Immunology Flashcards

1
Q

Functions of the immune system in health and disease

A
  • Immunological recognition
  • Immune effector function
  • Immune regulation
  • Immunological memory
  • Ultimately, protection from pathogens and support organ system health.
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2
Q

What is primary lymphoid organ and what does it do?

A

1* lymphoid organs consist of bone marrow (B-cell development and T-cell progenitor cells); thymus (T-cell development); and fetal liver (source of specialized immune cells that develop differently).

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3
Q

What organ is T cell educated at?

A

Thymus

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4
Q

What is secondary lymphoid organs and what does it do?

A

2* lymphoid organs consist of:
- Spleen: filter blood. White pulp: responsible for non-self components. Red pulp: responsible for dysfunctional erythrocytes.
- Lymph node: filter lymphatics
- Tonsils, Peyer’s Patches: filter antigens of upper resp and GI tract.
- Appendix: species specific functions

Functions:
- antigen is encountered
- immune cells activated
- differentiation occurs

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5
Q

Examination of the cellular and molecular components of the blood allows for a ________ assessment of the immune system.

A

PARTIAL

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6
Q

Why can we not able to distinguish immune cells?

A

The activation status of these leukocytes and tissue-resident immune cells are not being assayed by looking at only cell morphology and blood count.

What to do: cells have unique gene transcription profiles that contains unique proteins.

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7
Q

What is CD?

A

Clusters of differentiation.
- “CD” followed by a number refers to unique structures/molecules on cells.
- CD is a common way to refer to different proteins.
- CD is an external cell marker that useful for distinguishing cell types within lymphoid and other cell lineages.

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8
Q

What circumstances change leukocyte homeostasis?

A

Immune system activation

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9
Q

Where do leukocytes go for distribution?

A
  • In and out of 2nd lymphoid organs (except macrophages and DC).
  • Into non-lymphoid tissue (intestines).
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10
Q

Define antigen.

A

Antigen is a molecule that is derived from an “invader” (pathogenic, allergenic, self molecule that triggers an autoimmune response).

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11
Q

Define antigen receptor

A

Antigen receptor is a protein that binds an antigen and promotes immunogenic activity.

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12
Q

What happened during innate immune cell activation? Think of strangers and dangers.

A
  • Must be able to differentiate self vs. non-self, pathogenic vs. non-pathogenic.
  • Strangers: presence of PAMPs expressed on pathogen structure. PAMPs can be LPS or CpGs.
  • Dangers: presence of DAMPs - the cell internal proteins such as heat-shock proteins, HMGB1, ATP
  • DAMPs and PAMPs are conserved epitopes.
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13
Q

What types of cells are the bridge between innate and adaptive immune system?

A

Dendritic cell and NK cell.

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14
Q

What happen during adaptive immune cell activation?

A
  • Immune system must be able to differentiate self vs. non-self; pathogenic vs. non-pathogenic.
  • Protein-protein interaction between B- and T- cell receptor to epitope (recognized motif) on antigen.
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15
Q

What is the consequence of immune cell activation?

A
  • Tissue: secrete chemokines and cytokines.
  • Endothelial cells express selectin ligands
  • Leukocyte express selectins and change chemokine receptor expression
  • Leukocytes roll, activate integrins (firm adhesion) which bind to endothelial cells.
  • Cell transmigrate from blood into tissues following chemokine gradient.
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16
Q

What cells belong to both innate and adaptive?

A

NK cell and dendritic cell

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17
Q

Characteristics of innate immune system: time, cell numbers, sophistication, memory

A
  • Fast (1st line of defense)
  • Lots of cells
  • Non-sophisticated
  • No memory
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18
Q

Characteristics of adaptive immune system: time, cell numbers, sophistication, memory

A
  • 1-2 weeks
  • Fewer cells
  • Sophisticated
  • Yes memory
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19
Q

What are responsibilities of innate immune system?

A
  • Defense against exogenous threats
  • Defense against endogenous threats
  • Housekeeping/clean up
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20
Q

Describe exogenous roadmap

A
  • Breach of barrier
  • Recognition by sentinels
  • Recruitment of reinforcement
  • Pathogen elimination and resolution
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21
Q

What are the types of barrier in innate system, and what does each one do?

