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MICB 202 > Chapter 11 -I > Flashcards

Chapter 11 -I Flashcards

1
Q

Immune Response to pathogens

A

For a successful adaptive immune response 2 key events must occurs

  1. Innate immune response must sense danger - dendritic cells recruited to the sire of infection, mature and move into lymph node
    - Innate immune system must sense danger and activate
  2. TH cells must be activated - a dendritic cell must present a peptide complexed with MHC class 2 protein to the TH cell
    - Innate immune system must activate adaptive immune system
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2
Q

Extracellular bacterial Infections

A

Appropriate response: Antibody response

Goals of Antibody Response: 
depending on the class of antibodies they can:
- Neutralize
- Opsonize
- Activate complement to 
  MAC and kill bacteria

Main cell types involved:

  • B cells to synthesize and secrete antibody
  • TH cells to provide signals 2 and 3 to B cells to fully activate them
  • Dendritic cells to activate TH cells
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3
Q

Once infected

A
  • adaptive immune response starts at the nearest lymph node

- innate response starts at site of injury

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4
Q

The Immune response to infection

A
  1. pathogen enters the body
  2. innate responses: pathogen overwhelms innate response, immature dendritic cell engulfs bacteria- senses danger
  3. dendritic cells mature and moves to the lymph node
  4. Activation of TH cells by dendritic cells
  5. at the same times pathogen binds to BCR of B cells
  6. Interaction of B cell with TH cell
  7. Proliferation and differentiation of B cell
  8. Secretion of antibody into body fluids
  9. antibody function
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5
Q

Early Innate Response

A

starts within a few minutes

Mast cells release histamine causing vasodilation

Activation of complement via alternative complement activation

phagocytosis of bacteria by resident macrophages

a bit later, the production of alarm cytokines by resident macrophages to start the induced innate response

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6
Q

Immediate Innate response: complement

A

Complement component C3 is always spontaneously breaking down to C3a and C3b

The alternative complement pathway is activated as a result of the binding of c3b to the pathogen surface

Formation of the C3 convertase is followed by the formation of C5 convertase and ultimately to the formation of MAC

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7
Q

Immediate Innate Response: Mast cells

A

Mast cells are found in mucosal and epithelial tissue, and in the connective tissues below the epithelium

Mast cells express receptors for complement fragmentsC3a and C5a
(c3a and c5a bind to mast cells)

When complement receptors are engages, histamine and other inflammatory mediators are released (degranulise)

together these act to increase vascular permeability, increase fluid accumulation in tissue

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8
Q

Immediate Innate Response: Phagocytosis

A

Opsonic receptors recognize pathogens indirectly - they bind to complement fragments of IgG that is bound to the pathogen
- eg receptors that identify host-derived proteins on phagocytic cells

Non-opsonic receptors identify distinct molecular patterns to induce phagocytosis include:
- C types lectins, scavenger receptors (proteins that recognize a variety of negatively charged microbial ligands)

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9
Q

Induced Innate Response

A
  • Start within a few hours

Recruitment of neutrophils, monocytes, and dendritic cells to the site of infection

Phagocytosis of bacteria by newly arrived neutrophils

Maturation of newly arrived monocytes into macrophages

Phagocytosis of bacteria by macrophages and dendritic cells

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10
Q

Induced phase of the innate response

A

The pro-inflammatory cytokines (IL-Ib, IL -6, TNF-a)
produced by resident macrophages act on the endothelial cells of the blood vessels

leukotrienes help recruit neutrophils, promote cytokine production

Prostaglandins have various functions (eg vasodilation)
- NSAIDs prevent prostaglandin production

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11
Q

The Inflammatory response

A

Histamine released by resident mast cells result in vasodilation

cytokines released by resident macrophages cause changes in the blood vessel wall that allows neutrophils and monocytes to slow down, stop and be recruited to the site of infection

Presence of bacteria and chemokine IL-8 act as chemoattractants

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12
Q

Dendritic Cells - link between innate and adaptive immune response

A

Dendritic cells are in the tissue constantly sampling what is in its local environment

If dendritic cell phagocytoses pathogens, TLR signaling imitates its maturation pathways

Cytokines from other innate immune cells may also drive the dendritic cells towards the maturation pathway

The dendritic cells start to migrate towards the lymphatic vessels and into the lymphoid vessel

it will then begin to migrate to the nearest lymph node where they meet naive T cells to activate them

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13
Q

Dendritic cells

A

All dendritic cells move to the lymph node, it digests pathogen

It uses the exogenous pathway to display a peptide on the MHC class 2 protein

The ingested bacterium is digested in a phagolysosome, and peptides derived from it are loaded on MHC 2

Results in a dendritic cell displaying MHC class 2 and migrate to lymph node to find the T cell

