Term
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Definition
Macrophages, Endothelial Cells, Dendritic cells, Langerhans cells
Stimulates IL-2 receptor emergence in T cells
Enhances B cell activation and clonal expansion
Induces IL-6
Chemotactic for neutrophils and macrophages
Enhances activity of NK cells |
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Term
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Definition
Th1 cells
T-cell growth factor, proliferation, enhanced activity
Activates NK and B cells |
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Term
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Definition
T cells, NK cells
Stimulates hematopoiesis - growth and differentiation |
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Term
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Definition
T cells (Th2)
Stimulated B cell class switch to IgG or IgE
Down-regulation of IFN-gamma
Upregulated MHC Class II expression |
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Term
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Definition
T cells (Th2)
Stimulate growth/differentiation of eosinophils
B-cell growth factor, induces class switch to IgA |
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Term
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Definition
Monocytes, T cells, Endothelial cells
Induces acute phase reactants in hepatocytes
Fever
Late B cell differentiation --> Plasma cells
Ab secretion |
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Term
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Definition
Bone marrow, Thymic stroma
Stimulates differentiation into pre-B and pre-T cells |
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Term
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Definition
Monocytes, Endothelial cells, Lymphocytes, FIbroblasts
Chemotactic factor for neutrophils and T cells - induces adherence to endothelium and extravasation |
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Term
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Definition
T Helped Cells
T-cell mitogen |
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Term
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Definition
Th2 Cells
Inhibits IFN-gamma synthesis by Th1 cells
Suppresses other cytokine synthesis by Th1 cells |
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Term
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Definition
Bone Marrow
Stimulates Hematopoiesis
Increases acute phase protein synthesis |
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Term
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Definition
Macrophages, B cells
Promotes Th1 differentiation into CTLs and INF-gamma synthesis
Stimulates NK cells and CD8+ cells to cytolysis
Acts synergistically with IL-2 |
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Term
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Definition
Th2 cells
Inhibits inflammatory cytokines |
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Term
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Definition
T cells
T-cell mitogen
ENhances growth of intestinal epithelium |
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Term
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Definition
CD8+ cells, Eosinophils
Increases MHC Class II, chemotaxis, and CD4+ cytokines
Decreases antigen-induced proliferation |
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Term
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Definition
T cells
Increases inflammatory response |
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Term
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Definition
Activated macrophages
Increases IFN-gamma production and NK cell action |
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Term
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Definition
Macrophages, T cells, B cells, NK cells
Mediates recruitment of leukocytes to sites of infection
Cytotoxic for tumors
Mediates bacterial shock |
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Term
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Definition
T cells (Th1) and CTLs
Cytotoxic for tumors
Enhances phagocytic activity of macrophages and neutrophils |
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Term
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Definition
All cells
Inhibits proliferation of T and B cells
Induces class switch to IgA
Decreases cytokine receptors
CHemotactic for leukocytes
Inflammation and tissue repair |
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Term
| Anti-Thymocyte Globulin (ATG/ALG) |
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Definition
Anti-thymocyte
Use: Induction Tx. prior to organ transplant - acute organ rejection
MOA: binds lymphocytes inhibiting cell function and trigger cell destruction
Contra: Increase risk for serious infections
Side effects: anti-ATG Ab response, CRS, bone marrow suppression |
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Term
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Definition
Murine mAb
Use: Induction Tx.prior to transplant; reduces acute rejection
MOA: binds thymocytes & T cell CD3 proteins - triggers cell lysis
Contra: increases risk for serious infection - anti-mAb response
SIde effects: CRS, shock, seizures, pulmonary edema
Used infrequently |
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Term
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Definition
Anti-IL-2 Reeptor - "Humanized" mAbs
Use: Induction treatment, acute organ rejection
MOA: bind IL-2 receptor alpha-subunit - prevents T cell activation
Contra: acute hypersensitivity, CRS
Side effects: modest CRS, increased risk of infections |
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Term
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Definition
Anti-IL-2 Reeptor - "Humanized" mAbs
Use: Induction treatment, acute organ rejection
MOA: bind IL-2 receptor alpha-subunit - prevents T cell activation
Contra: acute hypersensitivity, CRS
Side effects: modest CRS, increased risk of infections |
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Term
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Definition
Normal human IgG Antibodies
Use: Immunodeficiency treatment, bone marrow transplant, autoimmune crisis
MOA: serves as replacement IgG and suppresses autoimmune responses
Side effects: headache, myalgia - risk of viral contamination |
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Term
| Rho(D) Immune Globulin, IgG |
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Definition
Rho(D)-factor directed human IgG Abs
Use: Admin. to RhoD negative mother with positive child
MOA: BLocks recognition of blood cell ThoD positive protein
Side effectsL allergy response, rarely anaphylaxis |
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Term
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Definition
IL-1 Receptor Antagonist
Use: Moderate to Severe Rheumatoid Arthritis
MOA: Binds IL-1 receptor, blocks IL-1 binding and T cell activation
Contra: no to be administered if allergic to E. Coli-derived proteins
Side effects: increased risk of serious infections
- 2nd line Tx. for std. treatment in unresponsive patients |
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Term
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Definition
Anti-TNF-alpha humanized mAbs
Use: Rheumatoid arthritis, psoriasis, Crohn's disease
MOA: binds TNF-alpha, prevents inflammatory responses
Contra: presence of dormant TB or fungal infection
Side effects: Resurgence of TB and fungal infection - rare lymphomas |
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Term
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Definition
Anti-TNF-alpha humanized mAbs
Use: Rheumatoid arthritis, psoriasis, Crohn's disease
MOA: binds TNF-alpha, prevents inflammatory responses
Contra: presence of dormant TB or fungal infection
Side effects: Resurgence of TB and fungal infection - rare lymphomas |
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Term
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Definition
Anti-TNF-alpha humanized mAbs
Use: Rheumatoid arthritis, psoriasis, Crohn's disease
