Immunology Flashcards

1
Q

What are the primary lymphoid organs? What is their major role?

A
  • (primary lymphoid organs are where lymphocytes are formed and matured)
  • 2 primary lymphoid structures: bone marrow and the thymus
  • bone marrow: site of T and B cell formation; site of B cell maturation
  • thymus: site of T cell maturation
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2
Q

What are the secondary lymphoid organs?

A
  • (secondary lymphoid organs are essentially filters that monitor the body’s fluids and organs for any pathogens; they are the sites of lymphocyte activation)
  • lymph nodes and vessels, spleen, tonsils, Peyer’s patches, MALT
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3
Q

What are the three major parts of a lymph node? What is found/what occurs in each?

A
  • follicle, paracortex, and medulla
  • follicle: (outer portion of cortex) site of B-cell localization and proliferation
  • paracortex: (inner portion of cortex) houses T-cells
  • medulla: site of lymph flow from afferent lymphatic to efferent lymphatic; contains medullary sinusoids and medullary cords (sinusoids are passages for lymph flow and contain macrophages and reticular cells; cords are lymphatic tissue made up of Ab-secreting plasma cells and lymphocytes)
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4
Q

What does the right lymphatic duct drain? The left lymphatic duct?

A
  • right lymphatic duct drains the right side of the body that lies above the diaphragm (includes the right upper limb)
  • left lymphatic duct drains everything else (it arises from the thoracic duct, which essentially drains the lower half of the body and abdomen via the cisterna chyli)
  • each duct drains into the junction between the left or right subclavian and internal jugular veins
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5
Q

Which lymph nodes drain each part of the body?

A
  • head and neck: cervical nodes
  • lungs: hilar nodes
  • trachea and esophagus: mediastinal nodes
  • upper limb, breast, skin above umbilicus: axillary nodes
  • liver, stomach, spleen, pancreas, upper duodenum (foregut): celiac nodes
  • lower duodenum, jejunum, ileum, colon to splenic flexure (midgut): superior mesenteric nodes
  • colon from splenic flexure through anal canal (hindgut): inferior mesenteric, internal iliac, and superficial inguinal nodes
  • bladder, vagina, prostate: internal iliac nodes
  • testes, ovaries, kidneys, uterus: para-aortic nodes
  • skin below umbilicus: superficial inguinal nodes
  • dorsolateral foot, posterior calf: popliteal nodes (these areas are not drained by the superficial inguinal nodes even though they are below the umbilicus)
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6
Q

What makes up the red and white pulps of the spleen? What is found in between the two pulps?

A
  • red pulp: RBCs
  • white pulp: T-cells (in the periarterial lymphatic sheath) and B-cells (in follicles/germinal centers)
  • the marginal zone (between the red and white pulp) contains APCs
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7
Q

Which organisms is an asplenic individual susceptible to? Why?

A
  • encapsulated organisms
  • asplenic patients have decreased levels of IgM, which means a lowered ability to activate complement, which means decreased opsonization (opsonization is needed to phagocytose encapsulated organisms)
  • SHiNE SKiS: Strep pneumoniae, Hib, Neisseria meningitidis, Escherichia coli, Salmonella, Klebsiella pneumoniae, Strep agalactiae (group B strep)
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8
Q

Quickly compare innate and adaptive immunity.

A
  • innate: nonspecific; rapid response (minutes to hours); neutrophils, macrophages, monocytes, complement, dendritic cells, NK cells; recognizes pathogenic PAMPs (pathogen-associated molecular patterns) via TLRs (a type of pattern recognition receptor, PRR)
  • adaptive: highly specific; develops over long periods, but subsequent exposures trigger faster and more robust responses; T-cells, B-cells, antibodies; recognizes pathogens via APCs and memory cells
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9
Q

What is MHC? What is its major purpose?

A
  • major histocompatibility complex; 2 classes: types I and II
  • humans have HLA (human leukocyte antigen)
  • MHC is needed to present antigen fragments to T-cells in order to trigger an adaptive immune response; it essentially allows for self-recognition vs. pathogen recognition
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10
Q

MHC Class I; which cells have it? What does it bind to? Which type of antigen does it work with? What is its function?

