immuno - immunodeficiency

what is immunodeficiency?

failure of immune system to protect host from disease-causing agents

what is primary immunodeficiency?

ID resulting from inherited or genetic defect in the immune system

what is secondary immunodeficiency?

loss of immune function that results from exposure to external agent

difference between primary and secondary ID

primary - congenital

secondary - needs exposure

AIDS is a type of ________ ID

secondary

what causes AIDS?

HIV - human immunodeficiency virus

what other factors can cause secondary ID

drug treatment, metabolic disease, malnutrition

immunodeficiency results in increased susceptibility to __________ and some _______. may also lead to reactivation of _______ __________

infections

cancers

latent infections

3 examples of latent infections that may reactivated with ID

CMW (cytomegalovirus)

Epstein Barr Virus

Tuberculosis

what is the most common type of primary ID

humoral

primary immunodeficiencies affect both ______ and ________ immune systems

innate and acquired

with humoral based primary ID, pt's will have increased _________ infections

bacterial

with phagocytic based primary ID, pt's will have increased _________ and ______ infections

bacterial and fungal

5 subtypes of primary ID

humoral, cellular, combined, phagocytic, complement

with T cell based primary ID, pt's have an increase in...

all types of infection

difference between monogenic and X-linked primary ID

monogenic: due to single gene defect

X-linked: autosomal inheritance

in someone with Severe Combined Immunodeficiency (SCID), without treatment, what will happen?

die in early infancy due to uncontrolled infection

DiGeorge syndrome is associated with developmental ______ defects

thymus

in someone with X-linked agammaglobulinemia (Burton's hypogammaglobulinemia) ____ is very low, and there is an absense of?

very low levels of IgG

absence of other Ig classes

5 types of treatment for people with primary immunodeficiencies

1. antimicrobial agents

2. hematopoietic stem cell transplantation

3. total isolation

4. passive immunity

5. replacement therapy

what is passive immunity

intravenous injections of pooled Ig's from healthy donors

replacement of _______ _______: administration of missing protein immunoglobulin

missing protein

replacement of _______ ____ ____ __ _______: bone marrow transplantation

missing cell type of lineage

replacement of _______ __ _________ ____: gene encoding for adenosine deaminase in SCID

missing or defective gene

in secondary ID, agent induced ID is the most frequent cause in _________ countries

developed

what may cause agent-induced ID

immunosuppressive and corticosteroid drugs

cytotoxic drugs or radiation treatments for cancer

how can extremes of age result in secondary ID?

premature babies: increased susceptibility to infection

elderly: risk factor for certain viruses, bacteria, and cancers

what is the most common cause of acquired immunodeficiency world wide?

malnutrition

secondary IDs can also be caused by metabolic disease. example?

diabetes mellitus

due to AIDS, in the US, greater than ________ have died. currently about __________ deaths/year, and ___% of those infected are unaware

700,000

13,000

13%

HIV-1 is a __________

retrovirus

HIV has a (long/short) incubation period

long

how does HIV-1 enter cells? what other enzymes are required for viral life cycle?

reverse transcriptase

protease and integrase

what is a provirus

copy by the DNA

the provirus in HIV is integrated into the ____ ______ and replicated with ____ ___

cell genome

cell DNA

explain the life cycle of HIV

1. infection of cells

2. production of DNA copy of the viral RNA & integration into host genome

3. expression of viral genes

4. production of viral particles

without treatment, AIDS progression destroys ______ cells. mainly ____ __ ___________. viral particles spread to _________ tissues throughout the body and continue to destroy.

immune

CD4+ T lymphocytes

lymphoid

4 fluids of transmission of HIV

infected blood, breast milk, semen, vaginal fluid

sexual transmission of HIV is the _________ of cases worldwide

majority

how is AIDS transmitted via parenteral

blood borne!!!!

receipt of infected blood or blood products

who is at risk for parenteral transmission of HIV?

IV drug users

which type of transmission results in talc retinopathy? what does this retinopathy look like?

parenteral

white particles in posterior pole

what is vertical transmission?

infected mom --> fetus

how can we prevent vertical transmission

zidovudine (AZT or azidothymidine) to mom and fetus

testing for HIV is __________. what are the 3 types of tests?

essential

- antigen/nucleic acid

- antibody

- combination

what are the window periods for HIV testing?

- 3+ weeks after exposure for antibody test

- 2+ weeks after exposure for antigen test

_____ allows for rapid and highly specific diagnosis of infectious diseases

PCR

PCR also permits identification of non-cultivatable or slow growing microorganisms such as ___________, _________ ________ or _______ from tissue culture assays and animal modesl

mycobacteria

anaerobic bacteria

viruses

2 criteria for AIDS diagnosis

evidence of infection

very specific AIDS defining conditions

how can you have evidence of infection (AIDS)

CD4+ T cell count < 200 or CD4+ lymphocyte percentage <4%

presence of AIDS defining condition

6 examples of AIDS defining conditions

1. pneumocystic pneumonia

2. CMV

3. kaposi's sarcoma (ONLY OVER 60 Y/O

4. extranodal lymphona

5. pulmonary TB

6. invasive cervial carcinoma

2 prevalent ocular associations with AIDS/HIV

CMW retinitis and ocular kaposi sarcoma

AIDS infection leads to gradual _________ of ___________ __________

impairment

immune function

what else is affect in AIDS other than CD4+ count and viral load

lymph node structure, antibody production (decreased), cytokines, decrease/absense of type IV HS response (low CD4+ cells), T cytotoxic cells decreased

without HAART/ART, the course of AIDS

gets way worse, increased viral load, decreased CD4+ counts, increased opportunistic diseases, disease symptoms, eventual death

4 types of inhibitors that treat AIDS? what type of antagonist?

1. reverse transcriptase inhibitors

2. protease inhibitors

3. fusion/attachment inhibitors

4. integrase inhibitors

- chemokine coreceptor antagonists

what medications are a reverse transcriptase inhibitor

nucleoside: AZT (zidovudine

which medication is a protease inhibitors

HAART/ART

ART for anyone with HIV

which medication is preventative for HIV

PREP (pre-exposure phophylaxis)

*Truvada*

truvada is a type of PREP, what else is?

descovy

people on truvada or descovy are HIV (positive/negative) and are tested how often

negative

once a month or so

what 2 questions should you ask a pt with HIV?

1. what is your CD4+ count?

2. what is your viral load?

risks increase if CD4+ counts are < _______

200

what is normal level of CD4

500-1000, no problems occur in this range

what is a good number for viral load? pt with this will report at _______

<500

negligible

treatment is recommended as soon as _________ __ _____, independent of _____count

diagnosis is made

CD4

for pt's taking combination agents, how do they take meds and frequency? what is in these meds?

1 pill once a day, typically contains 3 different drugs from 2 different classes

if pt is not great at med compliance, what may be a better option of treatment for HIV

anti-retroviral injections via IM (intramuscular)

get a shot once a month

progressive outer retinal necrosis may be due to _________ in pt's with HIV

herpes zoster