Immunology

Question 1

What is the evidence for the hygiene hypothesis?

Answer 1

More allergies in western world
First child more likely to be allergic
Farm children less like to be allergic- endotoxin exposure
Lack of exposure to germs early in life skew our CD4 T cells away from Th1 to Th2 phenotype of mast cell activation, IgE class switching, eosinophil activation and recruitment

Question 2

What are the classification of hypersensitivity mechanisms?

Answer 2

Type 1- IgE mediated mast cell degranulation and activated eosinophils eg. Anaphylaxis, venom/drug/food allergy
Type 2- antibodies produced by immune system bind antigens on the patients own cell surfaces and cause damage eg. Autoimmune haemolytic anaemia
Type 3- immune-complex reaction between circulating antigen and IgG eg. Serum sickness
Type 4- cellular immune response mediated by T cells eg. Contact dermatitis

Question 3

What is the significance of IgE in allergies?

Answer 3

Antigen binds specific IgE
Binds allergy effector cells via FcER1
Cross linking of IgE in mast cells by allergen lead to activation

Question 4

List some mast cell mediators and their effects

Answer 4

Histamine
Prostaglandins
Leukotrienes
PAF
Tryptase
-vasodilation, vascular permeability, heart rate and cardiac contraction, glandular secretion, bronchoconstriction

Question 5

Describe the killing of parasites

Answer 5

The evolutionary purpose of IgE mediated responses
Recognised by mast cells
IgE attaches to the parasite
Eosinophils bind to IgE
Parasite killed with toxic granules and O2-
IL13 from effector cells causes goblet cell hyperplasia and mucus production, increased contraction of smooth muscle in the gut leading to work expulsion

Question 6

Why do people get allergies?

Answer 6

Genes- polymorphisms (IL4 receptor or FrE receptor)
Fillaggrin- eczema
Environment- early exposure, infections, hygiene, maternal smoking, diet, air pollution, chlorine

Question 7

Describe complement deficiency

Answer 7

C3 deficiency- pyogenic infections
C5-9 deficiencies are associated with Neisseria
C1,4,2 deficiencies are linked to immune complex disease

Question 8

Describe some neutrophil disorders

Answer 8

Clinical presentation with septicaemia with bacteria and fungi, abscesses, dental cavities and mouth ulcers
Adhesion- LFA1 deficiency
Motility
Killing- chronic granulomatous disease- fungal and Staph. Infections, no respiratory burst, failure to activate enzymes, X-linked
Neutropenia

Question 9

Describe defects in phagocyte activation

Answer 9

Toll receptors- Myd88 deficiency associated with severe bacterial infections
IL12 and IL12R deficiency- salmonella and atypical mycobacteria
Interferon-gamma deficiency- atypical mycobacteria
(IL12 and IFNgamma not associated with viral infections and fungi

Question 10

Describe the result of a deficiency in natural killer cells

Answer 10

Overwhelming infections with herpesvirus
Human cytomegalovirus have mechanisms that prevent the expression of HLA class1 which normally is a trigger for NK cells to kill

Question 11

Describe clinical features of B cell defects

Answer 11

Recurrent pyogenic infections
Upper and lower respiratory tract infections
Diarrhoea
Encapsulated organisms (streptococcus pneumoniae, Haemophilus influenzae, staphylococcus aureus)
Rare viruses
Fungal infections uncommon

Question 12

Describe live-attenuated vaccines

Answer 12

The pathogenic virus if isolated and grown in non-permissive cells that encourage mutations that attenuate growth in the original host cells
Product viruses are screened for those with the correct antigens to produce an immunogenic response
Eg. Measles and Sabin type 3 polio vaccines

Question 13

Describe inactivated vaccines

Answer 13

Virus is inactivated with UV, chemicals or heat

Eg. The inactivated polio vaccine (IPV)

Question 14

Compare attenuated and inactivated vaccines

Answer 14

Not all pathogens can be grown in alternative hosts and the yield is low therefore the cost is high
Both have a limited shelf life and often require refrigeration
Risk of incomplete inactivation and reversal of attenuation
Immunity from an attenuated vaccine is more enduring

Question 15

Describe passive immunisation

Answer 15

Transfer off antibodies
Short lasting but immediate effect
Occurs naturally during breast feeding
Used as an antidote to acute toxins and sometimes in acute infection

Question 16

Describe recombinant vaccines

Answer 16

Virulent components are removed from virus proteins and DNA so they do not cause disease

Question 17

Describe herd immunity

Answer 17

Not everyone needs to be vaccinated
90% vaccination rate should prevent disease spread
Some people cannot be vaccinated- young children, old people and immunosuppressed or immunodeficiency

Question 18

What do adjuvents do in vaccination?

