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Flashcards in Overview of Fundamentals of Immunology Deck (43)
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1
Q

Describe 4 levels of protection from disease-causing pathogens

A

1) Anatomic Barriers (e.g. skin)
2) Complement/Antimicrobial proteins (e.g. C3, defensins, RegIII-y)
3) Innate immune cells (e.g. macrophages, granulocytes, NK)
4) Adaptive immunity (e.g. T cells, B cells/antibodies)

2
Q

Compare general differences between innate and adaptive immunity

A

Innate:

  • always available
  • first line of defense
  • specific for general types of pathogens but not individual pathogens
  • no lasting immunity

Adaptive

  • develops during lifetime as adaptation to infections with pathogens
  • antigen specific
  • confers long-lasting immunity
3
Q

List general categories of immune response

A

Immune recognition
Immune effector function
Immune regulation
Immunologic memory

4
Q

Pluripotent hematopoietic stem cell gives rise to 2 progenitor cells = ?

A

1) Common lymphoid progenitor

2) Common myeloid progenitor

5
Q

Common myeloid progenitor gives rise to which types of cells (terminal line)?

A
  • eosinophils, basophils, mast cells
  • neutrophils, dendritic cells, and macrophages
  • platelets
  • erythrocytes
6
Q

List granulocytes & their function

A

Neutrophil: phagocytosis and activation of bactericidal mechanisms
Mast cell: release of granules containing histamine and active agents
Eosinophil: killing of antibody coated parasites
Basophil: promoting of allergic responses and augmentation of parasitic immunity

7
Q

List phagocytes

A
  • Neutrophils
  • Monocyte (circulation in blood) –> macrophage (differentiation in tissue): reside in tissues and act as scavengers; poor APC
  • Dendritic cell: antigen uptake in peripheral sites –> good APC and phagocytose small particles
8
Q

Common lymphoid progenitor cell gives rise to?

A

Adaptive lymphocytes (unique receptor for Ag):

  • B-cells
  • T-cells

Innate-like lymphocytes (lack Ag receptors; produce cytokines)

  • NK cells
  • Innate Lymphocyte cells (ILCs)
9
Q

Overlapping functions of innate and adaptive cells - Effector modules:

1) Cytotoxicity
2) Intracellular immunity (Type 1)
3) Mucosal and barrier immunity (Type 2)
3) Extracellular immunity (Type 3)

A

1) Cytotoxcity
NK cells and CD8 T cells
-elimination of virally infected and metabolically stressed cells

2) Intracellular immunity
ILC1 and Th1 cells
-elimination of intracellular pathogens; activation of macrophages

3) Mucosal and barrier immunity
ILC2 and Th2 cells
-elimination and expulsion of parasites; recruitment of eosinophils, basophils, and mast cells

4) Extracellular immunity
ILC3 and Th17 cells
-elimination of extracellular bacteria and fungi; recruitment and activation of neutrophils

10
Q

Describe primary and secondary lymphoid organs

A

Primary lymphoid organs

  • thymus: site of T-cell development
  • bone marrow: site of myeloid and B-cell development

Secondary lymphoid organs

  • Lymph nodes: collect lymph and antigen from peripheral sites through lymphatic vessels
  • spleen: collect antigens from circulating blood
11
Q

Describe areas in LNs where immune cells reside

A

Primary lymphoid follicle: mostly B-cells
paracortical area: mostly T-cells
medullary cords: macrophages and plasma cells
germinal centers: mature activated B-cells

[see fundamental of immunology lecture 1 diagram: slide 17]

12
Q

What are Peyer’s patches?

