Immunodeficiency and infectious diseases

Question 1

what are primary and secondary immunodeficiency disorders?

Answer 1

primary immunodeficiency disorders- result from a an intrinsic genetic defect of the immune system, usually congenital leasing to a missing enzyme/ cell type or non-functioning component. usually manifest at earl age and are often very serious
secondary immunodeficiency disorders- they are acquired as a result of another disease, environmental factors, infections or drugs. these are much more common and can manifest at any age.

Question 2

what are the clinical features of immunodeficiency?

Answer 2

increased frequency, severity and duration of infection
unexpected complications or manifestations of infection
infections with organisms normally considered of low pathogenicity
non-infectious manifestations in GI, endocrine and haematological organ systems.

Question 3

what are common primary antibody immunodeficiencies?

Answer 3

PIDs:

1. selective IgA deficiencies- undetectable levels of IgA in blood/secretions with no other immune deficiencies. most common PID. 4 presentations: asymptomatic (majority), recurrent mucosal infections, allergies or autoimmunity.
2. transient physiological agammaglobulinaemia of the neonate- delayed IgG production. exaggerated in prematurity
3. X-linked agammaglobulinaemia- X-linked recessive disorder leading to defective B cell maturation
4. common variable hypoglobulinaemia- abnormal B cell function leading to a deficit in IgG and at leat one other Ig

Question 4

what are common secondary antibody immunodeficiencies?

Answer 4

chronic leukocyte leukaemia- affects ability of B cells to differentiate into plasma cells
multiple myeloma- cancer of plasma cells leading to abnormal antibodies

Question 5

what is the therapy for antibody immunodeficiencies?

Answer 5

immunoglobulin replacement

Question 6

what are the common manifestations of antibody immunodeficiencies?

Answer 6

bacterial infections (pneumococcus)causing otitis, pneumonia, sinusitis, GI disturbances

Question 7

what are the common manifestations of lymphocyte immunodeficiencies?

Answer 7

recurrent viral, fungal, protozoal and intracellular bacterial infections causing deep seated infections, thrush, p.jirovecii pneumonia, reactivation of latent viral infections

Question 8

what are some examples of primary leukocyte immunodeficiencies?

Answer 8

diGeorge syndrome- deletion of segment of chromosome 22 leading to an underdeveloped thymus affecting T cell number and function
wiskott-aldrich syndrome- affect T cell function due to WAS gene mutations- affect the immune synapse between antigen presenting cell and T cell
SCID- group of diseases which affect lymphocyte development: common gamma chain deficiency, adenosine deaminase deficiency, JAK3 kinase deficiency. rare but potentially fatal

Question 9

what are some examples of secondary leukocyte immunodeficiencies?

Answer 9

malnurtition- can lead to atrophy of the thymus. protein deficiency can lead to decreased T cell number
Hodgkins lymphoma- cancer of lymphocytes
infections: measles, malaria, leprosy, HIV- impaired T and sometimes B cell function
drugs- decrease lymphocyte proliferation and circulating number

Question 10

what are some common manifestations of phagocyte immunodeficiencies?

Answer 10

predominantly bacterial infections which occur at the interface between the host and the environment- accesses, pneumonia, seep seated infections, GI disturbances

Question 11

what are some examples of phagocyte immunodeficiencies?

Answer 11

neutropenia- reduced production or accelerated removal of granulocytes. can be PID or SID
PIDs:
leukocyte adhesion deficiency- failure to mobilise WBCs to tissues
chronic granulomatous disease- failure to kill infectious organisms
SIDs:
malnutrition- decrease in NK cells and abnormal phagocytosis
drugs- decreased phagocytosis

Question 12

what are some common manifestations of complement immunodeficiencies-

Answer 12

recurrent and/or serious bacterial infections
autoimmune disease
angioedema

Question 13

what are examples of complement immunodeficiency?

Answer 13

PID
C1 inhibitor deficiency (hereditary angioedma)- causes over activation of complement. treated with C1 inhibitor concentrate 
SIDs 
osteomyelitis 
endocraditis 
eculizumab- C5 inhibitor

Question 14

what are cutaneous fungal infections?

Answer 14

limited to the epidermis
include:
athletes foot (tinea pedis)- scaly, itchy skin on feet- between toes (interdigital) or more widespread (moccasin)
fungal infection of the skin (tinea corporis- ringworm)- single/multiple red flat or slightly raised circular ring shaped patches. itchy, scaly skin
fungal infection of the groin (tinea cruris)- scaly itchy skin on inguinal folds and medial thighs
fungal nail infection- abnormal, thickened discoloured brittle nail
tinea versicolor- multiple round discoloured macule commonly on back, chest and upper arms.
tinea capitis- scaly,itchy scalp, hair loss, pustules, crusting, associated fungal infection in other sites

Question 15

what are subcutaneous fungal infections?