MOA: binds TNF-alpha, prevents inflammatory responses
Contra: presence of dormant TB or fungal infection
Side effects: Resurgence of TB and fungal infection - rare lymphomas |
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Term
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Definition
Anti-lymphocyte mAb
Use: Aggressive B-cell non-Hodgkins Lymphoma
MOA: binds B-cell protein CD20, induces lysis and apoptosis
igh risk of hematologic toxicity and infections
Contra: prior infusion reaction
Side effects: acute infusion rxn, CRS, tumor lysis syndrome (TLS) |
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Term
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Definition
Anti-lymphocyte mAb
Use: Chemotherapy - refractory B-cell chronic lymphocytic leukemia
MOA: binds B & T cell protein CD52, induces lysis and apoptosis
Contra: Prior infusion reaction
Side effects: lymphopenia, neutropenia, anemia, infusion reaction
High risk of hematologic toxicity and infections |
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Term
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Definition
Interferon
Use: Hairy cell leukemia, chronic myelogenous leukemia, hepatitis C
MOA: binds IFN-alpha receptor, antiviral, anti-proliferation
Side effects: CRS potential, injection site rxns |
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Term
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Definition
Interferon
Use: Hairy cell leukemia, chronic myelogenous leukemia, hepatitis C
MOA: binds IFN-alpha receptor, antiviral, anti-proliferation
Side effects: CRS potential, injection site rxns |
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Term
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Definition
Interferon
Use; genital warts, Kaposi sarcoma; A-type multiple sclerosis
MOA: binds IFN-beta receptor, antiviral, anti-proliferation
Contra: No in children <18 - reports of suicide
Side effects: CRS, Altered menstrual cycle and moods, decreases steroid hormones |
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Term
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Definition
Interferon
Use; genital warts, Kaposi sarcoma; A-type multiple sclerosis
MOA: binds IFN-beta receptor, antiviral, anti-proliferation
Contra: No in children <18 - reports of suicide
Side effects: CRS, Altered menstrual cycle and moods, decreases steroid hormones |
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Term
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Definition
Interferon
Use: Chronic granulomatous disease
MOA: binds IFN-gamma receptor and stimulates granulocyte function
Side effects: CRS, injection site rxns |
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Term
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Definition
| Produce IFN-gamma, IL-2, TNF |
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Term
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Definition
Anti-metabolite
Use: Organ rejection; Autoimmunity (Arthritis, Crohn’s disease); Isoimmunities
- It’s products are immunosuppressive, cytotoxic antimetabolites – Esp. T and B cell proliferation
MOA – Pro-drug. Inhibits purine and DNA synthesis (S-phase specific) |
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Term
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Definition
Cytotoxic Agent
Use: Autoimmune responses (Lupus, Wegener’s granulomatosis, nephritic syndrome); Cancers (Lymphomas/Chronic Leukemia)
Suppresses T and B cell proliferation
MOA: covalently reacts with nucleotide bases/proteins. Crosslinks DNA bases
Side Effects: All proliferating cells are sensitive to its actions (Esp. bone marrow and mucosal cells); Carcinogenic and Secondary malignancies may develop; Teratogenic |
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Term
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Definition
Antibiotic
Most responsible for increasing patient survivability after organ transplant.
Use: Organ rejection; Autoimmunity
MOA: Binds to cyclophilin which downregulates the phosphate activity of Calcineurin (downregultes IL-2 and other cytokine production
Side effects: Renal toxicity, HTN, hyperkalemia, hyperglycemia, GI distress, hirsutism, increased statins
- Metabolized by p450, Long t1/2 |
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Term
| Mycophenolate Mofetil (MMF) |
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Definition
Anti-Metabolite
Use: Control rejection after organ transplant
MOA: Pro-drug- Hydrolyzes to an immunosuppressive reversible enzyme inhibitor or antimetabolite in T and B cells (S-phase specific); Blocks purine and DNA synthesis; Initiaties apoptosis
Side effects: GI disorders, diarhhea, nausea, vomiting, CRS, Teratogenic, Myelosuppression (with leucopenia)
BAD: Progressive Multifocal Leukeoencephalopathy – attacks the brain and CNS – fatal |
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Term
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Definition
Corticosteroid
Use: Organ rejection; Autoimmunities; Cancers; Inflammatory disease
Non-cytotoxic, affects receptor-mediated events; General anti-inflammatory and immunosuppressive
Actions: 1) Transient reduction in circulating lymphocytes; 2) T-cell activation inhibition; 3) PLA2 inhibition (downregulated prostaglandins, leukotrienes - inflammatory agents) |
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Term
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Definition
Antibiotic
Use: organ rejection, autoimmunity
MOA: Complexes and binds to mTOR to inhibit a kinase system to decrease cell growth and proliferation.
Side effects: bone marrow suppression, little renal toxicity. NOT approved for liver or lung transplantation |
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Term
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Definition
Antibiotic
Use: Organ rejection, autoimmunity
MOA: Downregulates the transcription processes (via calcineurin) that normally woulda been upregulated
Side effects: renal toxicity, HTN, hyperkalemia, hyperglycemia, GI distresss, neurotoxic, T1DM |
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Term
| Chronic Granulomatous Disease |
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Definition
Defect in Phagocytic Cells
- Deficiency in NADPH Oxidase subunit --> Failure to make superoxide anion and other O2 radicals
Symptoms: Recurrent infections with catalase-positive bacteria |
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Term
|
Definition
Defect in Phagocytic cells
- Granule Structural defect
Symptoms: Recurrent infection with bacteria; chemotactic and degranulation defects; Absent NK activity; Partial albinism |
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Term
| Myeloperoxidase Deficiency |
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Definition
Defect in Phagocytic Cells
- Granule Enzyme Deficiency
Symptoms: Mild or none
VERY COMMON - often unnoticed |
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Term
| Leukocyte Adhesion Deficiency |
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Definition
Defect in Phagocytic Cells
- Absence of CD18 - common beta chain of leukocyte integrins
Symptoms: Recurrent and chronic infections; No pus; Do not reject umbilical cord stump |
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Term
| X-linked Agammaglobulinemia |
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Definition
Defect of Humoral Immunity
- Deficiency of Bruton's Tyrosine Kinase that blocks B cell maturation
Symptoms: Low Ig of all classes; No circulating B cells; Pre-B cells in bone marrow in normal numbers; Normal cell-mediated immunity
Tx: monthly IgG replacement |
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Term
| Transient Hypogammaglobulinemia of Infancy |
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Definition
Defect of humoral Immunity
- Delayed onset of normal IgG synthesis
Symptoms: detected in 5-6th mos; resolved by 16-30 mos; Susceptible to pyogenic bacteria
Tx: Antibiotics and IgG replacement in severe cases |
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Term
|
Definition
Defect of humoral immunity
- Deficiency of IgA (most common)
Symptoms: Repeated sinopulmonary and GI infections
