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223 Cards in this Set

  • Front
  • Back
What is the target and clinical use of Muromonab-CD3 (OKT3)?
- target: CD3
- clinical use: prevent acute transplant rejection
What is the target and clinical use of daclizumab?
- target: IL-2 receptor
- clinical use: prevent acute rejection of renal transplant
What is the target and clinical use of digoxin immune fab?
- target: digoxin
- clinical use: antidote for digoxin intoxication
What is the target and clinical use of infliximab?
- target: TNF-alpha
- clinical use: Crohn's disease, rheumatoid arthritis, psoriatic arthritis, akylosing spondylitis
What is the target and clinical use of Adalimumab?
- target: TNF-alpha
- clinical use: Crohn's disease, rheumatoid arthritis, psoriatic arthritis
What is the target and clinical use of Abciximab?
- target: Glycoprotein IIb/IIIa
- clinical use: prevent cardiac ischemia in unstable angina and in patietns treated with percutaneous coronary intervention
What is the target and clinical use of Trastuzumab (Herceptin)?
- target: erb-B2
- clinical use: HER-2 overexpressing breast cancer
What is the target and clinical use of Rituximab?
- target: CD20
- Clinical use: B-cell non-Hodgkin's lymphoma
What is the mechanism of sirolimus (rapamycin)?
- binds to mTOR
- inhibits T-cell proliferation in response to IL-2
What is the clinical use of sirolimus (rapamycin)?
- immunosuppresion after kidney transplantation in combination with cyclosporine and corticosteroids
What is the toxicity of sirolimus (rapamycin)?
- hyperlipidemia, thrombocytopenia, leukopenia
What is the mechanism of Daclizumab?
- monoclonal Ab with high affinity for the IL-2 receptor on activated T-cells
What is the mechanism of Azathioprine?
- antimetabolite precursor of 6-mercaptopurine that interferes with the metabolism and synthesis of nucleic acids
- toxic to proliferating lymphocytes
What is the clinical use of Azathioprine?
- kideny transplantation, autoimmune disorders (including glomerulonephritis and hemolytic anemia)
What is the toxicity of Azathioprine?
- bone marrow suppression
- active metabolite mercaptopurine is metabolized by xanthine oxidase; thus, toxic effects may be increased by allopurinol
What is the mechanism of Muromonab-CD3 (OKT3)?
-monoclonal Ab that binds to CD3 (epsilon chain) on the surface of T cells
- blocks cellular interaction with CD3 protein responsible for T-cell signal transduction
What is the clinical use of Muromonab-CD3 (OKT3)?
- immunosuppression after kidney transplantation
What is the toxicity of Muromonab-CD3 (OKT3)?
- cytokine release syndrome, hypersensitivity reaction
What are the clinical uses of Aldesleukin (interleukin-2)?
- renal cell carcinoma
- metastatic melanoma
What are the clinical uses of Erythropoietin (epoetin)?
- anemia (especially in renal failure)
What are the clinical uses of Filgrastim (granulocyte colony-stimulating factor)?
recovery of bone marrow
What are the clinical uses of Sargramostim (granulocyte-macrophage colony-stimulating factor)?
recovery of bone marrow
What are the clinical uses of alpha-interferon?
- Hep B and C
- Kaposi's sarcoma
- leukemias
- malignant melanoma
What are the clinical uses of Beta-interferon?
- multiple sclerosis
What are the clinical uses of gamma-interferon?
chronic granulomatous disease
What are the clinical uses of oprelvekin (interleukin-11)
Thrombocytopenia
What are the clinical uses of thrombopoietin?
Thrombocytopenia
What is the mechanism of cyclosporine?
- binds to cyclophilins
- complex blocks the differentiation and activation of T cells by inhibiting calcineurin, thus preventing the production of IL-2 and its receptor
What is the clinical use of cyclosporine?
- suppresses organ rejection after transplantation
- selected autoimmune disorders
What is the toxicity of cyclosporine?
-predisposes patients to viral infections and lymphoma
- nephrotoxic (preventable with mannitol diuresis)
What is the mechanism of tacrolimus (FK506)?
