lecture 13 Flashcards

(41 cards)

1
Q

how does blood enter the lymphatic system

A

1) it must leave the blood vessels, leave the endothelial wall and move into the tissue to become interstitial fluid
2) this is how we see swelling during injury
3) eventually it is pushed from the tissue into lymphatic vessels where it becomes lymph
4) the thoracic duct then returns the lymph to the cardiovascular system

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2
Q

what are the antigens delivered to the lymph nodes

A

non-self (from infection) and self (your own cell debris)

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3
Q

can our lymph nodes be infected

A

yes - in a bad infection, living pathogens can enter the lymphatic system and infect

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4
Q

describe what happens with lymphatic vessels as infection gets worse and worse

A

1) as infection spreads through layers of tissue, it reaches blood vessels
2) this triggers local activation of the blood vessels
3) increased vascular permeability allows plasma to leak out into the tissue, raising interstitial fluid volume
4) also enables the recruitment of blood-borne neutrophils and monocytes/macrophages
5) resulting swelling pushes material from the tissue into the lymphatic vessels

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5
Q

what happens to your lymph node during an infection

A

they grow in size and can become painful

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6
Q

how does swelling during infection help

A

pushes antigens, cellular debris, immune cells and plasma into the draining lymphatic vessels

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7
Q

describe how lymph enters a lymph node

A

1) swelling pushes material from the tissue into the lymphatic vessels
2) these lead directly to lymph nodes
3) lymph nodes have afferent (enter) and efferent (exit) tubes going into them

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8
Q

are t-cells specific

A

yes: each t-cell has a unique t-cell receptor, so a single t-cell can only recognise one antigen

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9
Q

what are t-cells activated by

A

only antigen presenting cells

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10
Q

how are b-cells activated

A

they can recognise antigens as free proteins

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11
Q

where are b-cells and t-cells found

A

lymph nodes:
- b-cells: outer areas of lymph nodes
- t-cells: inner areas of lymph nodes

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12
Q

are t-cells and b-cells together or separated

A

separated, but at some point they must come together

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13
Q

what are b-cell antigens usually

A

full length proteins that fit into its receptor

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14
Q

describe the process of lymph flow through a lymph node with regards to b-cell activation

A

1) lymph moves through the sinus region of the lymph node
2) the lymph goes through smaller and smaller conduits (vessels)
3) some of the lymph percolates through the b-cell zone
4) when the correct antigen arrives, the corresponding b-cell is activated

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15
Q

describe how a b-cell is activated through an antigen

A

1) the b-cell “grabs onto” its antigen with its receptor, which activates a signal transduction through the receptor
2) then, the BCR is endocytosed
3) the antigen that was a full-length protein is cleaved into small fragments and packaged into vesicles inside the cell
5) the b-cell presents the small fragments on its surface via MHC class II molecules
6) the b-cell moves towards in the inner areas of the lymph node so it can reach a t-cell to present the antigen to
7) the t-cell receptor, too, is specific to the antigen fragment and recognises the peptide-MHC II complex
8) once the t-cell recognises the fragment, it produces cytokines that trigger the proliferation of that b-cell

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16
Q

how do b-cells and t-cells know where to go/find each other

A

signals by chemokines in the lymph node, laid out by other cells

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17
Q

what do CD40 receptors do

A
  • on the activated helper t-cell binds CD40 on the b-cell
  • this is the critical co-stimulatory signal necessary for b-cell activation
18
Q

what do cytokine receptors do

A
  • t-cell secretes cytokines which bind cytokine receptors on the b-cell
  • these drive proliferation and influence what antibody class the b-cell will eventually produce
19
Q

what are the types of t-cells

A
  • CD4: Tfh cells aka helper cells that coordinate the immune response by activating other cells
  • CD8: cytotoxic t-cells that directly destroy infected cells
20
Q

what is linked recognition

A

process where b-cells and T-helper cells recognize different parts of the same antigen to activate a high-affinity antibody response

21
Q

what does linked recognition occur for

A

thymus-dependent antigens: antigens that are typically soluble proteins and require cooperation between b-cells and t-helper cells

22
Q

what happens after the t-cell and b-cell have interacted

A

the b-cell is “told” it needs to migrate back to the follicular (outer) area of the lymph node, where it becomes a germinal centre

23
Q

what happens at the germinal centre

A

the b-cell, after interacting with the t-cell, undergoes proliferation to finally produce antibodies specific to the antigen

24
Q

what happen without linked recogntion

A
  • not enough b-cell proliferation
  • no long-term memory populations of b-cells
  • small amount of antibodies produced
25
what is the product of linked recognition
plasma cells and memory cells
26
what are plasma cells
b-cell proliferate then differentiate into plasma cells which are mass-antibody secreting cells
27
what is the primary immune response
- what happens the first time your immune system encounters a specific antigen - slow as naive cells are rare and need time to find antigen, activate, and expand
28
what is the secondary immune response
- happens when you encounter the same antigen again after already having memory cells from the primary response - much faster, much stronger because memory cells are abundant and don't need the slow naive activation process
29
what happens to antibody production in the primary immune response
it slowly rises, peaks, then comes back down after infection is over
30
describe the structure of an antibody
- heavy chains and light chains held together by the hinge region - Fc region - complement-binding region
31
what drives phagocytosis with regards to antibody structure
when the Fc receptor on neutrophils, macrophages and natural killer cells bind to the Fc region of antibodies opsonising a bacteria
32
what gives an antibody its specificity to an antigen
the hyper-variable regions on the heavy and light chains which give the antibody binding site its 3d shape
33
what is valency with regards to antibodies
how many antigen binding sites an antibody has, i.e. how many (of the same) antigens it can grab onto at once
34
what are the functions of antibodies
- neutralisation of specific molecular interactions - enhance phagocytosis - cause complement-mediated cytolysis - drive ADCC
35
describe the process of *direct* neutralisation
1) antibody binds to antigen on the surface of the virus 2) it gets in the way of the virus's receptor and its target on the host cell 3) this prevents the molecular interaction
36
describe the process of neutralisation of soluble factors
deals with soluble molecules, e.g. secreted by a pathogen 1) antibody binds to the secreted antigen 2) thus it inhibits its function by preventing it from interacting with its target on the host cell
37
what enables neutralisation by antibodies
they effectively block pathogen-host interactions due to their large size
38
in what cases does neutralisation not work
if the antibody can't bind the target, e.g. the target is inside the cell
39
describe antibody opsonisation
1) antibody coats the surface of the bacteria, with its Fc region sticking outwards 2) any cell with the corresponding Fc receptor will find and bind to the antibody 3) neutrophils, macrophages etc can bind to it and phagocytose it 4) OR natural killer cells will bind then inject an enzyme that will kill it
40
in what cases does opsonisation not work
if the antigen is inside the bacteria as the antigen would be unable to bind it
41
describe complement-dependent cytotoxicity
1) antibody binds surface antigen 2) this can trigger the classical complement pathway: 3) complement proteins are deposited on the bacterium, leading to the membrane attack complex (MAC) 4) the MAC punches holes in the bacterial membrane, causing cell lysis then death