Tx: ANtibiots (NOT IgGs) |
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Term
| Common Variable Hypogammaglobulinemia |
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Definition
Defect or humoral immunity
- Cause unknown
Symptoms: Onset in late teen/early 20s; B cells present in peripheral blood; Ig levels decrease with time; Increased Autoimmunity
Tx: Antibiotics |
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Term
| X-Linked HyperIgM Syndrom |
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Definition
Defect of humoral immunity
- Deficiency of CD40L on activted T cells (Can't activate B cells)
Symptoms: High titers of IgM w/o other isotypes; Normal B and T cell numbers; Susceptible to extracellular bacteria and opportunists
Tx: Antibiotics and IgG |
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Term
| Deficiency of Complement Components - Classical Pathway |
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Definition
Deficiency of C1, C2, or C4
SIgns: Marked increase in immune complex disease; increased infections with pyogenic bacteria |
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Term
| Deficiency of Complement Components - Alternative Pathway |
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Definition
Deficiency of Factor B or Properdin
Symptoms: Increased Neisseria infections |
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Term
| Deficiency of Complement Components - Both Pathways |
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Definition
Deficiency of C3
Symptoms: Recurrent bacterial infections; immune complexes diseases |
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Term
| Deficiency of Complement Components - Both Pathways |
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Definition
Deficiency of C5, C6, C7, or C8
Symptoms: Recurrent meningococcal and gonococcal infections |
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Term
| Deficiency of Complement Regulatory Proteins |
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Definition
Deficiency of C1-INH
Symptoms: Overuse of C1, C4, or C2; Edema at mucosal surfaces |
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Term
| Deficiency of Complement Regulatory Proteins |
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Definition
Deficiency of Decay-activating factor or homologous restriction factor
Symptoms: Paroxysmal noctural hemoglobinuria |
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Term
|
Definition
Selective T cell Deficiency
- Blocks T cell maturation: Stem Cell --> Pro-T
- Failure of formation of 3rd and 4th pharyngeal pouches, Thymic aplasia
Symptoms: Facial abnormalities; HypoPTH; Cardiac malformations; Depressed T cell numbers; Absence of T cell response |
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Term
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Definition
Selective T-Cell Deficiency
- Failure of TAP molecules to transport peptides to ER
Symptoms: CD8+ cell deficiency; CD4+ cells normal; Recurring viral infections; Normal DTH; Normal Ab production |
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Term
|
Definition
Combined partial T and B cell deficiency
- Defect in cytoskeletal glycoprotein
- X-linked
Symptoms: Defective response to bacterial polysaccharides; Depressed IgM; Gradual loss of humoral and cellular responses; Thrombocytopenia; Eczema |
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Term
|
Definition
Combined partial T and B cell deficiency
- Defect in kinase involved in cell cycle
Symptoms: Ataxia (gait abnormalities); Telangectasia (capillay distortions in eye); Deficiency of IgA and IgE production |
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Term
| SCID - Defect in common gamma chain of IL-2 receptor |
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Definition
Complete functional B and T cell deficiency
- X-linked
- Blocks T cell maturation: Stem Cell --> Pro-T
Symptoms: Chronic diarhhea; Skin, mouth, throat lesions; Opportunistic (fungal) infections; low levels of circulating lymphocytesl cells unresponsive to mitogens |
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Term
| SCID - Adenosine Deaminase Deficiency |
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Definition
- Blocks T and B cell maturation: Stem Cell --> Pro-B or Pro-T
Symptoms: Chronic diarhhea; Skin, mouth, throat lesions; Opportunistic (fungal) infections; low levels of circulating lymphocytesl cells unresponsive to mitogens |
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Term
| SCID - Defect in signal transductin from Tcell IL-2 receptors |
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Definition
| Symptoms: Chronic diarhhea; Skin, mouth, throat lesions; Opportunistic (fungal) infections; low levels of circulating lymphocytesl cells unresponsive to mitogens |
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Term
| SCID - Bare Lymphocyte Syndrome/MHC Class II Deficiency |
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Definition
| Symptoms: T cells present and responsive to nonspecific mitogens; No GVHDl Deficiency in CD4+ T cells, HypoIgG |
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Term
| Sterile Organs (No resident Microflora) |
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Definition
| Lungs, Liver, Bile, Conjunctive (very few), Pancreas, Bladder (very few), Kindeys, Uterus |
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Term
| Acute Inflammation Sequence |
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Definition
PART OF INNATE RESPONSE
1: Tissue Injury - chemical, physical, biological agents
2: Vasodilation - delivery of neutrophils, phagocytes, plasma proteins
3: Increased permeability - Exudate with complement and Igs enter injured area
4: Emigration of Leukocytes - Neutrophils/Macrophages adhere to endothelial cells of capillaries; Leukocytes extravasate
5: Chemotaxis - Neutrophils and marophages move to site of injury
6: Phagocytosis - bacteria endocytosed, degraded by O2 radicals and enzymes |
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Term
|
Definition
| Cell wall = PG and Pipoteichoic acid |
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Term
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Definition
| Cell = LPG and lipopolysaccharide |
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Term
| Toll-Like Receptors (Signaling Receptors) |
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Definition
On macrophages/neutrophils
- Binding of TLRs on host cells to microbial patters direct subsequent inflammatory response -- Cytokine released (TypeI IFNs, inflammatory cytokines)
- Get fever, flu-like symptoms
- Ultimately, T and B cells are activated |
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Term
|
Definition
1) NADPH oxidase reduces molecular O2 to superoxide
2) Superoxide dismutase converts superoxide to H2O2
3_ Myeloperoxidase (via granule fusion) converts Cl- into highly toxic hypochlorous ions |
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Term
|
Definition
Kill by:
-pH changes in phagolysosomes
-digestion via lysosomal enzymes
-action of bactericidal proteins (Lactoferrin, Lysozyme, Antimicrobial cationic proteins) |
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Term
|
Definition
- Cellular lysis
- Opsonization - C3b
- Release of inflammatory mediators
-Anaphylatoxins - C5a, C3a - increase vascular permeability
-Chemotactic factor for neutrophils
(C5a) |
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Term
| Classical Pathway - Complement |
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Definition
Initiated by Igs
- Abs bound to bacteria activate complement (C3b binds to bacteria to assist in phagocytosis by neutrophils)
- Engulfment is mediated by Fc receptors on neutrophils and complement receptors on bacteria |
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Term
| Alternative Pathway-Complement |
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Definition
Initiated by microbes
- Factor B, Factor D, Properdin |
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Term
| Lectin Pathway-Complement |
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Definition
