigenic site change
	Antigenic drift Genetic changes in Ag sites alter Ab binding			Antigenic shift
	None	Minimal	Major	Exchange of surface Glycoproteins
Clinical outcome	Little to no symptoms		Unpredictable (135)	Dependent of CD8+ T cell response •Limited by HLA alleles (136, 197) •Prior exposure to influenza (137–139) T cell memory pool and quality of T cell response (137–139) ⇒ Severe to fatal outcome with prolonged hospitalizations (137)
B cell response	Robust memory B cell response and protective Ab production (135)	Dominated by memory B cells against preserved antigenic sites, yielding a protective but focused Ab response that may not protect against future drift.	Cross-reactive memory B cells produce an early unadapted Ab response to limit virus replication and symptoms, and enter GC reactions to generate updated memory and PCs If enough Ag available, naïve B cells react and generate updated B cell memory	Very limited (if any) protection by memory B cells (31, 140)Response driven by naïve B cells
CD8+ T cell response	Cross-reactive Not responsive if B cells neutralize the virus			Cross-reactive but not neutralizing immunityHost-specific differences