Module 1 Flashcards
study guide
Organelles: nucleus
(the “recipe book”)
consists of: nuclear envelope, nucleoplasm, nucleolus, and chromatin
the control center housing genetic material
regulates cell activities through gene expression
nucleolus is responsible for ribosome production
organelles: mitochondria
(the power house of the cell)
consists of: double membrane with inner membrane forming christae (folds)
energy production (ATP) thru cellular respiration
plays role in apoptosis
have own DNA which supports endosymbiotic theory
organelles: cell membrane
(the cell bouncer)
consists of: phospholipid bilayer with embedded proteins, cholesterol, and carbs
facilitates communication via receptors and channels
protects cellular integrity
organelles: endoplasmic reticulum
(the “production” factory)
consists of a network of membrane-bound tubes and sacs
transport and synthesis of molecules
two subtypes:
smooth: lacks ribosomes, involved in lipid synthesis and detoxification
rough: studded with ribosomes, involved in protein synthesis
organelles: golgi apparatus
(the “Amazon” of the cell)
consists of stacks of flattened cisternae (membrane bound sacs)
modifies, sorts, and packages proteins and lipids for transport to their destination
produces lysosomes
works closely with ER to process and package proteins
organelles: lysosomes
(the “lysol/mr clean” of the cell)
consists of membrane bound vesicles containing hydrolytic enzymes
breaks down waste, damaged cell parts and invading pathogens
involved in apoptosis
role in maintaining cellular health by removing debris
organelles: ribosomes
consists of small, non-membrane bound organelles made of RNA and proteins
found in rough ER or free in cytoplasm
sites of protein synthesis (translation of mRNA into polypeptides)
role in gene expression and cellular function
organelles: cytoplasm
gel-like fluid where organelles are suspended. allows for the movement of materials within the cell
organelles: cytoskeleton
network of protein filaments and tubules that provide structure and aid in movement
organelles: vacuoles and vesicles
vacuoles: larger in plant cells but present in human cells for storage
vesicles: small membrane-bound sacs that transport materials within the cell
function: storage and transport of nutrients, waste and other materials
endocytosis
the process of bringing a substance into the cell that is too larger to enter by other mechanisms. the cell membrane surrounds the particles, engulfing them
phagocytosis
cell eating - endocytosis of a solid particle
pinocytosis
cell drinking - endocytosis of a liquid
exocytosis
the release of materials from the cell onto the cell membrane, usually with the assistance of a vesicle. examples of substances secreted by exocytosis: albumin, immunoglobulins and hormones.
diffusion
the movement of solutes from an area of higher concentration to an area of lower concentration (can be simple or facilitated) example - gases in the lung are exchanged by diffusion
simple diffusion
diffusion that requires no energy or the use of transport proteins. examples: small, nonpolar, and hydrophobic particles like oxygen and carbon dioxide
facilitated diffusion
diffusion that requires no energy but does use transport proteins (channel or carrier) to move substances from higher concentration to lower concentration. example: water is small molecule, but polar so it requires a channel
osmosis
the movement of water or any other solvent across the cellular membrane from an area of low solute concentration to an area of high concentration (water wants to dilute solutes) this allows cells to stay hydrated. passive transport. osmotic pressure refers to solute concentration (ie high solute concentration=high osmotic pressure)
active transport
the movement of a substance from an area of lower concentration to an area of higher concentration. energy in the form of ATP is required to go against the gradient
Primary - uses energy directly from ATP ie sodium-potassium pump, calcium pump, and proton pump
secondary - stored energy from the sodium-potassium pump is used by other molecules such as glucose and calcium. neurotransmitters also use secondary active transport.