Initiated by Mannose-binding lectin
- Mannose Binding Lectin, C2, C4 |
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Term
| Steps of Classical Pathway |
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Definition
1) IgG binds to microbe
2) C1 binds IgG and converts C4 --> C4a and C2 --> 2b forming C3 convertase
3) C3 convertase: C3 --> C3b + C3a
4) binds C3 convertase to make it C5 convertase
5) C5 convertase: C5 --> C5a + C5b
6) Formation of MAC |
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Term
| Steps of Alternative Pathway |
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Definition
1) C3 --> C3b, which binds to microbe
2) Factor B + C3b + Factor D makes stable C3 convertase
- Rest of pathway same as Classical |
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Term
|
Definition
1) MBL causes C2 + C4 --> C3 Convertase
- Rest of pathway same as Classical |
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|
Term
IFN-alpha and IFN-beta
(Type 1 Interferons) |
|
Definition
IFN-alpha: from leukocytes/other cells
IFN:beta: from fibroblasts
1) Induce resistance to viral replication in all cells
2) Increase expression of ligands for receptors on NK cells
3) Activate NK cells to kill virus-infected cells |
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Term
|
Definition
Fluid leakage
Increased hydrostatic pressure (Venous outflow obstruction, congestive heart failure)
Decreased colloid pressure (decreased protein synthesis - liver disease, or increased protein loss - kidney disease) |
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Term
|
Definition
Fluid and protein leakage
- A part of inflammation
- Vasidilation, stasis, and increased interendothelial spaces |
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Term
|
Definition
1) Rolling - Selectins
2) Adhesions - Integrins
3) Transmigration - PCAM-1 (CD31) |
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Term
| Systemic effects of Cytokines |
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Definition
Low quantity: Local inflammation (phagocyte activation, endothelial activation, complement activation)
Moderate: SYstemic effects (Fever, acute-phase reactants, leukocytes)
High: Septic Shock (low cardiac output and peripheral resistance, DIC, blood vessel injury, ARDS) |
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Term
|
Definition
Controlled by brain
Mediated by TNF-alpha, IL-1, IL-6
- Causes: infections, toxins, immune complexes, neoplasia |
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Term
|
Definition
|
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Term
|
Definition
Carbohydrate-binding proteins
Dectin, Mannose Receptor, Mincle, CLEC, Mannose Binding Protein
- Recognize: Mannans, Beta glucans, Mannose
- Actions: phagocytosis, complement activation, induce signal to promote inflammation
- Found on cell surface |
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Term
| Nucleotide Binding and Oligomerization Domain (NOD)-like Receptors |
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Definition
NOD 1, NOD 2, NLRC, NOD-like receptors 1-9
- Recorgnize: Bacterial/Viral DNA, Viral RNA, bacterial toxins, Flagellin, Fragments of PG, Monosodium urate, Asbestos, UV irradiation
- Actions: Promote inflammation, trigger cel; death, formation of inflammasome
- Found intracellularly |
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Term
|
Definition
TLR 1-10
- Recognize: PG, Lipoproteins, Lipopolysaccharide, DNA, RNA, Flagellin
- Action: Promote inflammation, release Type 1 interferons
- Found on cell surface and within cell |
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Term
| Retinoic Acid-Inducible Gene-1 Like Receptors (RLR/RIGs) |
|
Definition
RIG-1, MDA5, LGP2, IPS-1
- Recognize: Viral RNA and DNA (Influenza A/B, Rabies, Hep. C, West Nile, Respiratory Syncytial virus)
- Actions: Signaling generation of Type I interferons (important in controlling viral replication)
- Found intracellularly |
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Term
|
Definition
The part of heavy chain of Igs that mediates biological acitivity
- It's where complement binding occurs
- Its where Ab gets bound to macrophage to allow destruction of antigen its bound to |
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Term
|
Definition
- Made when you fuse normal B cells with myeloma cells
- Kill off only myeloma cells and you're left with hybridomas
- See which ones bind antigen -- make mAbs |
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Term
|
Definition
Most abundant in normal serum
- Important in Memory (secondary) response
- Opsonization
- Activates Complement
- Crosses the placenta (lasts until about 9 months after birth) |
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Term
|
Definition
First Ab present in Primary immune response
- Mostly in the bloodstream
- Activates complement
Highest Avidity (pentamer - 10 Ag-binding sites) |
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Term
|
Definition
Secretory IgA is a dimer (J chain) - found in breast milk, and in lumens
- Associated with mucosal (secretory) immunity |
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Term
|
Definition
Found mostly on surface of B cells
- Most important as a cellular receptor
- Marker of B cell maturity |
|
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Term
|
Definition
Trace levels in serum
- Role in allergies (immediate hypersensitivity)
- IgE-mediated degranulation of mast cells |
|
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Term
|
Definition
Ab-coated RBCs from baby's blood + Anti-human Ig --> Agglutination of RBC
- Tests for presence of RBCs with ANti-Rh Abs coating them |
|
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Term
|
Definition
RBCs not coated with Abs + serum with Ab to RBC = b-coated RBC + Anti-human Ig --> Agglutination of RBC
- Tests for presence of ANti-Rh Abs in maternal serum |
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Term
|
Definition
| Has V and J variable regions |
|
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Term
|
Definition
| Has V, D, and J variable regions (D+J is joined first) |
|
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Term
|
Definition
Stem Cell
Pro-B: Germline DNA, No Ig
Pre-B: Recombined H chain gene, mu mRNA
Immature B: Recombined H chain gene, light chain gene, mu and kappe or gamma mRNA,IgM
Mature B: ALternative splicing of primary transcript to form Cmu and Cdelta mRNA, IgM and IgD |
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Term
|
Definition
Signal from Helper T cells that stimulates Ig class switching in activated B cells
IgM --> IgG or IgE |
|
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Term
|
Definition
SIgns: absent, reduced follicles and germinal centers in lymphoid organs; Reduced serum Ig
Commmon consequences: Pyogenic bacterial infections |
|
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Term
|
Definition
Reduced T cell zones in lymphoid organs; reduced DTH reactions to common Ags; Defective T cell proliferative responses to mitogens in vitro
Common consequences: Viral/other intracellular microbial infections; Virus-associated malignancies |
|
|
Term
| Innate Immune deficiencies |
|
Definition
| Susceptible to pyogenic bacterial infections |
|
|
Term
|
Definition
Univalent
Heterodimer (alpha and beta chain)
V and C domain (beta chain has V, D, and J, alpha chain has V, and J)
Membrane bound, not secreted
No class switching
- The receptor itself does not perform effector functions
- REcognizes peptides displayed by MHC molecules on APCs |
|
|
Term
|
Definition
Multiple germline V regions
Combinatoria (Recombination of V and J, or V, D, and J regions)
Junctional DIversity - imprecise recombination at junctions, N-region diversification (TdT)
NO somatic hypermutation |
|
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Term
|
Definition
Multiple germline genes
Primary recombination of gene segments (mix and match V, D, and J regions)
Junctional diversity - imprecise recombination at junctions, N-region diversification (TdT)
Somatic hypermutation (mostly in hypervariable region of V genes) |
|
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Term
|
Definition
