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Microbiology & Immunology > Immune Cell Interactions > Flashcards

Immune Cell Interactions Flashcards

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Biology 101 flashcards
1
Q

Describe the BCR and Ig alpha/beta complex.

A
  • structure: membrane immunoglobulin, associates with Ig alpha/beta complex
  • function: receptor-mediated internalization of antigen
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2
Q

Describe the TCR and CD3 complex.

A
  • Structure
    • TCR: alpha and beta subunits
    • associates with CD3 complex
  • Function
    • interacts with MHC to recongize antigens
    • CD3 acts as signal transducing subunit
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3
Q

What are the surface molecules that interact with MHC?

A

CD4, CD8

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4
Q

Define CAMs.

A
  • Cellular Adhesion Molecules
  • facilitate T cell adhesion
  • augment signaling thru TCR
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5
Q

What are the Ig Superfamily of CAMs?

A
  • structure based on Ig fold
  • ICAM-1, ICAM-2, CD2, CD4, CD8
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6
Q

What are the Integrin Family of CAMs?

A
  • heterodimers of alpha and beta chains
  • LFA-1, MAC01, p150, p95
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7
Q

What are the Selectin Family of CAMs?

A
  • extracellular portion is lectin domain
  • binds to carbohydrate ligands, facilitate interactions between leukocytes and endithelium
  • L-selectin, P-selectin, E-selectin
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8
Q

What are the Vascular Addressins CAMs?

A
  • molecules w/ carbohydrate ligands recongized by L-Selectin
  • CD34, GlyCAM-1
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9
Q

How does signaling between T Cells and APCs work?

A
  • multiple interactions of CAM pairs
  • LFA-1 (integrin) on T cell interacts with ICAM-1 on APC
    • signal is weak unless TCR also connects with MHC II + peptide on APC -or- chemokine binds to T cell
    • integrin switched to high affinity state, T cell and APC interaction produces strong signaling
  • CD2 on T cell interacts with LFA-3 on APC
    • promotes cell adhesion
    • augments signal thru TCR
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10
Q

How does signalling between naive T cells and HEVs work?

A
  • L-selectin on naive T cell interacts with sulfated sialyl-Lewisx motif on GlgCAM-1 and **CD34 **molecules of the HEV cell surface
  • initiates rolling of naive T cell along endothelium so it can enter blood
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11
Q

What are the T Cell co-stimulatory molecules?

A

CD28 (positive) CTLA-4 (negative)

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12
Q

Describe the naive T Cell co-stimulatory mechanism.

A
  • naive T cells require TCR/CD3 activation and a second, co-stimulatory CD28 signal to be activated
  • **CD28 **on T cell interacts with B7 on professional APC
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13
Q

Describe the negative co-stimulatory mechanism.

A
  • CTLA-4 on naive T cell binds to B7 on APCs
  • outcompetes CD28, modulates T cell immune response
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14
Q

SUMMARY REVIEW: What are the T cell surface molecules responsible for antigen recognition?

A

TCR

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15
Q

SUMMARY REVIEW: What are the T cell surface molecules responsible for signal transduction?

A

CD3, CD4/CD8, CD2

Co-stimulation: CTLA-4, CD28

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16
Q

SUMMARY REVIEW: What are the T cell surface molecules responsible for adhesion?

A

LFA-1, L-selectin, CD2

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17
Q

Describe the B Cell co-stimulatory mechanism.

A
  • B cell and T cell interact for antigen presentation
    • B cell: MHC, B7
    • T cell: TCR, CD28
  • CD40L on T cell is expressed
  • **CD40 **on B cell interacts with CD40L
  • B cell proliferation
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18
Q

Describe the immunological synapse and SMACs.

A
  • point of interaction between T cell and APC
  • c-SMAC: center of cluster
    • T cell: TCR/CD3
    • APC: MHC/Ag
  • p-SMAC: border of cluster
    • T cell: LFA-1
    • APC: ICAM-1
  • formation initiates T cell signaling
19
Q

Name and define the methods of action for cytokines. Examples?

A
  • autocrine: cytokine acts on secreting cell
    • ex. Il-2 during T cell activation
  • paracrine: cytokine acts on neighboring cells
    • ex. chemokine recruitment of leukocytes to site of inflammation
  • endocrine: cytokine acts systemically
    • ex. IL-1, IL-6, TNF-alpha in septic shock
20
Q

What is the function of IL-2?

A

helps to activate naive T cells

21
Q

Describe the IL-2 receptor and its regulation.

