10.10 HIV Flashcards
The spleen is an important site for storage of _ and _
The spleen is an important site for storage of platelets and lymphocytes (B & T)
* The spleen is considered a secondary lymphoid organ
The spleen also filters the blood and removes _
The spleen also filters the blood and removes damaged RBCs/ platelets
The spleen is also the site of _ before the development of bone marrow
The spleen is also the site of hematopoiesis before the development of bone marrow
The (red/ white) pulp of the splenic parenchyma functions to filter out the damaged RBCs from circulation and is involved in lymphocyte development
The red pulp of the splenic parenchyma functions to filter out the damaged RBCs from circulation and is involved in lymphocyte development
* We have more red pulp than white in our spleens
The white pulp in the spleen serves the main function as _
The white pulp in the spleen serves the main function as repository for lymphocytes
* Acts as a secondary immune organ
The spleen is located in _ quadrant of the body
The spleen is located in left upper quadrant of the body
* Inside the peritoneum
* It is the largest lymphovascular organ
The spleen is located (in front/ behind) the stomach and (above/ below) the diaphragm
The spleen is located behind the stomach and below the diaphragm
The two main functions of the splenic capsule are to _ and _
The two main functions of the splenic capsule are to:
1. Discharge RBCs into circulation
2. Stretch to accommodate incoming RBCs
The contractile cells found in the spleen are called _ ; they help discharge RBCs into circulation
The contractile cells found in the spleen are called myofibroblasts; they help discharge RBCs into circulation
The splenic capsule also has a layer of dense _ that will stretch to accommodate incoming blood cells as needed
The splenic capsule also has a layer of dense fibroelastic tissue that will stretch to accommodate incoming blood cells as needed
At the hilum, the splenic capsule forms septa called _ that pierce the splenic parenchyma so that the splenic artery, vein, lymphatics, and nerves can get send blood out
At the hilum, the splenic capsule forms septa called trabeculae that pierce the splenic parenchyma so that the splenic artery, vein, lymphatics, and nerves can get send blood out
The _ ligament connects the spleen to the greater curvature of the stomach
The gastrosplenic ligament connects the spleen to the greater curvature of the stomach
* Also contains the gastric arteries and veins and the gastroepiploic artery and vein
The _ ligament connects the spleen to the left kidney; it also contains the splenic artery and vein as well as the tail of the pancreas
The splenorenal ligament connects the spleen to the left kidney; it also contains the splenic artery and vein as well as the tail of the pancreas
The splenic artery is a branch off of the _ artery and it enters and exits the spleen at the _
The splenic artery is a branch off of the celiac artery and it enters and exits the spleen at the hilum
The splenic vein travels towards the liver and merges with the superior mesenteric vein to form the _
The splenic vein travels towards the liver and merges with the superior mesenteric vein to form the portal vein
The splenic lymph nodes are found at the _ , next to the _
The splenic lymph nodes are found at the hilum , next to the tail of the pancreas
In open circulation, blood first enters the _ before RBCs can move through the sinusoids and back into circulation
In open circulation, blood first enters the splenic cords before RBCs can move through the sinusoids and back into circulation
What are splenic cords?
