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MEDICAL BIO > WEEK 2 - how the immune system works > Flashcards

WEEK 2 - how the immune system works Flashcards

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USMLE® Step 1 flashcards Biology 101 flashcards
1
Q

roles of the immune system

A

recognition
- of foreign substances and organisms that have penetrated out outer defences

elimination
- of such agents using a diverse repertoire of cells and molecules

immunological memory
- to learn from encounters with pathogens and maintain a reservoir of cells to respond quickly to a new infection

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2
Q

where do immune cells originate from

A

originate in the bone marrow from haematopoietic stem cells

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3
Q

immune cells
myeloid progenitor

A

immature Dendritic Cell
mast cell
macrophage

(tissues)

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4
Q

immune cells
lymphoid progenitor

A

b cells
t cells
natural killers cells
mature Dendritic Cell

(lymph nodes)
waiting for infection - innative

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5
Q

innate immunity

A

non specific targeting of pathogens

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6
Q

adaptive immunity

A

targets specific pathogens, has memory

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7
Q

immune responses must be proportional to the infectious threat

A

the immune systems can cause collateral damage to the body

chronic immune activation can occur where the immune system cannot recognise self and non self and mounts sustained responses against its own tissues –> autoimmunity

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8
Q

immune responses must be proportional to the infectious threat
- immune checkpoints

A

immune regulatory mechanisms (immune checkpoints) set thresholds for immune responses

failure of immune checkpoints can lead to conditions such as rheumatoid arthritis, crohn’s disease and cancer

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9
Q

DAMPs

A

damaged cells release danger-associated molecular patterns (DAMPs)
- this attracts macrophages

also termed alarmins

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10
Q

DAMPs
severe injury

A

uncontrolled cell death

–> Release of DAMPs (danger signals)

–> soluble Pattern recognition receptors (incl. Toll-like receptors and C-type lectin like receptors) and cell associated PRRs

this leads to an immune response

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11
Q

DAMPs
physiological stimuli

A

regulated cell death (apoptosis)

DAMPs remain hidden (silent, immune system isnt flagged)

recognition and phagocytosis of apoptotic cell by macrophage

immine system remains quiescent

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12
Q

pattern recognition receptors

A

also detect pathogen associated molecular patterns (PAMPs)
- which are present in common features of microbes

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13
Q

pattern recognition receptors
mechanism - cell associated PRRs

A

phagocytosis of PAMP and associated microorganism

activation of immune cell encountering PAMP

release of “cytokines” to amplify response

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14
Q

Pathogen-associated molecular patterns

A

common and invariant features of many frequently encountered microbes
e.g. flagellin and double-stranded RNA

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15
Q

pattern recognition receptors
mechanism - soluble PRRs

A

binding of microorganisms by soluble PRR molecules

enhancement of phagocytosis of PRR-bound PAMPs

proteolytic cascade resulting in lysis of microorganism

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16
Q

pattern recognition receptors triggering by DAMPs or PAMPs activates…

A

immune cells

cytokines (e.g. interleukin family) activate other cells and indice differentiation

chemokines serve as chemotactic factors to guide other cells to the site of infection

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17
Q

pattern recognition receptors triggering by DAMPs or PAMPs activates immune cells to…

A

CYTOKINES
endothelium
- cell contraction (can capture neutrophils and guide them to site of injury)
- cytokine secretion

macrophage
- cell activation

dendritic cell
- cell differentiation

CHEMOKINES
phagocytes
- cell migration

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18
Q

macrophage

A

one of the three types that are sentinels of the innate immune system

sentinels are cells that look for sites of infection

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19
Q

macrophages
derived from?