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14
Q

Dendritic cells activate naive tH cells

A

At the lymph node, the dendritic cell finds a naive TH cell to activate

Signal 1 - TCR complex of mature naive t cell binds to MHC class 2 foreign peptide complex on the dendritic cell, CD4 strengthens this bonds and CD3 delivers a signal to the nucleus

Signal 2 - involves binding of CD28 of T cell to B7 of the dendritic cell

Signal 3 -T cell makes and secretes IL-2 for itself. IL2 binds to IL2R on itself
the dendritic cell provides other cytokines for signal 3

Meanwhile:
bacteria in the tissue are pushed into the lymph fluid and are carried away to the nearest lymph node where they encounter B cells

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15
Q

Lymphatic

A

Flow of lymph fluid towards lymph node

the lymph vessel drain into the thoracic duct near the heat, returning fluid to the blood circulatory system

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16
Q

B cell Activation - I

A

In the lymph nodes, the bacterium encounters a B Cell that has. BCR that is complementary to a structure on the bacterium - it is recognized by B cell

Signal 1 - mature naive B cells bind the bacterium by its BCR, Iga/Igb relays a signal to the nucleus

THe BCR may be a IgM type of IgD type on the B cell
the different classes of mIg have the same antigen specificity

The BCR-Ag complex is brought into cell as an endosome to be digested

  • Lysosome fuses with the endosome containing the BCR - Ag complex to form the endolysosome
  • the bacterium is digested to form peptide fragments
  • peptide fragments from the bacterium are loaded onto MHC class 2 - and the new MHC class 1 - peptide complex is displayed on the surface
17
Q

B cell Activation - II

A

The partially activated B cell seeks a previously activated TH cell ( activated by same pathogen)

Signal 2 is the binding of CD40 on the B cell to CD40L on the T cell

The TH cells knows that it has to help this particular B cell because of the peptide being displayed on MHC class2 proteins

Signal 3 TH cells secrete cytokines that help support N cell division and differentiation into effect cell : Plasma cells or memory B cells

(plasma cells secrete antibodies)

18
Q

B cell activation in lymph node

A

Naive B cells are activated by the intact antigen that is transported into the follicle (B area ) of the lymph node

After activation, the B cells and the CD4 T cells migrate towards the edge of the follicle where they interact with each other forming cognate pairs

19
Q

How do the antigen activated B cells and CD4 TH cells know that they are meant for each other

A

B cells and CD4 cells know they are meant for each other because they present the same linear epitope in the same MHC class 2 peptide that the dendritic cell had when it activated TH cell (same antigen used)

20
Q

B cell activation

A

TH helper cell secretes cytokines that help support B cell division and differentiation into effector cells called plasma B cells or memory B cells

The secreted antibody lasts a few months

some plasma cells live a few months while memory B cells are long lived

is plasma migrate back to the bone marrow they become long lived plasma cells

21
Q

Immune response to pathogens

A

the antibodies secreted by B cells enter body fluids seeking out bacteria

Neutralization
IgM, IgG, IgA

Opsonization -
IgG

Complement activation - IgM, IgG

22
Q

Antibody response to Infection

A

Primary antibody response takes 7-10 days to fully develop
- most of the lag time is accounted fro by the changes in gene expression and proliferation of the naiver TH cells and Naive B cells

the proliferation of TH cells and B cells may cause swelling n lymph nodes

IgM wll be main antibody produced early in the response by short lived plasma cells

IgG may be produced late in the response by long lived plasma cells

23
Q

Immune response to Infection

A

When the pathogen is eliminated, the effector TH cells die, as do the short-lived plasma cells

The Member TH and memory B cells remain

Antibodies remain in circulation for ~ 6 months

Memory B cells may have class-switched before developing into memory cells, or they may class switch at the time of re-activation
- these cells are expected to secrete IgG or IgA antibodies (depending on the instruction from TH cells)

the secondary response takes only 2-3 days to develop
- memory cells are much easier to activate than naive

24
Q

Clonal Expansion - T cells

A

Proliferation of CD4 TH cells are B cells are impressive

the expansion of antigen-specific clones result from proliferation converts small pools of naive antigen specific lymphocytes into large numbers of cell required to eliminate the antigen

Before antigen is exposed, the frequency of naive T cells specific for any antigen is 1 in 10^5 -10^6 lymphocytes
this is why they need to constantly migrate trhoguh the lymph node - to increase chance at being activated by antigen

many of the progeny of the antigen stimulated T cells differentiate into effector cells: others differentiate into memory

25
Q

Clonal Expansion - b cells

A

The activation of B cells by antigen results in their proliferation and differentiation into antibody-secreting plasma cells and memory cells

MICB 202 (19 decks)

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