Esa 3 - I & I

Front 1

Describe a virus.

Back 1

A virus is a small, obligate intracellular parasite that causes infection by invading host cells and dividing within them, using host cell’s machinery. They have a relatively short extracellular period prior to invading cells and a much longer intracellular period. They contain DNA or RNA, a protein coat capsule and may or may not be surrounded by a lipopolysaccharide envelop from the host cell. The protein capsid coat consists of repeating units of capsomeres which are either icosahedral or helical. The capsid protects the virus from harsh environments and has ligands in naked virues (non enveloped) for receptor mediated endocytosis. An enveloped virus is more sensitive to phagocytosis as opsonisation does not need to take place.

Front 2

What are defensins?

Back 2

Defensins are small cationic proteins that prevent viral entry and replication and enhance phagocytosis.

Front 3

What at the cells and proteins involved in innate and adaptive immune mechanisms of viral immunity.

Back 3

The components involved in innate immune mechanisms are interferons and natural killer cells.
The components involved in adaptive immune mechanisms are neutrilising antibodies and cytotoxic t cells.

Front 4

Describe type 1 interferons and their role in immune mechanisms in viral infections

Back 4

Viral infection stimulates the production of type 1(alpha and beta) interferons by the infected host cell. type 1 interferons prevent viral and host cell replication, they increase antigen processing and presentation (MHC I), they activate professional APCs to initiate adaptive immunity and enhance the ability of natural killer cells to lyse the infected cell.
INF-alpha are used to treat hepatitis B & C.

Front 5

Describe natural killer cells and their role in immune mechanisms in viral infections.

Back 5

Natural killer cells are lymphocytes which are not antigen specific and so belong to the innate immune system. They have 2 receptors, one which recognises self MHC class 1 and so delivers and inhibitory signal to the cell and one which recognises non-self or stress signals on the cell and so activates the NK cell. The outcome of the NK cell depends on the balance of inhibitory and activating signals it receives. Tumour cells and virally infected cells express fewer MHC class 1 molecules and are therefore more susceptible to NK attack. An activated NK cell will lyse the cell by forming pores within its membrane and stimulating apoptosis. They also produce cytokines such as IFN-gamma which promote T cells. They have an IgG receptor for phagocytosis.

Front 6

What is the main advantage of NK cells in viral infections compared to antigen specific cells?

Back 6

There is no lag phase where recruitment and clonal expansion are taking place and so NK cells can limit the spread of infection in the early stage.

Front 7

Describe the role of antibodies in viral infections.

Back 7

Antibodies are most effective during the short extracellular period of the virus. The most effective antibodies are neutrilising antibodies, which binds to the virus envelope or capsid and blocks the virus from binding and entering the host cell. IgG anD IgM may perform opsonisation, enhancing phagocytosis of viruses. By the classical pathway, complements may be activated by the antibody coated virus particles. Viral proteins may be presented on some infected host cells acting as targets for virus specific antibodies, triggering compliment mediated lysis or triggering NK by ADCC. At mucosal surfaces, the virus may stimulate IgA.

Front 8

What is ADCC?

Back 8

In antibody directed cellular cytoxicity, antibodies bind to antigens and then the NK cells bind to the antibodies via CD16 FC receptors. These receptors cross link stimulating degranulation. Granules contain perforin which forms pores in the damaged host cell and proteases which cause apoptosis of the cell.

Front 9

Describe the 2 pathways that cytotoxic cells destroy virus invaded cells.

Back 9

The main pathway is stimulated by the t cell receptor binding to the specific MHC class 1 –antigen peptide complex. The t cell then releases granules which contain perforin, for pore formation in the host cell membrane through which granzymes enter the cell. granzymes are proteases which initiate apoptosis of the cell. in the second pathway, activated CTL express Fas ligand at the cell surface which can bind to and cross link Fas on the surface of the target cell. this cross linking signals to the target cell to undergo apoptosis.

Front 10

What are endogenous and exogenous antigens?

