Introduction to Immunology (9-14) Flashcards

Question

How do defensins lyse pathogens, but not our own epithelial surfaces?

Answer 1

Defensins are much more active on membranes that don't contain cholesterol → our membranes contain cholesterol

Answer 2

The innate immune system recognises pathogen-associated molecular patterns (PAMPs) that are common to many pathogens → PAMPs are absent in the host → e.g. N-formyl methionine (fMet), peptidoglycans from bacterial cell walls, bacterial flagellae, LPS from gram -ve bacteria, mannans, glucans, chitin from fungi, 'CpG' motifs in bacterial or viral DNA

Answer 3

PAMPs are recognised by soluble receptors in the blood and by cellular receptors: Pattern Recognition Receptors (PRRs) Blood receptors recognise peptidoglycans, mannans, chitin→ complement system → direct killing + aid phagocytosis Cell receptors recognise LPS, 'CpG' motifs, flagellae → toll-like receptors → an alarm system

Answer 4

Complement activation targets pathogens for lysis → complement: about 20 soluble proteins that are activated sequentially upon infection 1. early complement components - proenzymes that activated the next member by cleavage → amplified proteolytic cascade 2. pivotal proteolysis - cleaves C3 into C3a & C3b 3. C3a → calls for help - attracts phagocytes, lymphocytes stimulating inflammation 4. C3b → binds covalently to pathogen's plasma membrane 5. Pathogen-bound C3b stimulates local cascade (reactions C5-C8) 6. C9 is inserted into the membrane 7. A C9 pore breaches the membrane - form a membrane-attack complex 8. pathogen lysis

Answer 5

An alarm system → on the cell membrane of epithelial cells and macrophages, dendritic cells and neutrophils → looks out for PAMPs, signals to the nucleus, gene expression changes - promotes inflammation

Answer 6

The capsule of N. gonorrhoea lacks LPS, instead contains lipoligiosaccharide (LOS) → N. gonorrhoea can add sialic acid from host to its LOS → human cells display sialylates glycoproteins - allows to mask as a human cell evading the innate immune system

Answer 7

Phagocytes seek, engulf and destroy pathogens → 3 major classes: neutrophil, eosinophil, macrophage → contain numerous lysosomes and secretory vesicles (or granules)

Answer 8

Most common type of granulocyte, have multilobes nucleus → phagocytose and destroy microorganisms, mainly bacteria - have a key role in innate immunity to bacterial infection → short-lived cells, abundant in blood, not present in normal healthy tissues → rapidly recruited by: activated macrophages, peptide fragments of cleaved complement proteins, PAMPs

Answer 9

Larger and longer-lived than neutrophils → recognise and remove senescent, dead, and damaged cells in many tissues → able to ingest large microorganisms like protozoa

Answer 10

Team players, they help to: → destroy parasites → modulate allergic inflammatory responses → have double lobed nucleus

Answer 11

Phagocytes display cell-surface receptors for PAMPs and chemicals produced by the immune system (TLRs, antibodies, complement C3b protein) Binding activates them - → enhances killing power → causes release of cytokines to attract more white blood cells → induces actin polymerisation: the phagocyte's plasma membrane surround pathogen and engulfs in phagosome

Answer 12

Dense membrane-bound lysosomal derivatives → fuse with the phagosome membrane and release their contents (lysozyme acid hydrolases) inn an attempt to digest pathogen cell wall → contain defensins - destabilise pathogen's membranes

Answer 13

A respiratory burst (a transient increase in O2 consumption) by the phagocyte allows the NADPH oxidase complexes to produce highly toxic oxygen-derived compounds → e.g. superoxide O2-, hypochlorite HOCL, hydrogen peroxide H2O2

Answer 14

No - most macrophages can → neutrophils appear to be suicide squads - will use own DNA to trap bacteria preventing escape → dead neutrophils/pathogens = pus (can be green due to release of copper-containing compounds)

Answer 15

→ addition of sialic acid to capsule components avoids complement attack and subsequent engulfment (Neisseria gonorrhoeae) → some survive and replicate inside neutrophils - express virulence factors that protect against respiratory burst, until neutrophils die (Neisseria gonorrhoeae) → neutralise actin polymerisation and therefore phagocytosis, inject a toxin that disrupts assembly of the actin cytoskeleton (Yersinia pestis) → survive inside macrophages, which usually survive the killing frenzy (Salmonella)

Answer 16

Inflammation (good when controlled/acute) - blood vessels dilate, local swelling, accumulation of components of the complement cascade → activation of TLRs in epithelia and activated macrophages contribute to inflammation → macrophages secrete cytokines, including chemokines that attract neutrophils

