Week 11: Heritable and Non-Heritable Factors of Relevance to the Immune System, Foundations to Immunodeficiency

Technological advances

Flow cytometry, mass cytometry, single-cell gene expression analyses, analyses of serum proteins (bead array methods)

Time dependent immune variations: Immune system variation with age

Young children and elderly individuals are more susceptible to infections than other age groups

Time dependent immune variations: Infant immune system

Biased towards tolerance = cells with mostly naive phenotypes that mature when exposed to environment

Time dependent immune variations: Elderly immune system

Loss of immune cells, lymphopenia, reduced diversity of variable receptor genes on lymphocytes

Lymphopenia

Abnormally low levels of lymphocytes in blood

Degenrative changes

Associated with aging

Increased concentrations of __ cytokines such _ as have been found in the circulation of some __, which suggests there is a low-grade _ state in these individuals.

pro-inflammatory, TNF, elderly individuals, inflammatory

Time dependent immune variations: Seasonal and circadian

The incidence of autoimmune type 1 diabetes in childen

Varies over the seasons, higher in colder seasons, lower in summer (northern hemisphere)

Time dependent immune variations: Seasonal and circadian

Inflammatory manifestations like stiffness/pain

Often worst in the morning hours

Time dependent immune variations: Circadian variation in inflammatory manifestations is attributed to…

associated circadian regulation of endogenous hormones (e.g. cortisol — spike in IL-6)

In mice, __  have been shown to differ during certain times of the day, hence a _ encounters different __ in the daytime and at night,

antimicrobial responses, pathogen, immune responses

Interindividual variation

Human immune systems are variable between individuals

Interindividual variation: Human populations

Interindividual variation: Sex/gender

80% or more of patients with autoimmune diseases are women; ankylosing spondylitis is higher in men

Heritable influences

WBC counts (moderate heritability), Variants within cytokine genes and immune mediated diseases

Non-heritable inflluences

Exposure to microbes, diet, stress, sleep, environment + more

Non-heritable influence: Microbiota

Microbes encountered, particularly in the gut

Non-heritable influence: Microbial dysbiosis

Imbalance between specific species in the colonising microbiome, linked to conditions like asthma

Differences in gut microbiota can influence…

inter-indiviual variation in vaccine responses, microenvironment surrounding tumours and thus responsiveness to chemotherapy

Non-heritable influence: Viruses

Can influence immune cell populations and responses e.g. cytomegalovirus infection alters NK cells, increases CD8+ T cells

Non-heritable influence: Non-microbial environmental effect

Cigarette smoke

Current smokers have higher WBC counts, lower overall levels of serum Igs and NK cell functional activity, reversible upon smoking cessation

Immunodeficiencies

From defects in various components of immune system, infrequent

Primary immunodeficiency

Usually genetic and congenital, almost 100 types known + defective genes identified, rare

Most primary immunodeficienes become apparent by _ months of age when ___ disappear and the infant becomes dependent on their own __

six, maternally-derived antibodies, immune system

Secondary immunodeficiency

Usually caused by environmental causes, may occur at any time of life

Causes of secondary immunodeficiency

Infection, therapeutic treatments, cancer, malnutrition + more

Common characteristics of immunodeficiency

Recurrent or chronic infections, inability to clear infectious agents after standard antibiotic therapy, unusal infectious agents

Name two characteristics seen is limited sets of immunodeficiency

Failure to gain weight, Hepatosplenomegaly, Skin rashes, Diarrhoea, Recurrent absecces

Name two possible causes of primary immune deficiencies

Defects in: stem cells, T-cells, B-cells, phagocytes and NK cells, complement system

Name two possible causes of secondary immune deficiencies

Physiologic sequelae, Therapeutic treatment, Infection, Cancer