osmolarity
number of milliosmoles of solute in 1L of solution. amount of solutes in a solvent. ie high osmolarity=high concentration of solutes, low osmolarity=low concentration of solutes. preferred term for fluids outside the body ie IV fluids
osmolality
number of milliosmoles of solute in 1kg of solvent. preferred term when referring to fluids inside the body. ie a serum level
apoptosis
programmed cell death; occurs when cell division stops and growth ceases. triggered by the telomere reaching a particular length (telomeres are essentially a biological cell timer)
mitosis
Interphase: spends 90% of its time here (growth, DNA replication, cell function)
Prophase: condensing chromosomes in the nuclease
Metaphase: “middle” chromosomes lined up in the middle (no more nucleus)
Anaphase: 1/2 chromosome pulled by spindles away from center towards the centrioles
Telophase and cytokinesis: nucleus forms around each half of chromosomes and cytokinesis is when cells separate into two daughter cells, each containing a copy of the same chromosome
chromosome
consists of DNA and histone and non-histone proteins, packages of information in the nucleus, attached by centromere
histone
proteins that are basically the spools around which DNA wraps itself
chromatid
each of the separate identical copies created when the chromosome replicates; they attach to each other through a centromere
nucleotides
basic building blocks of DNA and RNA consists of pentose sugar molecules, phosphate (ladder’s sides) and 1 of 4 nitrogen containing bases
DNA
double stranded, contains deoxyribose sugar ATCG, stores genetic info
RNA
single stranded, contains ribose sugar AUCG (uracil replaces thymine), protein synthesis
nucleosome
a segment of tightly coiled DNA wrapped around a collection of histone proteins; the fundamental unit of chromatin
chromatin
DNA that is combined and wrapped around the histone proteins
base pair
nitrogen bases (steps) of nucleotide are either purine (adenine and guanine) or pyrimidine (thymine and cytosine)
gene
segment of DNA that codes for a protein or function. a gene refers to the trait
allele
a version of a gene. an allele refers to the variant of the gene
epigenetics
explains how environmental factors can alter gene expressionwithout altering underlying DNA sequence. Plays a significant role in development, disease, adaptation, and physical development.
methylation of DNA can turn genes on or off which regulates production of proteins (stops transcription).
histone changes also stop transcription
mitochondrial (cytoplasmic) inheritance
traits passed through mitochondrial DNA from mother to offspring. only moms can pass (ie leber’s hereditary optic neuropathy)
x-linked recessive
single gene disorder. recessive allele on x chromosome, affects males more than females. affected males only pass to daughters (ie hemophilia, duchenne muscular dystrophy)
x-linked dominant
dominant allele on x chromosome. more females affected but it’s more severe in males. affected males pass to all daughters but not sons (ie fragile x)
autosomal dominant inheritance
single gene disorder. trait appears in every generation. at least one affected parent. male and female equally affected (ie adult polycystic kidney disease, familial hypercholesterolemia, huntingtons, marfans). mostly structural disorders.
autosomal recessive inheritance
single gene disorder. skips generations. both parents have to carry the allele. males and females equally affected often through carrier parents (ie CF, sickle cell, PKU, tay-sachs disease). mostly enzyme deficiencies (including metabolic disorders)
genotype
transmitted genetic information that forms a blueprint of a person
phenotype
the outward physical expression of genes such as eye color
karyotype
a representation of a person’s individual set of chromosomes
genome
the complete set of DNA and genes (ie genetic instructions)
cellular injury
many different causes: physical agents, chemical, radiation, biologic, nutritional, hypoxia, genetics and free radicals. in general, ATP is depleted when cells are injured and a cascade of events leads to cell membrane dysfunction. free radicals (unstable atoms in the body) also cause membrane and cellular dysfunction (page 25 in book)
punnett square
a way to calculate the likelihood of inheriting dominant or recessive allele
aneuploidy
an abnormal separation during cell division leading to too many or too few chromosomes
polymorphism
a DNA segment that has multiple alternate forms across a population. sometimes benign, sometimes lead to disease or predisposes person to disease. can also include change in chromosomal numbers/structure or pieces of chromosome translocated.
meiosis
how sperm and ova cells divide
interphase (replication)
prophase I: replicated homologous chromosomes are paired
metaphase I: homologs separate
anaphase I, telophase I, and cytokinesis
prophase II: sister chromatids separate
anaphase II, telophase II, and cytokinesis: results in haploids
four cells (gametes), each containing a single copy of each chromosome
Phenylketonuria (PKU)
defect on chromosome 12 that codes for enzyme phenylalanine hydroxylase. autosomal recessive. brain fails to develop in infancy, leading to intellectual disability if untreated.
fragile X
duplication on X chromosome. x-linked dominant. more severe presentation of facial features (eg long face, prominent jaw, large ears) and intellectual disability in males
down syndrome
extra copy of chromosome 21 (trisomy 21). usually due to errors in parental meiosis. varies but often apparent in utero: hypotonia, facial features, congenital heart defects, simian crease, developmental delay, behavior issues, cataracts, poorly developed genetalia, delayed puberty
tay sachs
defect on chromosome 15 that codes for enzyme hexosaminidase A. autosomal recessive. deterioration of central nervous system (hyopotonia, spasticity, seizures, blindness) in infancy and death by age 2
klinefelter syndrome
extra x chromosome in males. 50% of cases due to errors in parental meiosis. sterile males with long limbs, small genitalia, breast development, and learning disabilities
genetic pedigree
Genetic Tree that shows how a genetic trait or disorder is passed down through generations.
