Healthcare Infections and The Adaptive Immune Response

Question 1

What are Healthcare Infections and how are they officially recognised in hospitals?

Answer 1

Infections arising as a consequence of providing healthcare.
In hospitals, patients who neither present or are incubating at the time of admission with an onset at least 48 hours after admission, as well as any infections in hospital visitors or healthcare workers.

Question 2

Why are healthcare infections important?

Answer 2

They are frequent (prevalence of 8% in inpatients), with a profound impact on health and healthcare organisations, plus they’re preventable. There is a large associated financial cost.

Question 3

What type of healthcare infections are most common?

Answer 3

HCAIs are commonly GI or UTIs, but a range of systems can be infected by numerous responsible organisms.

Question 4

Hand washing is vital, what does infection prevention aim to do?

Answer 4

Aims to stop the initial pathogen-patient relationship, mechanisms of disease and the infection giving out pathogens into the environment.

Question 5

Give some examples of the different types of HCAIs.

Answer 5

Viruses - blood borne, norovirus, influenza, chicken pox,
Bacteria - Staph. aureus (including MRSA), C. difficile, E. coli, Klebsiella pneumoniae, Pseudomonas neruginosa, Mycobacterium tuberculosis,
Fungi - Candida albicans, Aspergillus species,
Parasites - malaria.

Question 6

In healthcare infections, what are some patient factors?

Answer 6

Extremes of age, obesity/malnourishment, diabetes, cancer, immunosuppression, smoker, surgical patient, emergency admission.

Question 7

What are the 4 Ps of infection prevention and control?

Answer 7

Pathogen, patient, practise and place.

Question 8

What about a patient influences healthcare infection prevention and control?

Answer 8

General/specific patient risk factors for infections and interactions with other patients, visitors and healthcare workers.

Question 9

What about a pathogen influences healthcare infection prevention and control?

Answer 9

Virulence factors and ecological interactions - other bacteria, antibiotics/disinfectants.

Question 10

What about practise influences healthcare infection prevention and control?

Answer 10

General/specific actions of healthcare workers, policies and their implementation, organisational structure and engagement, regional and national political initiatives, leadership at all levels (government to the ward).

Question 11

What about a place influences healthcare infection prevention and control?

Answer 11

Healthcare environment with fixed and variable features.

Question 12

Give some examples of general patient interventions.

Answer 12

Optimise the patient’s condition (smoking, nutrition, diabetes), antimicrobial prophylaxis, skin preparation, hand hygiene.

Question 13

Give some examples of specific patient interventions.

Answer 13

MRSA screens, Mupirocin nasal ointment, disinfectant body wash.
Halting patient-patient transmission with physical barriers - isolation of infected and protection of susceptible individuals.

Question 14

What healthcare worker interventions may help prevent the spread of infection?

Answer 14

Keeping them healthy (disease free and vaccinated) and making sure they maintain good practise (clinical techniques, hand hygiene, personal protective equipment, antimicrobial prescribing).

Question 15

What environmental interventions may be necessary for infection prevention and control?

Answer 15

The build of the environment (spaces/layout, toilets, wash hand basins), furniture and furnishings cleaning (disinfectants, steam cleaning, hydrogen peroxide vapour), medical devices (single use equipment, sterilisation, decontamination), appropriate kitchen and ward food facilities - good food hygiene practise, theatres, positive/negative pressure rooms for immunosuppressed patients.

Question 16

When recognising and dealing with infections, it can be useful to ‘I five’ patients, what does this mean?

Answer 16

Identify (abroad, blood borne infections, colonised, diarrhoea and vomiting, expectorate, funny looking rash - A-F),
Isolate,
Investigate, 
Inform,
Initiate.

Question 17

Even with T cells and tumour/pathogen cells, there still may be no immune response, what is missing?

Answer 17

Antigen presenting cells.

Question 18

What are intracellular and extracellular microbes?

Answer 18

Intracellular microbes divide within a cell (including viruses), where as extracellular microbes do so outside. They are recognised as different by the immune system and trigger an innate and adaptive response.

Question 19

What are the three functions of antigen presenting cells?

Answer 19

Capture, processing and presentation.

Question 20

What are the different features of APCs?

Answer 20

Strategic locations (port of entry) of B and T cell interaction - skin, mucus membranes, lymphoid organs and blood circulation.
Pathogen capture - phagocytosis (whole microbe) or macropinocytosis (of soluble particles). 
Diversity in pathogen sensors (PRRs) for intra and extracellular pathogens.

Question 21

Describe 4 different types of antigen presenting cell, where they can be found and what they present to.

Answer 21

Dendritic cells at lymph nodes, mucous membranes and in blood present to naive T cells.
Langerhans cells in the skin present to naive T cells.
Macrophages in various tissues present to effector T cells.
B cells in lymphoid tissue present to to naive and effector T cells.

Question 22

What are PRRs and what are PAMPs?

Answer 22

PRRs - pathogen recognition receptors on APCs, specialised to recognise pathogens.
PAMPs - pathogen associated molecular patterns are molecules associated with groups of pathogens, which get recognised by the PRRs.

Question 23

When PAMPs are detected, there is antigen presentation by _________ _______________ ___________. Extracellular microbes trigger ________ immunity, with antibodies, complement and phagocytosis, whereas intracellular microbes trigger _____ __________ immunity with cytotoxic T lymphocytes, antibodies and macrophages.

