Immunology Flashcards
A normal immune response is composed of which three sequential phases?
- Immediate innate immunity - defensins, physical barrier
- Early induced innate immunity - PAMP/PRR interactions, mast cell activation, release of pro-inflammatory mediators
- Adaptive immune response - activation of naive T and B cells, production of antibodies and antigen-specific cells
What is vaccination?
Deliberate exposure to a pathogen-related antigen to induce immunological mediated response and to acquire immunological memory
What do memory cells allow for?
A rapid response when the same pathogen invades a second time
Symptoms will be eradicated or dampened down in second exposure
Memory cells can remain dormant and reactivate when foreign antigens previously detected are present
Effector cells are more quickly produced this way via clonal proliferation and differentiation of memory cells
What must occur for antibodies to be produced?
An antigen specific cell must be encountered
What is the first antibody produced in response to infection?
IgM
IgM production will change to production of what other antibody class during the adaptive response?
IgG
What is the reason for the change between IgM production to IgG production?
IgG has the same, but added functionality to IgM
What is the lag period?
This is the time when antibody levels are low as they gradually build
Pathogen proliferation is very high at this stage
Symptoms will likely be experienced at this stage
Where do long-lived plasma cell retreat after infection is eradicated and what do they do?
They retreat to the bone marrow
They will secrete antigen specific antibodies for an extended period of time
In a secondary response to an infection, which antibody class(es) are activated from the beginning?
IgG and IgM
How can IgG activate complement?
Via the classical pathway
Why is it often effective to swtich to IgA production during the secondary response?
IgA can form dimers which can cross epithelial tissues and that are able to block bacterial attachment to ucous membranes
What is unusual about how the immune system combats diptheria?
The toxin produced by the infection is targeted - not the microorganism
This means the toxin can be cleared, by the individual will still be a carrier
What happens to effector cells (non-memory B and T cells) when no antigen is present for binding?
They will undergo apoptosis
Why can memory B cells produce more functional differentiation than in the primary response?
They have already undergone Ig class switching (IgM to IgG) and hypermutation
How are memory cells superior to primary B cells produced?
- They have already undergone Ig class switching
- They have enhanced cell adhesion
- They have enhanced chemotaxis properties
Why do memory cells encounter antigens faster?
They are present in secondary lymphoid tissues unlike naive cells
This is because they have receptors on their surface which allows for binding with chemokines which causes entrapment within such tissues
What is active immunity?
This is protection obtained solely from an individual’s own immune system and can be stimulated by vaccine or occur naturally
What is passive immunity?
This is temporary immune protection transferred form one individual to another such as secretory IgA in breastmilk
Describe the methodology behind inactivated vaccines?
- These are termed attenuated vaccines
- This involves the vaccine being made up of components that were never alive such and only exist to minic the real antigen - they can be “edited” versions of the real antigen
- This will not produce immunity as effective as a live pathogen would
- The immune response will be mostly B cell mediated and less activity of T cells will be present as a live pathogen is absent
- Immunological memory will likely not last as long and repeat vaccine may be required
Why will there be a relatively weak T cell response to attenuated vaccines?
There are no live components for which T cells can act upon
How can an attenuated vaccine be created?
- Chemical fixatives - the structure can be preserved by formalin
- Heat denaturation
- Irradiation
What are the two main problems associated with attenuated vaccine preparation?
- Under-inactivation - pathogen is not inactivated correctly and viable pathogens remain present
- Over-inactivation - antigens on over-inactivated pathogens are too different from the real pathoegn and do not confer immunity against it
What are the main benefits to attenuated vaccines?
- Made quickly
- May elicit good antibody responses
- Easy to store and do not require refridgeration
- Usually safe to give to anyone - even the immunosuppressed
What are the main disadvantages to attenuated vaccines?
- Can be difficult to stimulate an immune response
- Poor at eliciting T cell responses
- May not give lasting immunological memory and require boosters
What are adjuvants?
A mixture of inflammatory substances to kick-start the immune system to activate B and T cells
This is required because a foreign antigen alone is not enough
What are the main downsides to the use of adjuvants in vaccines?
- Toxicity
- Altered immune response - the immune response may be directed aginst the pathogen/adjuvant conjugate rather than solely the pathogen
- CD4+ cells may only be able to recognise the carrier and not the free vaccine
What is sub-unit vaccination?
Recombinant DNA technology allows for the genes for a sole antigen to be isolated
This involves using a sole antigen, menaing disease cannot be caused
What are polysaccharide vaccines?
- These are vaccines directed against pathogens encapsulated by polysaccharide sugars
- The polsysaccharide sugar is the antigenic material
- To improve immune response, adjuvant toxoids can be added to this coating
- This is important in allowing both B and T cell responses to the toxoid
- This aids better class switching and antibody production
How can live attenuated vaccines be obtained?
Passaging
This is the process whereby attenuated strains are grown through repeated subculturing
The pathogen will become adapted to the environment it is grown in meaning it can be led down certain paths of adaptation to make it less effective in human tissues
What are the advantages to live attenuated vaccines?
