L3

Question 1

What is Anaphylaxis

Answer 1

• Serious, life-threatening allergic rxn
• If you are allergic to a substance, your immune system overreacts to this allergen by releasing chemicals that cause allergy symptoms

Question 2

What are the 4 types of hypersensitivity

Answer 2

ALL REQUIRE PRIMING. Allergic rxn only seen in SECOND exposure onwards.

1. Type 1 Hypersensitivity
   - Systemic anaphylaxis (anaphylactic shock)
   - Localized anaphylaxis
2. Type II (cytotoxic): Rh incompatibility btwn fetal blood and maternal blood. Maternal immune system attacks fetal blood and causes hemolysis.
3. Type III (immune complex): Serum sickness: allergy to serum (component of blood containing Ab)
4. Type IV (delayed): implant rejection, contact dermatitis (e.g. poison ivy)

Question 3

Which immunoglobulin do all types of hypersensitivity produce? Fxn of that immunoglobulin?

Answer 3

All involve IgE produced in response to Ag; IgE binds mast cells and basophils, both release granules with chemical mediators e.g. histamine. Can undergo process called degranulation and elicits much greater response than needed.

Question 4

Describe systemic anaphylaxis and how is it treated?

Answer 4

• Results when an individual sensitized to an antigen is exposed to it again
• May result in circulatory collapse and death
• Treated with epinephrine

Question 5

Describe localized anaphylaxis (allergy) and how is it treated?

Answer 5

• Usually associated with ingested or inhaled Ags
• Symptoms depend on the route of entry
• E.g. Hives, hay fever, and asthma
• Treatment vary depending on the issue e.g. asthma with bronchodilator

Question 6

Describe molecular mechanism of allergic contact dermatitis

Answer 6

Allergic response to things such as poison ivy, cosmetics, metals in jewelry, and latex. Using poison ivy as an example, individuals are not allergic to plant compounds themselves but once the compounds (called haptens; general term for such molecules) enter the skin and combined with proteins in the skin, producing an immune response.

PRIMARY CONTACT:

• No dermatitis
• Lasts for 7-10 days
• Sensitization step, T cells will create T memory cells

SECONDARY CONTACT

• 1-2 days
• Many active T cells
• Leads to dermatitis

Question 7

How to identify environmental factor causing dermatitis?

Answer 7

• Usually be determined using a patch test

- Samples are taped to the skin; after 48h the area is tested for inflammation

Question 8

What are auto immune disorders? Describe the mechanisms underlying autoimmune disorders.

Answer 8

Group of >40 diseases. Loss of self-tolerance, loss of appropriate thymic selection. T and B cells recognize self components as foreign.

Question 9

Do they affect each sex the same, why or why not?

Answer 9

1. Rare, but disproportionally affect women (~75% affect females). Possible explanation is that in mice, there are more auto-Ab producing cells in females, # increases with age. These cells activate with Toll like receptor (on X chromosome) = higher levels of Toll like receptor expression?

Question 10

Example of 2 autoimmune diseases that don’t involve cytotoxicity of healthy cells and their mechanism? Phenotypic symptoms?

Answer 10

Both diseases involve Ab reacting to cell-surface Ags, no cytotoxic destruction of cells

Grave’s Disease:

• abnormal Abs that mimic Thyroid Stimulating Hormone so the thyroid goes into overdrive and get overproduction of T3/T4
• goiter, bulging eyes

Myasthenia gravis:

• muscle weakening due to production of abnormal Abs that target nAChR on NMJ. Ab binds to nAChR, blocking them to inhibit —-.
• fatigue, ptosis, paralysis

Question 11

Example of 3 autoimmune diseases that involve cytotoxicity of healthy cells and their mechanism? Phenotypic symptoms?