A

monocyte precursors that circulate in the blood stream for a number of hours before exiting the circulation to take up residence in the tissues where they undergo differentiation into specialised tissue macrophages

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20
Q

activated macrophages increase…

A

phagocytic activity

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21
Q

phagocytic activity
mechanism

A

a) chemotaxis

b) adherence via PAMP recognition

c) cell activation via pathogen recognition receptor (respiratory burst and activation of NADPH oxidase)

d) initiation of phagocytosis

e) phagosome formation (damage by reactive oxygen intermediates)

f) phagolysosome formation (damage by damage by peroxidase, cationic proteins, antibiotic peptide defensins, lysozyme, lactoferrin)

g) bacterial killing and digestion

h) release of degradation products

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22
Q

activated macrophages secrete…

A

an array of cytokines and chemokines

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23
Q

active macrophages secrete
TNF:

A

activation of local endothelium; initiation of cytokine production; upregulation of adhesion molecules

initiation of immune response

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24
Q

active macrophages secrete
IL-6

A

triggers production of acute phase proteins from the liver; enhances antibody production from B cells; indices T cell polarization

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25
Q

active macrophages secrete
IL-8

A

triggering of neutophil chemotaxis; also chemotactic for basophils and T cells; activation of neutophils; promotes anglogenesis

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26
Q

active macrophages secrete
IL-12

A

activation of Nk cells; polarization of T cells to T helper cells

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27
Q

what occurs immediately after infection

A

the acute inflammatory reaction

see slides for diagram

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28
Q

neutrophils

A

a type of granulocyte
- important cells of the innate immune system

multi-lobed nucleus

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29
Q

neutrophils
effector/functioon

A

phagocytosis/intracellular killing

degranulation/extracellular killing

NET (neutrophil extracellular trap - release which mops up bacteria)

cytokine production

30
Q

neutrophils migrate?

A

migrate in large numbers to sites of infection

31
Q

neutrophil extravasation
what

A

migration from blood vessels into site of infection
Series of steps for neutrophils to get out of blood

32
Q

neutrophil extravasation
steps

A

Chemokine signals interact with endothelial cells
Endothelial cells upregulate expression of selectins molecules
Neutrophils form transient bonds with selectin (in yellow)

Firm adhesion but LFA-1 and ICAM-1
Neutrophil can find space to squeeze through endothelial cells

Neutrophils at the size within minutes

see slides for diagram

33
Q

neutrophil extravasation
monocytes?

A

monocyte recruitment is similar but occurs 6-8 hrs after neutrophils via a different chemokine and with the aim of phagocytosing bacteria filled neutrophils and to initiate wound healing

34
Q

neutophils (and macrophages) release…

A

anti-microbial neutrophil extracellular traps (NETs)

neutrophil activation –> granule lysis –> release and DNA and granule contents –> NET formation

NETs trap bacteria

35
Q

complement facilitates…

A

phagocytosis, recruitment of immune cells and bacterial lysis

36
Q

complement
(long)

A

the complement system comprises approximately 20 plasma proteins (many are proteases) that are activated in a cascade like manner upon binding to microbial polysaccharides

37
Q

complement
must abundant protein?

A

C3

(most abundant and pivotal)

38
Q

complement
oponisation

A

binding of complement proteins to bacteria is termed opsonization and enhances their phagocytosis

e.g. phagocytes have receptors for complement protein C3b

39
Q

complement
by products?

A

certain complement fragments (C3a and C5a) produced as a byproduct of complement activation
- act as chemotactic factors for phagocytes
- activate phagocytes
- activate local mast cells to release cytokines, chemokine and histamine (increase blood vessel permeability)

40
Q

complement
C3b induces…

A

C5b production which combines C6-C9 to form a membrane attack complex (a transmembrane channel) to lyse bacteria

Ultimate goal is to form the membrane attack complex
- Holes in bacteria
- Kills bacteria

41
Q

complement
- classical pathway

A

antibody binds to antigen

42
Q

complement
lectin pathway

A

lectin proteins binds to mannose on pathogens

43
Q

complement
alternative pathway

A

pathogen, injured tissues

44
Q

dendritic cells
job

A

linking the innate and adaptive immune systems

45
Q

immature dendritic cells

A

non motile
MHC low
highly phagocytic
B7 low (poorly co-simulatory)

reside in tissues and continuously sample their environment by phagocytosis and pinocytosis

46
Q

how are immatire DCs activated?

