The Immune System

Question 1

What is the role of the immune system?

Answer 1

Sixth sensory system?

Senses environmental change, coordinates a response including cellular, biochemical, physiological, psychological and behavioural changes, encodes a memory of the event for long term storage, self-regulates

Question 2

What does the immune system consist of?

Answer 2

A complex network of cells, tissues, organs, and the substances they make that helps the body fight infections and other diseases

The immune system includes white blood cells and organs and tissues of the lymph system, such as the thymus, spleen, tonsils, lymph nodes, lymph vessels, and bone marrow

Question 3

What are the three layers of the immune system?

Answer 3

1. Innate immunity (Anatomical and physiological barriers)
2. Adaptive immunity
3. Passive immunity

Question 4

What is innate immunity responsible for?

Answer 4

This innate immunity includes the external barriers of our body — the first line of defense against pathogens — such as the skin and mucous membranes of the throat and gut.

This response is general and nonspecific

If pathogens manage to bypass the innate immune system, macrophages will attack them. Macrophages will also produce substances called cytokines, which increase the inflammatory response.

Question 5

What is adaptive immunity responsible for?

Answer 5

Adaptive immunity creates immunological memory after an initial response to a specific pathogen, and leads to an enhanced response to future encounters with that pathogen

Antibodies are a critical part of the adaptive immune system. Adaptive immunity can provide long-lasting protection, sometimes for the person’s entire lifetime

For example, someone who recovers from measles is now protected against measles for their lifetime; in other cases it does not provide lifetime protection, as with chickenpox. This process of adaptive immunity is the basis of vaccination.

Question 6

What is passive immunity responsible for?

Answer 6

Passive immunity is provided when a person is given antibodies to a disease rather than producing them through his or her own immune system. A newborn baby acquires passive immunity from its mother through the placenta

Question 7

What makes up the anatomical and physiological barriers?

Answer 7

Intact skin
Cilliary clearance
Low stomach pH
Lysozyme in tears and saliva

Question 8

What is the difference between cell-mediated immunity and humoral immunity?

Answer 8

The major difference between humoral and cell-mediated immunity is that humoral immunity produces antigen-specific antibodies, whereas cell-mediated immunity does not

B cells activate humoral immunity, whereas T cells activate cell-mediated immunity

Question 9

What makes up innate immunity?

Answer 9

Cellular
- Natural killer cells
- Eosinophils
- Macrophages
- Neutrophils
- Mast cells
- Dendritic cells

Humoral
- Complement system (cascade of soluble proteins and membrane expressed receptors and regulators)
- Mannose binding lectin
- Antimicrobial
- LPS binding protein
- C-reactive protein

Question 10

What cells make up adaptive immunity?

Answer 10

Cellular
- T cells
- B cells

Humoral
- Antibodies

Question 11

What is neuroimmunology?

Answer 11

Interaction of the immune and nervous systems
Nervous system control of immune system function
Immune responses within the nervous system

Question 12

What is psychoneuroimmunology?

Answer 12

Interaction between psychological processes, the immune and nervous systems

Definitions usually also include endocrine system (psychoendoneuroimmunology)

Question 13

Explain the brain-immune interactions

Answer 13

Stressors in the brain trigger the release of corticotropin-releasing hormone (the central regulator of the hypothalamic-pituitary-adrenal (HPA) axis)

This triggers the release of adrenocorticotropic hormone which acts on the adrenal gland causing it to release glucocorticoids which act on the immune system

Immune system
- Bone marrow
- Lymph nodes
- Spleen
- Immune cells
- Thymus

Sympathetic nervous sytem and parasympathetic nervous system also acts on the immune system

Question 14

What is the immunity within the brain?

Answer 14

The brain has a critical resident population of immune cells which can sense damage or infection and trigger larger scale immune reactions

Can communicate via the neurovascular unit (BBB) to the wider immune system an mount a more generalised responses

Question 15

What is the primary immune cell of the CNS?

Answer 15

Microglia

Question 16

What did Brezzo et al (2020) investigate?

Answer 16

Hypothesised that systemic inflammatory challenges may cause a shift in NVU operation towards prioritising neuroinflammatory action and thus altering neurovascular coupling and resultant cerebrovascular changes

Rats were injected with lipopolysaccharide (LPS) to induce a systemic inflammatory response, or vehicle, and brain haemodynamic responses to sensory and non-sensory (hypercapnia) stimuli were assessed in vivo using optical imaging techniques

Following imaging, animals were perfused and their brains extracted to histologically characterise components of the NVU to determine the association between underlying cellular changes and in vivo blood flow regulation

Question 17

What did Brezzo et al. (2020) find regarding the neurovascular unit and the immune response?