Answer 11

Cell-mediated autoimmune reactions involves cytotoxicity of healthy cells

1. Multiple sclerosis
   - a progressive neurodegenerative disorder that often begins in early adulthood (females 2x more often than males)
   - T cells and macrophage attack the MYELIN sheath (either CNS or PNS). Decreases conduction velocity of nerve transmission causing cognitive/motor related effects.
   - Symptoms range from weakness and fatigue to severe paralysis
   - Genetic components, likely infectious agent acquired during early adolescence
2. Type 1 Diabetes:
   - T cells
3. Psoriasis:
   - itchy, red patches of thickened skin
   - Due to aberrant activity in T cells there is hyperproliferation of keratinocytes

Question 12

What is the immune system’s effect on cancer? Evidence? Three limitations?

Answer 12

1. Cancer cells are removed by IMMUNE SURVEILLANCE
2. Cell-mediated immunity likely EVOLVED to COMBAT CANCER (cancerous growth represented a failure of the immune system)
   - > Supported by observation that cancers most often occur in old (or very young, or immunosuppressed) individuals
3. Cancer cells have tumor-associated Ags that mark them as non-self
4. CTLs and macrophages lyse cancer cells
5. Limitations
   - Although cancer cells are expressing receptors/molecules that mark it as non-self, there is no antigenic epitope for the immune system to target.
   - Tumor cells reproduce too rapidly to eliminate
   - Tumor becomes vascularized, once it has its own blood supply it becomes invisible to the immune system

Question 13

What are 2 therapeutics to combat cancer

Answer 13

PREVENTATIVE

1. Vaccines used for prophylaxis
   - Involve inactivated/heat-killed pathogen with Ag injected into body
   - Gardasil for cervical cancer caused by HPV, Hep B can cause liver cancer

TREATMENT

2. Monoclonal Abs
   - Monoclonal Abs are a pool of Ab that recognize the same epitope
   - E.g. Break cancer is associated with overexpression of HER2. Herceptin (monoclonal Ab) for breast cancer neutralizes HER2
   - E.g. forming immunotoxin. Immunotoxin combines a MAb with a toxic agent. MAB will bind to target/cancer cell and whatever toxin it’s carrying will kill cancer cell. Theoretically, targets and kills a tumor without damage to healthy cells

Question 14

What does AIDs stand for

Answer 14

Acquired Immunodeficiency Syndrome

Question 15

Describe the discovery of AIDs? How does HIV fxn

Answer 15

1981 (U.S): cluster of cases of Pneumocystis pneumonia, Kaposi’s sarcoma, and loss of immune function discovered in young gay men
1983: discovery of a virus causing the loss of immune function (HIV)

• Selectively infects T helper cells

Question 16

What is HIV likely derived from?

Answer 16

• There are 2 types of HIV, HIV-1 and HIV-2; thus 2 species jumps had to occur. HIV-1 is more common than HIV-2 (less pathogenic, mainly present in Africa)
• HIV-1 likely was derived from SIVcpz crossing over into the human population in Africa from chimps (~1908). Bushmeat was a source of protein, consumption of undercooked primate meat would’ve led to the crossover event.
• HIV-2 likely was derived from SIVsmm crossing over into the human population in Africa from sooty mangabey. Again since bushmeat was a source of protein, consumption of undercooked primate meat would’ve led to the crossover event.
• Spread throughout Africa as a result of urbanization and increased sexual promiscuity

Question 17

Draw a HIV molecule and label its parts

Answer 17

Slide 9

1. Core containing viral RNA
2. Reverse transcriptase enzyme (inside core)
3. Protein coat
4. Capsid
5. Glycoprotein spike: gp120 and g40 (transmembrane protein)
6. Lipid envelope

Question 18

Describe the HIV attachment to Host and draw a diagram to go along

Answer 18

1. ATTACHMENT: The gp120 spike attaches to CD4 receptor AND CCR5/CXCR4 coreceptor on the CD4+ T cell
2. FUSION: The gp41 participates in fusion of the HIV w/in the cell
3. ENTRY: Following fusion w/the cell, an entry pore is created. After entry, the viral envelope remains behind and the HIV uncoats, releasing the RNA core for directing synthesis of the new viruses. Reverse transcriptase will convert viral RNA into dsDNA that will be integrated into host genome by enzyme integrase. At this stage it is called a provirus. This makes it hard for immune system to detect the virus because it is now in the genome, and not as antigens.

Question 19

How can someone be immune to HIV?

