SAQs Flashcards
Secondary immunodeficiency is more important than primary immunodeficiency – discuss the extent to which this statement is true then illustrate your argument with a range of relevant examples.
Immunodeficiencies can be classified as primary (PID) or secondary (SID), secondary immunodeficiencies are more prevalent and have broader public health implications.
Primary Immunodeficiencies (PID)
Primary immunodeficiencies are rare, inherited conditions that impair immune function. Examples include:
Severe Combined Immunodeficiency
(SCID): A severe disorder with defects in both T and B cells, leading to life-threatening infections if untreated.
X-linked Agammaglobulinemia (XLA): Results in a lack of B cells and increased bacterial infections.
Chronic Granulomatous Disease (CGD): Impairs phagocytosis, leading to recurrent infections.
While significant, these disorders are less common and often managed with treatments like bone marrow transplants or immunoglobulin therapy.
Secondary Immunodeficiencies (SID)
Secondary immunodeficiencies are more common and arise due to external factors. Examples include:
HIV/AIDS: HIV targets CD4+ T cells, leading to immune depletion and increased susceptibility to infections and cancers.
Cancer Treatment: Chemotherapy and radiation suppress immune function, leaving patients vulnerable to infections.
Corticosteroid Therapy: Long-term use can impair immune responses and increase susceptibility to opportunistic infections.
Malnutrition: Severe malnutrition weakens the immune system, making individuals prone to infections.
SIDs are often more prevalent and have significant clinical consequences, but many can be managed or reversed with treatment.
Importance of SID vs PID
While primary immunodeficiencies are rare, secondary immunodeficiencies are more widespread and can affect individuals of any age. SIDs, such as those caused by HIV or cancer treatments, are treatable and often reversible, making them a major focus in clinical practice.
Conclusion
Secondary immunodeficiencies are more clinically important than primary immunodeficiencies due to their higher prevalence, broad causes, and potential for treatment. Though PIDs are crucial for understanding genetic defects in immunity, SIDs represent a more pressing public health concern that can be managed with timely interventions.
Discuss the immunological processes involved in tumour immune evasion.
Tumor immune evasion involves several mechanisms that allow cancer cells to avoid detection and destruction by the immune system.
The tumour cells themselves downregulate the MHC I molecules and also MHC II and co-stimulators not expressed. This means if you don’t have MHC I or MHC II then you are not going to engage with the CD4 helper cells or cytotoxic t-cells so they wont be able to kill the tumours.
Suppressive tumour products released eg TGFb – tumour cells are famous for having in their environment a lot of phosphatin serum, the apoptopic cell maker, which can react with phosphotirium receptors and tell macrophage to respond in an anti-inflammatory way.
Neonatal tolerance – if you have got normal proteins that are in the neonate then you’re just tolerised and not going to respond.
Immunoselection – you have a heterogenous tumour and if your immune system is responding, it might remove 99% and all its cells but because it’s heterogeneous there might be a few cells that get left behind as the immune system doesn’t recognise them so antibodies don’t respond and get rid of them so you get this immunoselection for the cells that cannot be seen.
Antigenic modulation – if you look at a fast growing cancer cell the cells have a higher mutation rate so you can get antigenic modulation and they basically just keep changing their antigens so the antibodies you made no longer work.
Antigenic Masking – antigen masking is where the antigen that your antibody could respond to doesn’t have access to as it is masked by surrounding receptors.
Immunosuppression – with tumour immune evasion, immunosuppression can be mediated through the normal checkpoints, we don’t want the immune system to overreact or get instigated to easily so we have multiple receptors engagement and multiple signals to turn it on but we also have inhibitory signals including:
PD-1/PD-L1 – to control immune responses so cell-cell interactions and all it takes for is the cancer cell to upregulate this switch off signal.
T cell phenotype programming
What is a vaccination
A vaccine is a preparation of antigenic material used to induce immunity against pathogenic organisms. A vaccination is an intentional administration of a harmless or less harmful (attenuated) form of a pathogen to induce a specific immune response that protects that individual against later exposure to the same pathogen – the deliberated induction of an adaptive immune response
what is the purpose of having a vaccine?
The purpose is to generate memory cell to be there to fight pathogen for when infection comes about in secondary encounter. The antibody response is much faster and more effective than the first time around because the memory cells are at the ready to pump out antibodies against that antigen.
Vaccination is an important way of preventing the development of disease in our bodies and stopping us from being ill from infections.
List or outline the types of vaccines
Live Vaccine - Attenuated bacteria and Attenuated virus
Killed Vaccines
Toxoid Vaccines
Conjugate Vaccines
Peptide Vaccines
Outline the ideal requirements to generate ideal vaccines?
Safe
Provide long-lasting & effective protection
Neutralizing antibodies
Protective T-cells
Few or no side effects
Biologically stable
Easy to distribute & administer
Cheap to produce
Acceptable to general public
Can you state 5 signs that contribute to primary immune deficiency?
8 or more new ear infections in a year
2 or more serious sinus infections in a year
Antibiotics for 2 months without effect
2 or more pneumonia in a year
Recurrent, deep skin or organ abscesses
2 or more deep-seated infections such as osteomyelitis, cellulitis, or sepsis
Surgical intervention for chronic infections
Persistent thrush in the mouth or elsewhere on the skin after age 1 year
Failure to thrive
Family history of primary immunodeficiency
Why does the killed virus or bacteria treated by chemicals cause problems to the immune system.
