GENS340 - Midterm prep

People living with HIV in 2020

37.6 million [30.2 -> 45.0 million]

New HIV Infections in 2020

1.5 million [1.1 -> 2.1 million]

Deaths due to AIDS in 2020

690000 [480000 -> 1 million]

What does HIV stand for?

Human Immunodeficiency Virus

What is HIV?

- A retrovirus that leads to AIDS if left untreated

What does AIDS stand for?

Acquired Immune Deficiency Syndrome

What is AIDS?

- A life-threatening syndrome caused by a virus and characterized by the breakdown of the body's immune defenses (i.e. deterioration of the immune system)

Acquired in AIDS means?

Virus received from someone else

Immune in AIDS means?

Immune system; the human body's natural defense mechanisms against disease-causing microorganisms

Deficiency in AIDS means?

Deterioration of the immune system

Syndrome in AIDS means?

Group of signs and symptoms that together define AIDS as a human disease

When was AIDS reported

- For the United States, in June 1981 from immunodeficiency in gay men (e.g. "Rare Cancer Seen in 41 homosexuals")

- However, there were five cases in heterosexual women that weren't reported until October 1982 by Henry Masur

- July 1982: From Hemophiliacs, Blood Transfusions, Injecting drug users

First Definition of AIDS in 1982

- No single characteristic

- Cellular immune deficiency, absence of underlying cause (based on clinical description of symptoms)

-Modified '83, '85, '87: Onset of life threatening illness and end-stage of disease process

- Redefined '93, '94, '00:

The discovery of AIDS included

- July 1982: bodily fluids (blood, semen)

- Jan 1983: First case of AIDS in heterosexuals

- Mid '83CA

- All heterosexual & neither IDUs nor their partners

The discovery of HIV included

- HIV-1 discovered at Pasteur Institute (led by Luc Montagnier)

- Battling with Robert Gallo of HTLV 3

- HIV-2 85WA

1985 West Africa

- A, B, C, E, O subtypes

Attempts to name the Syndrome

- Four-H Disease

- Gay pneumonia

- Gay Related Immune Deficiency (GRID)

- Gay Compromise Syndrome

- A.I.D.S

- AIDS

- Gay Cancer

Early names for HIV/AIDS

- HTLV 3 (Human T Cell Lymphotropic Virus) by Robert Gallo

- LAV (Lymphadenopathy-Associated Virus) by Luc Montagnier

- GRID

- ARC (AIDS Related Complex)

1959

Oldest known infection of AIDS

Crossover from Chimpanzees

Chimpanzees acquired their infections from hunting & consuming infected primates (just like humans)

Zoonosis

Transmitted to humans from animals

- Chimpanzees & HIV-1

- Sooty Mangabey & HIV-2

What makes the epidemic unique?

- Transmitted primarily through sex

- Rapidly spreading

- Long asymptomatic period

- Attacks most productive age group

- Involved within politics & public health

- Expensive & toxic drugs

- Economic crisis

Koch's Postulates

CIRF

- Causative agent must be found in all cases

- Isolated from host

- Reproduce og disease in other hosts

- Found in experimental host infected

What is a virus

Microscopic particles of biological material "life-like agents"

- Genetic material within protein coat

- Viruses need host cell to replicate

- NOT self-sufficient living cells

Viral Genomes can...

be made from DNA or RNA

CD4 Cells

are T Cells & Macrophages that fight off infections; HIV destroys these cells

HIV attaches to what host cells

- CD4 Cells: T Cells, Macrophages

- Lymphocytes: T Cells, B Cells

HIV Life Cycle

BFRIRAB

1) Binding

2) Fusion

3) Reverse Transcription

4) Integration

5) Replication

6) Assembly

7) Budding

9 Genes of HIV

PEG

Pol, env, gag = Structural Proteins

TR

Tat, rev = Regulatory Proteins

NVVV

Nef, vif, vpu, vpr = Accessory Proteins

Most viruses are...

harmless

Viruses enter in various ways

FEH

- Flu through respiratory tract

- EBV through nose & throat

- Hepatitis through liver

Prior to 1970

biologists thought all genetic info flowed in one direction

- from DNA -> RNA -> Protein

Retrovirus

Contrasts with normal gene expression; creates DNA copy of RNA and inserts it into DNA of host cell

HIV Biological aspects

- 100k times smaller than human cell

- 9749 nucleotides that form genetic code for HIV

- 2009: Joseph Watts reported all the nucleotides that make up HIV

- HIV attaches to CD4 Cells via gp120 & gp41

What is the complete virus made of?

GP120 + GP41 = GP160

Envelope proteins supporting HIV binding

Genetic information of HIV

GM-GD.M.N.H.

- Genetic mutations create genetic diversity within the virus

- Mutations occur due to changes in nucleotides (e.g. addition, deletion, substitution)

- New HIV infection is ~1000 generations removed from og infection

- HIV mutates in every replication

HIV needs what to replicate

CD4 Cells; Copies of HIV are transcriptions

How many genes in HIV genome?

9 genes

Genes store genetic info that code for what

production of proteins

HIV-1 Groups

MNOP

- Main

- Nonmajor

- Outlier

- P is closely related to SIVgor

Which HIV-1 Group is responsible for most of HIV worldwide

Major

How many subtypes of HIV-2

6 Subtypes from A -> F letters

T Cell Roles

RHC

Regulatory/Suppressor, Helper, Cytotoxic

B Cells do what?

Produce antibodies (fight off antigens)

Regulatory T Cells

Involved in immune response

ORC

Orchestrating, Regulating, Coordinating

Helper T Cells

"CD4+ Cells"

"B Cells, make more antibodies!"