- similar to cyclosporine
- binds to FK-binding protein, inhibiting secretion of IL-2 and other cytokines
What is the clinical use of tacrolimus (FK506)?
- potent immunosuppressive used in organ transplant recipients
What is the toxicity of tacrolimus (FK506)?
- significant
- nephrotoxicity, peripheral neuropathy
- hypertension, pleural effusion
- hyperglycemia
What are the differences between autograft, syngeneic graft, allograft and xenograft?
- autograft: self
- syngeneic graft: from identical twin or clone
- allograft: from nonidentical individual of same species
- xenograft: from different species
Describe hyperacute rejection
- Ab mediated (type II) due to the presence of preformed antidonor Abs in the transplant recipient
- occurs within minutes after transplantation
- occludes graft vessels causing ischemia and necrosis
describe acute rejection
- cell mediated due to cytotoxic T lymphoctes reacting against foreign MHCs
- occurs weeks after transplantation
- reversible with immunosuppressants such as cyclosporine and OKT3
- vasculitis of graft vessels with dense interstitial lymphocytic infiltrate
Describe chronic rejection.
- T-cell and Ab-mediated vascular damage (obliterative vascular fibrosis)
- occurs months to years after transplantation
- irreverisble
- Class I-MHC (non-self) is perceived by CTLs as class I-MHC(self) presenting a non-self antigen
- fibrosis of graft tissue and blood vessels
Describe graft-versus-host disease.
- grafted immunocompetent T cells proliferate in the irradiated immunocompromised host and reject cells with "foreign proteins" resulting in severe organ dysfunction
- major symptoms include a maculopapular rash, jaundice, hepatosplenomegaly, and diarrhea
- usually in bone marrow and liver transplant (organs rich in lymphocytes)
- potentially beneficial in bone marrow transplant
Describe the defect found with severe combined immunodeficiency (SCID)?
several types:
- defective IL-2 receptor (most comon, X-linked)
- adenosine deaminase deficiency (failure to synthesize MHC II antigens)
- B and T-cell disorder
What is the clinical presentation of a SCID patient?
- recurrent viral, bacterial, fungal and protoxoal infections due to both, B and T-cell deficiency
what is the treatment for SCID patients?
bone marrow transplant (no allograft rejection)
What are the labs that you would find with a patient that has SCID?
- decreased IL-2 receptors --> decreased T-cell activation
- increased adenine --> toxic to B and T cells
- decreased dNTPs, and decreased DNA synthesis
Describe the defect found with ataxia-telangiectasia
- defect in DNA repair enzymes
- B and T cell disorders
What is the clinical presentation of an ataxia-telangiectasia patient?
Triad:
1. cerebellar defects (ataxia)
2. spider angioma (telangiectasia)
3. IgA deficiency
What is the labs that you would find with a patient that has ataxia-telangiectasia?
IgA deficiency
What is the defect found in Wiskott-Aldrich syndrome?
X-linked recessive defect
- progressive deletion of B and T cells
What is the clinical presentation of a patient with Wiskott-Aldrich syndrome?
Triad:
1. Thrombocytopenic purpura
2. infections
3. eczema
What are the labs that you would find with a patient that has Wiskott-Aldrich syndrome?
- increased IgE, IgA
- decreased IgM
What is the defect found in leukocyte adhesion deficiency (type 1)?
- defect in LFA-1 integrin (CD18) protein on phagocytes
- phagocyte dysfunction
What is the clinical presentation of leukocyte adhesion deficiency (type 1)?
- recurrent bacterial infections
- absent pus formation
- delayed separation of umbilicus
What are the labs that you would find in a patient who has leukocyte adhesion deficiency (type 1)?
- neutrophilia
What is the defect found in Chediak-Higashi syndrome?
- autosomal recessive
- defect in microtubular function with decrease phagocytosis
- phagocyte dysfunction
What is the clinical presentation of Chediak-Higashi syndrome?
- recurrent pyogenic infections by staphylococci and stretococci
- partial albinism peripheral neuropathy
What is the defect found in chronic granulomatous disease?