Back 10

Endogenous antigens are those that have been synthesised within the cell itself eg intracellular viruses. Exogenous antigens are those that have NOT been synthesised within the cell eg extracellular bacteria.

Front 11

What are the types of t helper cells and how do they come about?

Back 11

There are 2 types of T helper cells, formed depending on the cytokine released by antigen presenting cell during priming of the immune response.
- Th1 – formed if IL-12 is released from APCs
- Th2 – formed if IL-4 and/or IL-13 is released from APCS.

Front 12

Which cytokines are released in Th1 response? What do they stimulate?

Back 12

Th1 cells release IL-2, TNF, lymphotoxin and interferon gamma in response to antigen stimulation. These cytokines promote macrogphage activation, t cell proliferation and the delayed hypersensitivity response and they enhance NK and cytotoxic t cells.

Front 13

Which cytokines are released in Th2 response? What do they stimulate?

Back 13

Th2 cells release IL-4, IL-5 and IL-10,IL-13. These cytokines stimulate clonal expansion of b cells and maturation, antibody class switching of to IgE, IgG and IgA, and proliferation and differentiation of eosinophils and mast cells.

Front 14

Compare resting and activated macrophages.

Back 14

Resting macrophages are relatively poor at phagocytosis, show little respiratory activity and are only weakly able to present antigens to activate t cells.
Activated macrophages, in response to Th1 cytokines, are very good at phagocytosis, increased respiratory activity, increased levels of MHC class 1 and 2 expressed and enhanced antigen presenting capability. They release cytokines and growth factors that promote inflammation.
Activated macrophages also involves upregulation of Fc receptors to bind to immunoglobulins, promoting phagocytosis of opsonised bacteria and increased expression of PHOX enzyme needed to generate ROS.

Front 15

Describe delayed hypersensitivity response.

Back 15

Delayed hypersensitivity response or type IV and is one of the main cell mediated immune effector mechanisms in eliminating infections. It is classified by the hypersensitive response being delayed 48hrs or more after antigen challenge. Unlike other hypersensitive responses it involves the interaction of T cells, cytokines and macrophages instead of antibodies. The appearance is characterised by erythema and induration ( hardening). It is seen in many autoimmune and infectious diseases eg tuberculosis and granulomas.

Front 16

How is the delayed type hypersensitivity reaction used in investigations?

Back 16

The delayed type hypersensitive response can be used to determine if someone is sensitized to an antigen by a skin test eg heaf test or mantoux tests for tb. A small concentration of purified protein derivative of mycobacterium tb is injected into the dermis. If the individual is sensitised to mycobacterium, this will be a positive test and an erythematic and injurated patch will appear at site of injection 48 hrs after antigen challenge.

Front 17

Describe anergy and when it is seen.

Back 17

Anergy is unresponsive T cells. There may be specific anergy for an antigen as seen in miliary tb or the anergy can be widespread as seen in sarcoidosis. The reasons are unknown.

Front 18

Describe miliary disease.

Back 18

Miliary disease is disseminated tuberculosis. The granuloma liquefaction occurs and the infection spreads into a pulmonary vein, transporting the infection into the heart and into the systemic circulation. Sufferers present with non-specific symptoms such as a cough, fever, weight loss, enlarged lymph nodes. They may have enlarged liver and spleen and multi-organ failure.
T cells may have anergy to the mycobacterium.

Front 19

What are the cytokines involved IN inhibition of t cells.

Back 19

Interferon gama is released from Th1 cells and inhibits Th2 cells. IL-10 is released from Th2 cells and inhibits th1 cell activation.

Front 20

Detail the forms of leprosy.