Stem Cell
Double Negative Pro-T: CD4-/CD8-
Pre-T
Double Positive Immature T: CD4+/CD8+
Single Positive Mature T: CD4+ OR CD8+ |
|
|
Term
| Selection for Mature T cells |
|
Definition
Weak recognition of MHC Class II + Peptide = Mature CD4+ T cell
Weak recognition of MHC Class I + Peptide = Mature CD8+ T cell
No recognition of MHC + Peptide = Apoptosis (death by neglect)
Strong recognition of either MHC class + peptide = Apoptosis (negative selection) |
|
|
Term
|
Definition
CD8+ T cell + Virus-infected cell = Dead virus-infected cell
CD4+ T cell + Macrophage = Release of cytokines and activated macrophage
CD4+ T cell + B cell = release of cytokine and plasma cell + Abs |
|
|
Term
| MHC Class II - Processing of Antigen |
|
Definition
1) Uptake of extracellular proteins by APC
2) Processing in endosomal/lysosomal vesicle
3) Biosynthesis and transport of MHC Class II molecule to endosome
4) Processed peptides bind to MHC Class II molecules in vesicles (DM removes CLIP from peptide-binding site)
5) Expression of peptide-MHC complex on cell surface |
|
|
Term
| MHC Class I - Processing of Antigen |
|
Definition
1) Production of proteins in the cytosol
2) Proteolytic degradation of proteins
3) Transport of peptides into ER (by TAP)
4) Assembly of peptide-MHC complex in ER
5) Surface expression of peptide-MHC complexes |
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|
Term
| Binding of MHC to T cells |
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Definition
CD8 binds the alpha3 domain of MHC class I
CD4 binds the Beta2 domain of MHC Class II
TCR binds to the peptide-binding region of the MHC molecule |
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Term
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Definition
Heterodimer: Alpha (a1, a2, a3) and Beta2-microglobulin (only one allele) - alpha spans membrane
- 6 Possibilities if heterozygous at all loci
- Peptides lie in peptide-binding groove in extended structure
- Peptide-binding groove: one alpha polypeptide, more specific for peptide size than class II
- HLA-A, HLA-B, HLA-C |
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Term
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Definition
Heterodimer: Alpha (a1, a2) and Beta (b1, b2) - both span membrane
- 12 possibilities if heterozygous at all loci
- Peptides lie in peptide-binding groove in extended structure
- Peptide-binding groove: 1/2 alpha, 1/2 beta polypeptide. Ends are farther apart, tend to bind longer peptides than Class II
- HLA-DP, HLA-DQ, HLA_DR |
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Term
| MHC CLass I Cell DIstribution |
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Definition
T cells, B cells, Macrophages, Dendritic cells, Neutrophils
- Thymic and kidney epithelium, liver hepatocytes, brain |
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Term
| MHC CLass II cell Distribution |
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Definition
| Some T cells, B Cells, Macrophages, Dendritic Cells, Thymic epithelium |
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Term
| Effector Functions of Igs |
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Definition
Complement fixation
Phagocyte Binding (Opsonization)
- Also neutralizes toxins/microbes |
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Term
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Definition
1) Adhesion (non-specific) Integrins, LFA-1
2) Ag Recognition - TCR:MHC-Peptide
3) Co-stimulation - CD28 (T cell)-B7 (APC) |
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Term
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Definition
Expressed on B cells, macrophages, endothelial cells, , dendritic cells
- Bind CD40L
- Role in T-cell dependent B cell, macrophage dendritic cell, and endothelial cell activation |
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Term
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Definition
Th1, CTLs, NK cells
Enhances activity of macrophages
Increases expression of MHC Class I and II in many cell types
Inhibits proliferation of Th2 cells |
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Term
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Definition
| Bacteria, Fungi, Parasites, Viruses |
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Term
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Definition
Numerous granules (used to destroy bacteria)
Segmented nucleus (polys, segs)
Salmon-colored cytoplasm, no basophilia
Shortest T1/2 (1-3 days) |
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Term
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Definition
Numerous large granules with central crystalloid region
Bi-lobed nucleus
Intense eosinophilia
- Inflammation and destruction of parasites, Asthma |
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Term
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Definition
Numerous large granules (Heparin, Histamine)
Intense basophilia
Bi-lobed nucleus
- Inflammation, Allergic response
- DIfferentiate into Mast cell in tissue |
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Term
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Definition
Largest WBC
Few azurophilic granules
Pale cytoplasmic basophilia, lots of rER and Golgi
Horseshoe-shaped nucleus
- Differentiates into macrophages in tissues |
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Term
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Definition
Large, euchromatic nucleus
Cell processes
Numerous lysosomes
Prominent nucleolus
Extensive frothy cytoplasm |
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Term
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Definition
Same size as RBCs
Little cytoplasm
No granules, lots of rER and Golgi
Round nucleus |
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Term
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Definition
Clock faced nucleus
Intense cytoplasmic basophilia
Tons of rER |
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Term
| Innate Immunity - Components |
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Definition
Epithelial barriers, phagocytes, dendritic cells, NK cells, complement
- Recognize structures of different classes of microbes |
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Term
| Adaptive/Aqcuired Immunity - Features |
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Definition
Specificity
Memory
Diversity
Self-Tolerance |
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Term
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Definition
Mediated by Naive lymphocytes - They express Ag receptors but dont yet perform effector functions
- They then differentiate into Effector cells and Memory cells |
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Term
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Definition
B Lymphocytes
T Lymphocytes
NK Cells |
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Term
| Antigen-presenting cells - Types |
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Definition
Dendritic cells - Initiate T cell response
Macrophages - Initiation and effector phase of T cell response
Follicular Dendritic Cells - display Ags to B lymphocytes |
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Term
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Definition
Helper T cells, Cytotoxic T cells
Macrophages, monocytes
Granulocytes, neutrophils, eosinophils |
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Term
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Definition
NK cells, Neutrophils, Macrophages
- Express receptors specific for certain CLASSES of microbes |
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Term
| Peripheral lymphoid organs |
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Definition
Lymph nodes - lymph-borne pathogens
Spleen - blood-borne pathogens
Mucosal and cutaneous immune systems
- Function to maximize interactions of Ags, APCs and Lymphocytes to promote adaptive immune responses |
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Term
| Fact: A previous viral infection can predispose someone to a bacterial infection |
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Definition
Why?