Splenic cords are extravascular structures that contain tissue macrophages that phagocytose the old RBCs
* They also contain reticular cells and connective tissue as support
During open circulation, RBCs will percolate through the splenic cords; then the healthy ones re-enter the circulation through the _
During open circulation, RBCs will percolate through the splenic cords; then the healthy ones re-enter the circulation through the splenic sinusoids
Explain the components of the slit-like openings in the spleen
Stave cells are elongated endothelial cells
* They are surrounded by reticular fibers, in a barrel like fashion
Only (damaged/ healthy) RBCs pass through the slits in the spleen
Only healthy, nonsenescent RBCs pass through the slits in the spleen –> enter the sinusoids –> return to circulation
* Damaged RBCs are inflexible and cannot pass through the slits; they are left behind to be phagocytosed by macrophages in the splenic cords
The two structures found in the white pulp are _ and _
The two structures found in the white pulp are periarteriolar lymphoid sheath (PALS) and splenic follicles
The PALS component of the white pulp mostly contains (B cells/ T cells)
The PALS component of the white pulp mostly contains T cells
The splenic follicles component of the white pulp mostly contains (B cells/ T cells)
The splenic follicles component of the white pulp mostly contains B cells
The center of the follicle is called the _ and contains the activated B cells
The center of the follicle is called the germinal center and contains the activated B cells
The _ lies just outside of the germinal center (follicle) and it contains _
The mantle zone lies just outside of the germinal center (follicle) and it contains resting B cells
The _ zone is found outside of the mantle zone, it is an important link between B-cell containing follicles and the T-cell containing PALS
The marginal zone is found outside of the mantle zone, it is an important link between B-cell containing follicles and the T-cell containing PALS
Maraviroc & Enfuvirtide
Maraviroc & Enfuvirtide: HIV entry and fushion inhibitor
Tenofovir
Emtricitabine
Lamivudine
Abacavir
Zidovidine (AZT)
Didanosine
Stavudine
Tenofovir
Emtricitabine
Lamivudine
Abacavir
Zidovidine (AZT)
Didanosine
Stavudine
NRTIs - Reverse transcription inhibitors (nucleotide/ nucleoside)
Efavirenz
Nevirapine
Rilpivirine
Etravirine
Doravirine
Efavirenz
Nevirapine
Rilpivirine
Etravirine
Doravirine
NNRTIs- Reverse transcrption inhibitors (non-nucleoside)
Raltegravir
Elvitegravir
Dolutegravir
Bictegravir
Cabotegravir
Raltegravir
Elvitegravir
Dolutegravir
Bictegravir
Cabotegravir
Integration inhibitors
Darunavir
Atazanavir
Fosamprenavir
Indinavir
Lopinavir
Ritonavir
Saquinavir
Darunavir
Atazanavir
Fosamprenavir
Indinavir
Lopinavir
Ritonavir
Saquinavir
Budding/ maturation (protease inhibitors)
Maraviroc is a drug that prevents the binding of HIV to human cells by blocking the receptor, _
Maraviroc is a drug that prevents the binding of HIV to human cells by blocking the receptor, CCR5
Enfuvirtide blocks the entry of HIV by binding to glycoprotein _
Enfuvirtide blocks the entry of HIV by binding to glycoprotein gp41
* Becomes exposed once HIV binds to gp120
Tenofovir is an HIV nucleotide reverse transcriptase inhibitor that acts as a _ analog
Tenofovir is an HIV nucleotide reverse transcriptase inhibitor that acts as a adenosine analog
Emtricitabine & lamivudine are HIV nucleotide reverse transcriptase inhibitors that act as _ analogs
Emtricitabine & lamivudine are HIV nucleotide reverse transcriptase inhibitors that act as cytosine analogs
Abacavir is an HIV nucleotide reverse transcriptase inhibitor that acts as a _ analog
Abacavir is an HIV nucleotide reverse transcriptase inhibitor that acts as a guanosine analog
