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HIID > L7: Antigen Processing and Presentation > Flashcards

L7: Antigen Processing and Presentation Flashcards

1
Q

How do B cells “see” antigen?

A

Antibody on B cells or free antibody can recognize intact antigen (i.e. soluble antigens and cell surface antigens)

Proteins, nucleic acids, polysaccharides, lipids, and small molecules are antigenic for B cells

Can recognize conformation or linear epitopes: consecutive amino acids on a denatured protein would be a linear epitope; a 3-D structure would be a conformational epitope (could even be non-contiguous amino acids when they start to overlap)

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2
Q

How to T cells “see” antigen?

A

Recognize protein antigens as discrete peptides

Recognize linear epitopes (don’t recognize non-contiguous epitopes)

Recognize antigen only when it is bound to MHC

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3
Q

How do CD8+ cytotoxic cells “see” antigen? How do they respond?

A

“See” antigen complexed to MHC class I and respond by killing the infected cell

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4
Q

How do CD4+ helper cells “see” antigen? How do they respond?

A

“See” antigen complexed to MHC class II and respond by proliferation and production of cytokines

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5
Q

What must APCs express in order for T cell to recognize and respond to a foreign peptide antigen?

A

APC must express MHC molecules that are recognized as self

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6
Q

What are “self” MHC?

A

Those MHC antigens that the T cell encountered during development in the thymus

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7
Q

What are cytosolic pathogens presented to?

A

Presented to effector CD8 T cells

Effect is cell death

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8
Q

What are intravesicular pathogens presented to?

A

Presented to effector CD4 T cells

Effect is activation to kill intravesicular bacteria and parasites

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9
Q

What are extracellular pathogens and toxins presented to?

A

Presented to effector CD4 T cells

Effect is activation of B cells to secrete Ig to eliminate extracellular bacteria/toxins

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10
Q

What recognizes exogenous antigens?

A

CD4 cells

These antigens are processed and presented w/ MHC class II

The CD4+ T cells respond with proliferation and cytokine production

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11
Q

What are the professional antigen presenting cells? What do they do?

A

Dendritic cells

Macrophages

B cells

Either express constitutive MHC class II or very easily upregulate it

Antigen presenting cells are those special cells that can provide the high levels of MHC and co-stimulatory molecules required for T cell activation

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12
Q

What is the response of dendritic cell antigen uptake?

A

Naive T cell activation: clonal expansion and differentiation into effector T cells

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13
Q

What is the response of macrophage antigen uptake?

A

Effector T cell activation: activation of macrophages (cell-mediated immunity)

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14
Q

What is the response of B cell antigen uptake?

A

Effector T cell activation: B cell activation and antibody production (humoral immunity)

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15
Q

Where are dendritic cells found?

A

Found at all of the sites where there will be antigen entry

Skin: Langerhans cells and layer of dermal dendritic cells

GI tract

Respiratory tract

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16
Q

What occurs if antigen enters blood stream?

A

It is filtered out in the spleen and presented to T cells in the spleen

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17
Q

Compare the functions/properties of immature and mature dendritic cells

A

Immature: principal function is antigen capture (is constantly sampling); there is expression of Fc receptors and mannose receptors; expression of molecules involved in T cell activation is low

Mature: principal function is antigen presentation to T cells; downregulates its ability to take up antigen so it doesn’t waste energy sampling when it needs to present its antigen; high expression of molecules involved in T cell activation

18
Q

Dendritic cells vs. B cells as antigen presenting cells

A

DCs effectively deliver both signals needed to activate T cells; they are the most efficient APC to function in the primary immune response

B cells that are specific for a given Ag are rare in primary response, but dramatically expand in secondary response; they are therefore efficient as APC in the secondary

19
Q

Describe antigen uptake into endocytic components

A

Antigen is taken up from the extracellular space into intracellular vesicles → in early endosomes of neutral pH, endosomal proteases are inactive → acidification of vesicles activates proteases to degrade antigen into peptide fragments → vesicles containing peptides fuses w/ vesicles conaining MHC class II molecules

20
Q

If antigen is brought into cell by antibody (antibody mediated uptake), what happens to the antibody?

