Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

302: Scientific Bases of Medicine > Immunodeficiency Diseases > Flashcards

Immunodeficiency Diseases Flashcards

1
Q

What is classed as Secondary immunodeficiency?

  • commonality?
  • causes?
A
  • Immune defect is secondary to another disease process
  • Very common
  • Extremes of age
  • Malignancies (esp myeloma, lymphoma)
  • Metabolic eg diabetes
  • Drugs eg chemotherapy, steroids
  • Infection eg HIV
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is classed as Primary immunodeficiency syndrome (PID)?

  • commonality?
  • causes?
A
  • Immune defect is intrinsic to the immune system itself
  • Rare
  • Often genetic, but not always
  • Over 100 characterised PIDS
  • Mostly are fairly ‘new’ diseases
    • Fatal in pre-antibiotic era
    • Characterisation required developments in technology
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is Immunosenescence?

A

‘A combination of age-related changes in the immune system that result in greater susceptibility to infection and reduced response to vaccination’

  • many other factors of old age that impact this
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is Combined Immunodeficiencies

A
  • Immunodeficiency syndromes affecting both antibody production (B cells) and T cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is Immune dysregulation?

A

uncontrolled inflammation, autoimmune diseases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are some immunological aspects of immunosenescence?

A
  • Thymic involution
  • Telomere shortening in stem cells reduces both quality and quantity of leucocyte output
  • Reduced T and B cell receptor diversity
  • Reduced vaccine responses
  • Reduced neutrophil function
  • Reduced self-tolerance; inflammation switches from protection to damage
  • Expansion of T cell pool responding to cytomegalovirus (current research focus)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are some key features of Primary Immunodeficiency?

A
  • Low IgG; other isotypes may be affected, but low IgA/ M with normal IgG is rarely significant
  • Manifests with recurrent pyogenic infections of the upper and lower respiratory tract
  • Sometimes gut infections in addition
  • Infections typically respond to anti-microbials, but response may be sub-optimal and long courses required
  • If untreated, leads to irreversible lung damage (bronchiectasis)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the causes of antibody deficiency?

  • Physiological
  • Secondary
  • Primary
A

Physiological

  • Transient hypogammaglobulinemia of infancy

Secondary

  • IgG loss:
    • Renal: nephrotic syndrome
    • Skin: extensive burns
  • Impaired production:
    • Immunosuppressive drugs

Primary

  • X-Linked agammaglobulinemia
  • X-Linked hyper-IgM syndrome
  • (Common variable immunodeficiency – module 302)
  • Many others that are beyond scope
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is transient hypogammaglobulinemia of infancy?

A
  • In healthy infants there is normally a period of relative antibody deficiency around 6 months known as ‘transient hypogammaglobulinemia of infancy; this is a physiological state but can be correlated with increased infections
  • Infants with antibody deficiency usually present after 3-6 months; up until this time they are protected by maternal IgG antibody
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is XLA?

A
  • a prototype antibody deficiency syndrome
  • Signalling via Bruton’s tyrosine kinase (btk) required for signal transduction at pro-B stage
  • Maturation arrest occurs if absent: no heavy chain rearrangement, no B cells leave marrow, no immunoglobulin production
  • Disease is called X-linked agammaglobulinaemia (XLA); also known as Bruton’s disease, Btk deficiency or Bruton’s XLA
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What s X-linked hyper IgM syndrome?

A
  • CD40L deficiency
  • Failure of B cell maturation from primary to secondary
  • Low IgG & IgA, raised (or normal) IgM
  • Recurrent bacterial infections
  • Presents age 3-6 months
  • The immunological lesion actually resides on the T cell
    • CD40 ligand (also known as CD154)
    • Interaction with CD40 on B cells required for affinity maturation, however as this isn’t present maturation doesn’t occur
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How are antibody deficiencies treated?

A
  • Early recognition before lung damage occurs
  • Aggressive treatment of intercurrent infections
  • Replace immunoglobulin
  • Long-term suppressive anti-microbials
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is Cellular immunodeficiency?

  • manifestation/ presentation
A
  • CD4 T cell deficiency
  • When congenital, antibodies will also be affected (combined immunodeficiency)
  • Manifests particularly with:
    • Opportunistic infection
    • Viral infection
    • Fungal infection
    • Mycobacterial infection
  • Classic secondary cause is HIV infection
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are some conditions seen in cellular immunodeficiency especially in advanced HIV?