Answer 15

affect the dermis, subcutaneous tissues and bone
sporoctrichosis- causes raised bump which grows and becomes an ulcerated open sore
mycetoma- initially a painless lesion or abscess typically on feet which progresses to large sores that leak pus, blood and serum
chromomycosis- chronic infection begins as a painless lump that slowly progresses to form a crusty/scaly abscess

Question 16

what are the causative agents of systemic fungal infections?

Answer 16

coccidiomycosis- coccidiodes immitis. symptoms- flu-like, fatigue, cough, fever, SOB, headache, night sweats, aches and pains.
histoplasmosis- histoplasma capsulatum. symptoms similar to coccidiomycosis
blastomycosis- blastomyces dermatidis. symptoms similar to above
paracoccidiomycosis- paracoccidiodes. symptoms- usually asymptomatic, symptoms of lungs and skin, can have lesions in mouth/throat, weight loss, cough, fever, fatigue, swollen lymph nodes

Question 17

what are the opportunistic fungal infections?

Answer 17

candidiasis (thrush)- candida albicans, affects oral mucosa, gums, throat, vagina. can cause systemic infection in immunocompromised
cryptococcosis- cryptococcus neoformans. commonly mild lung infection. cryptococcal meningitis in AIDS patients
aspergillosis- aspergillus fumigatus. generally affects lungs- can be invasive systemic infection in brain, GI tract
murcomycosis- mucromycetes spp. rhinocerebral murcomycosis- sinus infection that spreads to brain, pulmonary murcomycosis
pneumocystis pneumonia- pneumocystis jivoreci cuases pneumonia

Question 18

what is the MOA and clinical use of terbinafine?

Answer 18

used in cutaneous fungal infections- oral or topical.

inhibits fungal production of ergosterol- essential component of fungal cell membranes

Question 19

what are the MOA and clinical use of azole anti fungals?

Answer 19

inhibit cytochrome P450 enzymes involved in the biosynthesis of cell membrane sterols
used mostly in cutaneous or opportunistic infection

Question 20

what is the MOA and clinical use of nystatin?

Answer 20

binds to ergosterol and forms pores- osmotic competence lost
used in candidiasis

Question 21

what is the MOA and clinical use of amorolfine?

Answer 21

inhibits ergosterol production

used in fungal nail infections

Question 22

what is the main causative agent of TB?

Answer 22

mycobacterium tuberculosis- aerobic rod shaped, gram stain doesn’t work, acid fast-stains pinky/purple

Question 23

what is the course of TB infection?

Answer 23

30% exposed to TB will be infected
90% will get immune activation and granuloma formation and the infection becomes latent- <10% will reactivate and cause active disease
10% will have a failure of immune activation leading to primary active disease.

Question 24

what are the symptoms of active pulmonary TB?

Answer 24

general symptoms- fever, weight loss, night sweats, malaise

pulmonary symptoms- persistent productive cough, breathlessness, haemoptysis

Question 25

what are the features of active extrapulmonary TB?

Answer 25

presents with symptoms specific to site involved- lymph nodes, CNS, bones and joints, pericardium, Genito-urinary

Question 26

what are granulomas?

Answer 26

cellular aggregates which contain the TB infection, important pathological hallmarks fro TB

Question 27

what is the treatment for TB?

Answer 27

active- 6 months of isoniazid (with pyridoxine) with rifampicin, supplemented with two months of pyrazinamide and ethambutol latent- 3 months of isoniazid (with pyridoxine) and rifampicin OR 6 months of isoniazid (with pyridoxine)

Question 28

how can TB be prevented?

Answer 28

vaccination (BCG), quality diagnosis, completing treatment regimen, contact tracing, latent TB screening

Question 29

what is the pathogenesis of CMV?

Answer 29

primary infection- lytic replication in wide range of organs latency- in blood cells- mainly CD34+ lymphocytes reactivation- due to loss of T cell based immunity

Question 30

what is the seroprevalence and transmission of CMV?

Answer 30

seroprevalence- about 40% in young adults and increases with age transmission- contact with infected secretions- saliva, sexual, blood (immunocompromised need blood transfusions free of CMV)

Question 31

what are the clinical features of CMV infection?

Answer 31

usually asymptomatic in immunocompetent (may possibly lead to long term conditions e.g atherosclerosis, immune senescence due to chronic inflammation) congeintal CMV- IUGR, hepatomegaly, encephalitis, neurological problems, developmental delay immunocompromised: CMV syndrome- fever, neutropenia organ invasive disease- retinitis, encephalitis, pneumocystis, myocarditis, hepatitis

Question 32

what are the CMV risks in transplant?

Answer 32

solid organ transplant- greatest risk if donor positive recipient negative stem cell transplant- greatest risk if donor negative recipient positive as donor bone marrow has no CMV specific T cells to control the infection

Question 33

how is CMV diagnosed, treated and prevented?