A
  • Mechanical: epithelia form specialized barriers, tight junctions, different based on tissue (skin has non-resorptive multilayer, intestine has resorptive single layer, lung has resorptive thin layer).
  • Chemical: release antimicrobial substance (lysozyme, defensins, cathelicidins)
  • Microbial: resident flora prevents colonization of pathogens.
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22
Q

What types of defensin got secreted in skin, gut, lungs, eyes/nose/oral?

A
  • Skin and eyes/nose/oral = BETA
  • Gut and lungs = ALPHA
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23
Q

What cells act as sentinels at epithelial barriers?

A

Dendritic cells and macrophages

24
Q

What is macrophage characteristics and its route?

A
  • Macrophage is phagocytic cell that consumes foreign pathogens and cancer cells. It stimulates response of other immune cells.
  • Migrate from blood vessel into tissues
25
Q

What is dendritic cell characteristics and its route?

A
  • DC presents antigens on its surface (act as APC) to trigger adaptive immunity [T cell is able to detect it].
  • DC present in epithelial tissue, including skin, lungs, and tissues of the digestive tract. Migrates to lymph nodes upon activation.
26
Q

What is neutrophil characteristics and its route?

A
  • First responser at the site of infection/trauma. Represent 50-60% of leukocytes. Release toxins that kill/inhibit bacteria/fungi, recruits other immune cells to the site of infection.
  • Migrates from blood vessels into tissue.
27
Q

What is NK cell characteristics and its route?

A
  • NK kills tumor and virus-related cells.
  • Circulates in blood and migrate to tissues
28
Q

What is monocyte characteristics and its route?

A
  • Differentiate into macrophages and DC in response to inflammation.
  • Stored in spleen, moves through blood vessels to infected tissues.
29
Q

Macrophages origin of tissues? Explain the 2 population.

A
  • Fetal: progenitor cells enter tissues, they self-renew throughout adult life.
  • Adult: progenitor cell goes on to bone marrow to form monocyte, then deliver to tissue.
30
Q

Fate of macrophages? In healthy tissue and injury tissue.

A
  • Healthy: TRM (tissue resident macrophages) clear apoptotic cells without recruiting other cell using scavenger receptors.
  • Injured: TRM assisted by MoM (monocyte derived macrophages) to clean apoptosis. MoM self renew within tissue at resolution.
31
Q

Where is macrophages located in skin, GI, lungs, liver, and brain?

A
  • Skin and GI: behind epithelial barrier
  • Lung: alveolar cells (white space in pic)
  • Liver: Kupffer cells
  • Brain: microglia
32
Q

Why macrophage is located in microglia in brain?

A

Because of blood brain barrier, less surveillance, need for local mop up crew.

Bonus: Hematogenous infection

33
Q

Innate immune receptors - characteristics? what can they recognize? what kind of receptors are they?

A
  • One cell has MANY receptor types and MANY specificities.
  • They recognize CONSERVED epitopes.
  • They are pattern recognition receptors (PRRs).
34
Q

Adaptive immune receptors - characteristics? what can they recognize? what kind of receptors are they?

A
  • One cell has ONE receptor type and ONE specificity.
  • They recognize ANY epitope.
  • They use lymphocyte antigen receptors.
35
Q

What is PAMPs and what do they do?

A
  • PAMPs mean pathogen-associated molecular patterns.
  • They are repetitive structures (LPS, unmethylated DNA) that are found across classes of pathogens (bacteria, virus, fungi).
  • PAMPs signal stranger and recognized by PRRs (what is PRRs?).
36
Q

What is TLRs?

A
  • TLRs = toll-like receptor
  • Belongs to PRRs family, located in extracellular, cytosolic, endosome.
  • 13 TLRs discovered!
  • Triggered when encountering molecules that don’t exit in host or show up in the wrong compartment.
37
Q

What is DAMPs?

A
  • DAMPs = danger-associated molecule pattern, released by cellular trauma or stress.
  • DAMPs are cellular material which released into the extracellular (the wrong!) environment.
  • Can be recognized by PRRs.
    (Endogenous molecule in wrong compartment).
38
Q

Function of PRRs and its category?

