ETA: Infectious Diseases Flashcards
define infectious diseases
caused by pathogens, passed from infected to uninfected people
define pathogens
disease-causing microorganisms including viruses, bacteria, fungi, protozoans, parasitic worms, prions (infectious proteins)
define immunity
resistance to diseases, escaping from infection / illness / sickness
made against infection by potential pathogens
define immune response
a collective and coordinated response to the introduction of foreign substances (two types: innate and adaptive)
define immune system
cells, tissues, and molecules that mediate resistance to infections
recognise “self” from “non-self” and rally defences when needed
define pathogenicity
ability of pathogen to inflict damage on the host
define antigen
any substance that can be recognised by the immune system
molecule that binds to an antibody or T-cell antigen receptor (TCR)
binds to antibody or TCR, eliciting B or T cell response respectively
define antigen
any substance that the immune system can recognise
molecule that binds to an antibody or T-cell antigen receptor (TCR)
binds to antibody or TCR, eliciting B or T cell response respectively
define antigen presentation
display of peptides bound by major histocompatibility complex (MHC) molecules
define an antigen-presenting cell (APC)
a cell that displays peptide fragments of protein antigens, in association with major histocompatibility complex (MHC) molecules on its surface, and activates antigen-specific T cells
define antibodies
a type of glycoprotein molecule, also called immunoglobulin (Ig), produced by B lymphocytes that binds antigens
help directly defend against pathogens
what are the three major functions of the immune system?
- recognising and removing abnormal “self” cells (eg. cancer)
- removes dead or damaged cells and old blood cells (scavenger cells like macrophages)
- protects body from disease-causing pathogens
what are the three types of immune system failures
- incorrect response (cannot distinguish “self” from “non-self”, autoimmune disease)
- overactive response (like allergies, out of proportion)
- lack of response (immune system malfunction)
what are the four steps an immune response must contain?
- immunological recognition: detecting an infection’s presence by white blood cells of innate immune system respond immediately, lymphocytes of adaptive immune system
- immunological effector functions: contain and eliminate pathogen by immune effector functions
- immune regulation: keep response controlled to prevent autoimmune diseases
- immunological memory: protect against recurring disease due to the same pathogen by generating memory, long-lasting immunity
name the three lines of defence for immunity
- non-specific external barriers
- innate immune response
- adaptive immune response
give examples of the physical / mechanical non-specific external barriers of the immune system
epidermis and keratinocytes (dead cells) of the skin
epithelium of mucous membranes of gastrointestinal, respiratory, urogenital tracts
cilia in respiratory tract
give examples and explain how non-specific external barriers of the immune system work
acidic pH of skin, stomach, vagina: most pathogens are very sensitive, acidic pH inhibits pathogen growth
microcidal (microbe-destroying) action of secreted molecules: eg. various cell types within the skin secrete antimicrobal peptides, sweat has lysozyme that breaks down bacterial cell walls
commensal microbes exist in a symbiotic relationship with the body, colonising skin and gastrointestinal tract
what are the features of the innate immune system?
non-specific components available before onset of infection
present from birth, always present in healthy individuals
immediate response to pathogens
instructs adaptive immune system to respond specifically to each microbe effectively
key participant for clearing dead tissues and initiating tissue repair
phylogenetically older (more primitive)
what are the three functions of the innate immune system?
block microbial invasion through epithelial barriers (physical / mechanical)
destroy many microbes that enter the body
control and eradicate infection
name all the cells in the immune system (both blood and tissue)
blood: neutrophil, eosinophil, basophil, monocyte, T-cell, B-cell, NK cell, platelets, red blood cell
tissue: tissue eosinophil, mast cell, macrophage, T-lymphocyte, plasma cell, NK cell, dendritic cell
which cells do the terms: [leukocytes, granulocytes, polymorphs, mononuclear cells, lymphocytes, phagocytes] refer to?
leukocytes: all cells in the blood (mentioned below)
granulocytes (irregular nucleus: basophil eosinophil neutrophil) VS mononuclear cells (regular nucleus: monocyte T-cell B-cell NK cell)
polymorphs = granulocytes
lymphocytes are mononuclear without monocyte: T-cell, B-cell, NK cell
phagocytes: neutrophil and monocyte, dendritic
what are phagocytes, their functions, and name the three types
group of white blood cells (leukocytes) ingest invaders by phagocytosis
function: recruited to infection sizes, recognise and ingest microbes for intracellular killing
neutrophil (blood), macrophage (tissue), dendritic cell (tissue)
what are the features, functions, half-lives of neutrophils?
