2P07 Class 3

Which substance released from damaged epithelial cells activates the extrinsic coagulation pathway? (a short fast series of chemical reactions that starts outside of the bloodstream in response to tissue or vessel injury, leading to formation of blood clot)

Tissue Factor (TF)

Damage to blood vessel walls initiates the intrinsic coagulation pathway through the activation of which factor?

Hageman Factor (Factor XII to XIIa)

What are the four primary physiological effects of bradykinin in the kinin system?

Blood vessel dilation, pain induction with prostaglandins, smooth muscle cell contraction, and increased vascular permeability.

Which immune cells serve as the primary link between innate and adaptive immunity by migrating to the lymphatic system to present antigens?

Dendritic cells

How long does a primary adaptive immune response typically take to develop after initial exposure to a novel pathogen?

7 to 14 days

Into which specialized cell type do activated B cells differentiate to act as antibody production factories?

Plasma cells

What is the primary function of T-cytotoxic ($T_c$) cells in adaptive immunity? (2)

Identifying and killing TARGETED host cells or pathogens.

Which subtype of T cells is responsible for suppressing inappropriate or excessive immune responses?

T-regulatory ($T_{reg}$) cells

How does active acquired immunity differ from passive acquired immunity regarding duration of protection?

Active acquired immunity provides long-term protection lasting decades or a lifetime, while passive acquired immunity is temporary.

A newborn receiving maternal antibodies via the placenta or breast milk is an example of which type of immunity?

Passive acquired immunity

Which direct antibody function involves inactivating or blocking the binding of antigens to cellular receptors?

Neutralization

In the context of direct antibody functions, agglutination is defined as _____.

clumping insoluble particles that are in suspension

Which immunoglobulin class is detectable first in circulation approximately 5 to 7 days following primary antigen exposure?

IgM

Why does a secondary immune response produce antibodies more rapidly and in larger quantities than a primary response?

Long-lived memory cells are present that require less differentiation upon re-exposure.

What immune mechanism drives Type I hypersensitivity reactions?

IgE antibody mediation

Why are Type IV hypersensitivity reactions classified as delayed reactions?

They are cell-mediated responses taking several hours to days to appear.

What primary chemical mediator released from mast cells drives bronchial constriction and vasodilation in Type I hypersensitivity?

Histamine

What localized skin reaction in IgE-mediated hypersensitivity results from local histamine release and increased vascular permeability?

Urticaria (hives)

Systemic anaphylaxis is a severe immediate reaction characterized by throat edema, bronchial smooth muscle contraction, and _____.

decreased blood pressure

Autoimmunity originates from a breakdown in immune tolerance, which is defined as the inability to _____.

tolerate an individual's own self-antigens

• immune system remains unresponsive to specific substances (Ex. harmless ones that would otherwise trigger an immune attack)

What structural organ change is considered the primary cause of immunosenescence in aging adults?

• gradual age related deterioration, remodelling of innate and adaptive immune systems

Thymic shrinkage (atrophy)

How does aging affect the synthesis of interleukins IL-1 and IL-2 in the body?

Synthesis of both IL-1 and IL-2 decreases.

What change occurs in autoantibody levels as part of the aging process?

Autoantibody levels decrease.

Which hypersensitivity reaction type is mediated by tissue-specific mechanisms?

Type II hypersensitivity

Type III hypersensitivity reactions are mediated by which specific immune component?

Immune complexes

Indirect functions of antibodies depend on activating which component of the innate immune response?

The complement system

What physiological change in the dermal layer of aging adults contributes to an increased potential for skin infections?

The dermal layer becomes thinner and breaks more easily.

What is a genetic mutation?

A genetic mutation is a permanent change to the usual DNA sequence.

How can a change in gene structure impact protein synthesis?

It can alter either the type or the amount of protein produced.

What are three environmental factors that can damage DNA sequencing?

Ultraviolet radiation, smoking, and chemotherapy.

Germline mutations are present on which specific cell types?

Oocyte and sperm cells.

How widely do germline mutations impact the cells of an individual's body?

They impact every cell in the body throughout the individual's lifespan.

What defines a somatic mutation?

An acquired DNA change occurring during a person's life that affects only cells descended from that single mutated cell.

• happens after you are born - not something inherited

Can a somatic mutation be passed on to the next generation?

No, somatic mutations cannot be inherited by offspring.

What are the three main classifications of genetic mutation disorders?

Single-gene disorders, chromosomal disorders, and multifactorial disorders.

What causes a chromosomal disorder?

A change in the number or structure of chromosomes.

Multifactorial genetic disorders result from the interaction of which components?

Interactions between genes, the environment, diet, aging, and lifestyle.

What are the three primary single-gene inheritance patterns?

Autosomal dominant, autosomal recessive, and X-linked.

How does the location of a gene dictate whether a disorder is classified as autosomal or X-linked?

Mutations located on an autosome are autosomal, while those on the X chromosome are X-linked.

What is the distinction between sex-limited and sex-influenced traits?

Sex-limited traits occur in only one sex, whereas sex-influenced traits occur more frequently in one sex than the other.