The affinity of the immunoglobulin will be affected when the memory cell encounters with the pathogen in real life.the treated immunogenic epitope structure will be changed compared to the real pathogen immunogenic epitope structure
if a patient comes with a hyper IgM result what is the first sign that really indicates this.
- it indicates that b lymphocytes lack CD4 receptors with the t cell so cannot receive IL-4 or signal from the t lymphocytes and therefore can not go into class switch.
A 14-month-old girl was immunized with the first dose of MMR (measles, mumps, and rubella) vaccine.
How can she produce antibodies to the different immunogens from measles, mumps, and rubella?
Combinatorial diversity – random gene rearrangement and H & L chain combination
Junctional diversity.
Somatic hypermutation.
A 14-month-old girl was immunized with the first dose of MMR (measles, mumps, and rubella) vaccine.
How can her T cells respond to the different immunogens from measles, mumps, and rubella and generate memory?
Combinatorial diversity – random a & b gene rearrangement and a & b chain combination
Junctional diversity.
An infant boy came for a clinical examination and the doctor found that the patient had small lymph nodes. Laboratory results showed a defective Bruton’s tyrosine kinase (BtK). Discuss with reference to clinical disorders of immunodeficiency the following questions:
What kind of immunological disorder does this infant have? (1 marks)
X-linked agammaglobulinemia aka Bruton’s Disease (Ab deficiency).
An infant boy came for a clinical examination and the doctor found that the patient had small lymph nodes. Laboratory results showed a defective Bruton’s tyrosine kinase (BtK). Discuss with reference to clinical disorders of immunodeficiency the following questions:
The infant has been experiencing recurrent bacterial infections that started after three months since he was born. What treatment in addition to antibiotics should be given to these patients and why? (3 marks)
Treatment with immunoglobulin (IV 1g) Because the patient cannot develop normal B lymphocytes
Define Primary and Secondary immunodeficiency? (2 marks)
Secondary immunodeficiency (SID) occurs when the immune system is weakened by another treatment or illness.
Primary immunodeficiency (PID) is a term used to cover a Large number of different conditions that affect how the body’s immune system works.
Why is IgA important?
Immunoglobulin A (IgA), as the principal antibody class in the secretions that bathe these mucosal surfaces, acts as an important first line of defence. IgA, also an important serum immunoglobulin, mediates a variety of protective functions through interaction with specific receptors and immune mediators.
How are sIgA antibodies transported?
IgA-mediated excretory pathway
Polymeric IgA binds to the pIgR on the basolateral surface of epithelial cells, and is taken up into the cell via endocytosis.
Why do antibodies need an Fc region?
the Fc region of antibodies is crucial for triggering immune responses. It interacts with immune cells and receptors to promote functions like phagocytosis and complement activation.
What are the causes of chlamydia?
Chlamydia is caused by the bacterium Chlamydia trachomatis
Chlamydia trachomatis is an Obligate intracellular pathogen – the bacteria can’t make enough ATP to sustain the metabolism outside of a host cell so therefore it acts as an almost energy parasite as it needs to infect host cells in order to replicate.
Chlamydia trachomatis is also Gram variable - both pink and purple cells due to the unique cell wall structure which is an important virulence factor.
What are the features of chlamydia?
2 major biovars of chlamydia
Trachoma – consist of serovars of Chlamydia trachomatis A, B and C so these serovars cause trachoma – trachoma is not sexually transmitted and is the worlds leading cause of infectious blindness. Transmitted through direct contact.
Urogenital biovars of Chlamydia trachomatis covers the serovars D-K so these serovars cause infection to the urogenital tract. Part of the urogenital biovar does also include serovars L1, L2 and L3 which cause lymphogranuloma venereum (LGV)
How is chlamydia spread? (transmission)
by sexual contact – unprotected vaginal, anal or oral sex and acute clinical manifestations are usually urethritis, cervicitis, proctitis
perinatal transmission – transmitted by infected mother to unborn child during delivery resulting in eye infections, conjunctivitis, or lower respiratory tract infections, pneumonia.
How is chlamydia treated?
Antibiotics – 95% successful if taken correctly: Doxycycline – 100mg twice a day for 7 days – it is a tetracycline antibiotic so the mechanism of action is it inhibits protein synthesis
Partner notification is important – both current and past so they can be tested, and advice is to abstain from sex.
Avoid sexual contact with high-risk partners – people that are likely to be engaging in unprotected sexual activity with multiple partners.
Why is infection of the male genital tract more symptomatic?
fewer microorganisms and bacterial cells in the lower pH environment in females and easier to miss unusual discharge in females whereas penile discharge is an obvious sign.
What is the developmental cycle of chlamydia?
Adherence of elementary bodies
internalised into cell by endocytosis
24 hours post infection of that cell, the elementary bodies undergo a kind or differentiation and reorganisation
40 hours post infection, the reticulate bodies will be differentiated and they return to elementary bodies and eventually the inclusion grows to such a size that through reverse endocytosis or through lysis of the cell, the elementary bodies are then released.
What might be the symptoms of the patient presenting with sepsis?
Temperature above 38.3 or less than 36
Heart rate greater than 90 beats per minute
Respiratory rate greater than 20 - elevated
And can actually alter mental state
Bloods will present as
White cells less than 4x109/l or greater than 12x109/l
Glucose greater than 7.7mmol/l (if the patient isn’t diabetic)