60% of peripheral blood leukocytes, most numerous
polymorphonuclear (PMN) cells bc of 2-5 nuclear segments
function: very effective at killing bacteria, motile (can move) and injest, kill, digest microbial pathogens
half-life: approximately 7h, 100 billion neutrophils enter circulation daily
death of neutrophils helps form pus
what is the relationship between monocytes and macrophages, and their features & functions?
monocytes in blood for 1-2 days, then cross the endothelium into extravascular tissues and differentiate into macrophages during inflammatory reactions for months
same cell lineage (mononuclear phagocytes system): monocytes –> macrophages
function: actively sample environment by phagocytosis, scavengers for cellular debris
what are the features and functions of dendritic cells?
named for branchlike cytoplasmic projections
primarily found in potential portals of microbial entry
functions: antigen-presenting cells (APCs) to that “communicate” and activate helper T-cells, cytotoxic T cells and B cells (adaptive immunity) by showing antigens to adaptive lymphocyte populations
also do phagocytosis, important bridge between innate and adaptive immunity
what are the features and functions of the natural killer (NK) cells?
large, non-phagocytic, granular lymphocytes (5-10% of all lymphocytes)
functions: non-specific defence against abnormal (infected or cancer) “self” host cells
destroy virus-infected cells before they have time to reproduce and spread, stopping viral infections
name all the cells involved in innate immunity
phagocytes (neutrophils, monocytes / macrophages, dendritic cells), natural killer cells, mast (both innate and adaptive for signalling
name all the proteins involved in innate immunity
cytokines, (FYI: complement system)
name all the mechanisms involved in innate immunity
inflammatory response, phagocytosis, fever (pyrexia)
what are the functions of cytokines, and what produces them?
secreted proteins that are mediators of immune and inflammatory reactions
produced by macrophages and NK cells
how do inflammatory responses protect the body?
tissue reaction that delivers innate immunity cells and proteins to sites of infection and damage, exudating plasma proteins into tissue for healing, triggering nerve endings
injured tissues and macrophages release chemokines (type of cytokine) that recruits immune cells to site
mast cells and macrophages secrete histamine and other factors, causing vasodilation and making them more permeable
neutrophils recruited for phagocytosis, other leukocytes also mediate damage
how does pyrexia combat large-scale infections?
increases activity of phagocytic leukocytes
increases rate of replication for immune cells
hampers rate of replication for bacteria due to heat and iron deficiency
stimulates release of interferon by virus-infected cells, making non-infected cells more resistant against infection and stimulating NK cells to destroy infected cells
what is adaptive immunity?
specific immune response that accounts for specificity in antigens
state the five important features of adaptive immunity
- specificity
- clonal expansion and selection
- immunological memory
- specialisation
- contraction and homeostasis
- immunological tolerance (FYI, no self-attack)
what is contraction and homeostasis in the context of immune responses?
immune responses are self-limited, decline as infection is eliminated
system resets, can respond to new antigens
state the two types of adaptive immunity
humoral and cell-mediated
what is humoral immunity?
mediated by antibodies (proteins) produced by B lymphocytes
what are the main functions of antibodies?
- bind specifically to toxins
- neutralise and eliminate microbes and their toxins
- stop microbes at mucosal surfaces in blood from accessing and colonising host cells and connective tissues
- prevent infections from ever being established
what is cell-mediated immunity?
defence against intracellular microbes, mediated by T-lymphocytes which recognise antigens produced by intracellular microbes
what are the functions of T-lymphocytes?
T helper: activate B lymphocytes
T cytotoxic: kill any host cells harbouring infectious microbes in cytoplasm
state the two anatomical components of the immune system
lymphoid tissues and cells responsible for the immune system
what are the two broad categories of lymphoid organs, and what do they consist of?
primary / generative: bone marrow (B and T), thymus (T only)
secondary / peripheral: spleen, lymph nodes, mucosal lymphoid tissues
what is the function of the bone marrow and thymus in the immune system?
bone marrow–
generates T and B cells
B cells mature
thymus: precursor T cells from bone marrow migrate and mature there
what are naive cells?
mature but unspecialised (until their first exposure to pathogen)
what is the function of peripheral / secondary lymphoid organs?
