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Defence > S1: Adaptive Immunity II > Flashcards

S1: Adaptive Immunity II Flashcards

1
Q

What are the characteristics of the innate immune system?

A
  • You are born with it (natural/native immunity)
    • In place before infection, it is the first line of defence
    • It is a rapid response (immediate, maximum response in hours)
    • Limited recognition capacity (less than 1000 structures)
  • Responds in the same way to repeated infections
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2
Q

What type of cells does the innate immune system use?

A

Phagocytes and Natural Killer Cells

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3
Q

What type of cells does the adaptive immune system use?

A

T and B lymphocytes

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4
Q

What are the characteristics of the adaptive immune system?

A
  • Triggered by exposure to microbes (acquired)
    • There is a lag time (exposure to max response takes a number of days)
    • It combats pathogens that evade/overwhelm the innate immune system
    • It is more efficient at eliminating infections
    • It has extremely high specificity, above 107 structures
    • It remembers pathogens
  • It becomes faster with each repeated exposure
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5
Q

What cells link the 2 immune systems together?

A

Dendritic cells (antigen presenting cells) link the two immune system together

Innate: barriers, cells, complement
Adaptive: Cellular immunity (T-lymphocytes), Humoural immunity (B-lymphocytes ->antibodies)

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6
Q

What is T cell mediated adaptive immune responses also called?

A

Cell mediated immunity

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7
Q

Name the 2 T cells

A

CD4+ Th (helper cells)

CD8+ (cytotoxic) T cells

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8
Q

Describe T helper cells

A

They express CD4

They activate macrophages and help B cells to produce antibodies

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9
Q

Describe cytotoxic T cells

A

They express CD8

They kill cells that are infected with microbes and kill tumour cells

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10
Q

Describe Treg cells

A

They inhibit function of other T cells and control the immune response (prevent excessive immune response)

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11
Q

What is the B cells main function?

A

Main function is to product antibodies

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12
Q

Describe the 3 highest conc of Ig in serum

A

IgG, then IgA, then IgM

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13
Q

What are the two forms antibodies can be found in?

A
  1. Membrane bound Ig on the B cell surface (antigen receptor)
    2, Secreted form (circulation, tissues, mucosa)
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14
Q

How does Ig on B cell membrane act as an antigen receptor?

A

Membrane bound Ig have a specific shape and will bind to its complementary antigen. There will then be B cell activation which forms a plasma cell that produces secreted Ig.

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15
Q

Where are T cell receptors (TCR) found?

What do they do?

A

On the surface of T cells

They can distinguish antigens of different microbes and antigens on the same microbe.

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16
Q

Why can TCR lead to autoimmune diseases?

A

Cells have to generate so many T cell receptor structures so by chance there may be synthesis of receptors/antibodies against own cell structures. Non self discrimination can fail leading to autoimmune diseases.

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17
Q

What is the difference in B cells and T cells in recognising antigens?

A

B cells can recognise antigens directly (soluble or cell bound)

T cells need the antigen to be processed and combined with other molecules and presented by antigen presenting cells - APC (e.g. macrophages, dendritic cells)
A activated B cell can also becomes a APC

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18
Q

What can antigens be made out of?

A

Proteins
Polysaccharides
Nucleic Acids

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19
Q

Antibodies bind to portions of the antigen (as antibodies are small) - These portions are called epitope

What are the 2 types of epitopes?

A
  1. Linear epitopes where there are adjacent amino acid residues
  2. Conformational epitopes are made of non-sequential amino acid residues spatially placed in the folded protein
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20
Q

How do antibodies work?

A
  • Bind to extracellular microbes and toxins
  • Neutralise microbes (prevent virus binding to receptor on cell, blocking entry of effects of antigen on cell)
  • They also eliminate microbes through opsonisation (increases phagocytosis)
  • Complement activation (increase opsonisation and can cause lysis of microbe)
21
Q

What is cell mediated immunity designed to fight?