Answer 19

Those with mutant CCR5 receptor or don’t express, are resistant to HIV.

Question 20

Compare and contrast latent and active HIV infection

Answer 20

1. LATENT INFECTION: Viral DNA integrated into cellular DNA as a PROVIRUS (viral DNA that’s been incorporated into host genome) that can later be activated to produce infective viruses. Thus, DNA is hidden from chromosome as a provirus.
2. ACTIVE INFECTION: The provirus is activated, allowing it to control the SYNTHESIS of new viruses. Viral DNA undergoes transcription and translation to get viral proteins and components of HIV cell like GP120 and GP41. Final assembly takes place at the cell membrane, taking up the viral envelope proteins as the virus BUDS from the T cell. Thus the new capsid is made from the host cell’s membrane.

Question 21

How can an HIV test still be able to detect virus even in latent phase?

Answer 21

HIV test looks for Abs against virus, so even in latent phase of infection still making Abs against virus.

Question 22

Why is HIV difficult to target with drugs and difficult to develop a vaccine?

Answer 22

1. HIV transcription and reverse transcriptase is error prone. Thus virus undergoes rapid antigenic changes and a high rate of mutation. Usually in HIV-infected individual, there’s a number of subtypes of the virus due to all the mutations that have occurred.
2. Once integrated into host genome, hard to detect esp because no Ags.

Question 23

Describe the phases of the HIV cycle and draw using a diagram OF SOMEONE NOT RECEIVING ANTI-HIV MEDS

Answer 23

3 phases:
Phase 1 - Asymptomatic or chronic lymphadenopathy
Phase 2 - Symptomatic; early indication of immune failure
Phase 3 - AIDS indicator condition

PHASE 1 (~Day 1 - 3 years)
1. Shortly after infection, viral load skyrockets. Flu like symptoms. ~2 months following initial infection, the population of HIV in the blood peaks at ~10mil per mL. 

2. Population of CD4+ T cells plunges during acute phase of HIV infection, then recovers as immune response appers.
3. Seroconversion: Detectable Abs against HIV appear, immune response causes rapid decline in HIV population
4. HIV in blood stabilizes at steady rate of 1000-10,000 per mL

PHASE 2 (~3 years - 8 years)
5. CD4+ T cell population declines steadily

6. Clinical latency or CHRONIC HIV infection can last up to 10years+, HIV continues to multiply
7. Clinical AIDS: CD4+ T cell population drops to 200cells/microL. AIDS is the final stage in HIV infection.

PHASE 3 (~8 years+)
8. HIV lvls in blood rise as the immune system breaks down. Death is usually due to secondary infection e.g. pneumonia cause immune system so weakened it can't mount an immune response.

Question 24

How can HIV be treated?

Answer 24

No cure for HIV but combo of anti-HIV meds (antiretroviral therapy) are recommended treatment. Individuals undergoing treatment can still transmit disease. Meds work in variety of ways: disabling or stopping proteins from making more copies of HIV, disrupting build blocks needed for viral replication, or blocking entry of virus into cells

Question 25

What is the clinical definition of AIDS?

Answer 25

CD4+ T cell population drops to 200cells/microL and one disease commonly associated with AIDS e.g. myobacterium tuberculosis.

Question 26

Give an example of a pathogen or disease associated with AIDS and disease description

1. Protozoa
2. Virus
3. Bacteria
4. Fungi
5. Cancers or Precancerous conditions

Answer 26

1. Protozoa
   a) Pathogen/Disease: Toxoplasma gondii
   b) Disease description: Encephalitis
2. Virus
   a) Pathogen/Disease: Herpes Simplex Virus
   b) Disease description: Vesicles of skin and mucous membranes
3. Bacteria
   a) Pathogen/Disease: Myobacterium tuberculosis
   b) Disease description: Tuberculosis
4. Fungi
   a) Pathogen/Disease: C. albicans
   b) Disease description: Overgrowth in esophagus, lungs (phase 3 stage of HIV infection)
5. Cancers or Precancerous conditions
   a) Pathogen/Disease: Cervical Dysplasia
   b) Disease description: Abnormal cervical growth