By analyzing a pedigree, geneticists can determine how a trait is inherited (dominant, recessive, X-linked, etc.) and predict the likelihood of it appearing in future generations.
huntington’s
single gene mutation. autosomal dominant. neurological symptoms develop in middle age. neurodegenerative: chorea, impaired coordination, dementia, muscle rigidity, difficulty speaking or swallowing, depression - fatal. 100% penetrance, tends to increase in severity from one generation to another
color blindness
most are x-linked recessive. inability to distinguish between green and red
PAMPS
pathogen-associated molecular patterns
DAMPS
danger-associated molecular patterns - endogenous molecules that are released when there are damaged cells without pathogen exposure
Prions
prefer the neurological system. they are folded and then unfold, reproduce when infectious prions convert normal prions into more infectious prions. binds to normal prpc and forces it to fold into the abnormal prpsc configuration
Creutzfeldt-Jakob Disease (CJD)
several types
1. sporadic
2. variant - acquired by consuming meat from a cow with bovine spongiform encephelopathy
3. familial - very rare genetic condition that causes abnormal folding of prions in adulthood
4. iatrogenic - accidentally transmitted through corneal transplant or blood transfusion
abnormal folding of prion protein can cause irreversible brain atrophy and causes vacuoles or “sponginess”
1/3 will exhibit each kind of symtom - neurological, vague (fatigue, sleep probs), focal signs (aphasia, motor weakness)
three mechanisms and which cells involved in innate immune response
- phagocytosis - neutrophils, macrophages, dendritic cells
- target lysis - neutrophils, macrophages and NK cells
- inflammation - cytokines and chemokines
role of innate immune system
physical and chemical barriers - skin, mucous membranes, sebum, microbiome
inflammatory response - non-discriminatory, PRR recognize PAMPS and DAMPS
phagocytes - ie macrophages and neutrophils, engulf and digest pathogens and provide constant surveillance
Natural Killer (NK) cells - detect and kill abnormal cells, essential in viral infections and early tumor defense. self peptide binds to major histocompatibility complex (MHC) on cell surface. help immune system distinguish between self and invader
Pattern recognition receptors (PRR) - detect pathogens associated with molecular patterns like toll-like receptors - the bridge to adaptive immunity
acquired immunity
immunity developed after exposure to an antigen
1. active - natural develops after exposure to pathogen, artificial after exposure to vaccine
2. passive - natural is passage of antibodies like from mothers to babies in placenta or breast milk, artificial is when antibodies are given through antibody therapy or immunoglobulins
role of adaptive immune system
cellular - immune cells directly attack and eliminate infected cells. T cells are primary cells in this type of immunity
-Helper T cells - activate other immune cells, including cytotoxic T cells and B cells
-cytotoxic T cells - directly kill infected cells by recognizing antigens on the surface
-regulatory T cells - help dampen immune response to prevent autoimmunity
humoral - B cells (bone marrow) produce immunoglobulins. these antibodies circulate in body fluids and eliminate pathogens by blocking entry into cells (neutralization), tagging pathogens for elimination by phagocytes (opsonization), activating the complement system (complement activation)
barriers of the innate immune system
physical barriers: skin (keratin and shed old cells+microbes), mucous membranes (line respiratory, GI, and genitourinary tracts - turn over and mechanically “wash off” microorganisms, mucus traps and expels, and cilia remove particles)
chemical barriers: skin is acidic to inhibit microbial growth, sebum and sweat act as barriers, hydrochloric acid in stomach, tears and saliva contain lysozyme that dissolves bacteria cell walls, cathelicidins and defensins can stimulate the adaptive immune system, microbiome
anti microbial peptides or AMPs. These are very small molecules and they really form a critical part of our immune system. They’re short proteins. They can consist of anywhere 10-50 amino acids. What they do is they directly kill a broad range of pathogens, including bacteria, fungal infections, viruses, and in some cases, even cancer cells.
TLRs (toll-like receptors)
a type of PRR with capacity to recognize cell membranes or microbe component of bacteria, yeast, parasite, virus. activation leads to production of cytokines and other inflammatory mediators. *bridge from innate to adaptive immunity, promotes the activation of antigen-presenting cells with present antigens to T and B cells
acute inflammation (include the stages)
*vasodilation, increased permeability, leukocyte migration
1. injury/initiation - when cells are damaged, body releases histamine, prostaglandins, and cytokines to activate the immune response and start the inflammatory process
2. vascular - vasodilation causes erythema and heat. blood vessels become more permeable to allow immune cells, proteins and fluid to enter injured tissue from bloodstream leading to edema
3. cellular - WBCs (leukocytes), esp neutrophils use phagocytosis to engulf and destroy pathogens. macrophages and lymphocytes arrive later to fight infection and initiate repairs
4. resolution - anti-inflammatory cytokines released to reduce immune response, dead cells removed by macrophages
chronic inflammation
prolonged inflammation from persistent infections or autoimmune disorders - simultaneous destruction and healing of tissue often leading to fibrosis and loss of tissue function
cellular mediators in acute inflammation
mediators promote inflammation to increase phagocytosis
mast cells release preformed mediators such as histamine and serotonin (granulated) - vasodilation, increased permeability
prostaglandins - vasodilation, pain, fever
leukotrienes -vasodilation, chemotaxis (draws attention to the site of damage)
interleukin - attracts neutrophils and macrophages to site, pain
cytokines
chemokines
complement proteins - chemotaxis, mark cells for phagocytosis, MAC
prostaglandins
lipid compounds that contribute to inflammation. cause pain, vasodilation, and fever. inhibit platelet aggregation, attract neutrophils and activate eosinophils.
leukotrienes
inflammatory mediators produced by leukocytes that increase vascular permiability and recruit other immune cells to the site of infection or injury
complements and complexes as mediators
series of proteins that enhance immune response. opsonization, lysis of pathogens and promotion of inflammation. 3 pathways: classical, lectin, alternative
like a key/lock system. forms puzzle pieces that clump together, floating around until the connect with the other puzzle pieces and locks together to intercept and disable.
good example: strep - causes complexes to release and attack tissues, so the complement goes out to lock it and disable it
other example: acute allergy reaction-complements and complexes activated in kidneys and liver (can be tissue specific)
blood cells in innate immune response
neutrophils - first on the scene, phagocyte, produced by bone marrow
basophils - initiate allergic response, bind to igE
eosinophils - contain proinflammatory, phagocytic, bind to large microbes, allergic rx
mast cells - WBC, contains granules (histamine), quick responder and why we check WBC to see if recent infection
dendritic cells - BRIDGE BETWEEN INNATE AND ADAPTIVE, phagocytice, antigen presentation to T cells, in skin and airways, travel in lymph to T cells
monocytes - WBC that replensih macrophages and dendritic cells, phagocytic and antigen presenting cells, in blood
macrophages - phagocytic and antigen presenting cells in tissue
innate lymphocytic cells (ILC) - mucosal surfaces that secrete cytokines (NK cells are ILCs)
What are immunoglobulins?
Proteins that are produced by plasma cells that act as antibodies. Key players in the immune response.
What is the structure of immunoglobulins?
-Heavy and light chains
-Variable and constant regions
-Have a Y structure
Heavy chains
-Large
-Form the backbone of the antibody, creating the Y-shaped structure.
-Determines the biological activity of the antibody and defines the class/isotype of the antibody.
-Contains the Fc region (constant region).
-Variable region contributes to the antigen-binding site.
-The type of heavy chain determines the class of the immunoglobulin.
Light Chains
-Small.
-Primarily contributes to the antigen-binding site.
-Positioned on the outer arms of the Y-shaped structure.
-The constant region is much shorter.
-Does not have an Fc region-does not directly interact with immune cells.
-2 types: kappa and lambda- a given antibody will have only 1 type.
Types of Immunoglobulins
IgA, IgG, IgM, IgE, IgD
Role of IgA
-Important in local immunity. Protects against pathogens at mucosal surfaces. Also plays a part in systemic immunity.
-Found in membranes of the respiratory and gastrointestinal tract, tears, saliva, mucus, and colostrum.
-Makes up 15% of Ig.
-Monomeric IgA: found in the bloodstream and acts as a standard antibody.
-Dimeric IgA: specialized for protecting mucosal surfaces (gut, RI tract).
Role of IgG
-The second response after IgM and eventually replaces it.
-Long-term immunity, neutralization, opsonization.
-Main defense against bacteria
-ONLY Ig that crosses the placenta to protect the fetus against infections, giving it passive immunity.
-Makes up 75% of Ig.
Role of IgM
-First responder: first Ig formed in response to antigen and a viral infection; can be detected within 3 days after infection.
-Fights blood infections and triggers additional production of IgG.
-Present in lymphocyte cells
-First antibody made by a developing fetus.
-Makes up 10% of Ig.
-Structure: pentameric form.
Role of IgE
-Responds to parasites and triggers allergic reactions.
-Protects the body through its presence in mucous membranes and skin and is attached to mast cells and basophils.
-Involved in conditions like asthma and anaphylaxis.
-Makes up <1%.
Role of IgD
Present in blood serum in small amounts and on B-cell surfaces. Receptor for antigens and helps anchor cell membranes. Makes up <1%.
Which immunoglobulin would be present in an acute viral infection?
IgM. It is the first antibody produced by the body in response to a new infection, making it a key indicator of an ongoing acute phase of a viral infection. Can be detected as early as 3 days after infection.
Which immunoglobulin would be present in previous exposure to a viral infection?
IgG. It shows that there is an immunity.
Key Genetic Variations in the Pediatric Population that influence disease susceptibility
Immune system maturity
Developmental stage-specific gene expression
Cancer predisposition genes
Infectious disease susceptibility
Immune system maturity: pediatrics
Children have an immature immune system which makes them more susceptible to certain infections and exhibit different immune responses compared to adults
Developmental stage-specific gene expression
Peds vs adults
Genes involved in growth, development, and tissue differentiation are expressed differently in children compared to adults, impacting disease progression and response to treatment
Cancer predisposition genes in peds
Certain genetic variants associated with childhood cancers, like mutations in TP53( Lifraumeni) or PX5(acute lymphoblastic leukemia) are more prevalent in pediatric populations
How do children and adults gene expression differ?
Cell proliferation and differentiation- during childhood genes related to cell division a differentiation are highly expressed, allowing for rapid growth and tissue development why these genes become less active in adults as most tissues reach maturity.
What is the role of epigenetic factors and shaping genetic expression and pediatric patients compared to adults?
Epigenetic factors plays significantly more prominent role and shaping, genetic expression and pediatric patients compared to adults, particularly during critical development. Windows were environmental influences can profoundly impact a child’s growth development and future health outcomes by altering. The way jeans are red and expressed even without changing the DNA sequence itself, this makes early life experiences, crucial for epigenetic programming, and potential disease susceptibility later in life.
How does low-grade inflammation contribute to the higher susceptibility to infections and chronic diseases in elderly population?
Chronic low-grade inflammation, contributes to the higher susceptibility to infections and chronic diseases in the elderly population by weakening the immune system, causing it to have the inability to clear inflammation factors that creates a cycle of inflammation and senescence that can damage organs and lead the disease chronic inflammation damages, healthy tissues, cells and organs can lead to internal scarring tissue, death, and DNA damage and increases the risk of disease, including cardiovascular disease, cancers, diabetes, and Alzheimer’s, and it contributes to Organ
damage by persistently Inflammation levels and organs like the liver lungs and bone marrow can lead to that their damage.
How can deterioration of physical barrier such as skin mucosal, linings and respiratory tract defenses and older adults increase their vulnerability to infections
With age, the epidermis layer becomes thinner leading to decreased keratin production, which is crucial for maintaining a barrier against bacteria and other pathogens. There’s also reduced moisture retention which causes dryness and cracking which creates an entry point for microbes there’s decreased immune cell function in the skin, which impairs the bodies ability to detect and respond to pathogens at the skin barrier, there are also mucosal lining changes lining the respiratory tract digestive tract and other body cavities that become thinner and less efficient and producing mucus which traps and removes pathogens there’s also ciliary dysfunction. They become less effective with age, allowing for pathogen accumulation..
Consequences of weakened physical barriers in adults
Increased infection rates , severity of infections and delayed wound healing
