Immunity Chapter 3 Flashcards
T/F Adaptive Immunity responses are initiated by the recognition of antigens by antigen receptors
True
T/F B and T lymphocytes differ in the types of antigens they recognize
True
What are the antigen receptors for B lymphocytes?
Membrane-bound antibodies which can recognize a variety of macromolecules (proteins, polysaccharides, lipids, nucleic acids) in soluble form or cell surface associated form as well as small chemicals
T/F T lymphocytes recognize peptide antigens that are bound to and displayed by MHC molecules of antigen presenting cells (APC)
True
What does TCR recognize?
Residual of peptide antigen and residues of MHC molecules that is displaying the peptide
Define Antigen presenting cells (APCs)
These are cells that capture microbial antigens and display them for recognition by T lymphocytes
T/F Protein antigens of microbes that enter the body are captured mainly by dendritic cells and concentrated in the peripheral lymphoid organs where immune responses are initiated
T
T/F At the same time as the DCs are capturing antigens, products of the microbe stimulate innate immune reactions by binding to Toll-like receptors (TLRs) and other sensors of microbes in the DCS resulting in the production of inflammatory cytokines such as tumor necrosis factor (TNF) and interleukin-1 (Il-1)
T
What happens when conventional DCs encounter microbes at epithelial barriers?
DCs are activated and they lose their adhesiveness for epithelia and begin to express the chemokine receptor CCR7 which is specific for chemoattracting cytokines (chemokines) produced by lymphatic endothelium and by stromal cells in the T cell zone in lymph nodes. These cytokines direct the the DCs to exit the epithelium and migrate through the lymphatic vessels to the lymph nodes draining that epithelium. During the process of migration, the DCs mature from cells designed to capture antigens to APCs capable of stimulating T cells.
What is the net result of the Q9?
The protein antigens of microbes are transported by DCs to the regions of the lymph nodes where the antigens are most likely to encounter T lymphocytes.
T/F Naïve T lymphocytes continuously recirculate through lymph nodes and also express CCR7 which promotes their entry into T cell zone of lymph nodes
T
T/F DCs bearing captured antigen and naïve T cells poised to recognize them come together in the lymph nodes
T
What are Major Histocompatibility Complex Molecules?
MHC molecules are membrane bound proteins on APCs that display peptide antigens for recognition by T lymphocytes
T/F The MHC was discovered as the genetic locus that is the principal determinant of acceptance or rejection of tissue grafts exchanged b/w individuals.
T
T/F The physiologic role of MHC molecules is to display peptides derived from microbial protein antigens to antigen specific T lymphocytes as the first step in protective T cell mediated immune response to microbes.
T
What is HLA?
Human Leukocycte antigens-a name for human MHCs.
What are Class 1 and Class II MHCs?
Class I and Class II MHC molecules are membrane proteins. Each contains a peptide-binding cleft at the amino-terminal end.
Describe the features of Class I MHCs.
- Consists of 1 alpha chain
- alpha chain noncovalently associated with a protein called beta-2-microglobulin(b2M).
- Amino terminal a1 and a2 domains of the Class I MHC molecule forms a peptide binding cleft or groove that is large enough to accommodate peptides of 8 to 10 AAs.
- Floor of the peptide cleft is region that binds antigen peptides for display to T-Ls
- Sides and tops of the cleft are regions that are contacted by T-cell receptor (TCR)
- Polymorphic residues of Class I MHCs, ie the AAs that differ among different indiviuals MHCs are located in the a1 and a2 domains
- a3 domain is invariant and contains the binding site for TC coreceptor CD8
T/F T cell activation requires simultaneous recognition of MHC associated peptide antigen and MHC molecules by coreceptors
T
Describe Class II MHC Molecule
- Consists of 2 chains; alpha and beta
- amino-terminal regions of both a and b chains are called the a1 and b1 domains
- a1 and b1 domains contain polymorphic residues and form cleft large enough to accommodate peptide chains of 10 to 30 AAs
- The nonpolymorphic b2 domain contains the binding site for T cell coreceptor CD4.