- Similar to natural infection
- Both B and T cells are properly activated
- There is a strong immune response initiated
- Good immunological memory is conferred
What are the main disadvantages to live attenuated vaccines?
- If immunocompromisation, patients can become very ill
- Any circulating antibody can interfere with the immune response
- The vaccine is fragile and refridgeration is key
- The pathogen can acquire new mutations and become virulent again
What are the two types of passive immunity?
- Naturally acquired
- Therapeutic
What is naturally acquired passive immunity?
This is when a foetus or baby obtains maternal antibodies
Secretory IgA is given to babies through breastmilk
What is therapeutic passive immunisation?
This involves injecting antibodies to specific pathogens
This is effective but cannot last long since the antibodies cannot be produced by the body
When may it be difficult to produce vaccines?
- The body can never clear infection (Tb and HIV)
- When there are many different strains of a pathogen
Which acronym is used to remember types of infections associated with immunodeficiency?
SPUR
- Serious (unresponsive to oral antibiotics)
- Persistent (can cause structural damage and become chronic)
- Unusual (may include opportunistic pathogens)
- Recurrent
What is primary immunodeficiency?
This is caused due to the immue system having components “missing” or functioning incorrectly
This is most often due to genetic disorders
What is secondary immunodeficiency?
This is caused by environmental factors
Most often due to immunosuppressant drugs
Which cells make up the innate immune system?
- Macrophages
- Neutrophils
- Mast cells
- NK cells
- Dendritic cells
Which proteins are involved in the innate immune system?
- Complement
- Acute phase proteins
- Cytokines
What do macrophages do at the end of infection?
Produce cytokines and other molecules which promote wound healing and tissue repair
Which pathogens are likely to cause recurrent infection?
- Staph aureus
- Burkholderia cepacia
- Mycobacteria Tb
- Fungi - candida and aspergillus
Where are neutrophils produced?
Bone marrow
Which cells produce which pro-inflammatory mediators and cytokines that allow activation of specific adhesion molecules (on endothelium) and neutrophils to occur?
Macrophages and mast cells
IL-1, IL-6 and TNFα
Which cells secrete which cytokine to superactivate macrophages?
NK cells and T cells
Interferon γ
What is Kostmann syndrome?
A syndrome affecting only the end part of the myeloid lineage that allows for neutrophil differentiation
How is Kostmann syndrome treated?
Since the immune system is weakened (no neutrophils) prophylactic antibiotic and antifungals can be given
Stem cell ransplants can also occur
Granulocyte colony stimulating factor can allow for maturation of neutrophils
What are some types of PRRs?
- Toll like receptors
- Scavender receptors
- Lectin receptors
Macrophages have what receptors that can bind to an opsonin/pathogen complex?
Fc receptors
When complement is bound to a protein, it can bind to a macrophage via which receptor?
Complement receptor 1 (CR I)
Why will a defect in the mechanism of one opsonin not necessarily be severly detrimentral to phagocytosis as a functional process?
There are many opsonins available
A chronic granulomatous disease may be due to what?
A genetic defect in the production of the NADPH oxidase complex
This means reactive oxygen and nitrogen species cannot be produced and pathogens are not so easily killed
Systematic infection may occur
How can chronic granulomatous disease be tested for?
The nitroblue tetrazolium test
This determines in neutrophils can kill pathogens by producing oxygen free radicals
Bacteria are exposed to patient neutrophils and production of hydrogen peroxide is tested for using a dye
How can granulomatous disease be treated?
Supportive
- Prophylactic antibiotics and antifungals
Definitive treatment
- Stem cell transplantation (bone marrow)
- Gene therapy
Infected macrophages produce which cytokine?
IL-12
IL-12 produced from infected macrophages has what effect?
It induces TH1 cells to secrete interferon gamma which can stimulate macrophages and neutrophils to produced TNF which can activate the oxidative pathways for producing NADPH
What will the neutrophil count be in:
- Congenital neutropaenia?
- Leukocyte adhesion defect?
- Chronic granulomatous disease?
- Absent
- Increased
- Normal
Will there be pus formation in:
- Congenital neutropaenia?
- Leukocyte adhesion defect?
- Chronic granulomatous disease?
- No
- No
- Yes
What will the level of leukocyte adhesion markers be in:
- Congenital neutropaenia?
- Leukocyte adhesion defect?
- Chronic granulomatous disease?
- Normal
- Absent
- Normal
What is the result of the nitroblue oxidative killing test in:
- Congenital neutropaenia?
- Leukocyte adhesion defect?
- Chronic granulomatous disease?
- Usually absent (lack of neutrophils)
- Normal
- Abnormal
The repertoire of cells in the adaptive immune system is:
a) Genetically encoded
b) Developed over time through maturation
b)
The repertoire is developed over time through maturation
Pre T-cells mature in the thymus gland by which process?
Thymopoeisis
What occurs during the T cell maturation process?
The cells have their alpha/beta chain genes rearranged allowing or specificity to a specific antigen
Only 10% of cells survive this process
Helper TH1 cells (CD4+) secrete which mediator which will activate whihc type of cell?
They release interferon gamma to activate macrophages