where mature naive lymphocytes are maintained and adaptive immune responses are initiated when they interact with pathogens
what happens to mature naive lymphocytes?
after B cells mature in bone marrow and T cells mature in thymus, they migrate into the bloodstream
what are lymph nodes and vessels, and what is their function in initiating an adaptive immune response?
lymph nodes are part of the lymphatic circulation, associated w capillaries
nodes interconnected by vessels, which drain extracellular fluid (lymph) from tissues through nodes and back into blood
what is lymph, and what does it carry?
lymph is the extracellular fluid drained by lymphatics
- carries antigens to lymph nodes
- recirculates lymphocytes from nodes into blood
state the four cells of adaptive immunity, and the two categories they fall into
antigen-presenting: dendritic and macrophages (also innate)
lymphoid lineage: B and T lymphocytes (only adaptive)
what is the function of antigen-presenting cells?
capture antigens
transport to peripheral lymphoid tissues
display peptide fragments of antigens to lymphocytes
activates antigen-specific T cells
where are antigen-presenting cells found?
in epithelium of common portals of entry for microbes (skin, GI tract, respiratory tract)
what do MHCs stand for, and what do they do?
major histocompatibility molecules
linked set of genes encodes group of proteins for antigen presentation
MHC proteins bind peptide fragments of protein antigens to display for T cell receptors
what is the function of dendritic cells in adaptive immunity?
act as an APC, display peptide fragments of antigen proteins to activate T cells
what is the function of macrophages in adaptive immunity?
- phagocytoses microbes in tissues and organs
- antigen-presenting
- activates naive T cells to proliferate and differentiate into effector cells
lymphocytes (B and T) are the only cells that do what?
produce clonally distributed receptors specific for diverse antigens
how are lymphoid lineage cells distinguishable?
surface proteins
name the Tc and Th cells, and their cluster of differentiation number
Helper T (CD4+) and Cytotoxic T (CD8+) cells
what are the only cells capable of Ig production, and where do they reside?
B cells AND plasma cells (further differentiated B cells)
bone marrow
what do the antibodies the B cells express do?
B cells express antibodies = receptors that recognise antigens
antigens bind to antibodies, leads to humoral immune responses
how do B cells react when first exposed to a pathogen?
- clonal selection
- clonal expansion
- some are plasma (short-lived)
- some are memory (long-lived, gives immunological memory)
define clonal selection
only specific cells with receptors complementary to antigen are stimulated to divide via mitosis
define clonal expansion
small clone of cells divides repeatedly by mitosis to produce huge numbers
what are monoclonal antibodies, and how are they produced?
with same antigenic specificity
produced by the same plasma cell
what cells undergo clonal selection and expansion, and why?
B and T cells: large repertoire each, needed cells are selected for and large numbers are produced
what is the function of Helper T (Th) cells, and what is their cluster of differentiation?
release cytokines
- makes B cells clonal selection and expansion, then become plasma cells
- makes B cells secrete antibodies
- some stimulate macrophages to phagocytosis more
- make Tc mitosises and differentiate to make vacuoles full of toxins
(effector) CD4+
what is the function of Cytotoxic T (Tc) cells, and what is their cluster of differentiation?
search for self-cells displaying foreign antigens from pathogens
- attach themselves to surface of infected cells, secrete granzymes (induce apoptosis) or toxic substances (eg. H2O2) to kill cell and pathogens inside
- create pores in cell wall with perforin and let osmosis do its thang
(effector) CD8+
what types of T memory cells exist?
Helper and Cytotoxic
what do naive lymphocytes do?
express receptors for antigens
cannot eliminate antigens
what are effector cells for both B and T lymphocytes?
differentiated progeny of naive cells that can eliminate antigens (usually short-lived)
B cells: plasma
T cells: helper and cytotoxic
what are memory cells, their function, and how many are there in the blood?
differentiated progeny of mature non-naive lymphocytes
more with age
functionally inactive, no effector functions unless antigen stimulated
what is the functional group on B lymphocytes cell surface? (FYI another two on T cell and APC)
surface immunoglobin
FYI: T-cell receptor and MHC on APC
what is immunodeficiency and immune dysfunction?
immunodeficiency: absence of elements in immune system
immune dysfunction: harmful immune function
define specificity in the context of the immune system
ability to distinguish between many different antigens
why is the lymphocyte repertoire so diverse, and what does this allow the immune system to do?