A
  • Candida oesophagitis
  • Cytomegalovirus retinitis
  • Kaposi’s sarcoma - driven by Herpes virus infection
  • Pneumocystis jiroveci pneumonia
  • Cerebral toxixplasmosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is Severe Combined Immunodeficiency disease (SCID)

  • presentation?
A
  • Rare, life-threatening primary immunodeficiency
  • Absent T cells
  • B cells may be present, but are non-functional
  • All basically present in a similar fashion
    • Usually soon after birth
    • Rash (graft versus host - maternal lymphocyte engraftment)
    • Failure to thrive
    • Chronic diarrhoea
    • Infections, especially opportunistic
      • Bacterial
      • Mycobacterial (esp BCG)
      • Viral (esp CMV, EBV)
      • Fungal (PCP, oral thrush)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are the three main causes of SCID?

A
  • Common gamma chain deficiency
  • JAK3 deficiency
  • RAG1/2 deficiency
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is Common gamma-chain deficiency

A
  • present in X-linked SCID
  • Common gamma chain forms part of membrane receptor for several cytokines, some of which are required for T cell maturation
  • Absent T cells
  • B cells present but non-functional
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is JAK-3 deficiency

A
  • Autosomal recessive SCID
  • JAK-3 is downstream of common gamma chain; deficiency likewise prevents signalling
    • T cell maturation does not occur
    • similarly, B cells are present but non-functional as they need T cell activation
  • Immunologically identical to gamma chain deficiency
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is RAG 1& 2 deficiency

A
  • An autosomal recessive form of SCID
  • RAG 1/2 required for somatic recombination events between V(D)J gene segments
  • No RAG1/2 means no T and B cell receptors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is the treatment for SCID?

A
  • Stem Cell transplant
    • HLA matched donor
  • given to recipient by infusion
  • they engraft in the bone marrow
  • and reconstitution of T and B cells
  • bubble boy no longer used
21
Q

What is DiGeorge Syndrome?

  • phenotype presentation
  • gene affected
  • clinical presentation
A
  • Failure migration 3th/ 4th branchial arches
  • Full phenotype:
    • Absent parathyroids (low calcium, tetany)
    • Cleft palate
    • Congenital heart defects
    • Thymic aplasia (low T cell numbers, immunodeficiency)
  • Most patients have microdeletions chromosome 22
  • Variable presentation
    • Huge spectrum of immunodeficiency from mild-SCID-like
    • Autoimmunity is also common
    • Patients with 22q11 microdeletions may have none of the above, all of the above and anything inbetween
22
Q

What is Terminal complement deficiency?

A
  • Deficiency of terminal complement components C5-C9 leads to specific susceptibility to Neisseria Species
  • Otherwise immunologically robust
  • Diagnose by functional complement assays
23
Q

What is the virologic background of HIV?

A
  • HIV is a retrovirus – Retroviridae family, subfamily Orthoretrovirinae, genus Lentivirus
  • HIV-1 and HIV-2
  • Zoonotic origin:
  • HIV-1 (chimpanzees and gorillas)
  • HIV-2 (sooty mangabeys)
  • Close genetic resemblance between HIV-1 and HIV-2 with the simian immunodeficiency viruses (SIVs)
  • HIV-1 is subdivided in four genetically distinct groups: M, N, O, P
  • HIV-2 has nine distinct groups (A-I)
  • HIV-1 group M has a global distribution; HIV-1 group N, O, P and HIV-2 are confined in West Central Africa
24
Q

Give some background of HIV-1 M

A
  • HIV-1 group M
  • Nine distinct genotypes (A-D, F-H, J, K)
  • Different sub-subtypes (A1-A4, F1, F2)
  • Numerous circulating recombinant forms (CRFs) and unique recombinant forms (URFs)
  • CRFs and URFs are the product of recombination of different subtypes
  • Central Africa has the highest HIV-1 genetic diversity
    • Outside this region, subtypes have a very specific geographic distribution; for example, subtype B is predominant in North America, Western Europe and Australia; subtype C in Eastern and Southern Africa, and India; CRF02_AG in Western Africa
25
Q

What is the structure of HIV-1

A
  • HIV-1
  • 100 nm in diameter
  • Envelope (outer membrane)
  • Membrane proteins: gp120 and gp41
  • Matrix
  • Viral capsid
  • 2 identical molecules of ssRNA
  • RT (reverse transcriptase)
  • IN (integrase)
26
Q

What is the structure of HIV-1

A
  • HIV-1
  • 100 nm in diameter
  • Envelope (outer membrane)
  • Membrane proteins: gp120 and gp41
  • Matrix
  • Viral capsid
  • 2 identical molecules of ssRNA
  • RT (reverse transcriptase)
  • IN (integrase)
27
Q

Review the HIV cycle

A
28
Q

How is HIV transmitted?