Back 20

Leprosy is caused by infection with mycobacterium leprae, a gram positive bacillus which is acid fast staining ( mycolic acid cannot be decolourised by alcohol or acid). Leprosy is a chronic disease affecting the skin and peripheral nerves ( macrophages and schwann cells).
In tuberculoid leprosy there is less tissue damage, fewer viable organisms and a strong delayed type hypersensitivity response to the infection, with T cell dependent granuloma formation consisting of activated macrophages, th1 cells, epitheliod cells, giant cells and containment of the organism. The th1 response occurs mainly in schwann cells.
In lepromatous leprosy, the DTH response is suppressed and the Th2 response is initiated with elevated antibody levels. The antibodies do not control the infection and there are a large number of organisms invading the body. Treatment is with rifampacin.

Front 21

Describe the 3 major types of t cell response to different types of pathogens.

Back 21

Cystolic pathogens eg viruses: they are degraded in the cytoplasm, peptides bind to MHC 1 and presented to CD8 T cells which result in cell death.
Intravesicular pathogens eg mycobacterium: they are degraded in acidified vesicles, peptides bind th MHC II and presented to CD4 T cells which results in activation of mactophages, NK and CTL to kill bacteria and parasites.

Extracellular organisms and toxins eg bacteria/parasites: they are degraded in acidified vesicles, peptides bind to MHC II and presented to CD4 T cells which stimulates activation of B cells to secrete ig to eliminate extracellular bacteria.

Front 22

How does the immune system recognise which group of pathogens an organism belongs to and whic type of immune response to mount in order to eliminate it?

Back 22

Professional antigen presenting cells have PRR( pattern recognition receptors- a type of toll-like receptor) which recognise PAMPs which indicates which pathogen group it belongs to, along with allowing endocytosis of molecule and antigen formation. These antigens are presented in the lymph nodes to t and b cells. To the t cells it instructs to most appropriate cytokine response, TH1 or TH2 to deal with the infection.

Front 23

A patient complains of recurrent, severe, persistant or unusual infections. What should be suspected?

Back 23

Immunodeficiency – one or more components of the immune system are defective.

Front 24

Describe secondary immunodeficiency with examples.

Back 24

Secondary immunodeficiency is when immunodeficiency is secondary to a primary disorder eg malnutrition, drug induced, tumours, infections, HIV, loss of protein/cells, asplenia or physiological such as pregnancy or age.
This is the most common form of immunodeficiency and is treated by addressing the primary disease.

Front 25

Describe HIV.

Back 25

HIV –Human immunodeficiency virus is the most common cause of acquired t cell immunodeficiency. CD4 t cells are destroyed by the virus, resulting in a progressive loss of circulating CD4 t cells. Measuring the CD4 count and the plasma viral load indicate the progression of HIV.
A cd4 count of below 200X109/L is a high susceptibility to opportunistic infections eg pneumonia.
HAART –highly active antiretroviral therapy reduces viral load.

Front 26

What are the causes of asplenia?What should asplenic patients take?

Back 26

Asplenia is loss of function of the spleen and may be a congenital condition or acquired due to damage caused by diseases such as sickle cell anaemia, tumour, trauma, autoimmune haemolytic disease and celiac disease. The damaged spleen may be removed in a splenectomy to prevent haemorrhaging.
Asplenic patients are more susceptible to encapsulated bacterial infections and so should be immunised against pneumococci, meningococci and haemophilus influenza type b and they should take broad spectrum prophylactic antibiotic, usually penicillin, for life.

Front 27

Describe celiac disease.

Back 27

Celiac disease is an autoimmune disease that is triggered by proteins in gluten (wheat). Tissue transglutaminase modifies the protein and the immune system cross reacts with small bowel tissue causing an immune attach on the small bowel. The villi become truncated and so nutrients are malabsorbed in the small intestine.
The patient may present with steatorrhea, weight loss or failure to thrive in children and anaemia.

Front 28

Describe primary immunodeficiency.

Back 28

Primary immunodeficiency is when the immunodeficiency is due to an intrinsic defect of the cells or components of the immune system and it is usually inherited.
Defects in:
- antibodies or complement – recurrent bacterial infections
- t cells – viral, fungal and/or mycobacterial infections
- phagocytic cells – bacterial and fungal infections

Front 29

What are the main primary immunodeficiency diseases involving phagocytic cells?