A
  • MHC class I (loci: HLA-A, HLA-B, and HLA-C)
  • found on all nucleated cells of the host (RBCs lack nuclei, so they lack MHC I)
  • binds to T-cell receptor (TCR) and CD8
  • function: presents endogenously synthesized antigens of its own cell (self-antigens, viral antigens, etc.) to CD8+ cytotoxic T-cells
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11
Q

MHC Class II; which cells have it? What does it bind to? Which type of antigen does it work with? What is its function?

A
  • MHC class II (loci: HLA-DR, HLA-DP, HLA-DQ)
  • found ONLY on APCs (macrophages, dendritic cells, B-cells, Langerhans cells in skin)
  • bind to T-cell receptor (TCR) and CD4
  • function: presents exogenously synthesized antigens gathered from the body (bacteria, etc.) to CD4+ T-helper cells
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12
Q

What are NK cells? How do they work? What do they target? How are they activated? Are they lymphocytes or monocytes?

A
  • NK cells are natural killer cells
  • they use perforin and granzymes to induce apoptosis in targeted cells
  • they target cells LACKING MHC I (tumor cells, virally infected cells)
  • MHC I binds to the NK cell’s inhibitory receptors (CD16), so without this signal, the NK cell gets activated
  • NK cells are also activated via antibody-dependent cell-mediated cytotoxicity (NK cell’s CD16 binds to Fc portion of bound IgG, triggering its activation)
  • they are lymphocytes, but are part of innate immunity!
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13
Q

In very simple terms, what are the major functions of B- and T-cells?

A
  • B-cells: recognize antigen and undergo somatic hypermutation to optimize antigen specificity; produce antibodies as plasma cells; maintain memory as memory B-cells
  • CD4+ T-cells: (helper T-cells) assist B-cells to make antibodies, release cytokines that activate other immune cells/responses
  • CD8+ T-cells: (cytotoxic T-cells) directly kill virus-infected cells, neoplastic cells, donor-graft cells by inducing apoptosis
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14
Q

What happens to naive T-cells in the thymic cortex? What about in the medulla?

A
  • in the thymic cortex, naive T-cells undergo positive selection: those that have TCRs able to recognize MHC molecules will SURVIVE (because MHC recognition is the basis for how these cells function)
  • those that survive move onto the medulla
  • in the medulla, they undergo negative selection: those that have TCRs with high affinity for self antigens will undergo APOPTOSIS (this creates self tolerance)
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15
Q

How many signals are needed for T-cell activation? B-cell activation? What are they for each?

A
  • both cell types require 2 signals to be activated
  • helper T-cells: APC’s MHC II-antigen complex binds to TCR + APC’s B7 binds to T-cell’s CD28
  • cytotoxic T-cells: infected cell’s MHC I-antigen complex binds to TCR + B7 binds to CD28
  • B-cells: B-cell’s MHC II-antigen complex binds to helper T-cell’s TCR (remember B-cells are also APCs!) + B-cell’s CD40 receptor binds to helper T-cell’s CD40 ligand
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16
Q

What triggers CD4+ helper T-cells to differentiate into Th1 cells? Th2 cells? Th17 cells? T-reg cells?

A
  • IL-12 causes differentiation into Th1 cells
  • IL-4 causes differentiation into Th2 cells
  • TGFb with IL-6 causes differentiation into Th17 cells
  • TGFb causes differentiation into T-reg cells
17
Q

What is the major role of Th1 cells? What do they secrete? How are they activated and how are they inhibited?

A
  • Th1 cells activate macrophages and cytotoxic T-cells (and NK cells)
  • they secrete IFN-gamma and IL-2 in order to do so
  • activated by IL-12 (IL-12 induces CD4+ T-cells to differentiate into Th1 cells), which is secreted by macrophages; the Th1 cells are then able to stimulate the macrophages (so they help each other in order to help each other)
  • inhibited by IL-4 (secreted by Th2 cells) and IL-10 (major anti-inflammatory factor; secreted by Th2 and T-reg cells)
18
Q

What is the major role of Th2 cells? What do they secrete? How are they activated and how are they inhibited?

A
  • Th2 cells recruit eosinophils to attack parasites, and promote IgE production by B-cells
  • they secrete IL-4, IL-5, IL-6, IL-10 (and IL-2, IL-13)
  • activated by IL-4 (they secrete it and are activated by it)
  • inhibited by IFN-gamma, which is secreted by Th1 cells
19
Q

What do T-reg cells do? How are they identified?