- lack of NADOH oxidase --> decreased reactive oxygen species (i.e. superoxide) and absent respiratory burst in neutrophils
- phagocyte dysfunction
What is the clinical presentation of chronic granulomatous disease?
- increased susceptibility to catalase-positive organisms (i.e. S. aureus, E.coli, Aspergillus)
What are the labs that you would find in a patient who has chronic granulomatous disease?
- negative nitroblue tetrazolium dye reduction test
What is the defect found in Bruton's agammaglobulinemia?
- B- cell disorder
- X-linked recessive (increased in Boys)
- defect in BTK, a tyrosine kinase gene --> blocks B-cell differentiation/maturation
What is the clinical presentation found in Bruton's agammaglobulinemia?
- recurrent bacterial infections after 6 months (decreased maternal IgG)
due to opsonization defect
What are the labs that you would find with patients with Bruton's agammaglobulinemia?
normal pro-B
- decreased maturation
- decreased number of B cells
- decreased immunoglobulins of all classes
What is the defect found in Hyper-IgM syndrome?
- B-cell disorders
-defective CD40L on helper T cells - inability to class switch
What is the clinical presentation of Hyper-IgM syndrome?
- severe pyogenic infections early in life
What are the labs you would find with patients with Hyper-IgM syndrome?
- increased IgM
- decreased IgG, IgA, IgE
What is the defect found in selective Ig deficiency?
- B-cell disorder
- defect in isotype switching --> deficiency in specific class of immunoglobulin
What is the clinical presentation of Selective Ig deficiency?
- sinus and lung infections, milk allergies and diarrhea
- anaphylaxis on exposure to blood products with IgA
What are the labs you would find with patients with Selective Ig deficiency?
- IgA deficiency most common
- failure to mature into plasma cells
- decreased secretory IgA
What is the defect found in common variable immunodeficiency?
- B- cell disorder
- defect in B-cell maturation
- many causes
What is the clinical presentation of CVID?
- can be acquired in 20-30s
- increased risk of autoimmune disease, lymphoma, sinopulmonary infections
What are the labs that you would find in a patient with CVID?
- normal number of B cells
- decreased plasma cells, immunoglobulins
What is the defect found with Thymic aplasia (DiGeorge syndrome)?
- T-cell disorder
- 22q11 deletion
- failure to develop 3rd and 4th pharyngeal pouches
What is the clinical presentation of DiGeorge syndrome?
- teatany (hypocalcemia)
- recurrent viral/fungal infections (T-cell deficiency)
- congenital heart and great vessel defects
What are the labs that you would find in a patient with DiGeorge syndrome?
- thymus and parathyroids fail to develop --> decreased T- cells, decreased PTH, and calcium
- absent thymic shadow on CXR
What is the defect found in IL-12 receptor deficiency?
- T- cell disorders
- decrease Th1 response
What is the clinical presentation of IL-2 receptor deficiency?
- disseminated mycobacterial infections
What is the labs you would find in a person with IL-2 receptor deficiency?
- decreased IFN-y
What is the defect found in Hyper-IgE syndrome (Job's syndrome)?
- T-cell disorder
- Th cells fail to produce IFN-y --> inability of neutrophils to respond to chemotactic stimuli
What is the clinical presentation of Hyper-IgE sydnrome (Job's syndrome)?
- FATED
- coarse Facies,
-cold (noinflammed ) staphylococcal Abscesses
- retained primary Teeth
- increased IgE
- Dermatologic problems (eczema)
What are the labs you would find in a patient with Hyper-IgE syndrome (Job's synrome)?
- increased IgE
What is the defect found in chronic mucocutaneous candiadiasis?
- T-cell dysfunction
What is the clinical presentation of chronic mucocutaneous candidiasis?
- Candida albicans infections of skin and mucous membranes
Which disorder is linked to antinuclear antibodies (ANA)?
- SLE (nonspecific)
Which disorder is linked to anti-dsDNA, anti-Smith?
- SLE
Which disorder is linked to antihistone?
drug-induced lupus
Which disorder is linked to anti-IgG (rheumatoid factor)?
rheumatoid arthritis
Which disorder is linked to anticentromere?
