Adaptive Immune system Pt 2: Oct 30 Flashcards

1
Q

what are APCs?

A

antigen presenting cells

  • degrade pathogens and their components and produce many small peptides (epitopes) fro the adaptive immune response
  • attach the peptides to the MHC receptors
  • the MCH + antigen fragments are then ttransproted to and displaed on the APC memrane for presentation
  • leftover fragments are expelled by exocytosis

**antigens must eb rpocessed to epitopes for recognition by MHC

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2
Q

describe what the processing and presentation means of antigens by APCs on MHC class I and II

A
  • MHC class I presenting self-peptides signals a healthy host :)
  • MHC class I presenting non self peptides = :(

*tags the presenign host cell for destruction by T cytotoxic cells

  • MHC class II presenting processed extracellular‘non-self’ antigens

*activation of Humoral adaptive immune responses - B cell activation and antibody prodution

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3
Q

What are T cells? what are the two borad groups?

A

T cells serve as a link between humoral immunity and cell mediated immunity

  • they develop in the thymus and contain T cell receptors (TCRs) and other surface antigens different from those of B cells
  • Mature T cells can be divided into two broad groups: helper T cells and cytotoxic T cells
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4
Q

compare Th cells and Tc cells

A

Helper T cells

  • Display the surfce antigens TCR & CD4
  • secrete cytokines which activate B cells and other T cells
  • associate with MHC class II proteins on APCs

Cytotoxic T cells

  • Display the surface antigens TCR & CD8
  • destroy infected host cells and the intracellular pathogens (within the host cell)
  • Associate with MHC Class I on APCs

**CD =cluster of differentiation

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5
Q

describe the effector functions of Th and Tc cells

A
  • both types of T cells mature int he thymus sot hat they do not recognize self-antigens too strongle

*they are tested ebfore they leave if cells bind too tightly to self peptide then they are destroyed

  • TH are traiend to memorize databanks of antigens and to alert B cells if circulating antigen is detected

*TH cells are like the detectives

  • Tc cells are trained to seek and destroy cells presenting harmful antigens on MHCI (indicating they may be infected)

*Tc are like the soldiers

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6
Q

what is TCR

describe the strcture

A

T cell receptor present on all T cells

  • complex composed of two transmmebrane antigen recognizing & binding peptides (alpha and beta) conencted by a disulphide bond)
  • assocaited with CD3 accessory molecules (not antigen binding)
  • each alpha and Beta peptide has a constant and variable region

*variable regions of BOTH peptides forms the eptiope-recognition binding pocket

  • TCR complex transduces signal itno the cell triggering T cell activation and proliferation
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7
Q

what are the different types of helper T cells

A
  • Naive or TH0 = precursor that can differentiate into effector and memory types but also regualtory (does nto promote imune resposne)

TH cells determine which cytokines will aloow the immune system to be most useful for the host during infection

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8
Q

what are teh different effector TH types the naive T cells can differentiate into

A
  • on activation, TH cells differentiate into one of 3 antigen-specific effector types TH1, TH2 and TH17

TH1: most active against intracellular bacteria and protozoa; activate Tc and phagocytes

TH2: activates humoral responses; most active against helminthi infections

TH17: important for defense agaonst chronic mucosal infections

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9
Q

what are memory TH cells

A
  • naive TH cells can differetnate into memory TH cells
  • retain antigen affinity of the originally activated T cell
  • used to act as a later effector cell during reinfection
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10
Q

what are regualtory TH cells

A
  • naive T cells can also differentiate into regulatory T cells
  • do not promote immune response but help to restore homeostasis after infection
  • lack of Treg cells is assocated with chronic inflammation
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11
Q

how are immune responses initiated?

A
  • Humoral immune responses start when an antigen triggers the differentiation of a B cell itno a plasma cell

*plasma cells are antibody producting factories

  • Cell mediated responses start when certain types of T cells become activated by antigen presented to them

*for a T cell to recognize an antigen it must be on MHC Class I or MHC class II

  • soem types of T cells can directly kill an infected cell, these are those that recognize MHC I, wehn activated they produce cytokines that attract to &strongly initiate macrophage activation at site of infection
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12
Q

Describe activation of a naive TH0 cell by APC presenting antigen in context of MHC class II

A

note train of thought: Cell mediated immunity, naive (hasn’t gone through selection yet to see if binds too tightly or intermediate), Tx think T helper cell so has role in activation of other things, APC think macrophage, MCH II binds to CD4