A
  • regulatory T-cells help maintain immune tolerance
  • they suppress CD4 and CD8 T-cells by releasing anti-inflammatory cytokines (IL-10 and TGF-beta)
  • T-reg cells have CD3, CD4, and CD25; they also have the FOXP3 transcription factor
20
Q

What is the structure and function of an antibody?

A
  • antibodies have 2 chains: a light chain and a heavy chain
  • the Fab portion (fraction of antigen-binding) is the unique variable part of the antibody that binds to the unique antigen
  • the Fc portion (fraction of crystallization) is the constant part of the antibody and determines the Ab isotype (G, A, M, D, E); involved in complement binding (only IgG and IgM), antibody-dependent cell-mediated cytotoxicity
21
Q

Which immunoglobulin isotypes are expressed on mature B-cells?

A
  • IgM and IgD
  • mature B-cells can then undergo class switching to produce and secrete IgG, IgA, or IgE
  • (IL-4 enhances class switching to IgE and IgG; IL-5 enhances class switching to IgA)
22
Q

What are the five isotypes of immunoglobulin and what are the major functions of each?

A
  • IgG: the main antibody in a secondary (delayed, re-exposure) response to an antigen; can fix complement; can cross the placenta to provide passive immunity; can opsonize bacteria; neutralization; antibody-dependent cell-mediated cytotoxicity
  • IgA: protects mucous membranes; abundant in secretions (tears, milk, saliva, mucus); secreted as a dimer
  • IgM: the main antibody in primary (immediate) response to an antigen; can fix complement; found on surface of B-cells; secreted as a pentamer
  • IgD: unclear function, found on surface of B-cells
  • IgE: binds to mast cells and basophils; cross-links and activates with exposure to allergens (involved in immediate/type I hypersensitivity); activates eosinophils to help mediate immunity against worms
23
Q

What are acute-phase reactants? Where are they produced? What do they respond to?

A
  • acute-phase reactants are serum factors whose concentrations significantly change (either increase or decrease) in response to inflammation
  • they are produced in the liver
  • induced by IL-6 (and also IL-1, TNF-alpha, and IFN-gamma)
  • upregulated: serum amyloid A, C-reactive protein (CRP), ferritin, fibrinogen, hepcidin
  • downregulated: albumin, transferrin
24
Q

What are the five positive/upregulated acute-phase reactants? What is each associated with?

A
  • (these are serum factors that are significantly increased in response to inflammation; they are produced in the liver)
  • serum amyloid A: can lead to amyloidosis
  • C-reactive protein (CRP): this is an opsonin, it helps fix complement and facilitates phagocytosis; a major clinical sign of ongoing inflammation
  • ferritin: binds to iron to inhibit microbial iron scavenging
  • fibrinogen: a coagulation factor; this is what increases the ESR
  • hepcidin: prevents the release of ferritin-bound iron; this is what causes anemia of chronic disease
25
Q

What are the two negative/downregulated acute-phase reactants? What is each associated with?

A
  • (these are serum factors that are significantly decreased in response to inflammation; they are produced in the liver)
  • albumin: by decreasing albumin production, the liver can increase the production of the positive acute-phase reactants
  • transferrin: these are what carry iron in the circulation; they are internalized by macrophages during inflammation in order to further sequester iron from microbes
26
Q

What is complement? What are the major complement proteins and their roles?

A
  • complement is a system of plasma proteins that assist in innate immunity and inflammation
  • C3b: major opsonin
  • C5a: neutrophil chemotaxis
  • C5b, C6, C7, C8, C9: form the membrane attack complex (MAC) to cause cell lysis
  • C4b2b: C3 convertase
  • C4b2b3b: C5 convertase
  • (note that C3a, C4a, and C5a play a role in causing anaphylaxis)
27
Q

What prevents complement activation on self cells?

A
  • decay-accelerating factor (DAF, AKA CD55)

- C1 esterase inhibitor

28
Q

What are the major cytokines secreted by macrophages? What is the role of each?

A
  • IL-1, IL-6, IL-8, IL-12, TNF-alpha
  • IL-1: endogenous pyrogen; fever; acute inflammation; activates endothelium to express adhesion molecules
  • IL-6: (also secreted by Th2 cells) endogenous pyrogen; fever; stimulates acute-phase reactants
  • IL-8: major chemotactic factor for neutrophils
  • IL-12: (also secreted by B cells) triggers helper T-cell differentiation into Th1 cells; activates NK cells
  • TNF-alpha: mediates septic shock; activates vascular endothelium to increase permeability; recruits leukocytes
29
Q

What are the major cytokines secreted by all T-cells? What is the role of each?