Viruses destroy the ciliated cells in the upper respiratory tract. |
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Term
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Definition
Armor - skin, mucous
Broom - Cilia, peristalsis/flow
Hose down - Tears, saliva, urine flow |
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Term
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Definition
| Organism in the vagina that makes the vagina acidic to prevent colonization of bad flora |
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Term
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Definition
Produces antibiotics (antimicrobials) that kill bacteria
Contain intraepithelial lymphocytes (T cell origin) with limited diversity of Ag receptors
Generate chemokines, cytokines |
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Term
| Pathogen-Associated Molecular Patterns (PAMPS) |
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Definition
Microbial molecules that are the target of innate immunity
- LPS (gram-negative bacteria)
- Lipotechoic acid (gram positive bacteria)
- PG (gram + or - bacteria, mycbacteria
- DOuble stranded RNA
- Manna (yeast cell walls), Flagellin |
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Term
| Pattern Recognition Patterns (PRR) |
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Definition
Receptors of innate immunity that recognize PAMPS on surface of pathogens
- Dendritic cells, macrophages, neutrophils, epithelial cells
- Endocytic PRRS vs. Signaling PRR (Toll-like receptors) |
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Term
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Definition
Beta agonist (Non-selective)
MOA: Nonselective B1 and B2 agonist at GPCR --> cAMP --> increased PKA --> decreased MLCK
Use: Status asthamaticus, anaphylactic shock
Side effects: Tachycardia, arrhythmia, ischemia |
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Term
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Definition
B agonist (Short-acting)
MOA: GPCR --> increase cMP --> Decrease MLCK (Also increase K channels)
- Binds mast cells to decreased histamine release
- Binds eos. and neutr. to decrease mediators released
- Bronchodilator
Use: 1st line acute asthma; mild intermitent COPD; ACute bronchospasm
- SIde effects: muscle tremor, peripheral vasodilation, transient arterial O2 tension, nervous/anxious |
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Term
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Definition
Beta agonist (Long acting)
MOA: GPCR --> increase cMP --> Decrease MLCK (Also increase K channels)
- Binds mast cells to decreased histamine release
- Binds eos. and neutr. to decrease mediators released
- Bronchodilator
Use: Persistent asthma, ALWAYS use in combo
Side effects: muscle tremor, peripheral vasodilation, transient arterial O2 tension, nervous/anxious |
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Term
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Definition
Corticosteroid (Inhaled)
Use: Asthma, COPD
MOA: Binds steroid receptor complex
Side effects: Oral Candida, hoarseness, adrenal suppression, may slow growth in kids - limit oral use
Teratogenic |
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Term
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Definition
Corticosteroid (Inhaled)
Use: Asthma, COPD
MOA: Binds steroid receptor complex
Side effects: Oral Candida, hoarseness, adrenal suppression, may slow growth in kids - limit oral use
Teratogenic |
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Term
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Definition
Corticosteroid (Inhaled)
Use: Asthma, COPD
MOA: Binds steroid receptor complex
Side effects: Oral Candida, hoarseness, adrenal suppression, may slow growth in kids - limit oral use
Teratogenic |
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Term
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Definition
Mast Cell Stabilizer
Use: Prophylaxis for exercise/allergen-induced asthma, allergic rhinitis
MOA: Blocks Cl- channels in mast cells to decrease mast cell degranulation, block sensory nerve firing, suppress late response
Minimal side effects.
- Poorly absorbed (aerosol) |
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Term
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Definition
Leukotriene Antagonist
Use: Maintenance or prophylactic for aspirin or exercise-induced asthma
MOA: inhibits 5-lipoxygenase to block leukotriene synthesis
Side effects: occasional liver toxicity (monitor)
NOT dilators, NOT for acute crisis |
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Term
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Definition
Leukotriene Antagonist
Use: Maintenance or prophylactic for aspirin or exercise-induced asthma
NOT dilators, NOT for acute crisis
MOA: reversible antagonist at Leukotriene 1 receptor
Side effects: suicidal behavior |
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Term
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Definition
Anti-IgE mAb
Use: IgE-dependent asthma
MOA: Binds Fc region of IgE to decrease levels of free IgE
Side effects: Well-tolerated, mild CRS, anaphylactic shock. Injection site rxns |
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Term
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Definition
1st Gen. Antihistamine (Sedating)
Use: IgE-mediated allergies, local anesthesia, sedation, urticaria, etc.
MOA: H1-receptor antagonist
Side Effects: sedation
- Not useful for anaphylaxis rxns or acute asthma |
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Term
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Definition
1st Gen. Antihistamine (Sedating)
Use: IgE-mediated allergies, local anesthesia, sedation, urticaria, etc.
MOA: H1-receptor antagonist
Side Effects: sedation
- Not useful for anaphylaxis rxns or acute asthma |
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Term
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Definition
1st Gen. Antihistamine (Sedating)
Use: IgE-mediated allergies, local anesthesia, sedation, urticaria, etc.
MOA: H1-receptor antagonist
Side Effects: sedation
- Not useful for anaphylaxis rxns or acute asthma |
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Term
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Definition
2nd Gen. Antihistamine (Non-sedating)
Use: IgE-mediated allergies, urticaria
MOA: Hi-receptor antagonist
Side effects: arrhythmias in O.D.
- Not useful for anaphylaxis rxns or acute asthma |
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Term
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Definition
2nd Gen. Antihistamine (Non-sedating)
Use: IgE-mediated allergies, urticaria
MOA: Hi-receptor antagonist
Side effects: arrhythmias in O.D.
- Not useful for anaphylaxis rxns or acute asthma |
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Term
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Definition
2nd Gen. Antihistamine (Non-sedating)
Use: IgE-mediated allergies, urticaria
MOA: Hi-receptor antagonist
Side effects: arrhythmias in O.D.