A
  • Innate immune cells express many different types of PRRs in which each PRR can recognize different PAMP or DAMP.
  • Each cell type express the SAME array of PRR.
  • Grouped based on 1) structure/signaling pathway induction [TLRs] OR 2) sub-cellular location: cell surface, endosome, cytosol.
39
Q

NK cells characteristics and functions?

A
  • Come from innate lymphoid cells.
  • Function: cytotoxicity = destruction of target cells.
  • Binds MHC-1 on the surface of the cells.
  • NK cell receptors are activating and inhibitory.
  • Lack of killing requires inhibitory signal from MHC-1 of target cell
  • Killing occurs by pore formation (perforin) and release of cytotoxic granules if lack of MHC-1 in target (cancer/viral) cells.
40
Q

Where would you expect to find neutrophils during steady-state?

A

Bone marrow and blood

41
Q

What does signal transduction of TLR do?

A

Signal transduction involves a signal from engagement of receptor CONVERTED into a cellular response, usually involve cascade of signaling molecules AND changes in gene expression.

42
Q

Define cytokines

A
  • Turn things on/off
  • Small soluble signaling molecules that act on receptors and regulate the activation of cell differentiation - many different functions.
43
Q

Define chemokines

A
  • Move cells from point A to point B.
  • Chemo-attractants. Regulate cell migration by binding to chemokine receptors. Naming based on structure.
    [Usually name CLR, CCLR, CXCLR, CX3CLR]
44
Q

What’s growth factors?

A

They are colony stimulating factors (CSF)

45
Q

Name some cytokines

A

Interleukins (IL- )
Tumor necrosis factor TNF (alpha or beta)
Interferons IFN (alpha, beta, gamma)
Transforming growth factor TGF

46
Q

Pro-inflammatory cytokines: origin? function? name the cytokines.

A
  • Released by macrophages upon activation via PRR.
  • Stimulate inflammation
  • Name some: TNF-alpha; IL-1; IL-6
47
Q

Anti-inflammatory cytokines: origin? function? name the cytokines.

A
  • Released by engagement of scavenger receptors during healing phase of response.
  • Name some: TGF-beta; IL-10
48
Q

Define autocrine, paracrine, endocrine

A
  • Autocrine: signal to “self”
  • Paracrine: signal to cells in close proximity
  • Endocrine: signal to distant cells
49
Q

Effects of pro-inflammatory cytokines in different organs?

A
  • Liver: acute-phase proteins for opsonization
  • Bone marrow: neutrophils for phagocytosis
  • Hypothalamus: increase body temp
  • Fat, muscle: protein and energy mobilization to increase body temp => decreased pathogen replication, increase antigen processing.
  • DC: migration to LN to initiate adaptive immune response.
50
Q

What is acute-phase protein and its role?

A
  • APPs (in liver!!) are a class of proteins whose plasma concentrations increase or decrease in response to inflammation.
  • Its role: opsonization, complement activation, chemotaxis, trapping microbes.
51
Q

How does the innate immune system kill?

A
  • Phagocytosis
  • NETosis
  • Complement system
52
Q

Explain phagocytosis.

A

Microbe bound by receptor on surface of phagocytes, internalized, fused with lysosome to become phagolysosome, formation of oxide radicals, lower pH for killing.

53
Q

Explain netosis.

A

Nuclear chromatin is released into extracellular space creating NETs (neutrophil extracellular traps) to capture microbes and facilitate phagocytosis more easily.

54
Q

Complement system purpose and origin?

A
  • Purpose: clear microbes, promote inflammation, attack pathogen cell membrane.
  • Origin: synthesize in liver, present in blood, 10% of globulin of blood serum.
55
Q

Complement system

A
  • 3 pathways: alternative, classical, and lectin pathways.
  • Cleave C3 to C3a and C3b. Cleave C5 to C5a and C5b.
  • “a” = inflammation
  • “b” = opsonization and phagocytosis
  • Also activate MAC for lysis of microbes.
56
Q

Effects of C3a, C4a, C5a?

A
  • AKA anaphylatoxins.
  • Increase vascular permeability, accelerate diapedesis.
57
Q
A