Back 29

Phagocytic cell deficiencies cause bacterial and fungal infections.
The common diseases are
- congenital neutropenias
- chronic granulomatous disease – PHOX enzyme -> can’t make ROS
- leukocyte adhesion defect
These all result in decreased respiratory burst.

Front 30

What are the main primary immunodeficiency diseases involving complement deficiencies?

Back 30

- Complement component deficiency eg C3, properdin, MBL
- Hereditary angiodema – C1 inhibitor deficiency, uncontrolled complement formation causing excessive bradykinin formation.

Front 31

What are the main primary immunodeficiency diseases involving antibodies?

Back 31

MOST COMMON ARE:
1. IgA deficiency – mucosal surfaces not protected
2. Common variable immunodeficiency.

other forms include
- Transcient hypogammaglobulinaemia of infancy
- X-linked agammaglobulinaaemia – BRUTON’S DISEASE
- IgG subclass deficiency
- Specific antibody deficiency

Front 32

What are the predominantly t cell or combined immunodeficiencies?

Back 32

- SCID –severe combined immunodeficiency
- Di George syndrome
- X-linked lymphoproliferative disease ( duncan’s syndrome)
- Type 1 cytokine/cytokine receptor deficiencies
- MHC class 1 and II deficiencies eg bare lymphoma ( MHC 11)
- X linked hyper IgM syndrome ( CD40 Ligand deficiency)
- Wiskott-aldrich syndrome

Front 33

Define neutropenia and agranulocytosis.

Back 33

Neutropenia means the reduction in neutrophil numbers in the blood. Agranulocytosis means the an absence of neutrophils. In neutropenia patients are more susceptible to candida fungal infections, especially if taking corticosteroids as this increasing investation. Also they are more susceptible to encapsulated bacteria infections eg staph aureus, neisseria, pneumococcus, haemophilus influenza type b

Front 34

Describe causes of a secondary neutrophil deficiency.

Back 34

A secondary neutrophil deficiency means that the cause of the low levels of neutrophils is not intrinsic to the neutrophils but caused by other factors. These factors may be:
1. Leukaemia – a specific lymphocyte is made in large numbers, suppressing normal neutropil production
2. Cytotoxic drugs – taken to suppress leukaemia and other tumour growths
3. Autoimmune antibodies which bind to patients own neutrophils, destroying them.

Front 35

Describe primary neutrophil deficiencies.

Back 35

Primary neutrophil deficiencies are rare and are usually inherited. They involve an intrinsic problem with the neutrophils ability to migrate, phagocytosise or the metabolic pathways involved in intracellular killing.
1. Leukcocyte adhesion defect is a genetic deficiency of the beta integrin molecule CD18. It affects both the neutrophils ability to migrate to site of infection as well as its ability to phagocytose.
2. Chronic granulomatous disease is a genetic defect of the enzymes, PHOX, involved in the formation of ROS needed for oxygen dependent intracellular killing. Therefore in CGD, there is a failure in respiratory burst. There are X linked and autosomal recessive variants.

Front 36

Describe the main problems and treatment of chronic granulomatous disease.

Back 36

Main problems:
• Catalase +ve bacteria (Staphylococci)
• Fungi (Aspergillus sp.)
• Skin infections / abscesses
• GI infections
• Osteomyelitis
• Invasive Aspergillosis -fungal
• Inflammatory problems (granuloma)
Management:
• Prophylactic anti-infectives- Septrin & Itraconazole
• Interferon-gamma
• Steroids (inflammatory problems)
• Stem cell transplantation (or gene therapy)

Front 37

Describe immune complex disease.

Back 37

Immune complex disease aka type 3 hypersenstivity reaction is when antibody and antigen concentrations are roughly the same so that cross links occur to form immune complexes that are smaller than usual and so are difficult to remove by macrophages. They enter small blood vessels and accumulate in glomeruli, & joints causing damage. Examples are SLE and glomerulonephritis.

