ch18 - immunological disorders

immunological disorders

Due to overstimulation of the immune system:

• Hypersensitivity – Abnormal, exaggerated immune response to harmless antigens (allergens) leading to damage of host tissues

  • Allergies (pollen, pet dander, penicillin, peanuts), tissue transplant rejection

• Autoimmune disease - when the immune system mistakenly attacks the body’s normal tissues

  • May occur after a serious infection

  • Can be organ-specific or systemic

  • Examples:

    • Rheumatoid arthritis

    • Type 1 diabetes

    • Lupus

Due to failures of the immune system

• Immunodeficiency: when the body cannot initiate or sustain an adequate immune response to prevent infection

  • Immunocompromised – vulnerable to infections

  • HIV – attacks helper T cells → shuts whole immune system down

immunodeficiency disorders; primary (congenital) - present at birth

Primary immunodeficiencies – rare

• Due to genetic defect (defective/missing genes)

• May affect B cells, T cells, natural killer cells, phagocytes, or complement components

• Examples

  • Selective IgA deficiency - most common

    • Little or no IgA is produced

  • DiGeorge syndrome

    • Recessive trait → no thymus gland (no T cells produced)

    • Treated with thymus cell transplant

  • Severe combined immunodeficiency disorder (SCID)

    • Neither B nor T lymphocytes are produced

    • Infections kill at early age

    • Cure with stem cell transplant

immunodeficiency disorders; secondary (acquired) - develops over an individual's life

Secondary immunodeficiencies - Acquired problems with immune function due to:

• Infection/disease, malnutrition, cancer, aging, or immunosuppressive drugs

• Depletion of certain immune cells

  • Measles virus - memory cells

  • HIV - CD4 helper T cells → AIDS

• Most serious widespread immunodeficiency is AIDS

immunodeficiencies

HIV/AIDS

• Viral STI

• TH (CD4) cells affected

Acquired Immunodeficiency Syndrome (AIDS)

1981

• U.S.: discover cluster of Pneumocystis pneumonia and Kaposi's sarcoma in young homosexual men; men showed loss of immune function.

1983

• Discovery of virus – HIV (human immunodeficiency virus)

HIV infection is not synonymous with AIDS

• HIV infection - virus enters body and is replicating

• HIV disease - infection is causing signs, symptoms

• AIDS - final stage of HIV disease

Causative agent: HIV

• Retrovirus (Lentivirus)

• Structure

  • Envelope with spikes

  • Protein capsid

  • Core:

    • Two copies of ssRNA

  • Three enzymes

    • Reverse transcriptase

    • Protease

    • Integrase

• Infect CD4 cells

origin of HIV

• Ancestor: endemic to monkeys/chimpanzees in Africa

• Between 1884 and 1924: Crossed to humans via infected blood when animals skinned and used as food

• Spread:

  • In Africa via urbanization and unsafe sexual practices

  • Throughout world via modern transportation and unsafe sexual practices

• 1970s: Enters United States

subtypes of HIV

HIV-1

• Related to viruses that infect chimpanzees and gorillas

• 99% of cases

HIV-2

• Related to viruses that infect monkeys and sooty mangabeys

• Not often encountered outside of Africa

• Less pathogenic than HIV-1

HIV

1. HIV attachment: HIV binds to CD4 cells (CD4 receptor + CCR5 or CXCR4 coreceptor)

• CD4 receptor: HIV's gp120 glycoprotein attaches to the CD4 receptor on the host cell.

• Coreceptor: HIV must also bind to a second receptor:

  • CCR5 – commonly found on macrophages and some T cells.

  • CXCR4 – commonly found on T cells.

2. Membrane fusion of HIV with cell

• HIV's gp41 glycoprotein helps the viral envelope fuse with the host cell membrane.

3. HIV entry

• The viral capsid (containing HIV RNA and enzymes) enters the host cell's cytoplasm.

• envelope remains behind

HIV infection

Inside the cell

• Viral RNA transcribed into cDNA using reverse transcriptase

• cDNA integrated into host's chromosomal DNA (integrase)

Acute infection symptoms (6 days to 6 weeks post-infection)

• Fever

• Head and muscle aches

• Enlarged lymph nodes

• Rash

Progression of HIV infection

acute infection

• acute retroviral syndrome (temporary flu-like symptoms) may occur

clinical latency

• asymptomatic interval

• cd4 lymphocytes

AIDS

• lymph node enlargement, fever, weight loss, fatigue, diarrhea, etc.

• opportunistic infections, malignant tumors

• circulating culturable HIV

• death

diseases associated with AIDS

Fungal infections

• Cryptosporidium hominis

• Pneumocystis jirovecii

• Histoplasma capsulatum

• Cryptococcus neoformans

• Candida albicans

Toxoplasma gondii

Herpes simplex virus

• Kaposi’s sarcoma

Varicella-zoster virus

• Shingles

survival with HIV infection

80% of HIV cases → AIDS (up to 10 years or more)

• Immune system slowly loses

• CD4 count steadily falls

Atypical cases (other 20%)

1. Disease progresses rapidly to AIDS within months

2. Long-term non-progressors

• Disease progresses slowly → do not experience fall/infection in CD4 cells

  • May be AIDS free for 20 years

  • Mechanism not known

  • have immune systems that are better able to control HIV replication, limiting damage to CD4 cells