Zidovudine (AZT) is an HIV nucleotide reverse transcriptase inhibitor that acts as a _ analog
Zidovudine (AZT) is an HIV nucleotide reverse transcriptase inhibitor that acts as a thymidine analog
Non-nucleoside reverse transcriptase inhibitors inhibit reverse transcriptase by _
Non-nucleoside reverse transcriptase inhibitors inhibit reverse transcriptase by binding directly to reverse transcriptase
One advantage to _ inhibitors is that they do not affect cholesterol or trigglycerides
One advantage to integrase strand transfer inhibitors is that they do not affect cholesterol or trigglycerides
_ inhibitors inhibit the final step of replication when polyprotein chains get chopped into smaller proteins that are mature HIV units
Protease inhibitors inhibit the final step of replication when polyprotein chains get chopped into smaller proteins that are mature HIV units
Protease inhibitors often require a booster of a CYP450 inhibitor, like _ or _
Protease inhibitors often require a booster of a CYP450 inhibitor, like ritonavir or cobicistat
Combination therapy is often used against HIV: including the use of two _ and one _
Combination therapy is often used against HIV: including the use of two NRTIs and one INSTI
In the US, the most common resistance to HIV medications is to _ class of drugs
In the US, the most common resistance to HIV medications is to NNRTIs class of drugs
The use of NRTIs can lead to mitochondrial toxicity, such as _ or _
The use of NRTIs can lead to mitochondrial toxicity, such as pancreatitis or neuropathy
_ is known to cause kidney injury or bone loss
Tenofovir is known to cause kidney injury or bone loss
* Due to reduced reabsorption of PO4- in the PCT
_ is known to cause bone marrow suppression (neutropenia)
Zidovudine is known to cause bone marrow suppression (neutropenia)
_ can cause pancreatitis
Didanosine can cause pancreatitis
_ is known to cause CNS toxicity and QT prolongation & changes in hepatic enzymes
Efavirenz is known to cause CNS toxicity and QT prolongation & changes in hepatic enzymes
Protease inhibitors may cause issues with _ or _
Protease inhibitors may cause issues with diabetes/ insulin resistance or hyperlipidemia/ dyslipidemia
_ may cause severe rash and fever and elevated liver enzymes
Darunavir may cause severe rash and fever and elevated liver enzymes
Efavirenz is an NNRTI that (induces/ inhibits) CYP450
Efavirenz is an NNRTI that induces CYP450
For high risk populations, PrEP can be adminstered; this is a combination of _ and _
For high risk populations, PrEP can be adminstered; this is a combination of tenofovir and emtricitabine
_ and _ are two examples of opportunistic infections that are more likely to occur in HIV patients
P jiroveci pneumonia and toxoplasmosis are two examples of opportunistic infections that are more likely to occur in HIV patients
Kaposi sarcoma
Kaposi sarcoma is a vascular tumor caused by herpesvirus 8 that causes brown and purple blotchy lesions in organ systems, mucous membranes, and on the skin
Life cycle of HIV virus
- HIV virus binds and fuses host cell
- HIV releases viral proteins like reverse transcriptase and integrase
- RT converts RNA –> DNA
- Inside the nucleus the DNA gets integrated into host DNA via integrase
- Integrated DNA is transcribed by host cell machinery to make new HIV RNA
- Assembly of viruses
- Protease cleaves mature HIV viruses
HIV damages the immune system by infecting _
HIV damages the immune system by infecting CD4
HIV binds to CD4 and to chemokine co-receptors CXCR4 or CCR5 binding _ and entering via fusion with _
HIV binds to CD4 and to chemokine co-receptors CXCR4 or CCR5 binding gp120 and entering via fusion with gp41
How do HIV patients normally present?
