L36. Factors influencing immune response

Question 1

What are the 2 types of immunodeficiencies and give eg.

Answer 1

1.Congenital/1’
a) genetic defect eg. selective IgA
Or
b) in utero disease compromising immune system development

2. Acquired or 2’
   a) Infection (eg. HIV)

b) Drugs (steroids)

c) Systemic disease leads to immune compromise
eg. malnutrition, renal failure, malignancy, burns

Question 2

What the 4 different subtypes of helper (CD4) T cells. What do they activate production of to help which type of infection

Answer 2

1. Th1:
   IgM, IgG, Cytotoxic T cells
   -Acute virus and bacterial infections
2. Th2:
   IgG, IgE, Mucosal immunity
   -Chronic infections - parasites
3. Th17:
   Mucosal immunity
   - Promote inflammatory processes

4.Treg
Inhib cytokines, checkpoint molecules
- Down regulate other classes of T cells

Question 3

What triggers the production of different T cell subtypes from a naive HT cell

Answer 3

Depending on how APC processed the antigens as well as co-stimulators/cytokines in the different antigen activation contexts

Leads to predominance of one type (still get all 4 types)

Question 4

Explain the process of checkpoint inhibition, give eg and a cancer treatment related to

Answer 4

1.Tumour cell presents a tumour antigen on class1 HLA which is recognised by Cytotoxic T cell TCR +CD8 as good to kill

2. However some tumour cells produce surface molecules that are usually on Tregs:
   CD80, PDL-1

that bind to inhibitory receptors on cytotoxic T lymphocytes :
CTLA4 , PD1.

3. This turns the killing off
4. This can be intercepted by immune checkpoint inhib drugs
   eg. nivolumab which block interaction with the tumour cells checkpoint molecules -PD1-PDL1

= Let killing

Question 5

What is a Chimeric Antigen Receptor T cell: process of production and job. What type of cancer

Answer 5

In cancers with cancer cell having proteins that T cells can’t recognise well.

1. T cell from patient is collected and genes for Chimeric antigen receptor is inserted.
   => this is for cancer cell antigen.
2. Link it with domain to co-stimulator signals so that T cell becomes activated when binding
3. Expand CAR-T cells in culture and infuse back into patient to kill

Question 6

How has Modern environment = cleaning, lifestyle affected our immunity - reasons and results

Answer 6

1. Reduced distribution of organisms exposed to
2. Additional antigens from synthetic sources
3. Cleaning - alters microbiome growing up

Result in different antigens and infections.

• Different profile of immune responses: eg Th2 >
• More allergies and hypersensitivities
• More inflammatory diseases + autoimmune diseases

Question 7

Describe the process of the Neuroimmune system connections after Infection/ tissue damage

Answer 7

1. Infection/tissue damage–> pro inflam cytokines IL1, IL6 Tnfa, adhesion molecules, acute phase reactants.
2. initiate inflammation & adaptive immune response
3. Pro-inflam cytokines have an effect on the
   a) HPA: produce cortisol which down regulates inflammation/immune response
   b) Brain stem- vagus: Energy, temperatire, behaviour changes
   c) Neocortex SAM (autonomic nervous output) (affected by psychosocial)
4. There is modulation on the adaptive immune response by

b) brain stem vagus: ACh
c) SAM: NE

Question 8

What are the 3 parts of the neuroimmune network

Answer 8

Autonomic nervous system, Endocrine system and Immune system

Question 9

How does the immune system affect the NS and give cytokine eg.

Answer 9

IL1: secreted by astrocytes, glial cells.
Acting on vagus nerve branches with neurotransmitter activity

General effects

• Increase body temp (metabolic rate)
• Increase slow wave sleep (conserve energy)
• Promote illness behaviours (withdrawal, anorexia, show others infectious)

Question 10

How does the autonomic NS affect Immune system

Answer 10

Autonomic sympathetic nerve terminals in cortical regions of lymph nodes (T rich)

• release NE which communicates with T cells- changing balance of Th subtypes - suppress antibody responses.

Question 11

How does Sociability affects sympathetic innervation of lymph nodes in rhesus macaques - what is it eg of

Answer 11

In low sociable macaques there is higher density of symp innervation of lymph nodes.

Psychosocial factors interaction with immune regulation.

Question 12

How does Stress affect the immune system

Answer 12

Adversely affects immune system - altering NS, ANS, HPA to impact healing rates, antibody production post vaccination etc.