Scleroderma (CREST)
Which disorder is linked to anti-Scl-70 (anti-DNA topoisomerase I)?
Scleroderma (diffuse)
Which disorder is linked to antimitochondrial?
primary biliary cirrhosis
Which disorder is linked to antigliadin, antiendomysial?
Celiac disease
Which disorder is linked to anti-basement membrane?
- Goodpasture's syndrome
Which disorder is linked to anti-desmoglein?
Pemphigus vulgaris
Which disorder is linked to antimicrosomal, antithyroglobulin?
- Hasimotos' thyroiditis
Which disorder is linked to anti-Jo-1?
- polymyositis
- dermatomyositis
Which disorder is linked to anti-SS-A (anti-Ro)?
Sjogren's syndrome
Which disorder is linked to anti-SS-B (anti-La)?
Sjogren's syndrome
Which disorder is linked to anti-U1 RNP (ribonucleoprotein)?
mixed connective tissue disease
Which disorder is linked to anti-smooth muscle?
autoimmune hepatitis
Which disorder is linked to anti-glutamate decarboxylase?
Type 1 diabetes mellitus
Which disorder is linked to c-ANCA?
Wegener's granulomatosis
Which disorder is linked to p-ANCA?
Other vasculitides
Define lymph node and its function
- secondary organ that has many afferents, 1 or more efferents
- encapsulated, with trabeculae
- functions are nonspecific filtration by macrophages, storage and activation of B and T cells, Ab production
What is a follicle?
- Site of B-cell localization and proliferation
- in outer cortex, primary follicles are dense and dormant
- secondary follicles have pale central germinal centers and are active
What is the medulla of a lymph node?
- consists of medullary cords (closely packed lymphocytes and plasma cells) and medullary sinuses
- medullary sinuses communicate with efferent lymphatics and contain reticular cells and macrophages
What is the paracortex of a lymph node?
- houses T-cells
- region of cortex between follicles and medulla
- contains high endothelial venules through with T and B cells enter from blood
- in an extreme cellular immune response, paracortex becomes greatly enlarged
- not well developed in patients with DiGeorge syndrome
What is the primary lymph node drainage site for the upper limb and lateral breast?
axillary
What is the primary lymph node drainage site for the stomach?
celiac
What is the primary lymph node drainage site for the duodenum jejunum?
superior mesenteric
What is the primary lymph node drainage site for the sigmoid colon
colic --> inferior mesenteric
What is the primary lymph node drainage site for the rectum (lower above pectinate line)?
internal iliac part, anal canal
What is the primary lymph node drainage site for the anal canal below?
superficial inguinal pectinate line
What is the primary lymph node drainage site for the testes?
superficial and deep plexuses --> para-aortic
What is the primary lymph node drainage site for the scrotum?
superficial inguinal
What is the primary lymph node drainage site for the thigh (superficial)
superficial inguinal
What is the primary lymph node drainage site for the lateral side of dorsum of foot?
popliteal
In general what does the Right lymphatic duct and thoracic duct drain?
- right lymphatic duct: drains right arm and right half of head
- thoracic duct: drains everything else
Describe sinusoids of spleen.
- long, vascular channels in red pulp with fenestrated "barrel hoop" basement membrane
- macrophages found nearby
Where are T cells found in the spleen?
- periarterial lymphatic sheath (PALS)
- white pulp of spleen
Where are B cells found in the spleen?
in follicles within the white pulp of the spleen
What is the function of macrophages in the spleen?
remove encapsulated bacteria
What are the features of splenic dysfunction?
- decreased IgM
- decreased complement activation
- decreased C3b opsonization --> increased susceptibility to encapsulated organisms "S SHiN"
1. salmonella
2. S. pneumonia
3. H. influenzae
4. N. meningitidis
Describe the features of thymus and its function.
- site of T-cell differentiation and maturation
- encapsulated
- from epithelium of 3rd branchial pouches
- lymphocytes of mesenchumal origin
- cortex is dense with immature T cells
- medulla is pale with mature T cells and epithelial reticular cells and contains Hassall's corpuscles
- positive (MHC restriction) and negative selection (nonreactive to self) occur at the corticomedullary junction
Describe the characteristics of the innate immune system.
