Week 3 - Antibiotics Flashcards
Familiarise with the scenario
Ambrose is a 2 years 3 months old boy who is attending a follow-up appointment with his paediatrician at Great Ormond Street Hospital to receive the results of his recent tests. He had been referred by his GP after repeated infections that started around 8 months of age. His mother reported that Ambrose had been breast fed for the first 6 months, and until 8 months he had been a bright and active child. Subsequently, he developed his first case of pneumonia, then over the next 12 months had five episodes of otitis media, several sinus infections, a single episode of erysipelas on his cheek, plus two further bouts of pneumonia - all the infections were successfully treated by antibiotics. He also seemed to have recurrent episodes of diarrhoea. Ambrose’s mother was concerned that he seemed to be constantly on antibiotics.
At the first appointment the paediatrician took a medical family history where Ambrose’s mother reported that;
· She had grown up in Sierra Leone.
· That she had a younger brother who had died from pneumonia when he was 2 years old.
· Ambrose’s grandmother is alive in Sierra Leone with no serious health problems.
· She has a sister who is alive and well, who has a healthy son and daughter.
· Ambrose has a healthy younger sister.
· There is no significant family history of any disease on Ambrose’s father’s side.
The paediatrician examined Ambrose and found that he had no visible tonsils, and ordered a full blood count and immunoglobulin profile to analyse the levels of immunoglobulins in Ambrose’s serum. The blood tests showed he had a normal white blood cell count (5000 cells/µl). The white blood cell differential and immunoglobulin profile were as follows:
More detailed laboratory studies using flow cytometry it was found that:
· 85% of his blood lymphocytes bound an antibody to CD3, a pan-T cell marker (normal).
· 55% were helper T cells reacting with an anti-CD4 antibody (normal).
· 29% were cytotoxic T cells reacting with an anti-CD8 antibody (normal).
· None of Ambrose’s blood lymphocytes bound an antibody against the B cell marker CD19 (normal = 12%).
· T cell proliferation indices in response to phytohemagglutinin, concanavalin A, tetanus toxoid, and diphtheria toxoid were 162, 104, 10, and 8, respectively (all normal).
The paediatrician considers that Ambrose might have some type of immunodeficiency and suggests that he begin a course of intravenous immunoglobulins.
What does otitis media mean?
An ear infection
What does erysipelas mean?
Cheek rash
What are the general types of immunity? What cells are involved in each?
Innate immunity which is non discriminative - - includes physical and chemical barriers such as the mucosal linings of our respiratory tract and GI tract
- macrophages which come from monocytes and secrete cytokines
- neutrophils, eosinophils, basophils
- natural killer cells
Adaptive immunity
- acquired
- small lymphocytes which include T cells and B cells (incl plasma cells)
How do macrophages work?
What do they recognise? What do they bind to? What do they secrete? What signalling cascade occurs? What is the general name of the immune response they are a part of?
Macrophages recognise bacterial or viral components such as lipopolysaccharides (LPS) or double stranded RNA (dsRNA)
via special receptors called Toll-like receptors
When TLR activation happens because they have bound to the above, this causes macrophages to secret cytokines (small molecules involved in cell signalling and attraction) AND phagocytise infected cells
The innate immune system then activates the adaptive immune system (B cells and T cells etc)
Explain generally how acquired immunity works
Mediated by lymphocytes which are either T cells or B cells
B cells secrete antibodies that bind to antigens which are proteins on the surface of cells or free floating in the body.
When an antibody binds, it triggers mechanisms that will attack and destroy infected cells.
Some B cells become memory cells
T cells can either be T helper cells or cytotoxic
Briefly explain how antibodies help prevent bacterial infections?
4 marks
Antibody is critical for defence against pathogens, especially extracellular bacteria:
· it binds to them to increase their uptake by phagocytes (for example, macrophages or neutrophils),
· or to induce their killing by complement activation
· or by cellular components of the immune system (antibody dependent cellular cytotoxicity, ADCC).