How many mutated alleles are required to alter the phenotype in an autosomal dominant disorder?

Only one mutated allele is required.

In autosomal dominant inheritance, how does a previous birth with a genetic condition affect recurrence risk?

The recurrence risk is independent of previous births.

In genetics, what does 'variable expressivity' describe?

It describes variations in the way a phenotype physically manifests.

• Variable expressivity simply means that people with the exact same genetic mutation can experience completely different symptoms or severity levels.

What are two examples of autosomal dominant disorders?

Von Willebrand disease (type 1) and hypertrophic cardiomyopathy.

An autosomal recessive disorder occurs in offspring under what parental genetic conditions?

When both parents are unaffected carriers of the mutated gene.

Why do carriers of a single autosomal recessive mutated gene show no phenotypic deviation?

Because the non-mutated dominant gene is expressed over the recessive gene.

Name three examples of autosomal recessive disorders.

Cystic fibrosis, sickle cell anemia, and Tay-Sachs disease.

Why do males display X-linked recessive disorders when they possess the mutated gene?

Because males have only one X chromosome and lack a second X chromosome to mask the phenotype.

Why are females typically carriers rather than affected by X-linked recessive mutations?

Their second normal X chromosome masks the expression of the mutated gene.

Which sex is affected by Y-linked gene mutations?

Males are affected because only males possess a Y chromosome.

What is an example of an X-linked disorder and a Y-linked disorder?

Hemophilia A is X-linked, and retinitis pigmentosa can be Y-linked.

What is the general definition of epigenetics provided by NHGRI?

The study of functional changes in DNA that alter gene expression without changing the underlying DNA sequence.

What are the three primary epigenetic mechanisms?

DNA methylation, histone modifications, and RNA-based mechanisms.

What chemical reaction occurs during DNA methylation?

A methyl group ($\text{CH}_3$) attaches to a cytosine base.

How does extensive DNA methylation lead to gene silencing?

It blocks transcription factors from accessing the DNA sequence.

What structural modification occurs to histones alongside DNA methylation?

An acetyl group is removed from the histone protein.

What are histones and what is their primary function?

Histones are proteins that support and organize DNA within the cell nucleus.

How do histone modifications regulate gene expression?

They alter the interaction between DNA and histones, changing how accessible the DNA is to transcription factors.

What condition is provided as an example of a disorder influenced by histone modification?

Congenital heart disease.

What role do noncoding RNAs (ncRNAs) play in cellular processes?

They regulate cellular processes such as RNA splicing and DNA replication.

Approximately how long are microRNAs (miRNAs)?

They are approximately 22 nucleotides long.

By what mechanism do miRNAs directly modulate mRNA translation?

They directly modulate translation by impairing ribosomal function.

Dysregulation of microRNA (miRNA) signaling pathways is linked to which disease process?

Carcinogenesis.

How does prenatal exposure to famine impact DNA methylation near the $IGF-2$ gene?

It typically leads to hypomethylation of the $IGF-2$ gene region.

When is the human embryo/fetus most vulnerable to nutrition-induced epigenetic changes?

At conception and during early gestation.

What metabolic conditions are associated with famine-induced epigenetic modifications? (2)

Type 2 diabetes and obesity.

How does high arched-back nursing and licking in rodents affect offspring gene expression?

It causes lower DNA methylation and higher transcriptional activity.

Which neuroendocrine axis is primarily modulated by epigenetic changes stemming from rodent parental care?

The hypothalamic-pituitary-adrenal (HPA) axis.

Why is the hippocampus particularly sensitive to epigenetic modifications related to stress hormones?

Because it contains a high density of glucocorticoid receptors.

What epigenetic mechanism is disrupted in fetal neural stem cells exposed to ethanol in utero?

DNA methylation patterns are pathologically altered.

How does ethanol exposure affect the differentiation of cultured neural stem cells?

It impairs their ability to differentiate into functional neurons.

Name three psychiatric conditions influenced by epigenetic modifications.

Schizophrenia, major depressive disorder, and bipolar disorder.

Why do older adults accumulate more non-beneficial epigenetic modifications over time?

Due to prolonged exposure to environmental and psychological factors such as smoking, pollution, and activity levels.

What negative cellular consequence arises from age-related epigenetic changes?

Loss of proper gene regulation and activation of inappropriate genes leading to increased inflammation or genomic instability.

In contrast to older adults, what primarily drives epigenetic markers in young adults?

Developmental processes rather than environmental exposures.

What are the three primary mechanisms of self-defense in the immune system?

Physical barriers, innate immunity, and adaptive immunity.

Which cellular structure prevents pathogens from pushing through epithelial barrier linings?

Tight junctions between epithelial cells.

Name four mechanical mechanisms the body uses to clear pathogens when physical barriers are breached.

Coughing, sneezing, vomiting, and flushing through urination.

How does the membrane attack complex of the complement system cause bacterial death?

It forms pores in the outer membrane, allowing water to enter and lysing the cell.

What is the clotting system?

A group of plasma proteins that form a blood clot when activated.

What are the three main functions of a blood clot during injury?

Plugging damaged vessels, trapping microorganisms, and providing a framework for repair and healing.