T/F MHC genes are codominantly expressed meaning that the alleles inherited from both parents are expressed equally
T
T/FMHC genes are highly polymorphic meaning that many different alleles are present among the different individuals of the population
T
T/F Class I molecules are expressed on all nucleated cells, but Class II molecules are expressed mainly by DCs, macrophages, and B lymphocytes
T
Name some features of MHC molecules and their significance
- Feature- Co-dominant expression: Both parental alleles are expressed equally
Consequence- Increases # of different MHC molecules that can present antigen peptides to T cell - Feature-Most Polymorphic Genes: Many different alleles are present in the population
Consequence- Ensures that different individuals are able to present and respond to different microbial peptides - Feature- MHC expressing cell types:
Class II- DCs, Macrophages, and B lymphocytes
Consequence- CD4+ helper TL interact with DCs, macrophages, and BLs
Class I- All nucleated cells
Consequence- CD8+ CTLs can kill any virus infected cell
T/F Each MHC molecule can present only one peptide at a time b/c there is only one binding cleft. But each MHC molecule is capable of presenting many different peptides
T
T/F MHC molecules bind only peptides and not other antigens
T
MHC molecules acquire their peptide cargo during their biosynthesis, assembly, and transport inside cells.
T
What source of antigen protein is recognized by both Class I and Class II MHCs?
Class I- acquire peptides from cytosolic proteins
Class II- acquire proteins that are taken up in the intracellular vessicles
T/F Only peptide-loaded MHCs are stably expressed on cell surface
T
T/F In each individual, the MHC molecules can display both self as well as foreign(microbial) proteins
T
Name some features and significance of peptide binding to MHC molecules
- Feature- Broad Specificity
Sig- Many different peptides can bind to the same MHC molecule - Feature- Each MHC molecule displays 1 peptide at a time
Sig- Each T cell response to a single peptide bound to an MHC molecule - Feature- MHC molecules bind only peptides
sig- MHC restricted T cells respond only to protein antigens and not to other chemicals - Feature- Peptides are acquired during intracellular assembly
Sig- Class I and Class II MHC molecules display peptides from different cellular compartments - Feature- Stable surface expression of MHC molecule requires bound peptide
Sig- Only peptide-loaded MHC molecules are expressed on the cell surface for recognition by T cells - Feature- Very slow off-rate
Sig- MHC molecules displays bound peptide for long enough to be located by T cell
What are the steps for antigen display by Class II MHC Molecules?
- Uptake of extracellular proteins in vesicular compartments of APC
- Processing of internalized protein in endosmal/lysosomal vesicles
- Biosynthesis and transport of Class II MHC molecules to endosome
- Association of processed peptide with Class II molecules in vesicles
- Expression of peptide-MHC complexes on cell surface
What enzyme blocks the antigen-binding cleft of class II molecules during processing (i.e before it is displaced and antigen bind)
CLIP
What are the steps involved in Antigen peptide display by Class I MHC molecules?
- Production of antigen proteins in the cytosol
- Proteolytic degradation of proteins
- Transport of peptides from cytosol to ER
- Assembly of peptide-Class I complex in ER
- Surface expression of peptide -Class I complexes
- Most professional APCs are ___ cells. Other examples of APCs are ____ and _______.
DCs
Macrophages and B lymphocytes
- MHC molecules can only display ____ molecules of the antigens.
Peptide
- Which peptide blocks the antigen-binding cleft of class II molecules during processing (i.e. before it is displaced and antigen binds)? ___
CLIP or Invariant Chain
- CD4 cells only recognize class ____ molecules, which allows for eradication of ___________ [(intracellular (cytoplasmic) or extracellular (vesicular)] microbes after recognition and activation; CD8 cells only recognize class ____ molecules, which allows for eradication of ____________ [(intracellular (cytoplasmic) or extracellular (vesicular)] microbes after recognition and activation.