Answer 23

Major Histocompatibility Complex
Humoral
Cell dependent

Question 24

Major Histocompatibility Complexes (MHCs) are all coded for by the p arm of chromosome 6, what is another name for them?

Answer 24

HLAs - Human Leukocyte Antigen.

Question 25

Where are MHC class I and class II found?

Answer 25

Class I are found on all nucleated cells and class II are only found on dendritic cells, macrophages and B cells (which still also express Class I).

Question 26

To increase the number of MHC molecules, class I and II have ______________ expression. The genes are also ______________, so different people have different alleles, so there’s more presentation of different antigens/microbes.

Answer 26

Codominant

Polymorphic

Question 27

What are the main functions of Class I and Class II MHCs?

Answer 27

Class I present peptides from intracellular microbes and Class II present peptides from extracellular microbes.

Question 28

Structure of MHC molecules:
What is the peptide binding cleft?
What’s the implication of broad specificity?
What are the respective responsive T cells for Classes I and II?

Answer 28

The peptide binding cleft is a variable region with highly polymorphic residues (for flexibility).
Broad specificity means many peptides are presented by the same MHC molecule.
MHC Class I is recognised by CD8+ T cells and Class II by CD4+ T cells.

Question 29

What are the different types of Class I and Class II MHCs?

Answer 29

Class I molecules: HLA-A, HLA-B and HLA-C.

Class II molecules: HLA-DR, HLA-DQ and HLA-DP.

Question 30

Antigen presenting pathway:
__________ pathway in all cells and _________ pathway in APCs. Both self and non self peptides are __________. All peptides from the same microbe are presented by ____________ MHC molecules - ___________ to infection depends on type of MHCs.

Answer 30

Endogenous
Exogenous
Presented
Different
Susceptibility

Question 31

What does HIV do to mess with the antigen processing pathway and what are ‘Elite controllers’?

Answer 31

HIV kills CD4+ cells. Some patients are called ‘Elite controllers’ or LTNPs (long term non progressors) have immune systems which can control the viral replication.

Question 32

How does different MHC expression between slow progressors and rapid progressors lead to different outcomes of the HIV infection?

Answer 32

HIV infected individuals who are slow progressors, have HLA-B27/B51/B57 and these MHC molecules present key (unmutated) peptides for the survival of the virus, resulting in an effective T cell response, whereas rapid progressors have HLA-B35 and are homozygotes in HLA-I alleles and these MHCs present mutated peptides (less critical for virus), leading to poor recognition and response from T cells.

Question 33

Aside from polymorphic MHC molecules, which component of the immune system can affect HIV progression?

Answer 33

Anti-HIV cytotoxic T lymphocytes (CD8+) affect disease progression - they remain high in long term survivors.

Question 34

Explain some clinical problems with MHC molecules.

Answer 34

Cause for organ transplant rejection - HLAs mismatch between donor and recipient. Graft vs Host - HLA association with autoimmune disease. Certain molecules present in Ankylosing spondylitis and Insulin-Dependent Diabetes Mellitus.

Question 35

Explain the pathway of an intracellular microbes in the adaptive immune response.

Answer 35

Exogenous and endogenous pathways of APCs - MHC class I and CD8+ T cells and cytotoxic T cells + MHC Class II and CD4+ T cells leading to cell dependent immunity (viruses, bacteria, Protozoa).

Question 36

T lymphocytes mature in the ________, have ___________ __________ (TCR) for antigens, __________ via gene rearrangement, there are ________ T cells and T helpers cells are classed by their production of __________. T cells have TCRs for antigen ___________ and CD glycoproteins are involved in signal ____________ in different T cells.

Answer 36

Thymus
T-cell receptor
Diversity
Memory
Cytokines
Recognition
Transduction

Question 37

Activation of T helper response:

____________ signals to activate T cells: __________ microbes - TH2 and TH17, __________ - TH1.

Answer 37

Costimulatory
Extracellular
Intracellular

Question 38

What is the T cell response against intracellular microbes?

Answer 38

TH1-CD4 activates macrophages for phagocytosis and B cells for isotope switching of antibodies to kill opsonised microbes.
Activation of CD8 leads to cytotoxic T lymphocytes targeting ‘infected’ cells with perofins (to make holes) and granzymes (to start the apoptotic process).

Question 39

What is the T cell response against extracellular microbes?

Answer 39

TH-17 with CD4 lead to neutrophil phagocytosis. TH-2 with CD4 activating eosinophils to kill parasites, B cells to switch antibodies leading to phagocytosis and complement and mast cells to produce local inflammation and in allergies (IgE).

Question 40

What are the characteristics of the antibody response?

Answer 40

On second exposure it is faster, stronger and longer in duration, with a higher affinity and an isotope switch (with IgG becoming more than IgM, which stays constant ish).

Question 41

What are the immune functions of the different antibodies?

Answer 41

IgG - Fe dependent phagocytosis, complement activation, neonatal immunity and toxin/virus neutralisation.
IgA - mucosal immunity.
IgE - immunity against helminths, mast cell degranulation (allergies).
IgM - complement activation.

Question 42

What medical achievements have been derived from the study of the adaptive immune response in: disease prevention, immunoglobulin therapies and diagnostic tests?

Answer 42

Vaccination (active immunisation), Ig therapies for immune deficiencies, immediate protection with passive immunisation (Ab transfer), Ab-based diagnostic tests for infectious diseases, autoimmune, blood and HLA types.