Front 38

How may a patient with neutrophil defects present? How are they treated?

Back 38

A patient with neutrophil defects may present with recurrent bacterial infections, recurrent skin abscesses often caused by staphylococcus aureus, fungal infections (invasive aspergillois) and poor would healing.
They are treated with appropriate antibiotics and anti fungal agents. Bone marrow transplantation or gene therapy may be used and always treat the primary condition of the neutrophil defect is a secondary deficiency.

Front 39

Describe complements roles in host defence and immune regulation.

Back 39

- Opsonisation: c3b binds to the pathogen, aiding phagocytosis. C3b is created via the classical pathway requiring antibody activation, the lectin pathway or the alternative pathway.
- Inflammation: c3a and c5a are chemotactic factors for the migration of neutrohpils and c2a causes an increase in vascular permeability.
- Lysis: MAC – c5b,6,7,8 &9 which form pores in the bacterial membrane.
- Solubilisation of immune complexes to allow their clearance.

Front 40

If there is a defect in the classical pathway, which complements may be deficient? What problems is this likely to cause.

Back 40

The complements are: C1,C4 or C2.
C1q, subcomponent of C1, is activated on binding with antibody (IgG or IgM), this causes the activation of c1s subcomponent to cleave C4 and C2 -> C4B and C2A – c4b2a = c3 convertase. Therefore c3b is not formed, so no opsonisation.
The patient will be more prone to infections by encapsulated bacteria as to deal with these bacteria the triad of antibody, complement and neutrophils is required.
Patients may also suffer from incomplete clearance of immune complexes eg glomerulonephritis, Systemic lupus erythematous (SLE), which commonly cause renal damage, joint problems and rashes.

Front 41

What are the consequences of deficiencies in the lectin pathway?

Back 41

A deficiency in manose binding lectin component is relatively common and will cause increased susceptibility to bacterial infections, SLE and recurrent miscarriage.

Front 42

What are the consequences of deficiencies in the alternative complement pathway?

Back 42

Deficiencies in properdin and factor D are relatively rate. properdin and factor D are required to form a stable C3b (H20) Bb - c3 convertase which activates C3 to C3b. Deficiency in properdin is an x linked disease, so more common with males, and is associated with increased susceptibility to bacterial meningitis ( meningococcal)- neisseria meningitis. Factor D deficiency is associated with respiratory tract infections.

Front 43

A `10 year old male presents with a history of 2 episodes of meningococcal meningitis. Which deficiency may he have?

Back 43

Properdin deficiency – x linked so more common in males and increased susceptibility to bacterial meningitis. However all complement deficiencies increase risk of reccurent neiseria infection

Front 44

What do c3 deficiencies usually cause?

Back 44

Increased susceptibility to infections with pyogenic bacteria and problems with immune complex mediated disease as solubility of immune complexes is decreased without complements

Front 45

Deficiencies in C5,6,7,8,9 increase susceptibility to which micro-organism?

Back 45

Mainly recurrent infections from neisseria bacteria present eg recurrent infections of neisseria meningitis.

Front 46

What is hereditary angiodema?

Back 46

Hereditary andioedema is an autosomal dominant disease resulting in deficiency of c1 inhibitor which causes episodic swelling in subcutaneous and submucosal tissues in limbs, trunk, gi trunk etc. This is because lack of c1 inhibitor causes inappropriate classical complement pathway activation, resulting in bradykinin formation. Bradykinin is a vasodilator which increases transmural pressure and causes tissue oedema. The swellings are painful and can be fatal if they affect the larynx, causing airway obstruction. It can also cause abdominal pain.
It can be treated by infusions of C1 inhibitor.

Front 47

Describe the condition systemic lupis erythematous.