· In addition, antibody can block infection by preventing the binding of pathogens to critical receptors on host cells and can neutralise the activity of toxins that cause disease.
Explain generally how acquired immunity works
B cells secrete antibodies that bind to antigens which are proteins on the surface of cells or free floating in the body
When an antibody binds, it triggers mechanisms that will attac and destroy infected cells
Some B cells become memory cells
T cells can either be T helper cells or cytotoxic T cells
Explain why Ambrose was healthy for the first 8-9 months of his life?
2 marks
The passive transfer of IgG across the placenta protected him plus (1 mark)
the fact that he was breast fed again protected him for the 1st 8 months. (1 mark)
From the family history of Ambrose what is the inheritance pattern and justify your answer
4 marks
· X-linked recessive (1 mark ½ mark for x-linked only)
· Only boys affected (Ambrose and the uncle) (1 mark)
· Ambrose’s mother is a carrier she has 2 X chromosomes the affected chromosome is transferred to Ambrose (1 mark) but even if his sister has this affected chromosome she does not have the condition so its recessive (1 mark)
Which Cohn fraction contains the gammaglobulins that are used in the treatment of Ambrose?
1 mark
Cohn fraction II
What condition does Ambrose have?
X linked agammaglobulinaemia
What is wrong with Ambrose’s immune system?
The B cells (acquired immunity - humoral) is not working properly
So the lymphocytes are present but are not mature and do not become plasma cells or memory cells
T cells and innate immunity is working fine
What are the components of the innate immune system?
Physical, chemical barriers Phagocytic leukocytes Dendritic cells Natural Killer Cells Plasma proteins (complement)
What are the components of the adaptive immune system?
Humoral immunity (B cells, which mature into antibody secreting plasma cells)
Cell-mediated immunity (T cells maturing into either hyper cells or cytotoxic T cells)
When is the innate immune system active?
Always
When is the acquired immune system active?
Normally silent
Only when triggered
Describe the response and potency of the innate immune system
Immediate response
Limited and lower potency
Describe the response and potency of the acquired immune system
Slower to respond
Over 1-2 weeks but is much more potent
Describe the specificity of the innate immune system
General
Recognised many classes of pathogens (bacteria, viruses, fungi, parasites) but cannot make fine distinctions
Describe the specificity of the acquired immune system
Recognises highly specific antigens
Describe the course of the innate immune system
Attempts to immediately destroy the pathogen, if it can’t it recruits the acquired immune system and contains it until it arrives
Describe the course of the acquired immune system
Slow to respond
Effector cells usually produced after 1 week
Entire response 1-2 weeks
Varies between individuals
Does the innate immune system have memory cells?
Nope
Reacts with equal potency upon repeated exposure to the same pathogen
Does the acquired immune system have memory cells?
Yes
Remembers specific pathogens
When re-exposed, the cells are produced much faster and more potent the second time around
What is the story behind Ambrose always being on antibiotics?
He has never produced any antibodies and the humoral immunity never worked but because he was being breast-fed, he was getting IgA from the breast milk and so wasn’t unwell, but as time went on he stopped breastfeeding and the IgA finished and so he started ‘always being on antibiotics’
Where IgA found and secreted?
What does IgA do?
Found in saliva, tears and breast milk
Mucosal areas such as gut, respiratory tract and urogenital tract
Protects against pathogens
Where IgD found and secreted?
What does IgD do?
Part of the B cell receptor
Activate basophils and mast cells to produce antimicrobial factors
Where IgE found and secreted?
What does IgE do?
Responsible for allergic reactions
(Binds to allergens and triggers histamine release from mast cells and basophils, involved in allergy)
Protects against parasitic worms
Where IgG found and secreted?
What does IgG do?
Secreted by plasma cells in the blood
Able to cross the placenta into the foetus (only one)
Provides the majority of antibody based immunity against invading pathogens
