immunodeficiency

Failure of one or more parts of the immune system to protect against pathogens

Immunodeficiency

• Present from birth

• Loose categorization of affecting innate or adaptive immune systems

Primary immunodeficiency

T cell deficiency

Opportunistic infection pneumocystis causes defect

B cells

Opportunistic recurrent bacterial infections cause defect of

Complement

Opportunistic Neisseria / meningococcal infections cause defect in

Can be due to many factors ex. Injury or infections

Secondary/acquired immunodeficiency

• AKA primary immunodeficiency

• Due to genetic or developmental factors

• Common causes a defects in signal transduction or cellular communication

Inborn errors of immunity

• combined (disrupt adaptive)

• B-cell (decreased production of 1+ AB types)

• Disruption to innate components

• Complement

• Disruption in immune regulation (can present as autoimmunity)

Types of primary immunodeficiencies

• low number of circulating lymphocytes

• Failure to mount T cell mediated responses

• Thymus is not developed

Characteristics of severe combined immunodeficiency

• IL2RG

• JAK3

• ADA

• RAG1/2

Common causes of severe combined immunodeficiency

• severe and recurrent infections

• Usually fatal in early life, early detection increases survival rate

Effects of severe combined immunodeficiency

• in the past the patient was confined to a sterile environment

• Now marrow transplants and gene therapy to repair leukocytes is used

Severe combined immunodeficiency treatment

Treated via replacement therapy

• replacement of missing protein

• Replacement of missing cell type or lineage

• Replacement of missing or defective gene

Immunodeficiency treatments

Has 2 RNA genomes and a reverse transcriptase enzyme

Structure of the HIV-1 virus

• CD4+ T cells

• Dendritic cells in infected areas can take up the virus and pass it to T cells

Affected cells in HIV infection

• HIV binds to cell receptor

• Fusion with cell membrane

• Nucleocapsid enters cell

• Viral genome and enzymes are released

• Reverse transcriptase catalyzes reverse transcription of ssRNA to form RNA-cDNA hybrid

• Original RNA template is degraded and second DNA strand is formed to yield dsDNA

• Viral dsDNA is translocated into nucleus and integrated into host DNA by viral integrase enzyme

Steps of HIV infections

• transcription factors cause transcription of proviral DNA into ssRNA then mRNA

• Viral RNA is exported to cytoplasm

• Host cell ribosomes synthesize viral precursor proteins that are cleaved by viral protease into viral proteins

• HIV ssRNA and proteins assemble beneath host membrane

• Membrane buds out forming viral envelope that when released viral particles complete maturation

Steps of HIV leaving infected cell

• acute: high HIV levels brought down by ABs formed

• Asymptomatic: possibly years long where there is a gradual decrease in CD4+

• AIDS: crash in CD4+ numbers, high HIV levels in blood, untreated opportunistic infections that occur in this stage can be deadly

Effects of HIV stages

• chemokine receptors

• Fusion inhibition

• RT inhibition

• Integrase inhibition

• Protease inhibition

Target steps in HIV cycle by antiretrovirals

• lowers viral load and relief from infection

• Targets specific parts in the viral replication cycle

• Can be prophylactically used

• High mutation rates make individual treatments less useful but combinations can be used

How antiretroviral treatment works