  • TH0 binds to MHC II on APCs
  • binding of an epitope to MHC needs to be strong for the TCR to recognize it properly
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13
Q

what does a T cell need to be activated

A
  1. TCR recognizes the specific foreign epitope+ MHC II
  2. CD4 must also engage MHC at a specific site
  3. Secretion fo cytokines form activates APCs and TH cells
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14
Q

activation of cytotoxic cells

A
  • TCR bidns MHC I present on all nucelated cells
  • if TCR recognizes and binds [epitope + MHC I] & CD* binds MHC I, then - cell is infected and must be destroyed by apoptosis, Tc sectretes perforin which forms pores in target ecll membrane, also secretes toxic granzymes that enter cell vai perform formed pores

*general recall - cytotoxic T cells can kill infected cell, part of cell mediated immunity, have CD8 to recognize MHC I

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15
Q

what are super antigens?

A
  • stimulare T cells be directly linking TCR with MHC on an APC without undergoing rpocessing and presentation on MHC

*bind to the outer surfaces of MHC and TCR by crosslinking/bridging the receptors and activvating T cells

-normal antigens are processed by APCs and resulting small peptides are palced in the antigen binding pocket of MHC class I or class II for presentation

*each diff peptide is recognized by 1-100 t cells/mollion

  • superantigens bypass the process - not presented on MHC so activation is not antigen specific

*activate large numbers of T cells causing massive release of cytokines resulting in a ‘cytokine storm’

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16
Q

maturation of B cells

A
  • B cells mature in bone marrow they express antigen binding receptors

*B cell antigen receptor is a membrane bound IgD or IgM monomer

  • immature B cells with functional receptors undergo Negative selection - elimination of cells whose receptors recognize self antigens
  • Naive mative B cells travel from bone marrow to the spleen and lymph nodes

*each B cell circulating in body or in lymphoid organ is programmed to synthesize antibodies that react with a single epitope

17
Q

explain the process of B cell differentiation

A
  • rpocess called clonal selection
  • an invading antigen will select which B-cell clone will proliferate to large numbers
  • all receptors on a single B cell recognize ONE specific epitope
  • when a B cell contacts its antigen, it is stimulated to proliferate and differentiate into plasma cells (which secrete antibodies) and memory cells
18
Q

Primary vs secondary antibody response

A

primary response

  • is induced after first time exposure to antigen via disease or vaccination
  • antibodies appear in seum after secreal days - response is short duration
  • B cells that bind antigen make IgM antibodies initially and later switch to IgG

*Isotope switching - IgG have higher affinity, opsonize and enter tissues

*some B cells become memory cells

Secondary Antibody response

  • Via seocnd exposure to pathogen to Ag booster dose
  • activation of memory B cells, antibodies appear within hours
  • get much bigger response, mostly IgG and longer duration
19
Q

how do we learn not to induce immune responses to self antigens or to antigens of our beneficial microbiota

A
  • Due to B cella dn T cell tolerance BUT antigen dose is also importnat
  • above a certain threshold value, B and T cells can be overstimulated
  • B cells fail to respond to re-exposure to antigens and fail to make antibodies
  • T cells fail to respond to the Antigen

*T cells are trained in thymus not to respond strongly to self antigens - selcted for lack of sensitivity to self antigens

20
Q

how does vaccination niduce immunity without disease

A
  • if you know what antigens fo a given pathogen are immunogenic can instil that nantigen into people who havent been espoed to stimualte a specific response
  • Vaccination uses cellular (killed/inactivated pathogens, live attenuated pathogens) or a cellular toxoid, engineered &/or subunit) antigen sources to induce an immune response without causing disease
  • immunological specificity is important
  • an antibody is amde to one epitope will not bind to another unless very similar

*if antigen MW <1000 (hapten) need to bind to a carrier protein first

  • B cells are long lived and so immunity through vaccination can last for many years
  • rpoduce neutralizing antibodies
21
Q

what are the 4 classificaions of immunity

A
  • Passive natural acquried (aquired trhough brest milk/ placenta

passive artificially aquired (gained through antibodes harvested from another perosn or animal)

  • Active naturally aquired (immunity gained trhough illness and recoery)
  • Active artificially acquired (through vaccine)

* passive immunity is short lived and active immunity is long lived