Class II
Extracellular
Class I
Intracellular
- Human MHC is also called as __________.
Human Leukocyte Antigen (HLA)
- If one cell type presents antigens of another cell and activates T lymphocytes specific for that cell type it is called _________.
Cross Presentation or Cross Priming
- The MHC class II molecule is made of ____________ and ________ chains.
alpha and beta
- A part of the antigen recognized by the immune system, specifically by antibodies, B cells and T cells is called an __________
Epitope or antigen determinant
- MHC restriction refers to ____ being restricted to recognize antigen presented by the______________
T Cells
MHC Molecules only
- HLA-A, HLA-B and HLA-C are the gene clusters that make up MHC class ____ and HLA-DP, HLA-DQ and HLA-DR make up MHC class ___.
I
II
- All cells express MHC molecules except these cells: _______________.
Mature RBCs
- Having the same exact MHC genes among individuals is highly unlikely except in ________________.
Identical Twins
- The cleft of MHC class __ is larger and can bind to a peptide size of about 10-30 amino acid residues.
II
- The peptide binding portion of MHC I is _____ and ______. CD8 binds to the _____ portion of the MHC I molecule.
alpha 1 and alpha 3
alpha 3
- The structure that removes the CLIP portion of the invariant chain is _____.
DM
II. True/False. Please correct the false statement.
1. An MHC molecule without a peptide is highly unstable and will be degraded. ______
- MHC I molecules typically display a larger peptide compared to MHC II. ______
- Class II MHC molecules are always present. ___
- MHC genes are codominantly expressed and are highly polymorphic. ____
- Each MHC molecule displays many peptides at a time. _____
- MHC molecule has broad specificity for the peptides they bind to. ____
- T cells have a very slow off-rate. __T___
- Only MHC molecules that are displaying peptides are expressed for recognition by T cells. _____
- T
- F MHC 1 displays a smaller peptide
- F only present when there is an infection
- T
- F only one peptide at a time
- T
- T
- T
III. Rearrange the following processes in the correct order:
- Migration of a dendritic cell:
a. Antigen presentation
b. Maturation of DC
c. Loss of adhesiveness
d. Antigen capture
e. Migration
d c e b a
- MHC protein synthesis and display of peptide:
a. Antigen presentation
b. Association of peptide to MHC
c. Processing of extracellular antigen
d. Synthesis of MHC molecule
c d b a
MHC protein synthesis and display of peptide:
a. Display of MHC with antigen
b. Transport of peptide into endoplasmic reticulum
c. Assembly of peptide to MHC
d. Ubiquitination
e. Antigen in cytosol
e d b c a
I. Fill in the blank
1. T lymphocytes only respond to peptide antigens bound to and displayed by _____________.
- Most professional APCs are ___________ cells.
- What receptor do activated dendritic cells express that is specific for chemoattractant cytokines produced in T cell zones of lymph nodes (leads to migration of dendritic cells to lymph nodes)? ____________________
- MHC molecules can only express _____________ antigens; therefore, CD4+ and CD8+ cells can only respond to ____________ antigens.
- What peptide blocks the antigen-binding cleft of class II molecules during processing (i.e. before it is displaced and antigen binds)? _______________
- MHC Proteins
- Dendritic cells DCs)
- CCR7
- Peptide Peptide
- CLIP
- What is the transporter used to transfer peptide antigens from the cytosol to class I MHC molecules? ___________________
- CD4+ cells only recognize class ___ molecules, which allows for eradication of ___________ (intracellular or extracellular) microbes after recognition and activation; CD8+ cells only recognize class ____ molecules, which allows for eradication of ____________ (intracellular or extracellular) microbes after recognition and activation.
- Human MHC is called_____________________.
- If one cell type presents antigens of another cell such as a microbe or tumor cell and activates T lymphocytes specific for that cell type it is called____________________.