- receptors that recognize pathogens are germline encoded
- response to pathogens is fast and nonspecific
- no memory
- consists of neutrophils, macrophages, dendritic cells, natural killer cells (lymphoid origin), and complement
Describe the characteristics of the adaptive immune system.
- receptors that recognize pathogens undergo V(D)J recombination during lymphocyte development
- response is slow on first exposure, but memory response is faster and more robust
- consists of B and T cells, and circulating Abs
What are MHCs? What is their function?
- major histocompatibility complex
- encoded by Human Leukocyte Antigen (HLA) genes
- present antigen fragments to T cells and bind TCR
Describe the characteristics of MHC I.
- HLA-A, B, C
- expressed on almost all nucleated cells
- NOT expressed on RBCs
- antigen loaded in RER of mostly intracellular peptides
- mediates viral immunity
- pairs with B2-microglobulin (aids in transport to cells surface (TAP))
- binds TCR and CD8
Describe the characteristics of MHC II.
- HLA-DR, DP, DQ
- expressed only on antigen-presenting cells (APCs)
- antigen is loaded folloing release of invariant chain in an acidified endosome
- binds TCR and CD4
Which disease is associated with the HLA subtype A3?
Hemochromatosis
Which disease is associated with the HLA subtype B27?
Psoriasis, Ankylosing spondylitits, Inflammatory bowel disease, Reiter's syndrome
Which disease is associated with the HLA subtype B8?
Grave's disease
Which disease is associated with the HLA subtype DR2?
-MS
- hay fever
- SLE
- Goodpasture's
Which disease is associated with the HLA subtype DR3?
Diabetes mellitus type 1
Which disease is associated with the HLA subtype DR4?
- Rheumatoid arthritis
- diabetes mellitus type 1
Which disease is associated with the HLA subtype DR5?
- pernicious anemia --> B12 deficiency
- Hashimoto's throiditis
Which disease is associated with the HLA subtype DR7?
steroid-responsive nephrotic syndrome
Describe the characteristics and function of Natural Killer cells?
- use perforin and granzymes to induce apoptosis of virally infected cells and tumor cells
- only lymphocyte member of innate immune system
- activity enhanced by IL-12, IFN-B and IFN-a
- induced to kill when exposed to a nonspecific activation signal on target cell and/or to an absence of class I MHC on target cell surface
What are the major functions of B-cells?
- Make Ab - opsonize bacteria, neutralize viruses (IgG); activate complement (IgM, IgG); sensitize mas cells (IgE)
- Allergy (type I hypersensitivity); IgE
- cytotoxic (type II) and immune complex (type III) hypersensitivity; IgG
- Hyperacute organ rejection (Ab mediated)
What are the major functions of T-cells?
- CD4+ T cells help B cells make Ab and produce y-interferon, which activates macrophages
- CD8+ T cells kill virus-infected cells directly
- delayed cell-mediated hypersensitivity (type IV)
- acute and chronic organ rejection
Which types of cells are APCs?
1. macrophages
2. dendritic cells
3. B-cells
What are the signals needed to activate a helper T-cell?
1. Foreign body is phagocytosed by APC
2. Foreign antigen is presented on MHC II and recognized by TCR on Th cell (signal 1)
3. "Costimulatory signal" is given by interaction of B7 and CD28 (signal 2)
4. Activated Th cells produce cytokines
What are the signals needed to activate cytotoxic T-cell activation?
1. Endogenously synthesized (viral or self) proteins are presented on MHC I and recognized by TCR on Tc cell (signal 1)
2. IL-2 from Th cell activates Tc cell to kill virus-infected cell (signal 2)
What are the signals needed to activate B-cells?
1. IL-4, IL-5, IL-6 from Th2 cell (signal 1)
2. CD40 receptor on B cell binds CD40 ligand on Th cell (signal 2)
What are the characteristics and function of Th1 cells?
- regulates cell-mediated response
- secretes Th1 cytokines (IL-2, IFN-y)
- activates macrophages and CD8+ T cell
- inhibited by IL-10 (from Th2 cell)
What are the characteristics and function of Th1 cells?