- Not useful for anaphylaxis rxns or acute asthma |
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Term
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Definition
Autocoid
Use: NONE
MOA: H1-4 receptor agonist (non-selective)
Contra: asthma, provokes bronchoconstriction
Side effects: allergic rxns, urticaria, G.I. distress, shock
Stored in mast cells, basophils, ECLs - rapid release & metabolism |
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Term
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Definition
| IL-8, C5a, Leukotriene, N-formyl Peptides |
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Term
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Definition
| The coating of particles with IgG or C3b (or both) to enhance phagocytosis |
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Term
| Second Signals in T cell activation |
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Definition
CD28 -- B7
CD4 -- MHC II
CD8 -- MHC I
LFA-1 -- ICAM-1 |
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Term
| Final signal in T cell Activations |
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Definition
Cytokines:
IL-1, IL-2, IL-6, TNA-alpha |
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Term
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Definition
Induced by IL-12 (from macrophages), IFN-gamma (from N cells)
They secrete: IFN-gamma, IL-2, TNF-beta
- They activate macrophages, CTLs, and NK cells
Inhibited by IL-4, IL-10 (from Th2 cells) |
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Term
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Definition
Induced when there is extracellular attack
They secrete: IL-2, IL-4, IL-5, IL-6, and IL-10
- They direct isotype switching by B cells - they activate B cells
Inhibited by IFN-gamma (from Th1 cells) |
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Term
| Natural Killer Cell Stimulation |
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Definition
IFN-alpha, IFN-beta, and IL-12
- Kill targets lacking MHC Class I
- Kill using granzymes and perforin |
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Term
| Cytotoxic T cell Stimulation |
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Definition
CD28 -- B7 interaction
IL-2 from Th1 cells |
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Term
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Definition
Immediate
Involve IgE and mast cell response
- Mounted against harmless environmental antigens in atopic/allergic individuals
- Immediate rxn: mast cells/histamine
- Late-phase rxn: products of arachidonic acid cascade |
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Term
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Definition
Tissue specific, Ab-Mediated
- Opsonization or activated complement
Ex: Myasthenia Gravis, T2DM, Graves Disease |
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Term
| Type III Hypersensitivity |
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Definition
Immune Complexes
- Cause systemic damage by activating complment wherever immune complexes are
Ex: Rheumatoid arthritis, SLE, serum sickness, Arthus rxn |
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Term
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Definition
Delayed Type (48-72 hours)
Caused by Th1 cells, CD8+ cells, and macrophages
- Common results of infection with persistent intracellular microbes
Ex: T1DM, MS, Hashimoto Thyroiditis |
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Term
| Graft Vs. Host Disease (GVHD) |
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Definition
| Occurs when mature T cells inside bone marrow transplants become activated against the MHC products of the graft recipient |
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Term
| TIssue Compatibility Testing |
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Definition
- ABO Blood Typing
- Mixed Lymphocyte Reaction (MHC CLass II)
- Microcytotoxic test (MHC Class I) |
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Term
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Definition
Increased neutrophils
- Bacterial infections, Burns, Tissue necrosis |
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Term
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Definition
Increased eosinophils
- Parasitic infections, Allergic disorders, Collagen vascular disease |
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Term
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Definition
Increased monocytes
- Chronic infections (TB), Malaria, IBD |
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Term
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Definition
Increased lymphocytes
- Viral infections, Bordatella, Pertussis
- W/ Monocytosis in TB |
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Term
| Erythrocyte Sedimentation Rate |
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Definition
Increased Sed. Rate is non-specific evidence of an inflammatory process
- Hastened rouleux formation by increased fibrinogen or IgG in plasma |
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Term
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Definition
CRP is secreted rapidly by the liver in response to inflammation
- Elevation persists while inflammation exists
- Nonspecific marker of a number of inflammatory conditions (Ex: atherosclerosis) |
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Term
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Definition
Short duration (1-3 days)
- Hyperemia, Edema, Neutrophils
- Causes: infection, foreign bodies, tissue necrosis, immune reactions |
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Term
| Vascular reactions of acute inflammation |
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Definition
1) Vasodilation - Histamine and NO (Redness and heat)
2) Increased permeability - Histamine, bradykinin, leukotrienes (Edema)
3) Vascular stasis (Redness) |
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Term
| Cellular Reactions of Acute Inflammation |
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Definition
1) Extravasation (Selectins --> Integrins --> PCA/CD31)
2) Chemotaxis (C5a, IL-8, N-formyl methyl peptides)
3) Activation - binding of acticating ligand
4) Phagocytosis - Recognition --> Engulfment --> Killing |
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Term
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Definition
| ANti-protease that acts against neutrophil enzymes that get released during inflammation |
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Term
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Definition
Proliferation of blood vessels, Fibrosis, Tissue destruction, MACROPHAGES, Lymphocytes, Plasma Cells
- Causes: Acute inflammation, persistent infection, prolonged irritation, autoimmunity |
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Term
| Granulomatous Inflammation |
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Definition
Type of Chronic Inflammation
- EPitheliod Macrophages
- Cause: Mycobacterium TB, Suture granuloma, HIstoplasma capsulatum
- Granuloma formation |
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Term
| Pain (Chemical Mediators) |
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Definition
| Bradykinin, PGE2, Substance P |
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Term
| Fever (Chemical Mediators) |
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Definition
TNF-alpha, IL-1, IL-6
- affect cyclo-oxygenase pathway to reset thermostat in hypothalamus |
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Term
| Chronic Mucocutaneous Candidiasis |
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Definition
Chronic Candida infections
- Caused by deficiency in Dectin 1 (A C-type lectin receptor) |
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Term
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Definition
Symptoms: diarrhea, tender abdomen, high WBC, low Hb, increased ESR, no bacteria/pathogens in stool culture, weight loss, ulcer in colon
- Caused by hyperactive NODs |
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Term
| Mannose Binding Protein Deficiency |
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Definition
- Recurrent memingitides; sudden nausea, vomiting, HA, fever, AMS, hypotension, increased RR, PURPURA, stiff neck
- Cause: Neisseria meningitides infection
- Dx: lumbar puncture (cloudy, cellular, high protein) |
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Term
| Herpes Simplex Incephalitis |
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Definition
95% mortality
- Young pt., seizures, fever, normal dvmt thus far
- Cause: TLR-3 Abnormality |
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Term
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Definition
1) Foreignness - more foreign, stronger trigger
2)Molecular size - >1000 D
3) Complexity - more complex, better
4) Dose
5) Route of administration - PO is poor
6) Adjuvants improve immunogenicity |
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Term
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Definition
Malignant Plasma cell tumor that secretes monoclonal antibodies
- A disease of bone -- multiple bone lesions
- Symptoms: fatigue, anemia, low WBCs, low RBCs, elevated ESR, one class of Ig highly elevated, other depressed
- Dx: Monoclonal spike, Bence Jones Protein (light chain dimer)
-Tx: resistant to chemotherapy, poor prognosis |
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Term
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Definition
| - They have Fc receptors for IgGs, thus leading to killing of antibody-coated cells |
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Term
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Definition
| Serum that contains antibodies. A type of passive immunity |
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Term
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Definition
Can be caused by giving heterologous (diff. species) products. You end up making a large amount of new products in response to an influx of new antigens.