lymphocytes express clonally distributed receptors for antigens, each clone has diff antigen receptor
immune system can respond to vast no. and variety of antigens
what does a clone of lymphocytes refer to?
a cell and all its subsequent differentiated progeny
define immunological memory
long-term protection against a prior infection, allowing immune system to mount larger, rapid, and more effective responses to repeated exposures
what is the primary immune response, and its characteristics?
adaptive immune response that occurs after first exposure of an individual foreign antigen
relatively slow kinetics and small magnitude
what mediates the primary immune response, and when does it peak?
naive lymphocytes that encounter antigen for the first time
10-17 days, where mature naive B and T become effector versions
what are secondary immune responses, and its characteristics?
responses that occur with subsequent encounters with the SAME antigen
more rapid, larger, better in eliminating antigen than primary
what mediates secondary immune responses, and what makes it possible?
long-lived memory B and T cells (both helper and cytotoxic)
immunologic memory: activates previous memory cells and generates more, combats persistent and recurrent infections
what are the general steps of the adaptive immune system? (TDAABS)
threat: antigen engulfed
detection: apcs active T
alert: Th into effector Th and memory
alarm: Th activates B and Tc
building specific defences: selection and expansion, B to plasma and memory, Tc to effector and memory
secretes: B gives antibodies
what are the different targets of antibodies by B cells and effector Tc cells?
B cells target extracellular pathogens
Tc cells target infected self-cells with intracellular pathogens
what occurs during the T phase of TDAABS?
threat: antigen without MHC passes first 2 lines of defence
- non-specific external barriers
- innate immunity
and enters body
what occurs during the D phase of TDAABS?
detection: APCs like macrophages or dendriticengulf and present peptide fragments of antigen proteins in association with MHCs
what occurs during the first A phase of TDAABS?
alert: helper T cell
- activated into effector Th cell
- also forms memory helper T cell
what occurs during the second A phase of TDAABS?
alarm: effector Th
- secretes cytokines, activates antibody production and Tc cells
- binds to B cells, encourages differentiation into plasma and memory
what occurs during the B phase of TDAABS?
building specific defences: clonal selection and expansion
B cells to memory and plasma
Tc cells to memory and effector Tc cell
what occurs during the S phase of TDAABS?
plasma cells (differentiated progeny of B cells) secretes antibodies
how do antibodies eliminate antigens (3 ways)? (humoral response)
neutralisation: binds to surface of virus, neutralising it
opsonization:
- promotes phagocytosis
- aggregation
complement system: FYI
how do Tc cells eliminate antigens? (cell-mediated response)
attack and destroy cells that display antigen fragments in MHC
releases cytotoxic pore-forming molecules called perforins, then granzymes into the cell, induces apoptosis
define active immunity
individual exposed to antigens of a microbe and mounts an active response to eradicate infection, makes their own antibodies
what is natural VS artificial active immunity?
natural: during an infection
artificial: vaccination of antigens through injection or orally
define passive immunity, and what it is useful for
receives antibodies or cells (eg. lymphocytes, only for genetically identical animals) from another individual with immunity, temporary! immunity only
rapidly conferring immunity before individual is able to mount active response
what is natural VS artificial passive immunity?
natural: newborns acquire antibodies from mother through placenta and breast milk
artificial: tetanus injection of antitoxin, from blood donors recently vaccinated against tetanus
what is a vaccine?
induce host to mount immunological response to render immunity (through immunological memory)
what is vaccination, and what does it confer?
introducing a vaccine into the body, contains antigens for disease by injection or mouth, confers artificial active immunity
list the six types of vaccines
- live attenuated (weakened virus by heat or chemicals)
- inactivated / killed
- toxoid (inactivated toxin by bacteria)
- extract (part of organism)
- recombinant (removal of reproductive / virulence genes)
- DNA (host cells express gene products)
what are the pros and cons of live attenuated and inactivated vaccines?
live attenuated:
stronger immune response, easy to create–may become virulent bc mutations, needs fridge
inactivated: more stable and safe, no fridge–weaker immune response, booster needed
what is another name for cytotoxic T cells (Tc cells)?
killer T cells…
what is the main change to the immune system after a vaccination?
memory cells of vaccine antigen produced
how does the immune system respond to the same pathogen after vaccination?
