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TOPIC
IMMUNO3
FAILURE OF IMMUNE HOST DEFENSES
IMMUNODEFICIENCY DISEASES
• A history of repeated infections suggests a diagnosis of immunodeficiency.
2 TYPES OF IMMUNODEFICIENCIES
1. PRIMARY à
o Caused by inherited gene defects (congenital)
o Most gene defects resulting in immunodeficiency are recessive and many caused by mutations in X
chromosome
o For example SCID caused by mutations in gene IL2RG on X. Encodes IL-2 receptor. Mutation causes problem in
signaling of all 1L-2 family cytokines
§ IL7, IL15 don’t work and so T-cells and NK don’t develop properly
§ Defects in T cell development: no Tcell dependent Ab response nor cell mediated
responses
§ They have severe combined immunodeficiency (SCID)
2. SECONDARYà
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o Acquired as consequence of other diseases or result of other issues such as starvation, medical
intervention
Examples of PRIMARY IMMUNODEFICIENCIES
IMMUNODEFICIENCIE DISEASES CAN HAVE
1) DEFECTS IN T CELL DEVELOPMENT CAN RESULT IN SEVERE COMBINED IMMUNODEFICIENCIES.
2) DEFECTS IN SIGNALING T-CELL ANTIGEN RECEPTORS CAN CAUSE SEVERE IMMUNODEFICIENCY.
3) DEFECTS IN B-CELL DEVELOPMENT RESULT IN DEFICIENCIES IN ANTIBODY PRODUCTION THAT CAUSE
AN INABILITY TO CLEAR EXTRACELLULAR BACTERIA AND SOME VIRUSES.
DEFECTS IN T CELL DEVELOPMENT CAN RESULT IN SEVERE COMBINED IMMUNODEFICIENCIES
§ Pathways that lead to circulating naïve B and T cells
§ Mutations in these pathways are shown in red and are known to cause human
immunodeficiency diseases
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, PROPERTY OF HIGHYIELD HUB CO -DO NOT COPY
DEFECTS IN B-CELL DEVELOPMENT RESULT IN DEFICIENCIES IN ANTIBODY PRODUCTION THAT CAUSE AN
INABILITY TO CLEAR EXTRACELLULAR BACTERIA AND SOME VIRUSES
§ Born with high level maternal IgG (moves across placenta)
§ IgG starts at 6 months; Total IgG falls because maternal IgG catabolized
§ IgG levels are low from 3months to 1 year of infant
§ After birth, IgM starts immediately
PRODUCTION OF BTK GENE IMPORTANT FOR B CELL DEVELOPMENT
§ Stimulation of the Pre B-cell receptor recruits cytoplasmic proteins including BTK (Bruton’s
tyrosine kinase) to transduce a signal that triggers B cell development
DISEASE: BRUTONS X-GAMMAGLOBINEMIA
PRO B CELL CANNOT BE CONVERTED INTO PRE B CELL IN DEVELOPMENT THEREFORE RECEPTOR IS NOT
FUNCTIONAL AND NOT ABLE TO PRODUCE APPROPRIATE SIGNAL
• X LINKED RECESSIVE (MEANING YOU NEED 2 LITTLE R’s to have disease
• In X-linked agammaglobulinema (XLA) the BTK protein gene on X chrom. is defective
• In males with XLA no signal transduced even though receptor is there
• In females half of the pre-B cells will have be expressing the defective BTK gene and will not develop
further. This is since one of the two X chromosomes in each cell is permanently inactivated early in
development
TOPIC
IMMUNO3
FAILURE OF IMMUNE HOST DEFENSES
IMMUNODEFICIENCY DISEASES
• A history of repeated infections suggests a diagnosis of immunodeficiency.
2 TYPES OF IMMUNODEFICIENCIES
1. PRIMARY à
o Caused by inherited gene defects (congenital)
o Most gene defects resulting in immunodeficiency are recessive and many caused by mutations in X
chromosome
o For example SCID caused by mutations in gene IL2RG on X. Encodes IL-2 receptor. Mutation causes problem in
signaling of all 1L-2 family cytokines
§ IL7, IL15 don’t work and so T-cells and NK don’t develop properly
§ Defects in T cell development: no Tcell dependent Ab response nor cell mediated
responses
§ They have severe combined immunodeficiency (SCID)
2. SECONDARYà
,PROPERTY OF HIGHYIELD HUB CO -DO NOT COPY
o Acquired as consequence of other diseases or result of other issues such as starvation, medical
intervention
Examples of PRIMARY IMMUNODEFICIENCIES
IMMUNODEFICIENCIE DISEASES CAN HAVE
1) DEFECTS IN T CELL DEVELOPMENT CAN RESULT IN SEVERE COMBINED IMMUNODEFICIENCIES.
2) DEFECTS IN SIGNALING T-CELL ANTIGEN RECEPTORS CAN CAUSE SEVERE IMMUNODEFICIENCY.
3) DEFECTS IN B-CELL DEVELOPMENT RESULT IN DEFICIENCIES IN ANTIBODY PRODUCTION THAT CAUSE
AN INABILITY TO CLEAR EXTRACELLULAR BACTERIA AND SOME VIRUSES.
DEFECTS IN T CELL DEVELOPMENT CAN RESULT IN SEVERE COMBINED IMMUNODEFICIENCIES
§ Pathways that lead to circulating naïve B and T cells
§ Mutations in these pathways are shown in red and are known to cause human
immunodeficiency diseases
,PROPERTY OF HIGHYIELD HUB CO -DO NOT COPY
, PROPERTY OF HIGHYIELD HUB CO -DO NOT COPY
DEFECTS IN B-CELL DEVELOPMENT RESULT IN DEFICIENCIES IN ANTIBODY PRODUCTION THAT CAUSE AN
INABILITY TO CLEAR EXTRACELLULAR BACTERIA AND SOME VIRUSES
§ Born with high level maternal IgG (moves across placenta)
§ IgG starts at 6 months; Total IgG falls because maternal IgG catabolized
§ IgG levels are low from 3months to 1 year of infant
§ After birth, IgM starts immediately
PRODUCTION OF BTK GENE IMPORTANT FOR B CELL DEVELOPMENT
§ Stimulation of the Pre B-cell receptor recruits cytoplasmic proteins including BTK (Bruton’s
tyrosine kinase) to transduce a signal that triggers B cell development
DISEASE: BRUTONS X-GAMMAGLOBINEMIA
PRO B CELL CANNOT BE CONVERTED INTO PRE B CELL IN DEVELOPMENT THEREFORE RECEPTOR IS NOT
FUNCTIONAL AND NOT ABLE TO PRODUCE APPROPRIATE SIGNAL
• X LINKED RECESSIVE (MEANING YOU NEED 2 LITTLE R’s to have disease
• In X-linked agammaglobulinema (XLA) the BTK protein gene on X chrom. is defective
• In males with XLA no signal transduced even though receptor is there
• In females half of the pre-B cells will have be expressing the defective BTK gene and will not develop
further. This is since one of the two X chromosomes in each cell is permanently inactivated early in
development
