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

WEEK 2 - how the immune system works 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

Damage-associated molecular patterns

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
active macrophages secrete IL-8
triggering of neutophil chemotaxis; also chemotactic for basophils and T cells; activation of neutophils; promotes anglogenesis
26
active macrophages secrete IL-12
activation of Nk cells; polarization of T cells to T helper cells
27
what occurs immediately after infection
the acute inflammatory reaction see slides for diagram
28
neutrophils
a type of granulocyte - important cells of the innate immune system multi-lobed nucleus
29
neutrophils effector/functioon
phagocytosis/intracellular killing degranulation/extracellular killing NET (neutrophil extracellular trap - release which mops up bacteria) cytokine production
30
neutrophils migrate?
migrate in large numbers to sites of infection
31
neutrophil extravasation what
migration from blood vessels into site of infection Series of steps for neutrophils to get out of blood
32
neutrophil extravasation steps
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 site within minutes see slides for diagram
33
neutrophil extravasation monocytes?
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
neutophils (and macrophages) release...
anti-microbial neutrophil extracellular traps (NETs) neutrophil activation --> granule lysis --> release and DNA and granule contents --> NET formation NETs trap bacteria
35
complement facilitates...
phagocytosis, recruitment of immune cells and bacterial lysis
36
complement (long)
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
complement must abundant protein?
C3 (most abundant and pivotal)
38
complement oponisation
binding of complement proteins to bacteria is termed opsonization and enhances their phagocytosis e.g. phagocytes have receptors for complement protein C3b
39
complement by products?
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
complement C3b induces... | which forms 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
complement - classical pathway
antibody binds to antigen
42
complement lectin pathway
lectin proteins binds to mannose on pathogens
43
complement alternative pathway
pathogen, injured tissues
44
dendritic cells job
linking the innate and adaptive immune systems
45
immature dendritic cells
non motile MHC low highly phagocytic B7 low (poorly co-simulatory) reside in tissues and continuously sample their environment by phagocytosis and pinocytosis
46
how are immature DCs activated?
PAMPs IL-1 TNF activate dendrites where injury has taken place
47
Mature dentritic cells
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
dendritic cells present antigens to helper T cells
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
MHC
major histocompatibility complex - presents peptides --> short peptides of the bacteria --> needs to find T helper cells that recognise the foreign sequence of peptides
50
antigen processing and presentation by MHC class I
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
antigen procesing and presentation MHC class II
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
T cell effector function
help for antibody production killing of virus infected cells regulatory role
53
B cells effector function
B cell receptor (membrane bound antibody molecule) antibody production
54
how do helper T cells assist other cells in the immune response
releasing cytokines to activate macrophages e.g. y-interferon
55
T cells clonal expansion
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
helper T cells assist
helper t cell --> cytotoxic t cell (killing) helper t cell --> macrophage (inflammation) helper t cell --> b cell --differentiation---> plasma cell --> antibody secretion
57
B cells clonal expansion
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
antibody isotypes IgG
75% of circulating antibody and provides majority of antibody-based immunity against pathogens subtypes IgG1-4 monomer
59
antibody isotypes IgA
present in mucosal secretions to protect muscosal surfaces from bacteria dimer
60
antibody isotypes IgM
on the surface of B cells and 10% of circulating antibody pentamer
61
antibody isotypes IgD
on the surface of B cells monomer
62
antibody isotypes IgE
bound to tissue cells (e.g. mast cells) and associated with allergic reactions only 0.002% of circulating antibody monomer
63
the antibody molecule links the...
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
antibody mediated activation of phagocytosis
microbe antibody Fc receptors cross linking trigger phagocytosis
65
primary immune response
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
secondary immune response
subsequent encounter with the same organism T and B memory lymphocytes enable much faster and stronger protection
67
viral infection innate
infection induced ligand for NK activating receptor natural killer cell (killer activating receptor mediated cytotoxicity)
68
viral infection innate and acquired
viral protein on cell surface recognised Ab and FcR receptors natural killer cells ADCC
69
viral infection acquired
cytotoxic T cell that recognises foreign peptide sequence MCH I and TCR receptors specific T cell cytotoxicity
70
cytotoxic granule dependent killing of...
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

MEDICAL BIO (17 decks)

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