Answer 17

LPS-treated animals showed changes in haemodynamic function and cerebrovascular dynamics 6 ​hours after LPS administration

Histological assessment identified a significant increase in astrogliosis, microgliosis and endothelial activation in LPS-treated animals (increase in astrocytes and microglia)

Evidence that changes in neurovascular unit function occur rapidly in response to immune activation

Question 18

What is LPS?

Answer 18

Lipopolysaccharides

A chunk of bacterial cell wall that leads to a ‘sterile’ immune response - a common model for studying inflammation/immune function

Question 19

What are all the direct and indirect routes allowing interaction between the immune system and brain systems?

Answer 19

Peripheral/autonomic nervous system via the BBB/neurovascular unit, cell-cell communication within the brain, circulating cytokines, HPA axis activation

Question 20

How do immune responses affect brain connectivity?

Answer 20

Felger et al. (2016)

Inflammation is associated with decreased functional connectivity within corticostriatal reward circuitry in depression

Biomarkers of inflammation (for example, cytokines and C-reactive protein (CRP)) are reliably elevated in depressed patients

Moreover, administration of inflammatory stimuli reduces neural activity and dopamine release in reward-related brain regions in association with reduced motivation and anhedonia

Question 21

What is CRP?

Answer 21

C-reactive protein (CRP) is a circulating marker of systemic inflammation

Question 22

How else are immune responses associated with brain connectivity?

Answer 22

Inflammation also associated with changes in function within brain networks underpinning cognition and in otherwise healthy individuals

Question 23

What did Walker et al. (2020) find regarding immune responses and brain connectivity?

Answer 23

Association of peripheral inflammatory markers with connectivity in large-scale functional brain networks of non-demented older adults

Inflammation linked to lower default mode and dorsal attention network connectivity

Question 24

What is a key component of generalised immune responses?

Answer 24

The induction of sickness behaviour (convalescence -
time spent recovering from an illness or medical treatment) - this promotes recovery/recuperation

Question 25

What did Maes et al. (2012) imply about sickness behaviour?

Answer 25

Energy saved by protecting the organism from the energy consuming effects of inflammation through lethargy, sleepiness, reduced locomotor activity etc leads to weight loss, fever, anorexia

Thus, sickness behavior is a short-term response to acute inflammatory triggers and is an adaptive motivational state induced to cope with these triggers and the consequent negative energy balance

Question 26

What are PICs?

Answer 26

Pro-inflammatory cytokines - substances secreted by the immune cells - often for communication/regulation - can be pro- or anti-inflammatory

Question 27

What did Couch et al. (2013) investigate?

Answer 27

Used pharmacological MRI to study the effects of systemic inflammatory events on central 5-HT function

Changes in blood oxygenation level dependent (BOLD) contrast were detected in selected brain regions of anaesthetised rats in response to intravenous administration of the 5-HT-releasing agent, fenfluramine

Further groups of rats were pre-treated with the bacterial LPS to induce systemic inflammation, or the selective 5-HT2A receptor antagonist MDL100907 prior to fenfluramine

Question 28

What did Couch et al. (2013) find?

Answer 28

In all regions, BOLD responses to fenfluramine were significantly attenuated by pre-treatment with LPS, but neurovascular coupling remained intact

These results suggest that systemic inflammation decreases brain 5-HT activity as assessed by phMRI

This might partly underlie sickeness behaviour

Question 29

Can sickness behaviour lead to depression?

Answer 29

Dantzer et al. (2008)
When activation of the peripheral immune system continues, such as during cancer or autoimmune diseases, the ensuing immune signalling to the brain can lead to an exacerbation of sickness and the development of symptoms of depression in vulnerable individuals

Inflammation is therefore an important biological event that might increase the risk of major depressive episodes, much like the more traditional psychosocial factors.

Question 30

What is the transition from adaptive sickness behaviour to clinical depression dependent on?

Answer 30

Dependent on the existence of risk factors - may be genetic, altered neurotransmitter functionality, amplified immune reactions etc

Prolonged exposure to stressors (psychological or physical) may be an important source of these additional risk factors

Question 31

How does stress affect immune function?

Answer 31

Stress triggers the release of cortisol from the adrenal gland

Cortisol suppresses immune function (anti-inflammatory)

Question 32

What is the potential adaptive function of cortisol being anti-inflammatory?

Answer 32

To prevent over-activation of immune responses to infection (a type of stressor)

When prolonged, can lead to quite complex dysregulation of immune function