Answer 17

Systemic release of inflammatory cytokines can lead to excessive blood vessel dilation, resulting in sudden lowering of blood pressure (shock) → if widespread inflammation, swelling and blood clotting occurs - septic shock → significant decrease in BP, blood supply to vital organs is reduced - organ failure

Answer 18

Interfere with viral infection → most important cytokines in virology → produced by cells in response to viral dsRNA → induce changes in the infected cell - autocrine action → induce changes in neighbouring cells - paracrine action

Answer 19

1. make virally-infected cells and neighbours into much less efficient factories - warn neighbouring cells of infections to induce expression of other cytokines, activate a ssRNA nuclease and other mechanisms that shut down host cell synthesis 2. limit viral spread by promoting apoptosis of infected cells 3. upregulate display or viral peptides - signals for recognition by activated T cells 4. stimulate expression of the immunoproteasome to process and destroy viral proteins 5. call for help: attract natural killer cells, activate macrophages 6. fight cancers

Answer 20

Viruses and cancers down-regulate expression of immune system recognition molecules - unusually low expression likely to be infected or transformed → NK cells recognise their targets by monitoring the level of expression of these molecules → NK cells are attracted to virally-infected cells by INFs → NK cells persuade cells to die by apoptosis

Answer 21

Destroys invading organisms and toxins they produce → highly specific to a particular pathogen → long-lasting protection (immunological memory) → recruited and trained by the innate immune system

Answer 22

(ANTIbody GENerators) Any substance capable of generating an adaptive immune response

Answer 23

1. an antigen is injected into a mouse in the form of a suspension containing adjuvant 2. adjuvant activates innate immunity responses, contains: → immunological stimulants - inactivated mycobacterial proteins → irritants - aluminium hydroxide 3. the activated innate response also responds to the antigen in the vaccine 4. the innate immune response trains the adaptive immune response - very specific

Answer 24

benefits → reduces reported cases due to immunological memory problems → anti-vax movements causing increase in cases (e.g. false link with MMR vaccine and autism)

Answer 25

White blood cells (T or B) that perform adaptive responses → develop in central or primary lymphoid organs - bone marrow, thymus → migrate to peripheral or secondary lymphoid organs - adenoids, tonsils, lymph nodes, spleen, skin, respiratory tract → highly concentrated in blood and lymph

Answer 26

Mice were heavily irradiated → unable to produce apatite immune responses, could still do innate Lymphocytes transferred into these mice restored adaptive immunity

Answer 27

Type of phagocyte and APC Display wide variety of TLR and pattern receptors → activated by binding of pathogen to any of these receptors → activated DC phagocytose and degrade invading microbes → peptides from degrade organisms are displayed on their cell surface → migrate to lymphoid organ to activate adaptive immune responses (training to recognise displayed peptide fragments)

Answer 28

innate immune response activates DC → digests pathogen → mature into APC → migrate to lymphoid organ → find T cells

Answer 29

T cells develop in thymus tissue from thymocytes derived from common lymphoid progenitor cells derived from a haemopoietic stem cell (liver - foetuses, bone marrow - adults)

Answer 30

1. DC present peptides to T cells in lymphoid organs 2. T cell TCR recognises 'self' antigen - no action taken 3. T cell TCR recognises no antigen - no action taken 4. T cell TCR recognises 'non-self antigen' - clonal expansion of specific T cells

Answer 31

highly specific 2 step recognition to stop groove proteins wrongly activating non T cells → co-stimulatory molecules on APC dock with T-cell specific co-stimulatory molecules → peptide held in groove of APC presenting protein and scanned by the TCR no recognition - no activation, cells undock recognition - T cells activated - migrate to site of infection

Answer 32

T regulatory (or supressor) T cytotoxic T helper

Answer 33

Activated macrophages (phagocytes), dendritic cells, B cells (lymphocytes) and maintain cytotoxic T cell activity by secreting variety of cytokines

Answer 34

Inhibit the function of helper T cells, cytotoxic T cells and dendritic cells → regulate inflammation, prevent too many cytokines released

Answer 35

Kill infected host cells by persuading them to undergo apoptosis → recognise the antigens that activated it, binds specifically to target cell forming an immunological synapse

Answer 36

1. secrete perforins, assemble and form channel in target cell wall → T cell secretes specific proteases which enter target and activate caspases (effector proteins of apoptosis) 2. bind to receptors on target cell that send a signal that activates caspases → apoptosis

Answer 37

The apoptotic bodies (causes by cytotoxic T cells) are phagoctyosed by antigen-presenting cells - can therefore retrain T cells → why T regulatory cells are needed