APCs ingest and display –> activate memory Th, Tc, B Tc specific to antigen –> memory B become plasma to produce antibodies and Tc kills –> memory cells retained again
what is herd immunity?
when vaccination of a significant portion of population provides protection for non-immune individuals
protects those vulnerable but can’t vaccinate
how was smallpox eradicated?
first disease to be eradicated by vaccination
global vaccination campaign by WHO: Smallpox Eradication Programme, done by 1980
what are the benefits and risks of vaccination
benefits:
- protects individuals against disease, reduces rate of death, milder form
- protect community: herd immunity for those who can’t take the vaccine
- eradicate some
- save money
risks:
- immunity may not be as effective
- live attenuated may revert to virulent form
- immunocompromised ppl don’t respond well
what are the three modes of transmission of bacterial pathogens?
- contact
- vehicle
- vector
what are the three forms of contact transmission?
direct contact transmission: no intermediary between infected and uninfected (touching, kissing, sex)
indirect contact transmission: non-living intermediates = fomites, eg. items
droplet contact transmission: airborne particles eg. sneezing, coughing, laughing
what are the four forms of vehicle transmission?
water-borne
food-borne
airborne: aerosol
bodily fluid: hospital setting
what are the two forms of vector transmission?
living intermediates (animals)
mechanical: passively carry pathogens
biological: also hosts for multiplication of pathogen
state the four steps of bacteria infecting host cells
- adherence to host cells
- invasion of host cells
- toxicity
- evasion of host defences
what are the features of a bacterial cell that adheres to its host?
- filamentous structures called pila / fimbriae
- cell surface adhesion molecules
- hydrophobic cell walls
what is the significance of infecting a host cell through adherence?
will not be carried away by mucus / urine / etc
forms a microcolony to invade and damage host tissue
state the two types of toxins bacteria may produce, and which are found in gram positive / negative bacteria?
exotoxins: proteins secreted by gram positive and gram negative
endotoxins: lipopolysaccharides integral in gram-negative bacterial cell walls
what are the three principal types of exotoxins released by bacteria?
cytotoxins: kill or affect function of general cells
neurotoxins: influences nerve cells specifically
enterotoxins: affect cells lining GI tract
what are endotoxins released by bacteria?
lipid portion of lipopolysaccharides in outer membrane of gram negative bacteria (septic shock)
what are the three ways bacteria can evade the innate immune system?
- evade complement system: capsules prevent activation of complement proteins
- resist phagocytosis: slippery mucoid capsule / surface proteins prevent adherence
- surviving inside phagocytic cells: prevent fusion of lysosomes with phagocytic vesicles
what are the two ways bacteria can evade the adaptive immune system?
- non-antigenic capsules / can change surface antigens
- IgA proteases, interfere with antibody-mediated opsonization (tag antigens)
what are the four immune response pathways triggered by bacterial infections?
- activity of complement system (FYI)
- activity of phagocytes
- role of adaptive immune system
- initiation of repair
what bacterium causes tuberculosis?
mycobacterium tuberculosis
how is mycobacterium tuberculosis transmitted?
droplet contact transmission and airborne transmission (vehicle)
coughs, sneezes, spits, speaks, sings, talks
what is the mode of infection of mycobacterium tuberculosis
escape phagocytosis:
- alveolar macrophages in alveoli engulf bacteria (innate)
- modifies endosomal compartment, macrophage cannot fuse with lysosome and get digested
- pathogen remains in endosomal compartment and replicates, macrophages swell and rupture
what are tubercles or granulomas, and when do they occur?
central core of M.tuberculosis bacteria, enlarged macrophages, and outer wall of fibroblasts, lymphocytes and neutrophils
latent stage of TB infection, no symptoms, not contagious
what occurs during the active stage of TB infection (to the tubercle, symptoms)
tubercle expands and ruptures, damages lung tissue and function
symptoms of chest pain, cough, shortness of breath
- contagious
- secondary infections in nodes, bones, gut
what is an antibiotic
substances that can kill or inhibit growth of bacteria
produced naturally by metabolic processes of some microorganisms OR synthetically produced
what are narrow and broad spectrum antibiotics?
effectiveness against limited / wide variety of microorganisms
what is selective toxicity of antibiotics?
ability to kill or inhibit growth of infecting microbial cells, but not host cells
what are the three types of antibacteria agents?
bacteriostatic (“pauses”)
bactericidal (kills)
bacteriolytic (lyses)
what are two standard assays for checking antimicrobial activity?