A

PAMPs
IL-1
TNF

activate dendrites where injury has taken place

47
Q

Mature dentritic cells

A

motile
MHC high
poorly phagocytic
B7 high (co-stimulatory)

migrate to lymph nodes to present antigen to help T cells to initiate adaptive immunity

48
Q

dendritic cells present antigens to helper T cells

A

peptide antigen fragments are presented bound to MHC molecules

T cell receptors are generated by genetic recombination during T cell development such that each T cell has a distinct TCR

TRCs are designed to recognise peptide-MHC complexes and activate the T cell upon successful engagement - signal 1

a naive T cell (not yet activate by peptide MHC) requires signal 2 provided by dendritic cells to become successfully activated

49
Q

MHC

A

major histocompatibility complex
- presents peptides
–> short peptides of the bacteria
–> needs to find T helper cells that recognise the foreign sequence of peptides

50
Q

antigen processing and presentation by MHC class I

A

MHC class I is expressed by all cells in the body

PRESENTS: MHC class I + peptide
(recognised by TCR of cytotoxic T cells)

protein from the interior (endogenous)

killing virally infected cells or cancer cells

see slide for diagram)

51
Q

antigen procesing and presentation MHC class II

A

MHC class II is only expressed by antigen-presenting cells e.g. dendritic cells

PRESENTS: MHC class II + peptide
(recognised by TCR of helper T cell)

protein from bacteria
- 20 base peptides from bacteria assembled on surface (for T cells to recognise

52
Q

T cell
effector function

A

help for antibody production

killing of virus infected cells

regulatory role

53
Q

B cells
effector function

A

B cell receptor (membrane bound antibody molecule)

antibody production

54
Q

how do helper T cells assist other cells in the immune response

A

releasing cytokines to activate macrophages

e.g. y-interferon

55
Q

T cells
clonal expansion

A

T cells undergo clonal expansion following activation

this occurs 5-7 days after the initiation of immune response

recognition of MHC+peptide triggers helper T cells to clone itself over and over (PROLIFERATION)

then differentiate:
- helper T cells
- cytotoxic t cells
- regulatory T cells

56
Q

helper T cells assist

A

helper t cell –> cytotoxic t cell (killing)
helper t cell –> macrophage (inflammation)

helper t cell –> b cell –differentiation—> plasma cell –> antibody secretion

57
Q

B cells
clonal expansion

A

b cells undergo clonal expansion following activation

each B cell has up to 100,000 antibody molecules on the cell surface (termed B cell receptors), all identical and produces by genetic recombination during B cell development

B cells can differentiate into plasma cells that produce soluble antibodies

some b cells become long lived memory B cells

58
Q

antibody isotypes
IgG

A

75% of circulating antibody and provides majority of antibody-based immunity against pathogens

subtypes IgG1-4

monomer

59
Q

antibody isotypes
IgA

A

present in mucosal secretions to protect muscosal surfaces from bacteria

dimer

60
Q

antibody isotypes
IgM

A

on the surface of B cells and 10% of circulating antibody

pentamer

61
Q

antibody isotypes
IgD

A

on the surface of B cells

monomer

62
Q

antibody isotypes
IgE

A

bound to tissue cells (e.g. mast cells) and associated with allergic reactions

only 0.002% of circulating antibody

monomer

63
Q

the antibody molecule links the…

A

pathogen to other components of the immune response

complement (assembles on the antibody allowing MAC to punch holes)

phagocytes

ADCC (antibody-dependent cellular cytotoxicity)

mast cells and basophils

64
Q

antibody mediated activation of phagocytosis

A

microbe
antibody
Fc receptors
cross linking
trigger phagocytosis

65
Q

primary immune response

A

first encounter with the organism
either as a disease causing infection or preferable as a harmless vaccine

response is fairly week and short lived but T and B memory lymphocytes are produces

66
Q

secondary immune response

A

subsequent encounter with the same organism

T and B memory lymphocytes enable much faster and stronger protection

67
Q

viral infection
innate

A

infection induced ligand for NK activating receptor

natural killer cell

(killer activating receptor mediated cytotoxicity)

68
Q

viral infection
innate and acquired

A

viral protein on cell surface recognised

Ab and FcR receptors

natural killer cells

ADCC

69
Q

viral infection
acquired

A

cytotoxic T cell that recognises foreign peptide sequence

MCH I and TCR receptors

specific T cell cytotoxicity

70
Q

cytotoxic granule dependent killing of…

A

target cells by cytotoxic t cells and NK cells

cytotoxic granules in NK or Tc releases granzymes

these granzymes go through perforin channels

Granzyme A and B both lead to apoptosis

71
Q
A

MEDICAL BIO (12 decks)

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