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
What is dendritic cell characteristics and its route?
- 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
What is neutrophil characteristics and its route?
- 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
What is NK cell characteristics and its route?
- NK kills tumor and virus-related cells. - Circulates in blood and migrate to tissues
28
What is monocyte characteristics and its route?
- Differentiate into macrophages and DC in response to inflammation. - Stored in spleen, moves through blood vessels to infected tissues.
29
Macrophages origin of tissues? Explain the 2 population.
- 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
Fate of macrophages? In healthy tissue and injury tissue.
- 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
Where is macrophages located in skin, GI, lungs, liver, and brain?
- Skin and GI: behind epithelial barrier - Lung: alveolar cells (white space in pic) - Liver: Kupffer cells - Brain: microglia
32
Why macrophage is located in microglia in brain?
Because of blood brain barrier, less surveillance, need for local mop up crew. Bonus: Hematogenous infection
33
Innate immune receptors - characteristics? what can they recognize? what kind of receptors are they?
- One cell has MANY receptor types and MANY specificities. - They recognize CONSERVED epitopes. - They are pattern recognition receptors (PRRs).
34
Adaptive immune receptors - characteristics? what can they recognize? what kind of receptors are they?
- One cell has ONE receptor type and ONE specificity. - They recognize ANY epitope. - They use lymphocyte antigen receptors.
35
What is PAMPs and what do they do?
- 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
What is TLRs?
- 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
What is DAMPs?
- 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
Function of PRRs and its category?
- 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
NK cells characteristics and functions?
- 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
Where would you expect to find neutrophils during steady-state?
Bone marrow and blood
41
What does signal transduction of TLR do?
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
Define cytokines
- Turn things on/off - Small soluble signaling molecules that act on receptors and regulate the activation of cell differentiation - many different functions.
43
Define chemokines
- 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
What's growth factors?
They are colony stimulating factors (CSF)
45
Name some cytokines
Interleukins (IL- ) Tumor necrosis factor TNF (alpha or beta) Interferons IFN (alpha, beta, gamma) Transforming growth factor TGF
46
Pro-inflammatory cytokines: origin? function? name the cytokines.
- Released by macrophages upon activation via PRR. - Stimulate inflammation - Name some: TNF-alpha; IL-1; IL-6
47
Anti-inflammatory cytokines: origin? function? name the cytokines.
- Released by engagement of scavenger receptors during healing phase of response. - Name some: TGF-beta; IL-10
48
Define autocrine, paracrine, endocrine
- Autocrine: signal to "self" - Paracrine: signal to cells in close proximity - Endocrine: signal to distant cells
49
Effects of pro-inflammatory cytokines in different organs?
- 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
What is acute-phase protein and its role?
- 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
How does the innate immune system kill?
- Phagocytosis - NETosis - Complement system
52
Explain phagocytosis.
Microbe bound by receptor on surface of phagocytes, internalized, fused with lysosome to become phagolysosome, formation of oxide radicals, lower pH for killing.
53
Explain netosis.
Nuclear chromatin is released into extracellular space creating NETs (neutrophil extracellular traps) to capture microbes and facilitate phagocytosis more easily.
54
Complement system purpose and origin?
- Purpose: clear microbes, promote inflammation, attack pathogen cell membrane. - Origin: synthesize in liver, present in blood, 10% of globulin of blood serum.
55
Complement system
- 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
Effects of C3a, C4a, C5a?
- AKA anaphylatoxins. - Increase vascular permeability, accelerate diapedesis.
57