5. Adaptive immunity Flashcards

1
Q

What activates the adaptive immune response?

A

Antigen presenting cells which capture, process and present pathogen/tumour antigen to T cells.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Where are APCs usually located in the body?

A

Strategically located at pathogenic portals of entry:

  1. skin (SALT)
  2. mucosal membranes (GALT, NALT, BALT, GUALT)
  3. lymphoid organs (lymph nodes, spleen) - better organised to maximise interaction between APCs and B/T cells
  4. blood (plasmacytoid and myeloid DCs)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Name the 2 processes by which APCs capture pathogens.

A
  1. phagocytosis

2. macropinocytosis (soluble particles)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Which type of AI will be stimulated by APC recognition of extracellular vs intracellular pathogens?

A

Extracellular path. recognition stimulates humoral immunity:

  • antibodies
  • complement
  • phagocytosis

Intracellular path. recognition stimulates cell-dependent immunity:

  • cytotoxic T lymphocytes
  • antibodies
  • macrophages
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Which APC type present to naïve T cells and where are these found?

A
  1. dendritic cells (mucous membranes, lymph nodes, blood)

2. Langerhans’ cells (skin epithelium)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Which APC type present to effector T cells and where are these found?

A
  1. macrophages (various tissues)

2. B cells (lymphoid tissues)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Why do macrophages present Ag to effector T cells?

A

required for proper phagocytosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Why do B cells present Ag to effector T cells?

A

required for antibody production

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Which cell surface molecule presents processed Ag to T cells?

A

MHC molecules - via peptide binding cleft

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are the 3 differences between Class I and Class II MHC molecules?

A

Class I

  • found on all nucleated cells (inc. APCs)
  • present peptides from intracellular pathogens
  • recognised by CD8+ T cells

Class II

  • found on DCs, macrophages and B cells (i.e. APCs)
  • present peptides from extracellular pathogens
  • recognised by CD4+ T cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Name the chromosome and genes encoding MHC molecules.

A

HLA (Human Leukocyte Antigen) genes on chromo. 6:

  • Class I = HLA-A, HLA-B and HLA-C
  • Class II = HLA-DR, HLA-DQ and HLA-DP
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Which 2 processes enhance MHC molecule diversity?

A
  1. co-dominant expression: both parental genes are expressed, increasing no. of different MHC molecules
  2. polymorphic genes: different alleles in different individuals - increases presentation of different Ag in a pop.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are the 2 different antigen processing pathways?

A
  1. endogenous (all cells)

2. exogenous (APCs)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Describe the endogenous Ag processing pathway.

A

i) all viral/tumour Ag and self-Ag are tagged by ubiquitin and degraded by immunoproteasome
ii) peptides transported into ER via TAP1 & 2 (Transporter associated with Antigen Processing) and loaded onto matching MHC-I molecule
iii) MHC-I-Ag complex transported to membrane via vesicle and activates CD8+ T cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Describe the exogenous Ag processing pathway.

A

i) exogenous Ag engulfed into vesicle and degraded by endolysosomal enzymes into peptides
ii) endosome fuses with exocytic vesicle which already contains MHC-II molecules and peptides bind to appropriate MHC-II groove by displacing CLIP
iii) MHC-II-Ag complex transported to membrane and activates CD4+ T cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Why do T cells not respond to self-Ag?

A

trained not to react during development

17
Q

What is the difference between elite controller and rapid progressor HIV patients?

A

Elite controllers/long-term non-progressors: possess HLA genes encoding MHC molecules that present peptides key for virus survival (cannot be mutated)… effective CTL response… normal CD4 T cell count and low viral load

Rapid progressors: low diversity in HLA genes and encode MHC molecules that present less critical peptides that can be mutated… poor T cell recognition… poor CTL response

18
Q

What causes graft vs host reaction?

A

HLA molecule mismatch between donor and recipient… organ transplant reaction

19
Q

Name 2 autoimmune diseases associated with HLA type.

A
  1. insulin-dependent diabetes mellitus

2. ankylosing spondylitis

20
Q

Where do T cells mature?

A

thymus

21
Q

What is the Ag receptor on T cells and how is diversity in this generated?

A

T cell receptor - recognises MHC-Ag complex

via gene rearrangement

22
Q

Which co-receptors are required by T cells for MHC recognition?

A

CD3: involved in signal transduction (all T cells)

CD4: MHC-II recognition/signal transduction (TH cells and Treg cells)
CD8: MHC-I recognition/signal transduction (CTLs)

23
Q

Describe the activation of CD4+ TH cells by APCs.

A

i) MHC-Ag complex on APC recognised by TCR and CD4 on naïve TH cell (TH0)
ii) TH cell matures, enhancing activation, but full activation also requires co-stimulatory signals:
- interaction between CD80/86 on APC and CD28 on TH cell
- cytokine release from APC

24
Q

Which 2 cell types can TH0 give rise to according to pathogen type?

A
  • TH2 or TH17 if extracellular path.

- TH1 if intracellular path.

25
Q

Which T cells will be activated in response to extracellular paths.? How will these act?

A

APC activates CD4+ TH2 cells and CD4+ TH17 cells.

TH2 acts to:

1) activate eosinophils via IL-5 release… killing of parasites
2) activate B cells via IL-4 release… B cells undergo isotype switching… produce Ab… phagocytosis and complement
3) activate mast cells via IL-4 release… local inflammation and allergies (IgE)

TH17 cells release IL-17… activates neutrophils… phagocytosis

26
Q

Which T cells will be activated in response to intracellular paths.? How will these act?

A

APC activates CD4 TH1 cells and CD8 cells.

TH1 acts to:

1) activate B cells via IFNy… B cells undergo isotype switching… produce IgG2-3… pathogen opsonisation, etc.
2) activate macrophages via IFNy… phagocytic activities… kill opsonised paths.
3) completes activation of CD8 CTLs

Activated CD8+ cell matures into CTL… binds via TCR to MHC-I-Ag on infected cells (so no bystander effect)… releases perforin - creates pores in infected cell membrane, and granzymes - enter infected cell and activate apoptosis.

27
Q

What is the role of the different Ab?

A

IgM: complement activation

IgG:

  • Fc-dependent phagocytosis
  • complement activation
  • toxin/virus neutralisation
  • neonatal immunity (placental transfer)

IgA:

  • mucosal immunity
  • breast milk

IgE:

  • immunity against helminths
  • mast cell degranulation (allergies)
28
Q

A high IgG:IgM indicates what kind of Ab response?

A

secondary resp.

29
Q

What is the difference between the primary and secondary Ab resp.?

A

Primary

  • 1st exposure to Ag
  • rapid IgM production - less specific

Secondary

  • subsequent exposure
  • faster and longer
  • stronger due to higher Ig affinity caused by isotype switching to IgG