Back 47

SLE is a systematic autoimmune disease ( type 2 hypersensitive reaction)where antibodies against double stranded DNA are produced. it causes a wide range of problems including renal, cardiovascular, musculoskeletal, liver and neurological. Children usually present with butterfly erythematous on the face and photosensitivity.

Front 48

Define agammaglobulinaemia.

Back 48

Agammaglobulinaemia is the absence of antibodies.

Front 49

Define hypogammaglobulinaemia.

Back 49

Hypogammaglobulinaemia means low levels of antibodies.

Front 50

Are primary antibody deficiencies more common in children or adults?

Back 50

They are more common in children but can occur at any age.

.

Front 51

Describe x-linked agammaglobulinaemia.

Back 51

x- linked agammaglobulinaemia is a sex linked genetic defect in a tyrosine kinase which results in the absence of mature b cells. There are very low levels of all the immunoglobulin isotypes (classes).

Front 52

Describe common variable immunodeficiency.

Back 52

It is a primary antibody deficiency affecting both males and femailes. B cells are present but they do not differentiate normally to plasma cells. Hypogammaglobulinaemia is also present. Defects of T cells are usually present, especially th2 cells which help in maturation of B cells

Front 53

What is the most common type of primary antibody deficiency?

Back 53

igA deficiency is the most common form. Usually patients are asymptomatic although they may suffer from increased infections at mucosal sites.

Front 54

Describe the problems and the treatments of primary antibody deficiencies.

Back 54

Problems:
• Recurrent upper and lower respiratory infections => bronchiectasis
• Infections are mainly caused by encapsulated bacteria eg streptococcus pneumonia, haemophilus influenza type b, neissera (NHS)
• GI complications including eg diarrhoea from infections from Giardia
• Encephalitis caused by echo virus
• Arthropathies caused by Mycoplasma / Ureaplasma infection
• Increased incidence of autoimmune disease
• Increased incidence of lymphoma & gastric carcinoma
Management:
• Prompt / prophylactic antibiotics
• Immunoglobulin replacement therapy (iv or sc)
• Management of respiratory function

Front 55

Describe di George syndrome.

Back 55

Di George syndrome is the failure of development of the 3rd and 4th pharyngeal pouches. This causes:
- conotruncal cardiac defects,
- hypocalcaemia due to parathyroid deficiency,
- insufficient thymus development resulting in t cell lymphopenia,
- dysmorphism
- learning difficulties
in 90% of cases this is due to microdeletion on chromosome 22q11.
Immunodeficiency can be minor to major. In complete di George syndrome they have the same symptoms as SCID.

CATCH 22
- Cardiac abnormally( tetrology of fallot), Abnormal facies, Thymus aplasia, Cleft pallate, hypocalcium ( hypoparathyroidism). microdeletion of chromosome 22q11

Front 56

Describe SCID, how will they present? What infections are they more susceptible to?

Back 56

Severe combined immunodeficiency is the main type of primary immunodeficiency syndromes that affect more than one aspect of the immune response.
A group of genetic defects ( autosomal recessive or X linked) which cause failure in signals to activate T cells, lead to the severe impairment of T cell development so that both cell mediated and humoral immunity are severely impaired.
It presents in the first few months of live with
- Failure to thrive
- Diarrhoea
- Hepatosplenomegaly
- Lymphopenia – due to failure of T cell development and sometimes NK and B cells too
Children are susceptible to all infections but particularly
- Candida – usually in specific areas eg vagina (thrush) but seen everywhere
- Respiratory viruses
- Pneumocytis jiroveci ( a yeast causing pneumonia)
- Bacterial infections later on due to early protection by maternal igG

Front 57

Why do babies with SCID present much later with bacterial infections?

Back 57

Babies are initially protected against bacterial infections by maternal IgG.

Front 58

For a person with T cell immunodeficiency, what should happen with live vaccines and blood products?

Back 58

Live vaccines should be avoided and blood products should be irradiated and screened as cyclomegalovirus negative. Cyclomegalovirus remains latent in humans and is usually unnoticed in healthy people but in immune suppressed or HIV positive patients, it can be an opportunistic disease and live threatening.