Answer 33

diagnosis- detection of viral DNA by PCR in blood, histology- owls eye inclusions treatment- ganciclovir (inhibits viral DNA polymerase) used in congenital and immunocompromised prevention- prophylaxis- oral valganciclovir (pro-drug) post transplant, pre-emptive monitoring

Question 34

what is the pathogenesis of EBV?

Answer 34

primary infection- replicates in wide variety of cells including epithelial and B cells latency- latent in B cells reactivation

Question 35

what is the seroprevalence and transmission of EBV?

Answer 35

95% seropositive by age 40 | transmission- direct contact with infected secretions- saliva- kissing disease

Question 36

what are the clinical features of EBV infection?

Answer 36

young children- usually asymptomatic, can have sore throat adolescence- infectious mononucleosis (mono, granular fever)- triad of low grade fever, lymphadenopathy, sore throat. can have abnormal liver function and splenomegaly.

Question 37

how is EBV diagnosed and treatment?

Answer 37

monospot test- detects antibodies in acute primary infection. serology- Viral capsid protein IgM AND IgG treatment- usually self limiting- no effective antivirals or vaccine

Question 38

what cancers is EBV associated with?

Answer 38

burkitts lymphoma- highly malignant B cell tumour nasopharyngeal cancer- tumour of head and neck post-transplant lymphoproliferative disorder (PTLD)- occurs in situations of reduced T cell immunity, results in uncontrolled EBV replication which causes uncontrolled B cell proliferation

Question 39

what are the clinical characteristics of HHV6 and 7?

Answer 39

transmission- contact with infected secretion symptoms- roseola infantum- rash in infants, fever can be asymptomatic complications- febrile convulsions, encephalitis

Question 40

what is the seropositivity and clinical features of HHV8

Answer 40

30% general seropositivity | associated with kapok's sarcoma- cancer of skin and mouth, seen mainly in HIV

Question 41

what is the mechanism of action and resistance of NRTIs?

Answer 41

nucleotide reverse transcriptase inhibitors e.g retrovir NRTIs mimic nucleotides and are picked up by reverse transcriptase and placed in the growing DNA chain which stops further replication mechanism of resistance- NRTI removed by mutant reverse transcriptase or lack of binding of reverse transcriptase to NRTI

Question 42

what is the mechanism of action of NNRTIs?

Answer 42

non-nucleotide reverse transcriptase inhibitors | bind directly to reverse transcriptase and prevents it from functioning

Question 43

what is the mechanism of action and resistance of protease inhibitors?

Answer 43

protease is an enzyme that is used to break up viral poly proteins which are used to make new viruses. protease inhibitors block the breakdown of these proteins so new viruses cannot be made resistance- conformational change in the protease

Question 44

what is the mechanism of action of fusion inhibitors, CCR5 inhibitors and integrates inhibitors?

Answer 44

fusion inhibitor T20- prevents fusion of HIV to CD4 cell by preventing hair pinning of the gp41 molecule CCR5 inhibitor- CCR5 tropic viruses require CCR5 for entry. CCR5 inhibitors therefore prevent viral entry integrase inhibitors- prevent integration of viral DNA into the host genome

Question 45

what is the principles of ART?

Answer 45

antiretroviral therapy- involves taking a combination of drugs to prevent resistance: dual NRTI and single integrase inhibitor dual NRTI and single protease inhibitor dual NRTI and single NNRTI

Question 46

what is post exposure prophylaxis?

Answer 46

PEP prevents HIV in these who have had recent exposure to HIV (needle stick, unprotected sex) raltegavir (integrase inhibitor) and Truvada (2x NRTI- tenofovir, emtricitabine)

Question 47

what is pre-exposure prophylaxis?

Answer 47

Truvada reduces risk of transmission in high risk populations

Question 48

what are the social and psychological factors of risk and risk taking behaviour?

Answer 48

psychological- optimism bias (it won't happen to me), perception of benefit or need may off set the perceptions of risk social- impact of media- misinformation, demographic factors- age, culture, ethnicity, access to health care

Question 49

what is the definition of stigma?

Answer 49

social judgement based on an enduring feature of identity conferred by a health problem or condition (HIV, epilepsy, MH)

Question 50

what is the stigma surrounding HIV/AIDS?

Answer 50

the irrational or negative attitudes, behaviours and judgements towards people living with or at risk of HIV. it can negatively impact the health and wellbeing of these people by discouraging them from learning their HIV status, accessing treatment, seeking HIV prevention or talking openly with their sexual partners populations disproportionately affected by HIV are also often affected by stigma due to things such as their race, gender, sexual orientation, gender identity, drug use or sex work

Question 51

what can be done about HIV stigma?

Answer 51

talk about HIV- normalise the subject, correct misconceptions, educate about appropriate language make testing more routine and easy to access education on the effectiveness of treatment options and how to live life with HIV education on safe sex and the risks of HIV