minimum inhibitory concentration determination (series of known conc of agent, MIC is lowest conc that completely inhibits growth of organism)
disk-diffusion test
- agent on filter-paper discs, placed on inoculated agar plate, size of zone of inhibition (we did this in bio lab once)
state the four main modes of action of antibiotics on bacteria
- inhibition of cell wall synthesis
- inhibition of RNA and DNA structure and function
- inhibition of protein synthesis
- interference with cell membrane structure and function
what enzymes are involved in bacterial cell wall synthesis?
transglycosylases: insert peptidoglycan precursors into growing cell wall
autolysins: make gaps by breaking NAG and NAM bond
transpeptidases: form cross-links btw alternate NAM residues
what is the structure of penicillin and its key mode of action?
beta-lactam antibiotic
binds and blocks transpeptidases from forming cross-links
autolysins alone weaken cell wall, cell bursts, bacteriolytic
how do antibiotics block the synthesis of nucleotides?
inhibits DNA replication or blocks transcription of DNA to mRNA
how do antibiotics inhibit protein synthesis (aminoglycosides and tetracyclines)
30S or 50S ribosomal subunits
aminoglycosides cause misreading of mRNA
tetracyclines block attachment of tRNA on A acceptor site, stop protein synthesis
define an immunogen
any substance that can evoke an immune response
(all immunogens are antigens, though not all antigens are immunogenic)
define an epitope / antigenic determinant
portion of an antigen that binds to an antigen receptor
what are the three components involved in antigen recognition?
T cell receptor
MHC: major histocompatibility proteins
CD4 / CD8 co-receptors
describe the structure of a T-cell receptor
membrane-bound heterodimeric protein
alpha and beta chain, each with one variable and one constant region
at the base: transmembrane region that anchors molecule in cell’s plasma membrane
antigen-binding site: variable regions of alpha and beta chains
what do BCRs and TCRs respectively bind to?
BCRs: epitopes of intact antigens
TCRs: antigens presented on host cells associated with MHCs
what are the functions of the CD4 (Th) and CD8 (Tc) co-receptors?
when TCR binds to peptide-MHC complex, co-receptor also binds to MHC on antigen-bearing cell, strengthening molecular interactions between cells and enhancing activation of T cell
what occurs to the first Igs made by a newly formed B lymphocyte?
inserted into plasma membrane of B cell, serve as antigen receptors (BCRs)
what type of Igs are antibodies, and when do B cells secrete large amounts of them?
soluble Ig, not membrane-bound
when activated by a Th cell
describe the structure of a BCR
Y-shaped
two identical antigen-binding sites (bivalent)
four peptide chains: 2 identical light, 2 identical heavy. each chain has constant and variable regions
asymmetric binding site for antigen: heavy V and light V
how does a BCR anchor into the plasma membrane?
transmembrane region near the end of each heavy chain (constant region) anchors, short tail region enters cytoplasm
constant: very little variation in aa sequence among different B cells
what is the general structure of an antibody?
four chains: 2 heavy 2 light
each chain has constant and variable regions
variable H and L form two identical antigen-binding sites
hinge region for flexibility (aggregation)
*carbohydrate protects from proteolytic degredation
what are the different functions of the variable and constant regions on an antibody?
variable (Fab): confers antigen recognition
constant (Fc): interacts with cell surface receptors
what is the role of an antigen receptor in cell signalling?
associated with invariant membrane proteins that deliver intracellular signals after recognising antigens
what are the five major classes of Igs?
IgG (heavy chain: gamma)
FYI: IgA, IgM, IgD, IgE
what is binding affinity in the context of adaptive immunity?
measurable strength of binding antibody to antigen: high-affinity antibody binds tightly to antigen
what are the two varieties of Ig light chains, and their difference?
kappa (k) and lambda
functionally indistinguishable (60% k, 40% l)
how are the chains in Ig molecules linked?
covalently, disulfide bridges
allows for unique generation of antigen binding regions
why are IgGs important, and what is its half-life like?
most common circulating antibody: 80% of serum Igs
produced in esp large amounts during secondary antibody responses
longest half-life
what are the four human IgG subclasses, and their respective heavy chains?
IgG2, IgG2, IgG3, IgG4
respectively
y1, y2, y3, y4 (y is gamma)
why do IgG molecules always have two identical antigen-binding sites
both light chains are identical (kappa or lambda), will not have one kappa one lambda
what does the tail region of an igG molecule bind to?
specific receptors on macrophages and neutrophils
what is somatic recombination, what molecules undergo it?