Front 59

Describe the X linked SCID.

Back 59

X linked SCID involves the defect in the gamma chain of IL-2, IL-7 an IL-15. Thus immature T cells cannot respond to these cytokines and fail to mature.

Front 60

Describe the autosomal recessive SCID.

Back 60

A mutation in JAK-3, a protein involved in intracellular signalling and activation of T cells.

Front 61

Describe the enzyme deficiencies resulting in t cell deficiency.

Back 61

Adenosine deaminase (ADA) deficiency or purine nucleotide phosphorylase (PNP) deficiency are T cell deficient because the developing t cells are sensitive to the toxic metabolites that build up due to the absence of these enzymes.

Front 62

What is the treatment for scid?

Back 62

Bone marrow transplant or gene therapy

Front 63

Describe nephrotic syndrome?

Back 63

Nephrotic syndrome is characterised by significant proteinuria which leads to hypoalbuminaemia and oedema. There is increased permeability of the glomerulus due to glomerular basement membrane damage ( loss of negative repulsion) and increase in pore size. This allows proteins to enter the nephron and be excreted in urine. The loss of albumin causes loss of osmotic pressure so oedema results. The decreased circulating volume triggers the RAAS causing further sodium and water retension and further oedema.
Complications include hyperlipidaemia, increased risk of thrombosis and immunosuppresion.
it can be caused by minimal change disease, membranous glomerulonephropath, focal segmental glomerulosclerosis. Secondary causes include SLE, tumour, amyloid, diabetes mellitis.

Front 64

Give a Th2 disease.

Back 64

Lepromatorus leprosy – it is highly infectious and poor control of replication.

Front 65

What are teh TH2 cytokines?

Back 65

IL-10, IL-13 , IL4, IL-5

Front 66

What role do NK cells play in viral immunity?

Back 66

- Initiate lysis via perforin and granulozymes
- Release gamma interferons which promote T cells
- ADCC- antibody directed cellular cytoxity

Front 67

What cytokines would you expect to be present in a viral infection?

Back 67

IL-12, interferon gamma, TNF alpha – th1 response

Front 68

What are the 2 main laboratory tests used to monitor disease progression in HIV infection? Describe their relationship from first infection

Back 68

Viral load and CD4 count.
When a patient initially is infected by HIV retrovirus, they present with opportunistic infections mirroring a full blown AIDS sufferer. After 6-12 weeks, the viral load will decrease and the CD4 levels will increase. For around 10 years no symptoms are experienced and then the viral load begins to rise and CD4 numbers plummet, resulting in AIDS.

Front 69

Name aids defining diseases

Back 69

TB, Karposi’s sarcoma caused by herpes virus, PCP – Pneumocytis jiroveci, systemic candida infections.

Front 70

What is panhypogammaglobinaemia?

Back 70

Very low levels of all classes of antibodies

Front 71

Describe the process of antibody replacement therapy.

Back 71

Antibody replacement therapy is used to treat patients with primary (and in some cases secondary) antibody deficiency where antimicrobial agents are not effective.
IgG fraction is separated from pooled plasma donations. They can be given intravenously or subcutaneously.
This is a form of passive immunity.

Front 72

Describe laboratory tests to rule out defect in phagocyte function.

Back 72

- Full blood count to check for number of neutrophils (neutropenia)
- Neutrophil function test ( check for chronic granulomatous disease)
- Adhesion molecule expression ( check for beta integrin CD18 for leukocyte adhesion defect)

Front 73

What happens in bare lymphocyte syndrome?

Back 73

There is an absence of MHC-II (HLA –DR,DQ,DP) so CD4+ T cells decrease. MHC-II is involved in activation, proliferation and maturation of CD4+ T cells (POSITIVE SELECTION).
T helper cells are required for b cell differentiation and antibody production.

Front 74

Describe the different types of antigens that are recognised by different toll like receptors.