"Heads up T Cells & Macrophages"

Cytotoxic T Cells

AKA

- Killer T Cells

- CD8+ T Cells

Macrophages help Cytotoxic T Cells

Activate and fight off diseased cell

Basic functions of immune system

FRD

- Filters out foreign substances

- Removes damaged & dead cells

- Destroys unknown, mutant, &/or cancerous cells

Two branches of immune system

CTHB

Cellular - T Cells (Cells)

Humoral - B Cells (Fluids)

Types of Sentinel Cells

DMM

Dendritic, Macrophages, Mast

Types of circulating phagocytes & granulocytes

MEN

Monocytes, Eosinophils, Neutrophils

Phagocytes do what

absorbs bacteria and kills them

Antibodies are what

I & Y

Immunoglobulin & Y Shaped to attach to antigens

Cell Mediated Immunity eliminates what and how

Eliminates pathogens within cell using CD4 Cells (T Cell Lymphocytes & Macrophages)

B Cell Lymphocytes

NA

Needs Helper T Cells to be activated; antibody binding to antigen

Macrophages help activate...

Activate T & B Cells

Dendritic Cells

First to make contact w/ antigen; tells Helper T Cell what antigen it is

Cellular Immunity provides

Immune protection given by phagocytes & T Cells

Monocytes & Macrophages are

phagocytes

Lymphocytes are white blood cells that have

LSR

antigen receptors on their surface (Lymphocyte Surface Receptors)

T Lymphocytes include....

KSH

Killer T Cells, Suppressor/Regulatory T Cells, Helper T Cells

Humoral Immunity

Circulating antibodies providing protection

Lymphocyte Surface Receptors are

Proteins on cell surfaces for communicating antigens

B Cells make antibodies in...

bone marrow

How do T Cells & B Cells help each other

T Cells create blast cell w/ antibody factories to help B Cells surround invader

HIV Gene Types

Structural, Regulatory, Accessory

PEG, TR, NVVV

What reduces Cell Mediated Immunity

Loss of helper T Cells, exposes individual to opportunistic infections

AIDS is diagnosed when...

CD4+ Cells drop below 200 per microliter of blood

exposure to immunodeficiency and opportunistic infections

HIV changes its expression which

keeps them concealed from antibodies

Antibody production can't keep up

with new virus production

Opportunistic Infections occur when

immune system is weakened, such as with AIDS

Opportunistic Infections affect

all parts of the body

Most common opportunistic infections are

BP

CE

P/D TB

MAC

HSR

PCP

Bacterial pneumonia, candidal esophagitis (yeast), pulmonary/disseminated TB, mycobacterium avium complex disease, herpes simplex reinfection, pneumocystis pneumonia

Types of fungi

HCP

Histoplasmosis, candida, pneumocystis pneumonia

How is Histoplasmosis spread?

Breathing spores in Mississippi & Ohio river valleys

Histoplasmosis symptoms

I SOB NS C MS RSB

- Influenza-like symptoms

- Shortness of breath

- Night sweats

- Chills

- Mouth sores

- Red skin bumps

Histoplasmosis is an initial OI in?

Two-thirds of AIDS patients

Pneumocystis Pneumonia's characteristics

L IS F DC SOB

- Lies dormant in lungs

- immune system keeps it in check

- fever

- dry cough

- shortness of breath

What is the most common OI in the US?

Pneumoncystis Pneumonia (PCP)

Virtually everyone 30-40 yrs old in the US has been exposed to what?

Pneumocystis Pneumonia (PCP)

What is PCP caused by?

Pneumocystis Jiroveci fungi

Thrush is caused by what?

CA

Candida albicans

Thrush's characteristics?

MV GI K O I

- mouth, vaginal area (yeast infections)

- Found in GI tract

- Kept in check by bacteria

- Overgrowth

- Immunocompromised; rapid multiplication

Types of bacteria

MAC, MTB, S, S, S, S, G, C

- Mycobacterium avium complex

- Mycobacterium tuberculosis

- Salmonella

- Streptococci

- Staphylococci

- Syphilis, Gonorrhea, Chlamydia

MAC is caused by?

Mycobacterium avium

How is MAC acquired?

By environment

FAWSS

Food, animals, water, supplies, soil

What does MAC infect & what does it cause?

Lung & intestines; wasting syndrome

Tuberculosis characteristics

- infects 1/3 of world's population

- leading cause of illness/death among HIV-infected individuals worldwide

- caused by mycobacterium tuberculosis

- most often affects lungs

- infected remains infected for years

- cannot eliminate infection w/o drugs

- may be latent or active

- HIV most likely to activate latent TB

- symptoms include cough & pneumonia

TB statistics

- estimated 10-15 million infected w/ TB in US

- 14% of AIDS patients in US co-infected w/ TB

- over 16 million HIV positive's worldwide will be infected w/ TB

- worldwide leading cause of death for HIV+

- TB deaths HIV+ = 470k/yr

Viruses include...

CEHH

Cytomegalovirus

Epstein-Barr

Hepatitis C

Herpes Simplex

What is CMV a member of

Herpes virus family

CMV is latent until

activated by immunosuppression

CMV is widely...

disseminated

CMV causes a broad spectrum of diseases including...

G F A SD LD R B

gastrointestinal, fever, anemia, severe diarrhea, liver disease, retinitis, blindness

Three types of protozoa

TCI

Toxoplasma gondii

Cryptosporidium

Isospora belli

Toxoplasmosis is caused by...

Toxoplasma gondii

Toxoplasmosis can infect and affect...

any warm-blooded animal and central nervous system (including brain)

Toxoplasmosis population stats

10-40% of adults in US are infected ; most are asymptomatic

Brain infection of Toxoplasmosis can...

cause encephalitis