A
  • IL-2 and IL-3
  • IL-2: stimulates helper, cytotoxic, and regulatory T-cells
  • IL-3: stimulates bone marrow stem cells to grow and differentiate
30
Q

What are the major cytokines secreted by Th1 cells? What is the role of each?

A
  • interferon gamma (and IL-2 and IL-3 as it’s a T-cell)
  • IFN-gamma: activates NK cells and macrophages; increases MHC expression/antigen presentation in nearby cells; has antiviral and anti-tumor properties; inhibits Th2 cell differentiation
31
Q

What are the major cytokines secreted by Th2 cells? What is the role of each?

A
  • IL-4, IL-5, IL-6, IL-10 (and IL-2 and IL-3 as it’s a T-cell)
  • IL-4: induces differentiation of helper T-cells into Th2 cells; promotes B-cell growth; enhances class switching to IgE and IgG
  • IL-5: promotes differentiation of B-cells; enhances class switching to IgA; stimulates eosinophils
  • IL-6: (also secreted by macrophages) endogenous pyrogen; fever; stimulates acute-phase reactants
  • IL-10: (also secreted by T-reg cells) an anti-inflammatory factor that inhibits T-cells; similar action as TGF-B
32
Q

What are the main functions of interleukins 1 through 6?

A
  • “Hot T-Bone stEAK”
  • IL-1: Hot; fever
  • IL-2: T; stimulates T-cells
  • IL-3: Bone; stimulates bone marrow stem cells
  • IL-4: E; stimulates IgE production (and IgG)
  • IL-5: A; stimulates IgA production
  • IL-6: K; stimulates “aKute” phase reactants
33
Q

What other interferons are there other than IFN-gamma? What is the role of each?

A
  • (IFN-gamma secreted by Th1 cells; it activates NK cells, increases MHC expression/antigen presentation in nearby cells, and has antiviral and anti-tumor properties)
  • IFN-alpha and IFN-beta also exist
  • they are secreted by virally-infected cells and act on nearby uninfected cells to “warn” them of the infection and “prime” them for viral defense
  • when a virus infects a primed cell, the cell essentially undergoes apoptosis (destroys the viral DNA/RNA and viral proteins in the process) to halt viral amplification
34
Q

Which cell surface proteins are found on all T-cells? Helper T-cells? Cytotoxic T-cells?

A
  • (all nucleated cells have MHC I)
  • TCR: binds to MHC-antigen complexes (helper T-cells will bind to MHC II on APCs, cytotoxic T-cells will bind to MHC I on all cells)
  • CD3: associated with the TCR for signal transduction
  • CD28: binds to the APC’s B7 (co-stimulation)
  • helper T-cells: CD4+ (marker) and CD40 ligand (binds to B-cell’s CD40 receptor to activate B-cell)
  • cytotoxic T-cell: CD8+ (marker)
35
Q

Which cell surface proteins are found on B-cells?

A
  • (all nucleated cells have MHC I)
  • CD19
  • CD20
  • CD21: a specific receptor for EBV
  • CD40: the receptor for T-cell’s CD40 ligand, binding activates the B-cell
  • MHC II: B-cells are APCs (binds to helper T-cell’s TCR)
  • B7: B-cells are APCs (binds to T-cell’s CD28 to provide necessary co-stimulation for activation)
36
Q

Which cell surface proteins are found on macrophages?

A
  • (all nucleated cells have MHC I)
  • CD14
  • CD40
  • MHC II: macrophages are APCs (binds to helper T-cell’s TCR)
  • B7: macrophages are APCs (binds to T-cell’s CD28 to provide necessary co-stimulation for activation)
  • Fc and C3b receptors (bind to antibodies and complement to enhance phagocytosis of opsonized microbes)
37
Q

Which cell surface proteins are found on NK cells?

A
  • (all nucleated cells have MHC I)
  • CD56: unique marker
  • CD16: binds to IgG’s Fc region to trigger antibody-dependent cell-mediated cytotoxicity; also provides inhibitory signals to the cell when bound to MHC I