A

Antibody gets effectively recycled to cell surface while antigen goes into meet w/ MHC class II

21
Q

Describe antigen processing for exogenous (extracellular) antigens

A

Uptake of extracellular proteins into vesicular compartments of APC → processing of internalized proteins in endosomal/lysosomal vesicles

Meanwhile, MHC class II molecules synthesized in ER → has invariant chain blocking MHC binding site so antigen can’t bind yet and also transmembrane region that aids in transport → transport through Golgi → ends up in “MHC class II compartment” → endosomal enzymes destroy the invariant chain except for CLIP peptide guarding MHC groove → fuses w/ vesicle containing antigen peptide → CLIP peptide release is catalyzed by HLA-DM → allows antigen peptide to bind to MHC class II molecule → expression of peptide-MHC complexes on cell surface

22
Q

What are endogenously expressed antigens (in the cytoplasm of the cell) presented to?

A

CD8+ cytotoxic T cells

23
Q

What are endogenous antigens presented with?

A

MHC class I

24
Q

What cells are targets for CTL?

A

Any cell that expresses MHC class I can be a target for CTL

This includes antigen presenting cells and basically any nucleated cell

25
Q

Where does processing of endogenuos antigens occur?

A

In proteasome

26
Q

What are some examples of endogenous antigens?

A

Viral
Tumor
Self (but body won’t have T cells that can respond to this self-antigen)

27
Q

What causes upregulation of proteasome components?

A

IFN (type I and II) signaling

Immunoproteasome

28
Q

What do proteasomes do?

A 
Makes peptides of varying sizes from proteins (that have been ubiquinated and thus targeted)
Some of these peptides will be appropriate for binding to MHC class I
29
Q

In endogenous antigen processing, how do peptides get from cytosol to where the MHC class I molecules are?

A

TAP1 and TAP2 actively take peptide and transport it across the lumen and into the ER

This process requires ATP

30
Q

Describe processing of antigen in the Class I pathway

A

Production of proteins in the cytosol → proteolytic degradation of proteins by proteasome → transport of peptides from cytosol to ER by TAP → assembly of peptide-class I complexes in ER (until MHC class I molecule has peptide, don’t assemble the entire molecule w/ the Beta-2 microglobulin) → transport to Golgi → Surface expression of peptide-class I complexes

31
Q

What prevents binding of Class I peptides to MHC class II in the ER (since these peptides are transported into the ER by TAP)?

A

MHC class II molecules have CLIP peptide blocking antigen binding site

CLIP is only removed when MHC class II molecules have moved into the endocytic ocmpartments

32
Q

What determines the outcome of an antigen?

A

Route of entry

33
Q

Why aren’t self-antigens presented by MHC molecules recognized by T cells?

A

There are either no T cells that recognize self-antigen or there is an inability to respond

34
Q

Immunodominant epitopes

A

Peptides that bind most avidly to MHC

35
Q

What is the effector function of CD4+ T cells?

A

Macrophage activation: destruction of phagocytosed antigen

B cell antibody secretion: antibody binding to antigen

36
Q

Cross-presentation by dendritic cells

A

DC can effectively take up antigen from outside (such as virus infected cells) and presented to CD8+ cells

37
Q

How is cross-presentation by dendritic cells advantageous?

A

Because DC doesn’t have to be infected and is therefore less susceptible to virus escape

If the only way a dendritic cell could get activated was to get infected, the virus would just have to mutate so it doesn’t actually infect the cells → this way, even material taken up will be presented

38
Q

Presentation of antigen by CD1

A

CD1 is a non-polymorphic MHC-like molecule that maps outside of the MHC region

Like MHC class I, associates w/ beta-2 microglobulin

Capable of presenting mycolic acid and lipoarabinomannan (lipid and glycolipid) from myobacteria to T cells; source of antigen is exogenous and requires processing

39
Q

What does CD1 on APC such as dendritic cells and thymic cortical cells do?

A

Able to present certain antigens (e.g. cerebrosides) to a population of CD4 T cells that express NK markers (NKT cells) or to some conventional T cells

These cells make cytokines, which helps shape the immune repsonse

40
Q

What are CD1 molecules similar to?

A

MHC class I molecules

Molecular structure is similar

Also expresses beta-2 microglobulin

41
Q

Superantigens

A

Bind outside of the peptide-binding cleft

Binds to the outside of the molecule and bring T cell receptor and MHC class II molecule together w/o processing

Superantigens can turn on a lot of different cells; end up w/ a lot of cells getting activated

Some bacterial toxins can thus damage the immune response

42
Q

How is antigen presentation relevant to clinical medicine?

A 
Transplantation (organs, bone marrow, stem cells)
Transfusion
Cancer: can tumor antigens be presented?
Infectious disease: upregulation and downregulation of MHC class I
Autoimmunity
Immunodeficiency
Immunotherapy
Vaccination

HIID (27 decks)

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