A

Intracellular microbes

These could be intracellular bacteria in the phagosomes of phagocytes that have failed to be destroyed or viruses in the cytoplasm of cells

The main effectors of these are T cells

22
Q

What is MHC restriction of antigen recognition by T cells?

A

Most T cells recognise peptides and antigens that are membrane bound (not in soluble form). The peptides from the foreign antigen will only be recognised when bound to MHC.

23
Q

How does MHC present antigen to T cells?

A

When microbe (antigen ) is broken down in
phagolysosome to peptides, these peptides are combined with MHC and expressed on the surface.
T cells then recognise the antigen processed and presented by APCs

24
Q

What are the two types of MHC?

A

MHC I

  • Recognised by CD8+ T cells
  • Expressed on all nucleated cells

MHC II

  • Recognised by CD4+ T cells
  • Expressed on antigen presenting cells (dendritic cells and macrophages)
25
Q

How does the T cell recognise MHC and peptide?

A

TCR recognises residues from the MHC and residues from the peptide.

The MHC-peptide complex binds to the variable region

26
Q

Explain the T cell receptor structure?

A
  • Made up of alpha and beta chain
  • Variable domain (at top)
  • Constant domain (at bottom)
  • Transmembrane portion
  • Cytosolic portion
27
Q

What does MHC stand for?

A

Major histocompatibility complex

28
Q

Describe structure of MHC class I

A

Made of alpha chain and beta 2 microglobulin
- Presentation of peptide to CD8 T cells (MHC II is found in all nucleated cells as all cells can be infected by virus or turn cancerous)

29
Q

Describe structure of MHC class II

A

Alpha and beta chains

- Presentation of peptides to CD4+ T cell

30
Q

Describe dendritic cells

A
  • Main antigen presenting cells
  • They are sentinel cells found in the skin, mucosa, tissue
  • They capture microbes through phagocytosis and then process pathogens and present the antigens to T cells
31
Q

What does MHC hold if no infection is present?

A

MHC is unstable if it isn’t bound to any peptide.

If no infection is present, MHC will just hold self peptides and T cells will not do anything (no immune response). This protein is called the invariant chain which sits in the groove between chains and stabilises it.

32
Q

Explain the signals needed to activate T cells

A

Signal 1: Antigen recognition
MHC presents the antigen to the TCR and if they match this is signal 1

Signal 2: In the case of naiive T cells that haven’t encountered to antigen before, they need a second signal to be activated (costimulation though co-stimulatory molecules –> CD80/CD86 interacting with CD28)

Signal 3: Cytokines

33
Q

How does CD4 and CD8 molecules help with T cell activation

A

They lower the threshold for activation of T cells by interacting with MHC II and MHC I respectively

34
Q

Describe the whole process leading up to CD4+ T cells recognising peptides bound to MHC II

A
  • Uptake of pathogen into a phagosome which fuses to form a phagolysosome (in phagocyte - all APC)
  • Proteins are chopped up and peptides generated from the bacteria
  • Vesicles containing the bacterial peptides travel around until they meet vesicles containing MHC molecules
  • MHC is generated in the ER and is transported in exocytic vesicles to the membrane. If phagocyte contains bacteria peptides in vesicles, the two will meet and if complementary, the pathogen peptide displaces the invariant chain and sits in the groove.
  • The peptide-MHC complex is then presented on the cell surface
35
Q

Describe the whole process leading up to CD8+ T cells recognising peptides bound to MHC I

A
  • The cell has to have a nucleus but doesn’t have to be a APC
  • The virus enters the cell and is free in to cytosol
  • The virus will start to replicate their viral proteins so these viral proteins will be in the cytosol
  • The viral proteins undergo ubiquination (gets tagged with ubiquitin)
  • This targets it to be degraded by a proteasome which chops up the viral protein into peptides which enter into the cytosol
  • The peptides get transported into the ER and are made into smaller peices where they fit into the shape of the groove in MHC I
  • The MHC I - viral peptide molecule is then transported to the membrane and presented on the surface to be recognised by CD8+ T cells
36
Q

