immunity and ageing Flashcards
(26 cards)
name some common diseases associated with ageing.
- neurodegenerative disease
- COVID-19
- autoimmune disease
- cancers
- cardiovascular disease
- pneumonia
- dementia
- CKD
- arthiritis
- osteoporosis
Describe how changes in different parts of the immune response (systemic, cellular and molecular levels) occur during ageing. JUST SYSTEMATIC
systematic level - reduced nutrient sensing:
- reduced nutrient sensing refers to the declining efficacy of the cellular pathways involved in sensing bodily nutrients - these regulate immune function and often decline with age.
- Reduced AMPK activity and increased mTOR signaling result in dysfunctional T cells, diminished memory T cell formation, and impaired macrophage phagocytosis.
- Overactive nutrient-sensing pathways (e.g., mTOR) impair the balance between immune activation and resolution, contributing to chronic low-grade inflammation
- Impaired autophagy during aging leads to the accumulation of cellular debris and dysfunctional immune cells.
Describe how changes in different parts of the immune response (systemic, cellular and molecular levels) occur during ageing. JUST CELLULAR
sensescent cells:
- reduced clearance of sescent cells with age due to immunosenscence - these accumulate and lead to chronic inflammation
senescence-associated secretory phenotype (SASP):
- senescent cells secrete many pro-inflammatory cytokines
- SASP can also induce senescence in neighboring cells - paracrine
- SASP also contributes to inflammaging (the low-level inflammation associated with ageing)
stem cell exhaustion:
- progressive decline in the regenerative capacity of stem cells with age
- as less cells are made, it takes longer for damaged cells to be replaced, meaning prolongued inflammation
- in some tissues it leads to fibrosis, further exacerbating tissue dysfunction
- imapred generation of new immune cells
altered intracellular inflammation:
- NLPR-3 (protein which forms in response to stress) - this activates caspase-1 which triggers the release of pro-inflammatory cytokines - found in blood vessels so can lead to atherosclerosis
- mTOR pathway becomes dysregulated with age, contributing to pro-inflammatory cytokine production
- similar with mitochondrial ageing - dna damage can cause release of pro-inflammatory cytokines
- senescent cells also do
outline what is meant by cellular senescence.
- state at which cells permanently stop dividing while remaining metabolically active
- natural cellular process triggered by stress or damage
- occurs in order to protect the cell from harm
- can be beneficial in some cases but in others the accumulation of senescent cells over time contributes to aging and age-related diseases
Describe how changes in different parts of the immune response (systemic, cellular and molecular levels) occur during ageing. JUST MOLECULAR
- Genomic Instability: As we age, DNA damage accumulates due to factors like oxidative stress and replication errors, affecting genes that are crucial for immune cell function. Specifically, damage to genes involved in T-cell receptor signaling or cytokine production reduces the immune system’s ability to respond to infections and increases susceptibility to autoimmune diseases such as rheumatoid arthritis or lupus.
- Epigenetic Alteration: Aging leads to DNA methylation changes and histone modifications, which affect the expression of key immune genes. For example, the loss of function in genes like FOXP3 (which is important for regulatory T cells) and IL-6 (a pro-inflammatory cytokine) can cause immune dysfunction, chronic inflammation, and an increased risk of age-related inflammatory diseases such as atherosclerosis or autoimmune disorders.
- Compromised Autophagy: The process of autophagy, which clears damaged cellular components like misfolded proteins and mitochondria, becomes less efficient with age. For example, p62 (a protein involved in autophagy) accumulates, leading to the buildup of damaged mitochondria and aggregated proteins in immune cells. This causes increased reactive oxygen species (ROS) production and inflammation, contributing to conditions like neurodegenerative diseases (e.g., Alzheimer’s) and muscle wasting.
- Telomere Shortening: Each time an immune cell divides, the telomeres at the ends of its chromosomes shorten, eventually leading to telomere attrition. This results in senescence or cell death, especially in T cells and B cells, which rely on continuous replication for immune responses. Shortened telomeres lead to a decreased ability to fight infections and contribute to diseases like cancer (due to a failure of tumor surveillance) and immunosenescence (weakened immunity).
- Loss of Proteostasis: Aging impairs the ability of immune cells to maintain proteostasis (protein homeostasis), resulting in the accumulation of misfolded proteins and damaged organelles, such as mitochondria. The failure of chaperone proteins like HSP70 and ubiquitin-proteasome system leads to the buildup of oxidized proteins and lipid peroxidation products, causing chronic low-grade inflammation and impairing immune function, contributing to neurodegeneration and autoimmune diseases.
- Mitochondrial Dysfunction: Mitochondria in immune cells experience DNA mutations, oxidative damage, and decreased efficiency in ATP production as we age. These dysfunctional mitochondria release cytochrome c, activating pro-inflammatory pathways like NLRP3 inflammasome and increasing ROS levels. This leads to chronic inflammation and immune cell dysfunction, contributing to cardiovascular diseases, metabolic disorders, and age-related neurodegeneration.
define senescence
Senescence is the process where cells permanently stop dividing after reaching a certain limit due to factors like DNA damage, oxidative stress, or telomere shortening. These cells no longer replicate but remain metabolically active, releasing various molecules that can negatively affect nearby cells and tissues.
define immunosensence.