Back 74

TLR-2 – Gram positive bacteria
TLR 4 – Gram negative bacteria – Lipopolysaccharide
Overzealous activation of these TLR4 receptors, will lead to increased endotoxic (lipopolysaccharides) shock!
TLR3,7,9 – Viruses
TLRs are part of the innate immune system and thus lack antigen specificity.

Front 75

What are the most likely viral infections for immunocompromised individuals?

Back 75

TORCH: toxoplasma, rubella, CMV, herpes simplex

Front 76

Define an Enveloped virus

Back 76

– genome + capsid + envelope – more sensitive to inactivation, ligand is on lipopolysaccharide envelope – new viruses are released from cell by budding as oppose to cell lysis in naked viruses

Front 77

Define Inclusion bodies.

Back 77

Inclusion bodies are sites of viral multiplication within a cell. They are very electron dense due to nucleic acid core.

Front 78

List integral and peripheral proteins in the erythrocyte cytoskeleton.

Back 78

Cytoskeleton – spectin (hetromers), actin, band 4.1,

Integral proteins in membrane: band 3 ( anion exchanger), glycoprotein 3, ankyrin

Front 79

Give examples of DNA enveloped virus.

Back 79

Hepatitis B, herpes viruses and small pox

Front 80

Give examples of DNA non enveloped viruses.

Back 80

Human papilloma virus – cervical cancer and warts
HPV 16 & 18 are high risk viruses

Front 81

Give examples of RNA enveloped viruses.

Back 81

Rubella, rotavirus (diarrhoea), HIV, ortho and para myxoviruses ( influenze, measles and mumps), coronaviruses ( colds, SARS- severe acute respiratory syndrome)

Front 82

Give an example of RNA non enveloped virus.

Back 82

Picornviruses – polio, hepatitis A and colds (rhinoviruses)

Front 83

How are viruses diagnosed?

Back 83

Diagnosis of viral infection: can be diagnosed through culturing in cell cultures, in embryonic egg cells or animals and immunocytochemical staining and identification of virus particles or antigens in tissue specimens.

Front 84

Define Cytopathic effect.

Back 84

Degenerative, destructive changes in cells caused by pathogen

Front 85

Describe the replication strategy of a virus

Back 85

.
DNA viruses are either double stranded or single stranded. Double stranded viruses include poxviruses, herpesviruses, adenoviruses, papovaviruses and polyomaviruses. Hepatitis B virus is double stranded with single stranded portions. Single stranded viruses include parvoviruses ( erythema infectiosum). DNA viruses usually replicate in the nucleus of the host cells, producing a polymerase which reproduces viral DNA.
For RNA viruses, replication strategy: uses hosts machinery to translate viral RNA.
- Negative (anti-sense) RNA must first be converted to m.RNA before it can be translated,
- Positive (sense) RNA can be directly translated,
- some RNA must be converted to DNA to be replicated eg HIV by reverse transcriptase.
New virus particles are released during cell lysis in non enveloped viruses or by budding in enveloped viruses.

Front 86

Describe the process of gram stains, gram negative and gram positive bacteria.

Back 86

Gram stains are useful in classifying most bacteria.
- Crystal violet solution is added to the bacteria which can pass through the cell wall of both types of bacteria, gram positive and negative.
- Iodine is then added which forms large complexes with crystal violet inside the cell.
- In gram positive bacteria, their cell walls are too thick to allow the large complex molecule to pass through. Therefore gram positive bacteria appear dark blue/purple.
- A decolourising agent is then added which removes the outer membrane from gram negative bacteria, and so the iodine complex can leave the cell as the cell wall is thin.
- Red stain is added to give the gram negative bacteria colour.

Gram positive bacteria stain dark purple/blue and have thick peptidoglycan walls.
Gram negative bacteria stain red and have thin peptidoglycan walls and a thin outer membrane around the cell wall. The outer membrane is made of lipopolysaccharides.