- Numbers Ab-Ag interactions activate lots of complement, and C5a attracts neutrophils |
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Term
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Definition
- Semiquantitative method
1) take serum from immunized individual
2) Make 1:2 dilutions of the antiserum
Primary response: can't detect after 1:32
Secondary response: can detect longer, out to 1:512
- Can use to determine what stage of immune response a person is in |
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Term
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Definition
- Used for initial screening for HIV
- Inactivated HIV antigen in each well + Patients serum w/ Abs + Anti-human Ig + Enzyme to change color (>.500)
- Can get false positive (esp. if multiparous)
- False negative in period between infection and serum conversion |
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Term
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Definition
Confirmatory test for positive ELISA (HIV)
- More specific, can see Abs against viral proteins
- HIV cells are lysed, SDS-PAGED and blotted on membrane and incubated with Pt. serum (w/ Ab), ANti-human Ig, and substrate
- + result = gp120 or gp160 AND p24 or p31 |
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Term
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Definition
Immune complexes comprised of antibodies and cells or large particles
- A way of visualizing clumps of RBCs
- Used diagnostically for bacteria'microbes |
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Term
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Definition
Naturally occuring Abs against AB blood antigens.
- IgM mediated - do not cross placenta
- Responsible for the transfusion reaction |
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Term
| IgGs against Rh antigen CAN cross placental barrier, unlike isohemagluttinins |
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Definition
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Term
|
Definition
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Term
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Definition
| Ensures that only one heavy and one light chain per cell are expressed |
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Term
| RAG (Recombinase Antibody Generation) |
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Definition
Responsible for recombination of Igs and TCRs to create diversity
- Deficiency of RAG = SCID |
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Term
| B Cell deficiency Typical Infections |
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Definition
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Term
| If a virus has a mechanism to avoid the MHC Class I pathway, NK cells can recognize that the cell lacks MHC CLass I molecules on the surface, and will kill it (no inhibitory signal) |
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Definition
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Term
| The most influential arm of the immune system is T cells |
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Definition
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Term
| You can't take T effector cells from one person and give them to another person because of MHC Restriction (TCR won't recognize foreign MHC molecules) |
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Definition
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Term
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Definition
- Having more different alleles is correlated to being more resistant to sickness
- Most polymorphic genes is population, used for paternity testing
- Important in transplant rejection |
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Term
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Definition
Toxins that don't get degraded. They bind to all MHC CLass II molecules and stimulate T cells through TCR.
- Sytokine storm
- Ex: TSST |
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Term
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Definition
CD = CLusters of DIfferentiation
- Pan-T cell markers
- Monoclonal Ab
- COmplexed to TCR receptor - important in signal transduction |
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Term
| CONditions causing detachment of Neutrophils from endothelium |
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Definition
| Hypoxia, GLucocorticoids, Exercise, Stress, Aspirin, Epinephrine |
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Term
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Definition
"Lack of neutrophils"
- Chemotherapy (kills rapidly diving cells)
- Autoimmune Abs to neutrophils
- Hereditary - unknown mechanisms
Tx: Give GM-CSF, or G-CSF to stimulated neutrophil production |
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Term
| Leukocyte Adhesions Deficiency (LAD) |
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Definition
Neutrophils can't stick and migrate in to fight infections.
- Lack of LFA-ICAM (Rolling cells)
- "Cold," nontender abscess
- Will have high neutrophil count (trapped in bloodstream) |
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Term
| Patients with altered white cell function are subject to infections by bacteria and fungi |
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Definition
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Term
| Nitroblue Tetracolium Test (NBT) |
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Definition
Assesses oxidative burst - cells should turn blue/purple
- Can use to Dx. CGDm |
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Term
| Antibiotics plus neutropenia make you susceptible to fungal infections |
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Definition
Risk factor for candida - low WBC and using broad spectrum antibiotics
Risk factor for Aspergillus - neutropenia (b/c you're always breathing it in) |
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Term
| Hereditary ANgioneurotic Edema |
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Definition
- Cause: Deficiency of C1-INH
- Subject to recurrent swelling of skin, intestine and airway - diarrhea, vomiting, abdominal pain
- Triggered by exercise, trauma, mental stress, extreme temperatures, menstruation |
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Term
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Definition
- The CD4 molecule acts as receptor for HIV
- Eventually, CD4 cells are destroyed by the virus faster than they're produced -- cell-mediated immunity falters
- Host is susceptible to opportunistic infection |
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Term
| Indicator of HIV infection? |
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Definition
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Term
| Promdromal symptoms of AIDS |
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Definition
| thrush, low-grade fever, enlarged lymph nodes, night sweats, weight loss |
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Term
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Definition
| CD4 count between 200-400 |
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Term
| Contact sensitivity to poison ivy |
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Definition
- Type IV Hypersensitivity (DTH)
No fever, rash (2-3 days after exposure)
- Pentadecacatechol acts as a hapten to create hapten-specific effector Th1 cells
- Tissue damage and inflammatory response caused by macrophages and T cells
- Mast cells release histamine - itching
- CD8 cells also get activated
- Tx: COrticosteroids (topical or oraL) |
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Term
| DTH (Delayed Hypersensitivity Reactions) |
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Definition
- Measures CD4 cell function
- Tuberculin reaction (pts vaccinated with BCG)
- Candida test |
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Term
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Definition
Severe muscle weakness - ptosis (droopy eyelids), diplopia
- Cause: IgG Ab against ACh receptors
- More severe symptoms (full body) in young people |
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Term
| ADCC (Ab-Dependent Cell-Mediated Cytotoxicity |
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Definition
Part of cell-mediated immune defense - Effector cells of innate immunity lyse cells with specific antibodies.
- NK Cells; Neutrophils, Eosinophils
- Recognition of IgG via Fc receptors |
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