List all the T cells involved with cell-mediated immunity

A

Th1 (CD4+): Help phagocytes to kill ingested microbes
Th2 (CD4+): Help eosinophils/mast cells to kill helminths
Th17 (CD4+): role in defense against bacteria & fungi
CTL (CD8+): Kill cells with microbes in the cytosol

Regulatory T cells (CD4+CD25+FOXP3+): inhibit immune responses

37
Q

What is the main cytokine in Th1 mediated response and explain the role this takes

A

IFN- y
The main role is to activate phagocytes which increases destruction from intracellular pathogens.

  • It also stimulates production of IgG antibodies from B cells (tells B cells that IgM is no longer needed) which further increases phagocytosis due to opsonisation and complement
38
Q

Microbes that cannot be killed by macrophages alone persist in phagosomes and Th1 helps by activating macrophages.

What 2 Th1 (help) signals are there?

A
  1. Contact mediated signals CD40L-CD40 (ensure that only the infected macrophage will receive help from Th1 cells - specificity)
    1. Soluble signals: IFN-y
      Th1 signals 1 and 2 induce macrophage activation
39
Q

How does activating macrophage increase its action?

A
  • Increased ROS, NO
  • Increased lysosomal enzyme
  • Secretion of cytokines (TNF-a, IL-1, IL-12) causes local inflammation which increases neutrophils and monocyte recruitment increasing phagocytosis
  • Tissue repair
40
Q

What T helper cell mediates responses against infections with helminths?

A

Helminths are often too large to be phagocytosed and have a thick coat (resistant to microbial activities/enzymes of the macrophages)

Th2 are responses against infections with helminths

41
Q

How does Th2 help destroy helminths?

A

The Th2 cells help B cells produce Abs that opsonise helminthes. The abs activate eosinophils/mast cells to destroy the helminths.

42
Q

What cytokines does Th2 produce and what do they do?

A

The Th2 cytokines produced are IL-4, IL-5, IL13

IL4 and 5 stimulate the B cell to produce IgE. The IgE produced then opsonises helminths. Eosinophils have receptors that bind to the Fc of IgE and once vound, IL-5 activates the bound eosinophils to kill helsminths.
Eosinophils then release their granule content which destroy the worms.

Mast cells also bind and degranulation causes local inflammation to help destroy the parasite.

43
Q

What two cells are involved in killing the helsminth in Th2?

A

Eosinophils

Mast cells

44
Q

What is the Th17 response?

A

The Th17 cells are mainly present in the mucosa (GI tract) and they provide defence against intestinal infections by recruiting neutrophils to sites of infection. They respond against extracellular bacteria and fungi by mainly by promoting neutrophil mediated inflammation.

45
Q

What happens when Th17 collaborates with Th1?

A

Th17 also collaborate with Th1 in phagocyte mediated CMI - Th17 recruit neutrophils and monocytes to sites of infection and Th1 cells activate phagocytes to ingest and kill microbes.

46
Q

What cytokines are produced from Th17?

A

IL-17A, IL-17F, IL-22

IL-17 produces chemokines which recruits neutrophils. It also produces antimicrobial substances called defensins.
IL-22 increase barrier function of epithelia

47
Q

What is the main function of regulatory T cells (treg)?

A

Main function is to maintain immune tolerance and works by suppressing immune responses

They do this by inhibiting:
- CD4+ T cells and CD8+ T cells

They use mechanisms such as anti-inflammatory cytokines.

48
Q

What infection does CD8+ CTL (cytotoxic T lymphocytes) eliminate?

A

These eliminate intracellular microbes growing in the cytosol. These are usually viruses. The method of elimination is simply to kill the infected cells.

49
Q

How does CTL kill infected cells?

A

CTL delivers a lethal hit and then detaches. Target still dies as this releases cytolytic proteins stored in secretory granules. Cytolytic proteins trigger apoptosis in the target cell.

Defence (5 decks)

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