- regulates humoral response
- secretes Th2 cytokines (IL-4, IL-5, IL-10)
- helps B cells makes Ab (IgE>IgG)
- inhibited by IFN-y (from Th1 cell)
Describe the features and functions of cytotoxic T cells.
- kill virus-infected, neoplastic, and donor graft cells by inducing apoptosis
- release cytotoxic granules containing preformed proteins (perforin, granzyme, and granulysin)
- have CD8, which binds to MHC I on virus-infected cells
What are perforins?
- preformed proteins that help to deliver the content of granules into target cells
What are granzymes?
- serine protease that activates apoptosis inside target cell
What are granulysin?
- antimicrobial
- induces apoptosis
Which part of the antibody recognizes antigens?
variable part of Light and Heavy chains
Which portion of the antibody fixes complement?
Fc portion of IgM and IgG
What is the function of the Fab portion of the antibody?
- antigen-binding fragment
- determines idiotype: unique antigen-binding pocket; only 1 antigenic specificity expressed per B cell
What are the features and function of the Fc portion of the antibody?
- constant
- carboxyl terminal
- complement binding at Ch2 (IgG + IgM only)
- carbohydrate side chains
- determines isotype (IgM, IgD, etc)
How is antibody diversity generated?
1. random "recombination" of VJ (light-chain) or V(D)J (heavy-chain) genes
2. Random combination of heavy chains with light chains
3. Somatic hypermutation (following antigen stimulation)
4. Addition of nucelotides to DNA during "recombination" by terminal deoxynucleotidyl transferase
Describe the characteristics of IgG.
- main Ab in secondary (delayed) response to an antigen
- most abundant in blood
- fixes complement
- crosses the placenta (provides infants with passive immunity)
- opsonizes bacteria
- neutralizes bacterial toxins and viruses
Describe the characteristics of IgA.
- prevents attachment of bacteria and viruses to mucous membranes
- does not fix complement
- monomer (in circulation) or dimer (when secreted)
- crosses epithelial cells by transcytosis
- found in secretions (tears, saliva, mucus) and breast milk (colostrum)
- picks up secretory component from epithelial cells before secretion
Describe the characteristics of IgM
- produced in the primary (immediate) response to an antigen
- fixes complement but does not cross the placenta
- antigen receptor on the surface of B cells
- monomer on B cell or pentamer
- shape of pentamer allows it to efficiently trap free antigens out of tissue while humoral response evolves
Describe the characteristics of IgD.
- unclear function
- found on the surface of many B cells in serum
Describe the characteristics of IgE.
- binds mast cells and basophils
- cross-links when exposed to allergen, mediating immediate (type I) hypersensitivity through release of inflammatory mediators (histamine)
- mediates immunity to worms by activating eosinophils
- lowest concentration in serum
Describe the characteristics and function of T-independent antigens.
- antigens lacking a peptide component;
- cannot be presented by MHC to T cells (i.e. lipolysaccharide from cell envelope of gram-negative bacteria and polysaccharide capsular antigen)
- stimulate release of IgM Abs only and do not result in immunologic memory
Describe the characteristics and function of T-dependent antigens.
- antigens containing a protein compoent (i.e. conjugated H.influenzae vaccine)
- class switching and immunologic memory occur as a result of direct contact of B cells with Th cells (CD40-CD40 ligand interaction) and release of IL-4, IL-5, and IL-6
What is complement?
- system of proteins that interact to play a role in humoral immunity and inflammation
What is the function of the membrane attach complex of complement?
defend against gram-negative bacteria
- activated by IgG or IgM in the CLASSIC pathway
- also activated by molecules on the surface of microbes (especially endotoxin) in the ALTERNATIVE pathway
Which are the two primary opsonins in bacterial defense?
- C3b and IgG
- C3b aids in clearance of immune complexes
What is the function of decay-accelerating factor (DAF) and C1 esterase inhibitor?
help prevent complement activation on self-cells (i.e. RBCs)
A deficiency of C1 esterase inhibitor leads to which disorder?
hereditary angioedema
A deficiency of C3 leads to which disorder?