Immunosenescence refers to the gradual decline in immune system function with age. It includes reduced T-cell production and response, weaker B-cell antibody production, and slower responses to infections. This makes older adults more susceptible to infections, cancer, and autoimmune conditions.
define inflammaging.
Inflammaging is the chronic, low-level inflammation that increases with age. It results from factors like the accumulation of senescent cells, altered immune responses, and long-term low-grade infections. This inflammation contributes to a variety of age-related diseases, including heart disease, diabetes, and neurodegenerative disorders.
name the 4 hallmarks of senescent cells.
- cell-cycle withdrawal
- macromolecular damage
- secretory phenotype (SASP)
- deregulated metabolism
Macrophages: Reduced phagocytosis, increased pro-inflammatory cytokines (IL-6, TNF-α), and impaired tissue repair contribute to chronic inflammation and slower immune responses. Decreased antigen presentation and decreased number and function.
Neutrophils: Impaired chemotaxis, reduced phagocytosis and oxidative burst, and altered cytokine production increase inflammation and reduce infection control.
Dendritic Cells: Decreased antigen presentation and T-cell activation weaken the adaptive immune response, leading to poor immune activation.
Natural Killer (NK) Cells: Reduced cytotoxic activity and increased inflammatory cytokines (TNF-α, IFN-γ) contribute to chronic inflammation and weaker immune surveillance.
Natural Killer T (NKT) Cells: Reduced function impairs the response to infections and tumors by failing to effectively bridge innate and adaptive immunity.
Pattern Recognition Receptors (PRRs): Altered signaling in Toll-like receptors (TLRs) weakens the ability to detect and respond to pathogens.
Overall Impact: Aging reduces the innate immune system’s ability to detect, respond to, and clear infections, increasing susceptibility to infections, chronic diseases, and cancer.
whats the common theme of the number of immune cells with age?
- all of them are decreased apart from the memory cells in comparison with younger age
outline the changes with immunosenscense to the cells of the adaptive immune system.
- decrease in size of thymus
- decrease in naive T cells and recent thymic emigrants
- increase in memory T cells
- increase in senscent T cells
- decrease in antibody production
- decrease in B cell progenitor cells
- decrease in hematopoitec bone marrow
- decrease in naive b cells
- increase in memory B cells
name the alterations of neutrophills due to immunoscesence.
- dec in chemotaxis
- dec in phagocytosis
- dec in superoxide generation
- dec in NET generation
name the alterations of monocytes due to immunoscesence.
- same number of them
- dec chemotaxis
- dec phagocytosis
- dec superocide gen
- dec cytokine secretion
name the alterations of NK due to immunoscesence.
- inc in numbers
- inc in CD56 cells
- dec in NKp30 and NKp46
- dec in cytotoxicity
name the alterations of dendritic due to immunoscesence.
- dec in recruitment to lymphoid organs
- dec in phagocytosis
- dec in antigen presentation
define macrophage efferocytosis
Macrophage efferocytosis refers to the process by which macrophages (a type of immune cell) clear away dead or dying cells, particularly apoptotic cells (cells that are programmed to die). This is an important part of maintaining tissue homeostasis and preventing inflammation.
name some age-related diseases which SASP contributes to.
- heart failure
- atherosclerosis
- chronic obstructive pulmonary disease
- parkinsons
- alzeimers
- age-related macular degeneration
- presbycusis
- benign prostatic hyperplasis
- osteoporosis
- osteoarthiritis
- type 2 diabetes
- NAFLD
describe how changes in the immune system with ageing result in disease.
- fewer T and B cells - more suseptable to infections
- persistent low-grade inflammation and SASP factors - contributes to atherosclerosis, type 2 diabetes, alzeimers and arthiritis
- impared macrophage and neutrophill function - increases risk of chronic infections and impared wound healing
- overactivation of immune cells due to disregulated signalling pathways causes tissue damage, making autoimmune diseases more common eg arthiritis
- accumulation of senscent cells - more SASP factors - drives tissue dysfunction, cancer progression and inflammation
- decline in immune surveilance - reduced activity if NK and T-cells - more likely to develop cancer
outline how lifestyle changes can support healthy ageing.
nutrition:
- vitamins A, C, E support immune cell fucntion
- omega-3 fatty acids - anti-inflammatory properties
- fiber supports gut microbiome health - influences inflammation
- avoiding sugar and processed foods helps reduce systemic inflammation
regular physical activity:
- improves function of immune cells
- enhances cardiovascular health, bone stregnth, muscle mass, reducing fratility
- increases circulation, promoting effecient immune surveilance
adequate sleep:
- restored T-cell activity and reduces pro-inflammatory cytokine levels
stress management:
- lowers cortisol levels (cortisol supresses immune responces and promotes inflammation)
what foods can be eaten to protect against age-related disease?
- Mediterranean diet
- ketogenic diet
- antioxidant nutritional formula
- vitamin C
- long-chain fatty acids
- olive oil
- nuts
what are some pharmalogical interventions against age-related diseases?
- senolytic
- senomorphic
- anti-inflammatory drugs
- antioxidants
what is added to vaccines to promote the immune response?
- adjuvants
what are the innate immune system responses after vaccination?
increased:
- hematapoetic stem cell differentiation skewed towards myeloid lineage
decreased:
- macrophage capacity
- chemotaxis
- phagocytosis