Answer 38

Both derived from common lymphoid progenitor cells, which are derived from haemopoietic stem cells but, T cells → develop the thymus, recognise antigens from dendritic cells B cells → develop in bone marrow, recognise antigens as soluble proteins

Answer 39

1. soluble antigens in blood or lymph 2. B cell receptor (BCR) recognises 'self' antigen - no action taken 3. BCR recognises no antigen - no action taken 4. BCR recognises 'non-self' antigen - activation, mitosis and clonal expansion of specific B cells

Answer 40

Differentiate into effector B cells (plasma cell) → increase in ER, can secrete lot of antibodies → specific to antigen that activated in lymphoid organ

Answer 41

Tetrametric - Y shae → 4 polypeptide chais, 2 identical heavy chains and 2 identical light chains → held together by covalent disulphide binds at the hinge between H and L chains

Answer 42

2 identical antigens

Answer 43

Antibodies can cross-link the antigens making small cyclic complexes or linear complexes → antibody cross-linking can generate lattices → antibodies with different specificity can co-operate

Answer 44

Ability to cross-link antigens + flexible hinge region → soluble antigens and viruses can be trapped in large cross-linked networks that often precipitate

Answer 45

Collective name for antibodies is immunoglobulin (Ig) IgM - μ heavy chain IgD - δ heavy chain IgG - γ heavy chain IgA - α heavy chain IgE - ε heavy chain

Answer 46

The most primitive immunoglobulins → the first antibodies B cells will make → expressed my immature B cells in bone marrow → once B cell has IgM and IgD can respond to antigens → T helper cells aid clonal expansion

Answer 47

IgMs bound to targets can activate the complement pathway (classical pathway)

Answer 48

Phagocytic cells don't have a receptor for IgM → ineffective at assisting phagocytosis but IgM is very efficient at activating complement - considered opsonin → targets antigens for phagocytosis → IgM is part of humoural arm of adaptive immune system

Answer 49

→ toxic neutralisation → binding to micro-organisms and opsonisation by coating pathogen + activating complement - phagocytosis → provision of passive immunity to foetuses (pinocytosis) and newborns (maternal milk)

Answer 50

A dimer of two tetrameric structures held together by a J chain and S chain which allows secretion into → saliva, tears, milk and mucus

Answer 51

Heavy chain changes only → specificity stays the same IgM can switch to: IgG, IgA, IgE

Answer 52

Standard tetrametric structure → same specificity as IgM → bound IgE acts as receptors for the particular antigens → triggers mast cell/basophil degranulation → results in histamine release - pro inflammatory mediator → uncontrolled IgE - hay fever, asthma

Answer 53

The n-terminal domains of both heavy and light chains are called variable (V) domains → the antigen binding site is made from V light and V heavy domain interactions

Answer 54

Cy1, Cy2 - bind complement components Cy2, Cy3 - bind Fc receptors on neutrophils Cy3 - binds Fc receptors on macrophages and NK

Answer 55

Mature B cells → can switch classes from IgM to other Ig classes → whilst maintaining the same specificity for antigens → required same variable chains and different heavy chains

Answer 56

There is one antibody H chain gene → Ig H gene encodes a variable (VH) domain and all the H chain constant regions separated by non-coding regions

Answer 57

Somatic recombination of DNA → cuts out small segments of DNA to allows expression of variable heavy chain with different constant components

Answer 58

Primary response → antigen stimulates clonal expansion of B and T cells, that already have receptors that already recognise the antigen → mature B cells produce IgM → can switch antibody heavy chain classes by somatic recombination, maintaining their variable domains and specificity

Answer 59

Following infection an antigen activates only lymphocytes committed to respond to it → they display cell surface recptors that specifically recognise the antigen → upon encountering the antigen lymphocytes undergo clonal expansion and differentiation

Answer 60

To do with variable domains that encode specificity 1. there are only 3 antibody genes → two classes of light chains which increases diversity and possible binding sites 2. there are multiples gene segments encoding V domains that can be combined with C domains by somatic recombination 3. the somatic recombination used to select V gene segment is complex → link V domain with constant domains at protein level creating 10^14 proteins with unique potential antigen binding sites

Answer 61

Over time antibodies made by B cells improve in affinity and become more specific → due to accumulation of point mutations in the V domains → occurs in the lymph nodes → evolution of a high affinty antibody

Answer 62

Second exposure results in a greater and more efficient secondary response with a short lag period → immune system has memory → greater and more specific as it made up of class-switched antibodies that have undergo somatic hypermutation

Answer 63

After clonal expansion T and B effector cells produced → some antigen-stimulated cells multiple and differentiate into memory cells → memory cells can be induces to become effectors by antigenic stimulation → most effectors die after an immune response, memory cells do not