- severe, recurrent pyogenic sinus and respiratory tract infections
- increased susceptibility to type III hypersensitivity reactions
A deficiency of C5-c8 leads to what?
- Neisseria bacteremia
A deficiency in DAF (GPI-anchored enzyme) leasd to what?
- complement-mediated lysis of RBCs and paroxysmal nocturnal hemoglobinuria (PNH)
What are the characteristics and functions of IL-1?
- an endogenous pyrogen
- causes fever, acute inflammation
- activates endothelium to express adhesion molecules
- induces chemokine secretion to recruit leukocytes
Which type of cells secrete IL-1?
macrophages
Which type of cells secrete IL-6?
macrophages, Th cells
Which type of cells secrete IL-8?
macrophages
Which type of cells secrete IL-12?
macrophages, B-cells
Which type of cells secrete TNF-alpha?
macrophages
What are the characteristics and functions of IL-6?
- endogenous pyrogen
- causes fever and stimulates production of acute-phase proteins
What are the characteristics and functions of IL-8?
major chemotactic factor for neutrophils
What are the characteristics and functions of IL-12?
induces differentiation of T cells into Th1 cells
- activates NK cells
What are the characteristics and functions of TNF-alpha?
- mediates septic shock
- activates endothelium
- causes leukocyte recruitment, vascular leak
Which cells secrete IL-3?
T- cells
What are the characteristics and functions of IL-3?
- supports the growth and differentiation of bone marrow stem cells
- functions like GM-CSF
Which cells secrete IL-2?
Th1 cells
What is the function of IL-2?
- stimulates growth of helper and cytotoxic T cells
Which cells secrete interferon-y?
Th1 cells
What is the function of interferon-y?
-activates macrophages and Th1 cells
- suppresses Th2 cells
- has antiviral and antitumor properties
Which cells secrete IL-4?
Th2 cells
What is the function of IL-4?
- induces differentation into Th2 cells
- promotes growth of B cells
- enhances class switching to IgE and IgG
Which cells secrete IL-5?
Th2 cells
What is the function of IL-5?
promote differentiation into Th2 cells
- enhances class switching to IgA
- stimulates the growth and differentiation of eosinophils
Which cells secrete IL-10?
Th2 cells, regulatory T cells
What are the functions of IL-10?
- modulates inflammatory response
- inhibits actions of activated T cell and Th1
- activates Th2
What are interferons? What are their functions?
- interferons (alpha, beta, gamma) place uninfected cells in an antiviral state
- induce the production of ribonuclease that inhibits viral protein synthesis by degrading viral mRNA (but not host mRNA)
- activate NK cells to kill virus-infected cells
What is the function of interferon alpha and beta?
- inhibit viral protein synthesis
What is the function of interferon gamma?
increase MHC I and II expression and antigen presentation in all cells
What are the cell surface proteins found on T-cells?
- TCR (binds antigen-MHC complex)
- CD3 (associated with TCR for signal transduction)
- CD28 (binds B7 on APC)
What are the cell surface proteins found on helper T cells?
- CD4
- CD40L (binds CD40 on B cells)
What are the cell surface proteins found on cytotoxic T cells?
- CD8
What are the cell surface proteins found on B cells?
- Ig (binds antigen)
- CD19, CD20, CD21
What are the cell surface proteins found on macrophages?
- MHC II, B7, CD40, CD14
- receptors for Fc and C3b
What are the cell surface proteins found on NK cells?
- receptors for MHC I
- CD16 (binds Fc of IgG)
- CD56 (unique marker for NK)
What are the cell surface proteins for all cells except mature RBCs?
MHC I
Define anergy
- self-reactive T cells become nonreactive without costimulatory molecule
- B cells also become anergic, but tolerance is less complete than in T cells
Describe the effect of superantigens.
- i.e. S. pyogenes, S. aureus
- cross-link the B-region of the TCR to the MHC class II on APCs
- results in the uncoordinated release of IFN-y from Th1 cells and subsequent release of IL-1, IL-6 and TNF-alpha from macrophages
Desribe the effect of endotoxins/lipopolysaccharid (gram-negative bacteria).