A
  • Blood exchange prom person to person (parenteral exposure)
    • Blood transfusion >90%
  • Sexual contact - 1.4%-0.08%
    • risk increased in the presences of other sexually transmitted infections due to higher number of target cells
  • Vertical - Mother to child

risk increased in high HIV viral load

29
Q

What is the HIV reservoir?

A

Quiescent (or latent) infection within memory CD4+ T cells – maintained indefinitely through homeostatic proliferation

Long-term infection of naïve CD4+ T cells, monocytes and macrophages

Current antiretroviral treatment (ART) cannot eliminate the integrated viral DNA from the infected cells, hence cannot eradicate the infection

Although ART is highly effective in suppressing viral replication, residual replication seems to occur and to maintain the HIV reservoir

The HIV reservoir is the source of recrudescence in effectively treated individuals who discontinue ART

30
Q

What is the adaptive immunity Host response to HIV infection?

A

The HIV decline after acute infection is mediated by HIV-specific CD8+ cytotoxic T lymphocytes (CTL), which over time fail to durably control the virus

HIV is capable of generating CTL escape mutants

31
Q

How does HIV evade the host immune system?

A
  • Increasing glycosylation of the envelope as a shielding mechanism
  • Evasion from cellular restriction factors (APOBEC3)
32
Q

What is the Pathogenesis of HIV infection?

A
  • HIV infection profoundly alters the architecture of lymphoid tissues
  • Changes in the intestinal lymphoid tissues lead to a marked increase in microbial translocation due to the disruption of the physiological gut barrier
  • Increase plasmatic circulation of lipopolysaccharides, a component of the bacterial cell wall, enhances persistent immune activation, along with other bacterial products (flagellin, peptidoglycan, and bacterial CpG-rich DNA domains) via Toll-like receptors
  • Slow depletion of circulating and tissue-based CD4+ T cells
  • CD4+ T cells play an essential role in regulating the immune response
  • Their depletion leads to immunosuppression with development of opportunistic infections and AIDS-related malignancies
  • Constant state of immune-activation, activation of the endothelium and of the coagulation system
  • Increased proinflammatory cytokines (type I IFNs, IL-6, TGFβ, IL-8, IL-1α, and IL-1β)
  • Serum markers of inflammation including sCD14, CRP, cystatin C, D-dimers
  • Low CD4/CD8 ratio
  • Exhaustion and senescence of T cells and monocytes
33
Q

What is the consequence of the inflammatory sate caused by HIV?

A
  • Premature ageing observed in people living with HIV
  • Multi-organ disease:
  • Premature onset of cardiovascular disease (atherosclerosis, myocardial infarction)
  • Neurocognitive decline
  • Liver disease (non-alcoholic fatty liver disease)
  • Metabolic syndrome
  • Osteoporosis
  • Onset non-AIDS related cancers
  • Overall increase in mortality
34
Q

What other regions in the body does HIV effect?

A
  • In the central nervous system, the virus can infect, via a CD4-independent mechanism, the astrocytes
  • In the kidneys, HIV can infect renal epithelial cells
  • These mechanisms are at the basis of the onset of HIV-associated neurocognitive disorder (HAND) and HIV-associated nephropathy (HIVAN), respectively
35
Q

How can Primary HIV infections present?

A
  • Easy to miss - transient symptoms, overlap with more common infections (e.g. EBV), reluctancy to test (stigma)
  • Characterised by high viral load and high risk of transmission
  • High inflammatory response, responsible for systemic symptoms
  • Viral dissemination and establishment of the reservoir in the lymphoid tissue

50-90% of patients have symptoms

36
Q

What Viral infections are potential differentials when presented with primary HIV type 1 infection?

A
  • Epstein-Barr virus
  • Cytomegalovirus
  • Primary herpes simplex virus
  • Influenza
  • Early-stage hepatitis
  • Parvovirus B19
  • Rubella
37
Q

What Bacterial infections are potential differentials when presented with primary HIV type 1 infection?

A
  • Streptococcal disease
  • Secondary syphilis
  • Lyme disease
  • Rickettsial disease (spread by mite, causes chicken pox like rashes)
  • Disseminated gonococcal infection
38
Q

What are Parasitic infections are potential differentials when presented with primary HIV type 1 infection?

A

Acute toxoplasmosis

39
Q

What are Non-infections differentials when presented with primary HIV type 1 infection?