Answer 18

Improve the effectiveness of vaccines by increasing the antigenicity if the antigen
1. Changes the physically state- particulates are engulfable
2. Creates an inflammatory environment to attract cells and increase the activation of those cells
Adjuvants may be adsorbed onto crystal surface or held within the adjuvent and act directly on cells
Or act indirectly through danger signals

Question 19

Briefly describe mechanisms of adjuvent action

Answer 19

Antigen depot (?)
Attract innate cells to the area
Activate migrated cells
Inflammation
Debdritic cells then migrate to draining lymph
Alum crystals- 10% left after 24 hours, induce CCL2-4 and IL8 and induces the maturation of monocytes to macrophages
MF59- 10% left after 6 hours, also induce CLL2-4, IL8 and chemokine and cytokine production in migrated cells

Question 20

List some adjuvents in use

Answer 20

Aluminium salt gels (alum) eg. Aluminium potassium sulfate
Oil in water eg. Squalene/MF59
Saponin based eg. Quil-A
TLR agonists eg. Complete Freund’s adjuvent

Question 21

What are conjugate vaccines?

Answer 21

If the antigen is not a peptides then there is a T cell independent response, put the antigen with a protein and the T cells will respond and long lasting immunity to that antigen will be established

Question 22

What’s CAR?

Answer 22

Chimeric antigenic receptor
DNA that codes for antibodies is inserted into T cells that give it specificity to something eg. Cancer cells
Van also insert co-stimulator portions to maintain the T cell response and DNA coding for cytokines
However T cells must overcome tumour immunosuppression

Question 23

Describe mechanisms of loss of tolerance

Answer 23

Ignorance/immune privilege
Break ignorance leads to production of T cells against antigens previously invisible to the immune system
Cell death
Normally T cells that present self antigens die but under infection they can be activated
Loss of regulatory cells
Contributory genetic factors to autoimmunity

Question 24

Describe some organ specific autoimmune diseases

Answer 24

Rheumatoid arthritis- associated with auto antibodies in most patients, inflammation leads to joint damage- anti-citrullinated protein antibodies (ACPA)-present in 60% are associated with severe disease
Hashimoto’s thyroiditis- anti-TSH receptor IgG blocks TSH binding and function, induces thyroid tissue destruction
Grave’s disease- anti-TSH receptor IgG continuously stimulates TSH leading to cell division and thymidine release Can be temporary passed into a foetus in utero
Goodpasture’s syndrome- specific antibodies to the capillary basement membrane of glonerukus and lung alveoli
Type 1 diabetes- specific antibodies to beta cells in the islets of Langerhans are produced which kill the celkks and stop insulin production

Question 25

Give an example of systemic autoimmunity

Answer 25

Systemic lupus erythematosus- antibodies against nuclear proteins. Immune complexes of soluble auto-antigens in the kidney

Question 26

Define outbreak

Answer 26

An occurrence of a disease clearly in excess of normal expectancy

Question 27

Define Endogenous

Answer 27

Infection derived from normal flora

Question 28

Define Exogenous

Answer 28

Infection derived from microbes in the environment

Question 29

Define zoonosis

Answer 29

An animal disease which can spread to humans

Question 30

Define vector

Answer 30

A living creature which can transmit infection from one host to another

Question 31

Describe routes of entry

Answer 31

Direct contact
Inhalation
Ingestion
Inoculation
In through mouth to GIT or lungs
Conjunctiva
Through skin
Urogenital tract

Question 32

Describe types of outbreaks

Answer 32

Point outbreak- group of individuals exposed to a single source of infection at a defined point in time
Common source- group of individuals exposed to a single source but at differing times
Person-to-person- no common source, chain of infection between individuals

Question 33

What is the difference between case control and cohort studies?

Answer 33

Case control- retrospective
Exposure histories sought from cases and healthy controls
Controls chosen from the same population as cases
Relative risk of exposure to postulated source of outbreak is calculated for cases and controls
Relatively cheap
Cohort study- prospective study, disease outcomes compared between two groups; those exposed to a suspected source and those not exposed
More time consuming and expensive

Question 34

Describe prevention and control of infection

Answer 34

Primary- pre-exposure immunisation, improve living conditions and life style- safe food, hygiene, safe sex
Secondary- post-exposure immunisation, contact tracing, screening of food handlers, chemoprophylaxis, surveillance
Tertiary- treatment of acute infection, management of post infectious disorders