3. Exposed, but not infected

• No CCR5 gene → no coreceptor

• Mutated CCR5 gene (CCR5-delta32 mutation) → smaller, so no longer on outside of cell

  • People immune to or has some protection against HIV infection

Mutation occurs in 20% of Caucasians of northern Europe descent → may have confer resistance to smallpox

diagnostic methods

Rapid diagnostic tests (RDTs) – most common

• Detects presence/absence of HIV antibodies in blood or oral fluid and/or antigens in blood

  • FDA approved HIV self-tests

  • In clinical labs – ELISA (looks for HIV antibodies) or western blotting

PCR – detects HIV nucleic acid (viral RNA/DNA)

• PCR amplifies specific segments of HIV genetic material, making them easier to detect

• Can measure plasma viral load (PVL) → number of viruses within a sample

• HIV testing: essential for preventing HIV transmission and prompt treatment

HIV transmission

Requires direct contact with infected body fluids:

• Sexual contact

• Blood-contaminated needles

• Blood transfusion/organ transplants

• Artificial insemination

Vertical transmission:

• Transplacental infection of fetus, during birth, or breastfeeding

• Without intervention, transmission rates can be 15–45%

Not spread by insect bites or casual contact

Worldwide

• Most common mode: Heterosexual intercourse

• Other mode: Injected drug use (IDU)

USA - 2024, 38,793 new cases of HIV

• New HIV Diagnoses by Transmission Category

Global HIV Statistics, 2025

U.S. Epidemic 2024

New HIV infections: over 38,793

• Highest rate among men

• Highest rate among those aged 25-34

New HIV infections: over 38,793

• Highest rate among people of color (73%)

People living with HIV/AIDS: 1,158,701

• 86% of people infected knew; 14% didn’t know

Deaths: 4,296

• Males (77%)

• Black/African American persons (41%)

Initiative to end HIV epidemic

treatment of HIV infections

• No cure, but can be controlled

  • HIV integrates its genetic material into the host cell's DNA (provirus).

  • Can remain latent inside host cells, forming reservoirs.

  • Difficult to eliminate because medications cannot completely remove latent HIV from every infected cell.

  • ART prevents viral replication and allows people with HIV to live long, healthy lives

• AIDS now considered a treatable chronic disease in the developed world

• Medications (antiretrovirals)

  • Designed to block replication of HIV - prolongs life by reducing viral load

  • Generally, cocktails of different drugs (pills)

    • Shots considered for cases with undetectable viral load

Classes of FDA-approved drugs: All prevent entry or replication of virus

• Fusion/entry inhibitors

• Reverse transcriptase inhibitors

• Integrase inhibitors

• Protease inhibitors

• Tetherins

drugs that inhibit HIV life cycle

Fusion/entry inhibitors

• Targets the gp41 protein

• Stops fusion of HIV with CD4 cells preventing HIV entry

• if they cant attach, they cant fuse, and therefore cant enter and infect the host cell

Reverse transcriptase inhibitors

• RNA genome is converted into DNA molecule

• Both stop the function of reverse transcriptase

  • Nucleoside reverse transcriptase inhibitors (NRTIs)

  • Non-nucleoside reverse transcriptase inhibitors (NNRTIs)

• very essential step in infection will be stopped → prevents the virus from converting its RNA genome into DNA, preventing further viral replication

Integrase inhibitors

• integrase is the enzyme that incorporates viral DNA (cDNA) into the host cells chromosome

• Inhibit integration of cDNA into host chromosome

Protease inhibitors

• Inhibit cleaving of viral precursor proteins into structural and functional proteins

• protease: an enzyme that cuts large viral precursor proteins into smaller, functional proteins needed to assemble new viruses

  • protease cuts up the protein into individual parts, including proteins needed to form the capsid

• if protease is inhibited, the viral proteins remain as long, unprocessed precursor proteins and cannot properly assemble into mature, infectious viruses. this prevents the virus from becoming fully functional and inhibits replication strand

Tetherins

• Tether viruses to cells, preventing release

treatment: chemotherapy

Highly Active Antiretroviral Therapy (HAART) or HIV ART:

• Began in 1997

• A combination of at least three of the above drugs (NRTIs, NNRTIs, etc)

• Prevent resistance: if it’s resistant to one hopefully the other ones will work

32.1 million people [28.2 million-33.4 million] were accessing antiretroviral therapy in 2025

• a lot more people are living longer bcuz of that

HIV prevention

Sexual Contact

• Abstinence

• Use of condoms

• Take PrEP (pre-exposure prophylaxis) medicine

• Regular testing

Blood

• Blood and blood product screening

• Never share needle

• Take PEP (post-exposure prophylaxis)

Vertical transmission

• Chemotherapy

• Cesarean section delivery

• No breast feeding

Health-case workers

• Use universal precautions

  • Wear gloves, gowns, masks, goggles

  • don’t recap needles

Vaccine prospects

• No FDA approved vaccine

• Challenges

  • High error rate for reverse transcriptase → Mutations

    • HIV frequently changes its genetic makeup, making it difficult for the immune system to recognize it

  • Different clades/subtypes

    • HIV has different genetic variations (strains), making it difficult to create one vaccine that protects against all of them

  • Proviruses/Latent viruses

    • difficult to target because the virus hides inside the host cell’s DNA and may not produce viral proteins for the immune system to recognize