1.2: Immunity, Inflammation, and Infection

What type of disorder is systemic lupus erythematosus (SLE)?

An autoimmune disorder and type III hypersensitivity

What is an autoimmune disorder?

Heterogenous groups of disorders that occur when the body’s immune system fails to differentiate “self” from “non-self” and mounts an immunologic response against the host tissues

How does SLE work?

Autoantibodies (antinuclear antibodies) are produced, which form immune complexes that attack healthy tissue

What are the risk factors of SLE?

Female assigned at birth, sun exposure, vitamin D deficiency, and smoking

How is SLE diagnosed?

• Antinuclear antibodies (ANA): very sensitive, but not very specific

• Anti-double-stranded DNA (anti-dsDNA): better specificity

What is the treatment of SLE?

There is no cure, focus on lifestyle changes (e.g., reducing UV exposure and taking vitamin D supplements)

What is immunodeficiency?

An abnormality of one or more parts of the immune system that results in an increased susceptibility to disease states that are normally eradicated by a properly functioning immune response

What is primary immunodeficiency?

Heritable

What is secondary immunodeficiency?

Acquired later in life

What are some causes of secondary immunodeficiency?

• Malnutrition

• Infection

• Neoplastic disease

• Immunosuppressive therapy

What are the four major categories of immunodeficiency disorders?

• Humoral (antibody) immunodeficiency: B lymphocytes

• Cell-mediated immunodeficiency: T lymphocytes

• Complement-related immunodeficiency

• Phagocytosis-related immunodeficiency: neutrophils and macrophages

How is HIV/AIDS transmitted?

Through sexual contact, blood-to-blood contact, and perinatally

What kind of virus is HIV/AIDS?

A retrovirus (meaning it carries its genetic information in RNA rather than DNA)

Step #1 in the replication of HIV?

Attachment: the virus binds to CD4 receptors and CCR5 T cells

Step #2 in the replication of HIV

The viral envelope fuses to the CD4 T cell membrane, resulting in the uncoating of the virus (which releases 2 single strands of RNA, reverse transcriptase, integrase, and protease into the cell)

Step #3 in the replication of HIV

DNA synthesis: reverse transcriptase converts the single-stranded RNA into double-stranded DNA

Step #4 in the replication of HIV

Integration: integrase inserts the viral DNA into the host’s DNA, creating a provirus that becomes a permanent part of the cell’s genome

Step #5 in the replication of HIV

Transcription: double-stranded DNA forms single-stranded mRNA with instructions to build new viruses

Step #6 in the replication of HIV

Translation: rRNA (ribosomes) use the viral mRNA instructions to make a polyprotein containing several HIV proteins and ezymes

Step #7 in the replication of HIV?

Cleavage/maturation: the viral protease enzyme cuts the polyprotein into individual proteins that make up new viruses

Step #8 in the replication of HIV?

Core proteins migrate to the cell membrane, acquire a lipid envelope, bud off from the cell membrane, assemble, and release

What are the diagnostic methods for HIV?

• ELISA (enzyme-linked immunosorbent assay) to screen for IgG antibodies

  • Western blot antibody detection tests for HIV infection (confirmatory test)

• Polymerase chain reaction (PCR) to detect viral DNA

What are the three phases of HIV?

• Acute infection phase

• Chronic asymptomatic or latency phase

• Overt AIDS phase

What are the characteristics of the acute infection phase?

• Lasts 2-4 weeks

• Rash and flu-like symptoms: fever, fatigue/malaise, myalgias, sore throat, night sweats, GI problems, lymphadenopathy, and headache

• Rapid replication of the virus and depletion of CD4+ T cells

What are the characteristics of the chronic asymptomatic/latency phase?

• Asymptomatic

• May last 10 years or longer, or progress faster without treatment

• People who take HIV treatment may not move to the third phase

What are the characteristics of the overt AIDS phase?

• CD4+ cell count of less than 200 cells/uL or an AIDS-defining illness

• Without antiretroviral therapy, this stage can lead to death within 2-3 years or less