A
  • LNs on the surface of the intestinal lumen

- covered by an epithelial layer containing specialized cells called M cells

13
Q

Give examples of diffuse aggregates of lymphocytes/follicles

A
  • Peyer’s patches
  • NALT (nasal associated lymphoid tissue)
  • BALT (bronchus associated lymphoid tissue)
  • GALT (gut associated lymphoid tissue)
14
Q

Spleen

1) function
2) architecture

A

1) collects Ag from circulating blood and eliminate old RBCs; important for blood-borne pathogens
2) Red pulp = RBC disposal. White pulp = leukocytes with B-cells, T-cells, macrophages

[see lecture 1 diagram - slide 20]

15
Q

List 4 classes of pathogens that the immune system defends against

A

1) viruses
2) intracellular bacteria, protozoa, & parasites
3) extraceullar bacteria, fungi, & parasites
4) Parasitic worms (extracellular)

Pathogens with different lifestyles require different response for immune system recognition and destruction

16
Q

How are innate immune system responses initiated?

A

Initiated upon recognition of “danger signals” by pattern recognition receptors

17
Q

Give examples of danger signals & pattern recognition receptors

A

Danger signals

  • pathogen-associated molecular patterns (PAMPs)
    e. g. bacterial proteins, viral DNA/RNA
  • damage-associated molecular patterns (DAMPs)
    e. g. products of dying cells

Types of PRRs (can be on cell surface or intraceullar)

  • toll-like receptors (TLR)
  • c type leptin receptors
  • NOD-like receptors (NLRs)
  • RIG-I like receptors
18
Q

How do infectious agents cause an inflammatory response?

A

1) Bacteria trigger macrophages to release cytokines and chemokines
2) vasodilation and increased vasc. permeability –> redness, heat, and swelling
3) inflammatory cells migrate to tissue, releasing inflammatory mediators that cause pain

(adaptive cells come later)

19
Q

What are some functional differences between immature and mature DCs?

A

Immature DCs = very efficient at Ag processing

Mature DCs = very efficient at Ag presentation

20
Q

How are Ag processed on MHC Class I after being infected by virus?

A

Virus infected cell –> viral proteins synthesized in cytosol –> Peptide fragments of viral proteins bound by MHC class I in ER –> bound peptides transported by MHC Class I to the cell surface

[see slide 26]

21
Q

MHC Class I is expressed by ______ cells and presents peptides from the ________.

A

nucleated; cytosol

22
Q

MHC Class I/peptides recognized by ______

MHC Class I proteins recognized by ______

A

CD8+ T cells; NK cells

23
Q

How do macrophages process Ag?

A

Bacterium infects macrophage and enters vesicle, producing peptide fragments –> bacterial fragments bound by MHC class II in vesicles –> bound peptides transported by MHC Class II to the cell surface.

[see slide 27]

24
Q

How do B-cells process Ag?

A

Ag bound by B-cell receptor –> Ag internalized and degraded to peptide fragments –> fragments bind to MHC class II and are transported to the cell surface

[see slide 27]

25
Q

MHC Class II typically expressed by ______ and presents peptides derived from ________ proteins. MHC Class II/peptides are recognized by ____.

A

professional APCs; exogenous; CD4 T cells

26
Q

What’s an important bridge between innate and adaptive responses?

A

DC = important for initiating adaptive immune responses.

immature DC reside in peripheral tissues –> DC migrate via lymphatic vessels to regional LNs –> mature DC activate naive T cells in lymphoid organs such as LNs

27
Q

_____ are responsible for the effectiveness of adjuvants

A

PAMPs

28
Q

Describe the structure of antigen receptors

A

Antibody

  • variable region = antigen binding site
  • constant region for effector function
  • Ab can be on cell surface and be secreted

T-cell receptor

  • variable region = antigen binding site
  • constant region

Constant region = shared among many cell types
variable region = unique

29
Q

How is Ag receptor diversity generated?

A

Gene rearrangement

  • inherited gene segments –> unique combo of segments becomes joined by somatic gene rearrangement –> chain pair to give unique receptor for each lymphocytes
  • Recombination [used for Ig & TCR; irreversible; different in each cell; generates vast combinations of receptors within organisms]
  • Occurs in development before cell sees antigen
30
Q

What is an epitope?