A
  • part of common gamma chain family of receptors
  • on naive T cells, expressed as form w/ only beta & gamma chains
  • when secreted IL-2 binds, alpha chain of IL-2R binds with beta & gamma increases affinity of IL-2R
  • IL-2: IL-2R binding signals T cell proliferation
22
Q

What is the process for neutrophil extravasation to a site of infection?

A
  1. rolling: selectin on endothelium binds to carbohydrate ligand on neutrophil
  2. activation: chemokine binds to GCPR on neutrophil to activate **integrin **
  3. firm adhesion, transmigration: **integrin **on neutrolphil binds to ICAM on endothelium
23
Q

What is LAD? What’s the molecular basis?

A
  • Leukocyte adhesion deficiency
  • caused by beta-integrin gene mutation, neutrophils can’t get out of blood stream
  • suffer from bacterial and fungal infections
24
Q

What is the function of MHC (HLA)?

A

when bound to peptide, they interact with TCRs

25
Q

Does MHC bind to anything other than TCR?

A

Yes, ex. NK cell receptors. ONLY T cells recognize peptide in MHC

26
Q

Where is Class I MHC found?

A

all nucleated cells (not RBCs)

27
Q

Where is Class II MHC found?

A

restricted to professional APCs (DCs, B cells, macs)

28
Q

What are the genes on the Class I MHC locus?

A

HLA-A, HLA-B, HLA-C

29
Q

What are the genes on the Class II MHC locus?

A

HLA-DR, HLA-DP, HLA-DQ

30
Q

What is the patterns of inheritance for MHC genes?

A

co-dominant: both alleles of each gene (one from each parent) are expressed and are functional

31
Q

Define MHC gene polymorphism.

A
  • many known alleles for each MHC gene locus
  • polymorphisms occur in regions of MHC that contact the peptide and the TCR
32
Q

What is the structure of Class I MHC?

A

alpha heavy chain

beta2 light chain (not on MHC locus)

peptide groove: closed on the ends, only holds short peptides

33
Q

What is the structure of Class II MHC?

A

alpha and beta chains

groove for peptide: open on both ends, can hold short and long peptides

34
Q

Where do the peptides associated with MHC come from?

A
  • cytosolic (endogenous): host cell structural proteins, viral pathogens
    • MHC Class I
  • extracellular (exogenous): host serum proteins, bacterial pathogen proteins
    • MHC Class II
35
Q

Describe the endogenous pathway of MHC Class I antigen processing and presentaiton.

A
  1. production of proteins in cytosol
  2. proteolytic degradation of ubiquitinated proteins
  3. transport of peptides from cytosol to ER via TAP
  4. peptide- class I MHC complexes form in ER
  5. complex becomes exocytotic vessicle and gets expressed on membrane surface
36
Q

Describe the exogenous pathway of MHC Class II antigen processing and presentaiton.

A
  1. extracellular proteins taken into APC cytoplasm and processed in endolysosome
  2. Class II MHC are synthesized in ER
    1. Class II MHC + Invariant Chain (Ii)
  3. Class II MHC-Ii fuses with endosome-lysosome containing antigen peptide
  4. Vessicle binds with CLIP that digests Ii
  5. Vessicle moves to cell surface so MHC II + peptide can be expressed
37
Q

What is the function of invariant chain (Ii)?

A

blocks peptide binding site of MHC II while in ER so it cannot bind with other peptides (like those going into MHC I)

38
Q

What are there 2 types of MHC/ antigen processing pathways?

A
  • MHC I: important for intracellular pathogens, all cells are vulnerable to such infections
  • MHC II: important for extracellular pathogens which can be readily accessed by phagocytosis
39
Q

What determines peptide binding specificity of MHC?

A
  • binding specificity is determined by size and shape of pockets in peptide-binding groove of MHC molecule
  • different MHC alleles bind certain types of peptides
    • peptide-binding pockets of MHC alleles bind to unique or chemically similar AA side chains (anchor residues)
40
Q

How do TCRs recognize MHC?

A
  • TCR recognizes specific combinations of MHC and peptide
  • peptide residues not buried in MHC groove serve as binding sites for TCR
41
Q

How do CD8 and CD4 recongize MHC?

A
  • bind to non-polymorphic regions of MHC I and II
42
Q

What is MHC restriction?

A
  • a given TCR will only recognize a specific MHC molecules in complex w/ a unique (or a few similar) peptides
43
Q

What is the clinical relevance of MHC polymorphism?

A
  • rejection of tissue transplants
    • basis for need to “cross-match” donor and recipient
  • autoimmune diseases
    • HLA-typing is the most useful test in definitive diagnosis of many autoimmune diseases

Microbiology & Immunology (7 decks)

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