5. Immunideficiency + HIV Flashcards
LOs
What can the immune system be divided into?
- Innate immune system
↳ the one we’re born with
↳ first to respond
↳ eg phagocytes, complement - Adaptive (or acquired) immune system
↳ changes throughout life
↳ eg. T cells, B cells
Func of immune system
- Central role to protect host against microbial pathogens
- Comprised defence if one or more components absent or deficient
What is immunodeficiency? What does it result in?
- Immunodeficiency results in increased susceptibility to infection by specific classes or types of microbes
- Repeated or unusual infections is an indication of immunodeficiency
What is Primary immunodeficiency and secondary immunodeficiency?
Primary immunodeficiency:
• Genetically determined or result of developmental anomalies
• Inherited, congenital, and rare
Secondary immunodeficiency:
• Acquired → Caused by disease or an immunosuppressive treatment
More common
Primary immunodeficiency causes?
Complement cascade deficiencies? (Links to innate immunity lecture )
Phagocytosis deficiencies?
Hummoral/antibody deficiencies?
T cell deficiencies
Clinical features of immunodeficiencies?
• Chronic and recurrent infections
• Unusual microbial agents
• Incomplete responses to treatment
• Skin lesions, warts
• Diarrhoea
• Recurrent abscesses
• Autoimmunity
• Failure to thrive
Secondary Immunodeficiencies examples?
- much more common than primary immunodeficiencies
• Therapeutic drugs (cancer chemotherapy, radiation therapy, post-transplant immunosuppression)
• Infection (HIV/AIDS)
• Metabolic / chronic disorders (ex: diabetes)
• Malnutrition, aging
• Burns/trauma (loss of immunoglobulin via damaged skin)
What is HIV?
- human immunodeficiency virus
- single stranded RNA virus with a DNA intermediate
- Baltimore virus classification: Group VI (ssRNA virus with a DNA intermediate)
- Causative AIDS agent
What makes HIC special?
- Hallmarks: Reverse transcription (RNA -> DNA) and chromosomal integration
- these properties ensure that once virus enters cell, it will be copied and maintained in host when cells divide
what would need to be done to cure HIV?
- kill all infected cells
HIV structure
HIV is composed of an
- outer layer = envelope
- contains HIV envelope proteins
- inside it has a core composed of the viral protein capsid
- inside capsid - viral RNA genome + important viral enzymes
what is going on in this diagram?
- represents the viral DNA that is integrated into the host = proviral DNA diagram
- flanked by 2 long terminal repeats = LTR
- 3 main genes = gag = goes for structural proteins
= pol = goes for viral enzymes
= env
what is going on in this diagram?
- once virus merges with cell, looks like rounded particle with an envelope which is derived from cellular plasma membrane
- as it matures it will form a core with a characteristic conical shape
Human Immunodeficiency virus life cycle and cell entry (how virus infects cells)?
1
RECEPTOR BINDING
- virus recognises target cell via it’s envelope
- the viral envelope protein will be interacting with the host protein C4 )viral main receptor)
- also a co receptor (either CCR5 or CX04)
2
MEMBRANE FUSION + ENTRY
- after engagement of these host receptors, the viral inflow proteins triggers fusion of the viral membrane with the target cell membrane
- virus enters cell
3
UNCOATING + REVERSE TRANSCRIPTION
- viral RNA is reverse transcribed into DNA
- by viral RT enzyme
4
NUCLEAR UPTAKE
- in nucleus, the viral integrase mediates the integration of the viral DNA into a host chromosome
- where it will stay until the cell dies
5
INTEGRATION
- once integrated the viral DNA is then able to start transcription of viral RNAase
6
TRANSCRIPTION
- processed and exported to the cytoplasm where they will be translated into viral proteins (such as gag, pol, env, etc)
7
RNA PROCESSING
8
NUCLEAR EXPORT
9
TRANSLATION
10
ASSEMBLY
11
BUDDING
12
MATURATION
cellular infection by HIV
- attachment factors
- receptors
- co-recpetors
(attachment factors are NOT essential unlike, receptors)
Attachment factors:
• Heparan Sulphate Proteoglycans
• Galactosylceramide
• a3b7 integrin (alpha, beta)
• DC-SIGN
Receptor
• CD4
- HIV will only infect CD4 cells, will need co-receptor
Co-Receptors
• CCR5 (macrophages and DCs)( including langerhan cells)
• CXCR4 (T cells)
HIV course of infection
- shows acute HIV infection (usu 2-4 weeks)
- grey line goes to very high levels
- it rapidly multiplies
- the virus attacks and destroy T-cells
- during acute stage, high levels of HIV greatly increase risk of HIV transmission
- chronic stage (may be called asymptomatic or clinical latency)
- people may have no HIV symptoms but have a detectable level of antibodies
- AIDS is final stage
- without ART (medicine name???) chronic HIV usu progresses to AIDS in about 10 years
- if take medicine correctly as prescribed then can have little to no risk of transmitting
acute HIV infection main symptoms
when is someone considered to have AIDS?
- latest stage of HIV infection
- CD4 T cell numbers are reduced -> opportunistic infections
(clinical set point = 200 T cells/ ml)
infections and malignancies in people with AIDS
- infections = when patient has AIDS, the host will not be able to have a proper immune response to…
- malignancies = common in people with AIDS
Infections:
• Parasites (Toxoplasma spp, Cryptosporidium spp, Leishmania spp)
• Bacteria (Mycobacterium tuberculosis, Salmonella spp)
• Fungus (Pneumocystis carinii, Cryptococcus neoformans, Candida spp)
• Viruses (Herpes simplex, Cytomegalovirus, Varicella zoster)
Malignancies:
• Kaposi’s sarcoma (Human Herpesvirus 8 /Kaposi sarcoma-associated herpesvirus)
• Non-Hodgkin’s lymphoma (including Burkitt’s lymphoma)
• Primary CNS lymphoma
• Invasive cervical cancer
• Increased rates of other cancers
