1. Host Defense Pathways: Role of Redundancy and Compensation in Infectious Disease Phenotypes 
Simone Nish, Ruslan Medzhitov 
Immunity 
Volume 34, Issue 5, Pages (May 2011)
DOI: /j.immuni
Copyright © 2011 Elsevier Inc. Terms and Conditions

2. Figure 1 Different Types of Host Pathway Interactions
There are three different types of host pathway interactions: cooperation, complementation, and compensation: (A) cooperating pathways induce the same effector mechanism more efficiently when engaged simultaneously; (B) complementing pathways induce distinct effector mechanisms (EM1 and EM2), which complement each other to form one functional unit; and (C) compensation between two pathways occurs when one pathway is deficient and the other intact. Compensation can take place at the level of sensors (C, top), or at the level of effectors (C, bottom). “P” refers to pathogens, “A” and “B” refer to microbial sensors, and “EM” refers to effector mechanisms.
Immunity  , DOI: ( /j.immuni )
Copyright © 2011 Elsevier Inc. Terms and Conditions

3. Figure 2
Compensation between Host Defense Pathways and Its Role in Infectious Disease Phenotypes
Defect in pathway A can be compensated by pathway B in the case of pathogen Px (A), but not in the case of pathogen Py (B). Defect in EM1 can be compensated by EM2 if EM2 is sufficient to provide protection against pathogen Px (C). If EM2 is not sufficient to protect against Py, then EM2 will not compensate for EM1 deficiency (D). Solid lines indicate intact pathways; dashed lines indicate inactive pathways. Pathway deficiency can result from mutations or can be due to pathogen evasion.
Immunity  , DOI: ( /j.immuni )
Copyright © 2011 Elsevier Inc. Terms and Conditions

4. Figure 3
Compensatory Enhancement of Host Defense Pathways Can Result in Immunopathology
If more than one pathway is induced by a given infection, they can provide optimal protection with minimal immunopathology, because they do not have to be induced to a maximal level (A). If one pathway is deficient, the intact pathway will have to be induced to a higher level, thus increasing the potential for tissue damage (B).
Immunity  , DOI: ( /j.immuni )
Copyright © 2011 Elsevier Inc. Terms and Conditions

5. Figure 4
“Redundancy” in Host Defense Pathways Is Conditional on the Nature of Infection
Pathways B is “redundant” when the host is exposed to pathogen Px, but nonredundant when the host is exposed to pathogen Py. Pathways A and B are redundant with regards to the common function (activation of EM1), but nonredundant with regards to activation of EM2. Thus, conclusion of “redundancy” can be affected by both the exposure rates of Px and Py, and by the “readout” (whether EM2 activation is measured or not).
Immunity  , DOI: ( /j.immuni )
Copyright © 2011 Elsevier Inc. Terms and Conditions