DNA recombination to make diff types of Igs
what enzyme catalyses somatic recombination?
V(D)J recombinase
what are the three types of diversity in the primary immunoglobulin repertoire?
multiple variable gene segments
combinatorial diversity (somatic recombination)
junction diversity (hinge)
what are the two processes that occur during maturation of secreted antibodies?
affinity maturation through somatic hypermutation
class switching
what is somatic hypermutation and what does it result in?
- extensive mutation that occurs in variable region of DNA sequence of immunoglobulin of heavy and light chains
- produce variant immunoglobins, some with higher antigen affinity: affinity maturation
- mutations affect only somatic cells, not inherited through germline transmission
in what cells do somatic hypermutation and class switching occur in?
activated mature B lymphocytes
what occurs during class switching?
somatic recombination of antibody’s heavy chain: switches production of antibodies of class IgM to IgG, IgA, IgE
occurs during adaptive immune response
what processes allow antigen-binding diversity, and what allows functional diversity?
antigen-binding:
- V(D)J recombination during B-cell development
- somatic hypermutation after antigenic stimulation
functional diversity: class switching
what are the six sources of antibody diversity?
- presence of multiple Variable gene segments
- combinatorial diversity from random recombination of V(D)J segment combinations
- junctional diversity, changes in V-D and D-J junctions
- multiple combinations of light and heavy chains
- somatic hypermutation
- class switching
what is the mode of transmission of the influenza virus?
through respiratory droplets (coughing, sneezing)
what do the different types of influenza infect?
A: animals
B: only humans
C: only humans and pigs
how does the influenza virus enter the host, and what is the first line of defence against it?
through oral or nasal cavities
epithelial cells that line respiratory tract that initiate antiviral immune response once virus detected
first line of defence is physical barriers like mucus: respiratory tract covered with mucociliary layer with ciliated cells, mucus-secreting cells, and glands
Neuraminidase on influenza cell membrane cleaves sialic acid residues to prevent virus from being trapped in mucus
how does the immune system react upon influenza’s entry, and (briefly) how does influenza infect the host?
influenza initiates antiviral signalling cascades, produces cytokines and pro-inflammatory responses
macrophages: phagocytosis and APC
Tc: lyse infected host cells
dendritic: APC
what are the signs and symptoms of influenza? (memorise!)
cough: reflex exacerbated by inflammatory response
runny / stuffy nose: inflammation of nasal tissue
fever or chills: cytokines lead to pyrexia
sore throat: loss of epithelial lining due to new virus budding off
shortness of breath: destruction of alveoli
muscle or body aches, headaches and fatigue
what is HIV (type of virus, mode of function)
retrovirus (has reverse transcriptase)
infects and destroys Th cells (naive, effector, memory) –> allows opportunistic infections
how is HIV transmitted?
semen and vaginal fluids during sexual intercourse
infected blood
contaminated syringes
mother to fetus across placenta or at birth
mother to infant in breast milk
how does the HIV virus disable the immune system (macrophages and helper T cells)
macrophages: makes them lose their ability to ingest and kill foreign microbes
HIV specifically attacks Th cells with primary CD4 receptor + macrophages + dendritic cells
what is needed for the viral entry of the HIV virus?
co-receptor, either CCR5 or CXCR4
list the three phases of a typical HIV infection
acute HIV infection
clinical latency
Acquired Immunodeficiency Syndrome (AIDS)
what occurs during acute HIV infection?
flu-like symptoms: fever, swollen glands, sore throat, rash, muscle and joint aches and pains, headache
due to production of pro-inflammatory cytokines
active replication fo new viral particles –> infects as many Th cells as possible, highest no of virus in bloodstream
depletion of Th cells
at viral set point, Th cell count rebounds but not fully
very high risk of transmission
what occurs during the clinical latency / chronic phase of HIV?
integration of viral DNA into host genome, infected Th cells invade immune system
asymptomatic HIV infection
reproduces at very low levels
macrophages are major reservoirs for virus in tissues
viral load will eventually rise
what antibiotics are described as bacteriolytic?
- binds and blocks transpeptidases that form
the cross-links between NAM residues - weakens the peptidoglycan, take up water by osmosis
- weakened cell wall cannot withstand the pressure potential exerted
- cells eventually burst (lysis)
