Factors influencing immune responses

Question 1

What does this trilogy of proinflmmatory cytokines do? : IL-1, IL-6, TNFalpha

Answer 1

Early, induce acute phase proteins
Temperature (fever) and behavioural changes
Tissue repair
T and B activation

Question 2

What is TNFalpha triggered by?

Answer 2

Bacterial LPS (lipo poly saccharide molecules)

Question 3

Give some examples of tissue repair?

Answer 3

Bone resorption
Fibroblast proliferation
Collagenase synthesis
Leukocyte adhesion

Question 4

What cytokines control the mobility of cells around the body

Answer 4

Chemokines

• Acid chemotaxis (e.g. neutrophils)
• Direct effector cell traffic

Question 5

What cytokines are important in viral infections?

Answer 5

Interferons

• Induce transient antiviral state
• Activate NK cell activity
• Upregulate HLA expression (improves cytotoxic T cell killing)

Question 6

How to CD4 helper T cells function?

Answer 6

Start of naive, can be activated in different ways, in which the context and antigen combination are presented to them, this helps determine what they become
In any response you get a mix of Th1 and Th2

Question 7

Th1 helper cells?

Answer 7

Produce cytokines that are valuable in activating cytotoxic T cells and for B cells to produce IgM and IgG and to facilitate the responses we need to deal with acute viral and extracellular bacterial infections

Question 8

Th2 phenotype Helper cells

Answer 8

IgG and IgE
Mucosal immunity
Chronic infections, especially parasites

Question 9

Th17 cells?

Answer 9

Mucosal immunity and promote inflammatory processes

Question 10

Treg cells?

Answer 10

control and down regulate other classes

Question 11

Primitive vs modern environment, what changes affect immunity?

Answer 11

Primitive human environment:
- Diverse environmental antigens
- Diverse verities of infectious organisms
- restricted environmental antigen range
- Parasites
Modern human environment
- Much more restricted range of diverse environmental antigens, and within those a set that we’re exposed to in quite high concentrations on a routine basis
- Microbial universe much smaller than it used to be, absence in developed countries of the parasite class

Question 12

Micro biome and environmental antigens change over time?

Answer 12

are now quite different from what they were for most of human history

Question 13

2d map summary of primitive human immune responses

Answer 13

Th1: acute bacterial and viral infections
Th1 and Treg: Mycobacterial and protozoan infections
Th2: Limit chronic immunopathlolgy
Th2 and Treg: Helminth infections

Question 14

Conversely how has the 2d map changed for modern humans

Answer 14

less treg responses, as a response to that Th1, 2 and 17 don’t get controlled as well so we get an over expression of responses that could become pathogenic for us:
Th2 and Th17 = allergies
Th1 and Th17 = autoimmunity and inflammatory diseases

Question 15

Example of a 6 month old child with immunodeficiency symptoms

Answer 15

3.5 Kg at birth appeared normal 
3/12: runny nose, persistent dry cough 
4/12: Ottis media 
5/12: Pneumonia in both lungs 
Persistent nappy rash 
Little weight gain 
Thrush (candida in the mouth)

Question 16

SCID?

Answer 16

Severe combined immunodeficiency - absence of T cells, therefore you cant make helper T cells or control any immune responses or make cytotoxic effectors
- is a primary immunodeficiency syndrome (rare)

Question 17

What is a congenital/ primary immunodeficiency syndrome?

Answer 17

Genetic defect
- Selective IgA deficiency is common (1 in 500) - often asymptomatic
- Other congenital deficiencies are rare
In utero disease, that affects the development of the immune system (not the result of a genetic mutation)

Question 18

Acquired / secondary immunodeficiency

Answer 18

Infection (e.g. HIV)
Drugs (e.g. steroids and cytotoxic drugs)
Systemic disease (renal failure, malnutrition, malignancy, burns)

Question 19

If the patient is getting predominantly extracellular bacterial infections (e.g. streptococci), what sort of immunodeficiency are they likely to have?

Answer 19

IgM and IgG, complement, phagocytosis

Question 20

Intracellular bacteria (e.g. tuberculosis) what sort of immunodeficiency?

Answer 20

T cells, macrophages

Question 21

Viruses (e.g. measles) what sort of immunodeficiency?

Answer 21

T cells, IgG, IgA, interferon (complement)

Question 22

Parasites (e.g. ascaris) what sort of immunodeficiency?

Answer 22

IgE, eosinophils, mast cells, T cells

Question 23

Fungi (e.g. candida) what sort of immunodeficiency?

Answer 23

T cells, IgA, neutrophils

Question 24

Dont have to learn all the above but, know that the spectrum of immune response gives indication as to what type of infection the person has

Answer 24

yay

Question 25

The timing of the onset of symptoms is a consequence of?

Answer 25

What happens in early life
Because we are protected by mums antibodies in the first few months of life it will only be after then that the congenital immunodeficiencies become evident

Question 26

What if foreign antigens are similar to self antigens?

Answer 26

Poor response
HLA affects antibodies presented (some people have weird haplotypes that means they cant present the correct epitopes to imitate a proper immune response)

Question 27

IgM vs IgG in terms of stimulating or down regulating the B cell response

Answer 27

IgM stimulates B cells

IgG down regulates B cells

Question 28

The 3 components of the neuroimmune network

Answer 28

ANS
Endocrine system
Immune system
(linked via, nerves, hormones and cytokines)

Question 29

Pro inflammatory cytokines and the nervous system interactions result in

Answer 29

Increase body temperature
Increase slow wave sleep
Promote lines behaviours (social withdrawal, anxiety, sleeping a lot)

Question 30

How do the pro inflammatory cytokines interact with the immune system

Answer 30

IL-1 act on vagus nerve branches
IL-1 secreted by astrocytes and glial cells
IL-1 has neurotransmitter activity

Question 31

How does the autonomic nervous system influence immunity?

Answer 31

sympathetic autonomic nerves innervate lymph nodes and terminate in the paracortical region where the CD4 cells reside (norepinephrine NT)

Question 32

The Rhesus Macaques monkey study

Answer 32

Took a bunch of high and low sociable monkeys, anaesthetised them and biopsied their lymph nodes. Found that the low sociable animals had a lot more nerve termini in their lymph nodes than the highly sociable monkeys
Implications:
Sociability affected by the amount of autonomic innervation in our secondary lymphoid organs
OR
Autonomic nerve system innervation effects immune function and therefore high and low sociable animals might have a different spectrum of immune responsiveness.
… Sociability affects sympathetic innervation of lymph nodes

Question 33

Summary of autonomic nervous system and immunity

Answer 33

Extensive innervation of lymphoid organs
Predominantly sympathetic (norepinephrine)
terminate in T cell rich areas
Density related to social temperament