How are TCR epitopes different from Ab epitopes?

A

Region on Ag recognized by Ab.
-Ab recognizes portions of proteins

Epitopes recognized by TCR is usually buried in the protein structure and thus need to be processed and presented on MHC class molecules

31
Q

What’s the central principle of adaptive immunity?

A

1) single progenitor cell –> large #lymphocytes with unique Ag receptors
- vast pool of immature cells (non-functional)

2) Removal of potentially self-reactive immature lymphocytes by clonal deletion
- shapes repertoire of Ag responsive cells

3) Pool of mature naive lymphocytes
- cells that recognized specific Ag = very rare
- this explains why adaptive response takes more time

[Ag recognition –> activation]

4) Proliferation and differentiation of activated specific lymphocytes to form a clone of effector cells following recognition of Ag (activation)
- effectors are all derived from same parent cell
- all have same Ag receptor/specificity

32
Q

What’s the mechanism of central tolerance?

A

Elimination of cells that can recognized self Ags

33
Q

How long does lymphocyte activation take? What occurs during this time?

A
  • Process takes 4-5 days

- Expansion and acquisition of effector functions

34
Q

Where does lymphocyte development and activation occur?

A
  • Development in primary lymphoid tissues

- Activation in secondary lymphoid tissues

35
Q

Activation of T & B cells occurs through?

A

Signal 1 = antigen receptor
Signal 2 = costimulatory molecule

Absence of costimulation—> peripheral tolerance = backup for central tolerance

T-cells activated by mature DC
B-cells activated by T-cells

36
Q

Describe subtypes of T-cells

A

CD8+ T-cell = cytotoxic T-cell
-recognized MHC Class I/peptide and kills cell
CD4+ T-cell = helper T-cell
-recognizes MHC Class II and helps activate B cells
Other subtypes = Th1, Th2, Th17, and Tregs

37
Q

What are Ab functions that are produced by B-cells?

A
  • Neutralize
  • Block protein functions
  • Promote engulfment
  • induce complement mediated lysis

Different types of Ab Classes = IgM, IgG, IgE, IgA

38
Q

What is opsonization?

A

coating of a particle with proteins that facilitate phagocytosis of the particle by tissue macrophages and activated follicular dendritic cells (FDCs) as well as binding by receptors on peripheral blood cells

39
Q

What is different in the secondary immune response compared to the primary immune response?

A

Larger, faster, and more effective response.

Memory can lasts for decades

40
Q

Describe the dominant response for the types of pathogens

1) extracellular bacteria, parasites, fungi
2) intracellular bacteria, parasites
3) viruses (intracellular)
4) parasitic worms (extracellular)

A

Dominant response

1) Macrophages, Bcells - IgG
2) CD8 T cells, CD4 T cells
3) CD8 T cells, IgG
4) CD4 T cells, IgE

41
Q

What are MDSCs?

A
  • heterogeneous, immature myeloid phenotype
  • produce immunosuppressive cytokines, IL-10, TGF-B
  • Expand during inflammation, infection, and cancer
  • enriched in the TME
42
Q

What are T-regulatory cells?

A
  • inhibit or suppress other adaptive immune responses
  • recognize self Ag
  • Produce TGF-B and IL-10
  • Different subsets: 1) generated during development or 2) induced from naive T cells in the periphery
  • enriched in the TME
43
Q

Compare the receptors in innate vs adaptive immunity

A

Receptors in Innate immunity

  • specificity inhered in the genome
  • expressed by all cells of a particular type (e.g. macrophages)
  • triggers immediate response
  • recognizes broad classes of pathogens
  • interacts with a range of molecular structures of a given type

Receptors in Adaptive immunity

  • encoded in multiple gene segments
  • requires gene rearrangement
  • clonal distribution
  • able to discriminate between even closely related molecular structures