A
  • Adult Still disease ( inflammatory disease 15-25, 36-46 )
  • Systemic lupus erythematosus
  • Systemic vasculitis
  • Drug reaction
40
Q

What is the progression of Primary HIV infection?

A

Fiebig stages

  • Eclipse: no plasmatic markers found in plasma - initial replication of the virus at the inoculation site and subsequent spread to the satellite lymphoid organs
  • I: HIV RNA becomes detectable in plasma
  • II: positive p24 antigen (Ag) in plasma
  • III: seroconversion (anti-HIV antibodies)
  • IV: indeterminate Western Blot
  • V: reactive WB with negative p31 Ag
  • VI: reactive WB with positive p31 Ag
41
Q

What is seen in Fiebig stage VI in HIV infection, how is it relevant?

A
  • HIV viral load ‘set-point’, which progressively increases during the asymptomatic phase
  • HIV viral load in Fiebig stage VI is predictive of the rate of disease progression (the higher the viral load, the faster the CD4 count decline)
  • Progressive decline in the CD4 count
  • Persistent immune activation
42
Q

What is the AIDS stage of HIV defined as?

A
  • CD4 count <200 cells/mm3 (advanced HIV infection)
  • Marked rebound in HIV viral load
  • Onset of opportunistic infections and malignancies
43
Q

What opportunistic infections are common in the AIDS stage of HIV?

A
  • Bacterial infections, multiple or recurrent (only among children aged <6 years)
  • Candidiasis of bronchi, trachea, or lungs, of oesophagus
  • Coccidioidomycosis, disseminated or extrapulmonary
  • Cryptococcosis, extrapulmonary
  • Cryptosporidiosis, chronic intestinal (>1 month’s duration)
  • Cytomegalovirus disease (other than liver, spleen, or nodes), onset at age >1 month, Cytomegalovirus retinitis (with loss of vision)
  • Encephalopathy, HIV-related
  • Herpes simplex: chronic ulcers (>1 month’s duration) or bronchitis, pneumonitis, or oesophagitis (onset at age >1 month)
  • Histoplasmosis, disseminated or extrapulmonary
  • Isosporiasis, chronic intestinal (>1 month’s duration)
  • Mycobacterium avium complex or Mycobacterium kansasii, disseminated or extrapulmonary
  • Mycobacterium tuberculosis of any site, pulmonary (only among adults, adolescents, and children aged ≥6 years), disseminated, or extrapulmonary
  • Mycobacterium, other species or unidentified species, disseminated or extrapulmonary
  • Pneumocystis jirovecii pneumonia
  • Pneumonia, recurrent (only among adults, adolescents, and children aged ≥6 years)
  • Progressive multifocal leukoencephalopathy
  • Salmonella septicaemia, recurrent
  • Toxoplasmosis of brain, onset at age >1 month
  • Wasting syndrome attributed to HIV
44
Q

What are examples of AIDS-related malignancies

A
  • Cervical cancer, invasive (only among adults, adolescents, and children aged ≥6 years)
  • Kaposi’s sarcoma:
    • small, painless, flat and discoloured patches on the skin or inside the mouth. They’re usually red or purple and look similar to bruises.
    • Over time, the patches may grow into lumps known as nodules and may merge into each other.
    • Internal organs can also be affected, including the lymph nodes, lungs and the digestive system
  • Lymphoma, Burkitt’s (or equivalent term)
  • Lymphoma, immunoblastic (or equivalent term)
  • Lymphoma, primary, of brain
45
Q

What receptors do viral tissue and host cells express that support pathogenesis of Viral infections?

A
  • Viruses recognise specific receptors on the host cell membrane (e.g., CD4 and CCR5/CXCR4 for HIV; CD54 for rhinoviruses) that mediate cell-recognition and fusion
  • The host cells have proviral factors – host molecules that promote viral replication (e.g., the hepatitis C virus and its interaction with miR-122, expressed specifically in the hepatocytes)
  • Viruses inhibit the host restriction factors, which are host proteins that actively inhibit a virus’s ability to replicate and cause disease (e.g., APOBEC
46
Q

What specific receptors does HIV recognize in a host cell membrane?

A

CD4

CCR5/CXRCR4

47
Q

What specific receptors does Rhinovirus recognize in a host cell membrane?

A

CD54

48
Q

What are cytopathic effects caused by viruses replicating in the host cell?

A
  • Inhibition of cell transcription/translation
  • Changes in membrane permeability
  • Alterations of the cytoskeleton or trafficking pathways
  • Cell-cell fusion
  • Induction of apoptosis

302: Scientific Bases of Medicine (9 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions