biol 485 quiz 1 (lectures 1-3)

what is immunity?

what is immunity?

the state of protection against foreign pathogens or substances (antigens)

can we generate immunity without inducing disease?

yes, through vaccination

what does vaccination do?

prepares the immune system to eradicate an infectious agent before it causes disease

immunity protects you _______ you are infected

before

antibiotics/antiviral protects you _______ you are infected

while

what are the four main categories of pathogens?

viruses, bacteria, fungi, and parasites

how are immune responses tailored?

the type of organism involved and depends on the structure of the pathogen and its location

what are the two interconnected immune systems that vertebrates use?

innate immunity and adaptive immunity

what is the response time for innate immunity?

minutes to hours

what is the response time for adaptive immunity?

days

what is the specificity of innate immunity?

limited and fixed

what is the specificity of adaptive immunity

highly diverse; adapts to improve during the course of the immune response

what is the response to repeat infection in innate immunity?

same response each time

what is the response to repeat infection in adaptive immunity?

more rapid and effective with each subsequent exposure

what are the major components of innate immunity?

barriers (e.g. skin); phagocytes; pattern recognition molecules

what are the major components of adaptive immunity?

T and B lymphocytes; antigen-specific receptors; antibodies

innate immune responses are ________ of defense

first line

innate immune responses uses ____________ recognition molecules

germ-line encoded

innate immune responses also use ______ cells

phagocytic

what are the two types of adaptive immune responses?

humoral and cell-mediated responses

adaptive immune responses use _________ generated ________ receptors

randomly; antigen

adaptive immune responses are ________ specific to individual ________ molecules

highly; antigen

how does humoral immunity combat pathogens?

via antibodies

what produces antibodies?

B cells

what does cell-mediated immunity involve?

primarily T lymphocytes

what can T lymphocytes do?

eradicate pathogens, clear infected self-cells, or aid other cells in inducing immunity

what are the 2 main types of T cells?

helper and cytotoxic

what do helper T cells do?

help other immune cells, oftentimes will secrete cytokines that can activate the other immune cells

what do cytotoxic T cells do?

recognize virus-infected cells and tell the viral-infected cells to kill themselves (apoptosis)

where do B and T cells congregate?

lymph nodes and the spleen

what is the hallmark of adaptive immunity?

memory

what is the primary response?

initiated upon 1st exposure to an antigen. innate system immediately responds, but is limited. memory lymphocytes are left behind after antigen is cleared

what is the secondary response?

initiated upon 2nd expsore to the same antigen that stimulates memory lymphocytes. stimulation yields faster, more significant, better response

memory is _____ present in innate immunity

NOT

what are the two broad categories of dysfunctions of immunity?

overly active/misdirected immune responses and immunodeficiency

what are examples of overly active/misdirected immune responses?

allergies/asthma and autoimmune disease

what is primary immunodeficiency?

genetic loss of immune functionw

hat is secondary immunodeficiency?

acquired loss of immune function

what leads to immune overstimulation that results in inflammation?

imbalance or dysbiosis

how does our body detect non-self molecules?

through receptors

how does receptor-ligand binding occur?

via multiple noncovalent bonds

what is the dissociation constant (Kd)?

a measure of strength of ligand binding

the ______ the Kd, the stronger the interaction between the receptor-ligand pair

lower

what is avidity?

the combined strength of binding of multiple receptor binding domains on one molecule to multiple, covalently-attached ligands

what is affinity?

the strength of attraction between an individual receptor binding domain and its ligand

receptor-ligand binding interactions have _______ affinity but ______ overall avidity

weak; high

what does multivalency increase?

avidity of the interactions

what does ligand-receptor binding induce in the receptor?

conformational change, dimerization/clustering, change in location in the membrane, and covalent modification

what cascades of intracellular events does receptor alterations induce?

activation of enzymes and changes in intracellular locations of molecules

what strength of immune response do we have if there is little receptor clustering

weak response

what strength of immune response do we have if there is high receptor clustering?

strong

what are MAMPs?

microbe-associated molecular patterns

what molecule on gram neg bacteria indicates it is non-self to our immune system?

lipopolysaccharide (LPS)

what molecule on gram pos bacteria indicates it is non-self to our immune system?

peptidoglycan

what do MAMPs represent?

motifs of recurring patterns on bacteria, yeast, and parasites

what is MAMPs used for?

used by innate immune system to tailor the immune response to be more effective to the group of pathogen it belongs to — generates a generic response

what are receptors for MAMPs?

integral membrane proteins, intracellular proteins, or extracellular proteins

what is needed besides detection of MAMPs to initiate a response?

some sort of danger signal

how do we detect viruses?

conserved patterns on the inside of the virus

what are pattern recognition receptors (PRRs)?

families of proteins that detect conserved microbial molecules through pattern recognition

what are the 4 types of PRRs?

toll-like receptors (TLRs), lectin receptors, nod-like receptors (NLRs), and RIG-I-like receptors (RLRs)

what do TLRs detect?

a variety of bacterial, fungal, and viral molecules

what do lectin receptors detect?

generally conserved fungal sugar moieties

what do NLRs detect?

intracellular bacterial cell wall components

what do RLRs detect?

intracellular viral RNA

what is the ligand binding domain of TLRs?

leucine-rich repeat domain

what is the signaling domain of TLRs?

TIR domain

what happens when TLRs bind with a ligand?

it will dimerize and trigger signaling for a response

what are homodimers?

when two individual copies of the same protein interact to form a dimer (oftne due to ligand recognition)

what are heterodimers?

when two different proteins (but often related phylogenetically) interact to form a dimer (often due to ligand recognition)

what do plasma membrane toll-like receptors detect?

extracellular MAMPs

what do endosomal toll-like receptors detect?

viral nucleic acids in the lumen of an endosome

how do endosomal toll-like receptors detect viral nucleic acids?

the cell has to endocytose the virus and acidify/release enzymes into the endosome to break open the virus so that the nucleic acid comes out for the receptors to detect

how do we detect DNA as non-self?

unmethylated CpG site

what does the TIR domain of the TLF intiate?

a phosphorylation signaling cascade

what is the end result of plasma membrane TLR signaling?

expression of cytokines (to cause inflammation), expression of chemokines (to attract immune cells to the are), and expression of antimicrobials

what is the end result of endosomal TLR signaling?

activation of transcription factors NF-ᴋB and AP-1 to induce a response + interferon regulating factor (IRF3/7) pathways are activated

what do plasma membrane lectins detect?

extracellular MAMPs, usually fungal

how are NLRs activated?

by MAMPs in the cytoplasm

what does NLRs induce?

expression of genes encoding antimicrobial proteins & peptides

what does NLRs initiate?

autophagy by forming autophagosomes that fuse with lysosomes to then kill bacteria

what does RIG-I-like receptors detect?

cytoplasmic dsRNA

what does RLRs trigger?

signaling pathways that activate IRFs to trigger antiviral interferon responses and NF-ᴋB transcription factor and proinflammatory cytokines

B-cell receptors have high specificity for?

a non-self molecule that is usually extracellular

where are BCRs found?

surface of the B cell or can be secreted

what are BCRs when they are secreted?

antibodies

T-cell receptors (TCRs) have high specificity for?

small peptides derived from degraded non-self protein presented on the surface of host cells, usually intracellular antigens or extracellular antigens that have been recycled by an immune cell

what are antigens?

“unique” molecules detected as non-self that elicit an immune response, often related detection by the adaptive immune system

describe the structure of a B cell receptor

a quaternary protein w/ 2 identical heavy chains and 2 identical light chains

what is antibody effector activity?

phagocytosis and complement fixation; is a function of the interaction of the constant regions of the heavy chain of B cell receptor

what do germ-line encoded genes (PRRs) bind to?

MAMPS

what do recombined genes (B- and T-cell receptors) bind to?

very specific antigens

what is clonal expansion?

make a bunch of random copies of B cells; majority will recognize nothing; when you’re infected with something, your immune system will select the few B cells that will recognize the infection and clone it so that it is overpopulated and trigger an immune response

describe the inflammatory response

• 1) Cuts or injuries that breach physical barriers result in release of chemical signals and activation of nearby macrophages that release cytokines and vasodilators (that cause relaxation of blood vessel walls)

• 2) Fluid, complement proteins, and blood clotting elements are released to the site

• 3) Chemokines released by local cells attract neutrophils and macrophages to the site

  • 4) Neutrophils and macrophages kill microbes at the infection site

what genes do PRR signaling pathways activate?

antimicrobial peptides, type I interferons, cytokines, and chemokines

how are cytokine signals usually generated?

by the binding of a ligand to a complementary cell-bound receptor

what does cytokine-signaling end results induce?

a change in the transcriptional program of the target cell

what is a cytokine signal?

any event that instructs a cell to change its metabolic, defense, or proliferative state

what are the effects of cytokines?

• Can cause changes in the localization (or movement) of a target cell by changing the expression of adhesion and chemokine receptors

• Can cause target cells to proliferate, differentiate, or modulate effector functions through changes in gene expression or effecting enzymatic activity

• Can instruct cells to survive or die

  • Can instruct cells to turn on defenses

what are the mechanisms of action of cytokines?

endocrine signaling, paracrine signaling, autocrine signaling, and signaling by plasma-membrane-attached proteins