Acute HIV illness may occur 2-4 weeks after infection
* Fever
* Sore throat
* Rash
* Lymphadenopathy
* GI upset
* Myalgia
Might mimic mono
Severely immunocompromised HIV (progression to AIDS) is defined as a CD4 count less than _
Severely immunocompromised HIV (progression to aids) is defined as a CD4 count less than 200 mm3
We often diagnose HIV with _ test, which can detect antibodies; we confirm with HIV-1/ HIV-2 differentiation ELISA and Western blot
We often diagnose HIV with ELISA test, which can detect antibodies; we confirm with HIV-1/ HIV-2 differentiation ELISA and Western blot
What illnesses are common < 200 mm3
What illnesses are common < 100 mm3
What illnesses are common < 50 mm3
Within about 2 days post HIV infection, dendritic cells are presenting and infecting the CD4+ cells –>
About 3 days after HIV infection, the infected cells have traveled to the _ –>
After 3 days (72 hours) the infection has entered the bloodstream and affected target organs (brain, spleen, GALT, GU)
Within about 2 days post HIV infection, dendritic cells are presenting and infecting the CD4+ cells –>
About 3 days after HIV infection, the infected cells have traveled to the regional lymph nodes –>
After 3 days (72 hours) the infection has entered the bloodstream and affected target organs (brain, spleen, GALT, GU)
The structural gene env encodes for the glycoprotein _ which allows attachment for HIV
The structural gene env encodes for the glycoprotein gp120 which allows attachment for HIV
The structural gene env encodes for the glycoprotein _ which allows for fusion/entry of HIV into cells
The structural gene env encodes for the glycoprotein gp41 which allows for fusion/entry of HIV into cells
The primary problem with HIV infection is that the virus causes direct lysis of _ cells
The primary problem with HIV infection is that the virus causes direct lysis of CD4+ cells
Downstream effects of CD4+ cell death:
Downstream effects of CD4+ cell death:
* Thymic dysfunction
* Bone marrow dysfunction
* Limited ability of T cells to expand in periphery
* CD8
* Decreased innate immunity: Th1 normally stimulates macrophages (INF-gamma)
* Drop in IgG, IgE, etc :can’t get class switching
Acute HIV usually involves a sharp increase in viral load; _ cells are responsible for bringing this down
Acute HIV usually involves a sharp increase in viral load; CD8+ cells are responsible for bringing this down
Acute retroviral syndrome can present with no symptoms or may present with symptoms that mimic _
Acute retroviral syndrome can present with no symptoms or may present with symptoms that mimic mono
The gag gene encodes for the capsid proteins, including _
The gag gene encodes for the capsid proteins, including p24
The pol genes encode for the important enzymes _ , _ , and _
The pol genes encode for the important enzymes reverse transcriptase , integrase , and protease
Recall that HIV is a _ retrovirus
Recall that HIV is a +ssRNA retrovirus
The four stages of HIV viral replication that are targeted by HIV drugs:
- Fusion/entry
- Reverse transcription
- Integration
- Proteolysis
(gp120/ gp41) attaches to CD4 marker on the host cell
gp120 attaches to CD4 marker on the host cell
(gp120/ gp41) attaches to CCR5 receptor on the host cell
gp41 attaches to CCR5 receptor on the host cell
_ drugs can cause lactic acidosis
NRTIs drugs can cause lactic acidosis
NRTIs can cause _ effects on the liver
NRTIs can cause hepatic steatosis
_ drugs can cause peripheral fat wasting
NRTIs drugs can cause peripheral fat wasting (lipoatrophy)
Hepatotoxicity is a side effect of _
Hepatotoxicity is a side effect of efavirenz
Hyperlipidemia, insulin resistance, and diabetes are side effects of _
Hyperlipidemia, insulin resistance, and diabetes are side effects of protease inhibitors
We can boost the efficacy of protease inhibitors by adding _
We can boost the efficacy of protease inhibitors by adding cobicistat or ritonavir which act as CYP3A4 inhibitors
The standard HAART regimen is two _ and one _
The standard HAART regimen is two NRTIs and one PI or Int-I (usually integrase inhibitor used)
* Common: tenofovir + emtricitabine, abacavir + lamivudine
During the 1st trimester of pregnancy, (integrase/ protease) inhibitor should be used in HAART
During the 1st trimester of pregnancy, protease inhibitor should be used in HAART
After the 1st trimester of pregnancy, (integrase/ protease) inhibitor should be used in HAART
After the 1st trimester of pregnancy, integrase inhibitor should be used in HAART
Post-exposure (PEP) HIV treatment is _
Post-exposure (PEP) HIV treatment is standard HAART (2 NRTI + 1 integrase inhibitor)
Pre-exposure (PreP) HIV treatment is _ or _
Pre-exposure (PreP) HIV treatment is two NRTIs or one NRTI + one integrase inhibitor
* Ex: tenofovir + emtricitabine
* Ex: raltegravir + lamividine