-directly stimulate macrophages by binding to endotoxin receptor CD14
- Th cell are not involved
What is active immunity?
- induced after exposure to foreign antigens
- slow onset
- long lasting protection (memory)
What is passive immunity?
- based on receiving preformed Abs from another host
- rapid onset
- short life span of Abs (half-life 3 weeks)
- i.e. IgA in breast milk
Describe type I hypersensitivity
- Anaphylactic and atopic
- free antigen cross-links IgE on presensitized mast cells and basophils triggering release of vasoactive amines that act at postcapillary venules (i.e. histamine)
- reaction develops rapidly after antigen exposure due to preformed Abs
What is the test used to test type I hypersensitivity?
- scratch test and radioimmunosorbent assay
Which types of hypersensitivity are Ab mediated?
I, II, III
Describe Type II hypersensitivity
- Antibody mediated
- IgM, IgG bind to fixed antigen on "enemy" cell, leading to lysis (by complement) on phagocytosis
What are the three mechanisms in which Abs lead to phagocytosis during Type II hypersensitivity?
1. opsonize cells or activate complement
2. Abs recruit neutrophils and macrophages that incite tissue damage
3. binds to normal cellular receptors and interfere with functioning
What is the test used to to test Type II hypersensitivity?
direct and indirect Coombs
What are the types of reactions that are classified as Type II hypersensitivity?
1. Immune complex
2. Serum sickness
3. Arthus reaction
What is an immune complex?
- antigen-Ab (IgG) complexes activate complement, which atracts neutrophils
- neutrophils release lysosomal enzymes
What is serum sickness?
- immune complex disease (III) in which Abs to the foreign proteins are produced (takes 5 fays)
- immune complexes form and are deposited in membranes, where they fix complement (leads to tissue damage)
- more common than arthus reaction
What is Arthus reaction?
- local subacute Ab-mediated hypersensitivity (Type III) reaction
- intradermal injection of Antigen induces Abs, which form antigen-Ab complexes in the skin
- characterized by edema, necrosis, and activation of complement
What is the test used to test for Type III hypersensitivity?
immunofluorescent staining
Describe Type IV hypersensitivity.
- Delayed (T-cell mediated) type
- sensitized T lymphocytes encounter antigen and then release lymphokines (leads to macrophage activation; no Ab involved)
- not transferable by serum
What is the test used to test for Type IV hypersensitivity?
patch test (i.e. PPD)
Which disorders are associated with Type I hypersensitivity?
- anaphylaxis (i.e. bee sting, some food/drug alelrgies)
- allergic and atopic disorders (i.e. rhinitis, hay fever, eczema, hives, asthma)
Which disorders are associated with Type II hypersensitivity?
- Hemolytic and pernicious anemia
- idiopathic thrombocytopenic purpura
- erythroblastosis fetalis
- acute hemolytic transfusion reactions
- rhematic fever
- goodpasture's syndrome
- Bullous pemphigoid
- pemphigus vulgaris
- graves disease
- myasthenia gravis
What is the clinical presentation of type I hypersensitivity?
- immediate
- anaphylactic
- atopic
What is the clinical presentation of type II hypersensitivity?
disease tends to be specific to tissue or site where antigen is found
Which disorders are associated with Type III hypersensitivity?
- SLE
- rheumatoid arthritis
- polyarteritis nodosum
- poststreptococcal glomerulonephritis
- serum sickness
- arthus reaction (i.e. swelling and inflammation following tetanus vaccine)
- hypersensitivity pneumonitis (i.e. farmer's lung)
Which disorders are associated with Type IV hypersensitivity?
- Type 1 DM
- MS
- Guillan-Barre Syndrome
- Hashimoto's thyroiditis
- Graft-vs-host disease
- PPD
- contact dermatitis (i.e. poison ivy, nickel allergy)
What is the clinical presentation of type III hypersensitivity?
can be associated with vasculitis and systemic manifestations
What is the clinical presentation of type IV hypersensitivity?
response is delayed and does NOT involve Abs