- Name the APCs present in the lymph nodes and the spleen responsible for displaying antigens. ____________
- Which immunoglobulins would be present to indicate a mature B lymphocyte?_______ and ______________.
- MHC molecules bind:
a. Carbohydrates
b. Nucleic acids
c. Lipids
d. Peptides
- TAP
- II Extracellular
I Intracellular - Human Leukocyte Antigen (HLA)
- Cross Presentation
- Dendritic cells
- IgM and IgD
- d
II. True/False.
- All nucleated cells can present antigens derived from microbes in the cytoplasm to CTLs. __________.
- The restriction of T cells to only recognize antigens displayed by MHC molecules allows T cells to recognize antigens associated with intracellular and extracellular microbes. ___________.
- T
2. F
I. Use these words to fill in the blanks:
Key terms: a. Peptide, b. MHC, c. TAP, d. CLIP, e. dendritic, f. intracellular, g. I, h. CCR7, i. II, j. macrophages, k. B-lymphocytes
1. T lymphocytes only respond to peptide antigens bound to and displayed by __b MHC_.
- Most professional APCs are _e) dendritic__ cells. Other examples of APCs are __j) macrophages___ and _k) B lymphocytes___.
- What receptor do activated dendritic cells express that is specific for chemoattractant cytokines produced in T cell zones of lymph nodes (leads to migration of dendritic cells to lymph nodes)? __h) CCR7_____
- MHC molecules can only express _a) peptide__ antigens; therefore, CD4+ and CD8+ cells can only respond to __ a) peptide __ antigens.
- What peptide blocks the antigen-binding cleft of class II molecules during processing (i.e. before it is displaced and antigen binds)? __d) CLIP__
- What is the transporter used to transfer peptide antigens from the cytosol to class I MHC molecules? ___c) TAP____
- CD4+ cells only recognize class i) II molecules, which allows for eradication of ___________ (intracellular or extracellular) microbes after recognition and activation; CD8+ cells only recognize class __g) __ molecules, which allows for eradication of ____________ (intracellular or extracellular) microbes after recognition and activation.
- MHC
- DCs Macrophages and B Lymphocytes
- CCR7
- Peptide Peptide
- CLIP
- TAP
- II Extracellular
I Intracellular
Key Terms: a. MHC restriction, b. T lymphocytes, c. lymph node, d. B lymphocytes, e. antibody, f. DP, g. A, h. C, i. spleen, j. DQ, k. B, l. DR, m. DM, n. alpha-1, o. alpha-2, p. alpha-3, q. beta-1, r. beta-2, s.proteosome
- __b) T lymphocytes___ can only interact with proteins, whereas _d) B lymphocytes__ can interact with proteins, polysaccharides, nucleic acids, and lipids.
- The fact that T cells can recognize peptides only when they are presented by MHC molecules is called __a) MHC restriction_____.
- B cell recognizes epitopes using __e) antibody_____.
- If a dendritic cell enters a lymphatic vessel, it typically reaches __c) lymph node____, whereas if it enters a venule it typically reaches __i) spleen_______.
- Class II MHC locus carries __DP__, __DQ__, and _DR___ gene segments. Class I MHC locus carries _A___, __B__, and __C___ gene segments.
- The peptide binding portions of MHC I is __alpha 1___ and __alpha 2____. CD8 binds to the __alpha 3___ portion of the MHC I molecule.
- The peptide binding portion of MHC II is __alpha 1____ and _beta 1___. CD4 binds to the __beta 2______ portion of the MHC II molecule.
- The structure that removes the CLIP portion of the invariant chain is ___DM___.
- If ubiquitin uncoils the protein, __proteasome___ breaks the protein into small peptides.
- T Lymphocytes B Lymphocytes
- MHC Restriction
- Antibody
- Lymph Node Spleen
- DP, DQ, and DR MHC genes; HLA-A, HLA-B, and HLA-C
- alpha 1 and alpha 3 alpha 3
- alpha 1 and beta 1 beta 2
- DM
- Proteosome
