Term
| T cell maturation occurs in the |
|
Definition
|
|
Term
| Immature T cell has these 2 types of surface proteins |
|
Definition
|
|
Term
| If no recognition of MHC and peptide during T cell maturation |
|
Definition
| Apoptosis (failure of positive selection) |
|
|
Term
| Weak recognition of MHC I and peptide leads to |
|
Definition
| Mature CD 8 t cell (positive selection) |
|
|
Term
| Weak recognition of MHC II and peptide leads to |
|
Definition
| Mature CD 4 t cell (positive selection) |
|
|
Term
| T cells that strongly recognize an MHC molecule results in |
|
Definition
| Apoptosis (negative selection) |
|
|
Term
|
Definition
|
|
Term
|
Definition
| effector function to KILL |
|
|
Term
CD4 T cell activation requires 2 signals
1.
2. |
|
Definition
1. MHC/Peptide antigen binding to TCR
2. Costimulatory molecule on APC binding to specific receptors on T cell.
This is B7 on APC binding to CD28 on T cell |
|
|
Term
| B7 and CD28 needed to release ____ |
|
Definition
|
|
Term
| CD4 and CD8 T cell activation occurs in the |
|
Definition
| peripheral lymphoid organs |
|
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Term
|
Definition
| APC phagocytoses infected cell --> Cross presentation via MHC class II to CD4 and class I to CD8. CD4 t cells secrete cytokines to activate CD8 t cells. Infected APC expresses B7 co-stimulator which triggers the T cell to secrete self-activating cytokines |
|
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Term
| Effector function of CD4 T cells |
|
Definition
Activation of macrophages
-CD4 T cells express CD40L
-CD40L binds to CD40 on macrophages
-CD4 t cells secrete cytokines (IFN gamma)
-Results in macrophage killing the phagocytosed microbe |
|
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Term
| Effector function of CD4 T cells |
|
Definition
Activation of a B cell.
-CD4 t cell expresses CD40L
-CD40L binds to CD40 on B cells
-CD4 t cells secrete INF gamma
-Results in B cell secreting antibody |
|
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Term
| Production of Th1 CD4 T cells |
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Definition
| Macrophages and dendritic cells respond to bacterial or viral infections by secreting IL-12. The IL-12 causes naive CD4 T cells to differentiate into Th1 cells. |
|
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Term
| Function of Th1 CD4 T cells |
|
Definition
Th1 cells secrete INF gamma. This stimulates macrophage activation.
-Stimulates expression of MHC Class II
-Stimulates expression of B7 costimulators
-Stimulates microbial killing |
|
|
Term
| Function of Th1 CD4 T cells |
|
Definition
Th1 cells secrete INF gamma
-B cells then produce IgG instead of IgM (class switch)(involved in phagocytosis) |
|
|
Term
| Production of Th2 CD4 T cells |
|
Definition
| If there is no IL-12 produced by APC then the T cell will secrete IL-4 inducing its differentiation into Th2 cell. This happens with large infections that cannot be phagocytosed. |
|
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Term
| Function of Th2 CD4 T cell |
|
Definition
Th2 cells secrete IL-4. This stimulates IgE production (class switch) by B cells.
Th2 cells also secrete IL-5. This activated eosinophils (which also use IgE)
Th2 cytokines (such as IL-4) inhibit macrophage activation and Th1 mediated immunity.
THINK TH2 --> parasitic infection |
|
|
Term
| Effector Function of CD8 Cytotoxic T lymphocytes |
|
Definition
Recognize MHC Class I with peptides on infected cells.
Differentiated CD8 cells do not require costimulation or T cell help for activation. |
|
|
Term
| Effector function of CD8 cytotoxic lymphocytes |
|
Definition
| CD8 cells kill target cells by releasing granule contents. (Perforin to create pores in target cell membrane and Granzymes to enter target cell through perforin pores and activate caspases to result in apoptosis) |
|
|
Term
Humoral Response
-Antigen recognition phase |
|
Definition
| Naive B cell express membrane bound IgM and IgD |
|
|
Term
Humoral Response
-Activation phase |
|
Definition
T cell dependent
T cell independent
Clonal Expansion
Differentiation (Ab secretion, Class Switch, Affinity Maturation, Memory Cells) |
|
|
Term
| Primary Antibody Response |
|
Definition
| Lag of 5-10 days following infection for Ab peak. Smaller response of mostly lower affinity IgM (some IgG). IgM IgM IgM!! |
|
|
Term
| Secondary Antibody Response |
|
Definition
Lag of only 1-3 days (due to memory B cells).
Larger response of mostly higher affinity IgG. IgG IgG IgG!!! |
|
|
Term
|
Definition
T cell-dependent (protein antigens)- Helper T cells utulized to stimulate naive B cell.
T cell independent (Polysaccharide, lipid, and other nonprotein antigens) - Does NOT utilize helper T cells to stimulate naive B cells. (IgM) Thus, no 2nd signal provided and no Antibody class switch. |
|
|
Term
| T cell independent B cell activation |
|
Definition
Primary signal
Ig Clustering makes it easier for antigens with multiple identical epitopes (non proteins such as polysaccharides)
Polyvalent antigens trigger a primary signal response
-Since they are not proteins, these antigens do not induce a strong overall B cell response.
Signal is transduced by Ig alpha and Ig beta, then antigen is endocytosed. |
|
|
Term
| Consequences of primary Signal |
|
Definition
Mitosis
Increased cytokine receptor expression
Reduced chemokine receptor expression (B cell wanders out of follicle)
Secretion of low levels of IgM (no class switch) |
|
|
Term
| Antigen Presentation by B-Cell |
|
Definition
B cell recognizes the foreign protein and activates the 1st signal. It processes the foreign protein and presents peptides in MHC class II molecules. It then expresses B7 co-stimulator.
The T cell recognizes peptide/class II MHC with TCR. It binds B7 with CD28 |
|
|
Term
| T helper Cell-Mediated B-Cell activation |
|
Definition
CD40 on B cell binds to CD40 ligand
Cytokines stimulate B cell (2nd signal)
B cell activates proliferation and differentiation (class switch and affinity maturation) |
|
|
Term
| Central T lymphocyte tolerance |
|
Definition
Occurs in the THYMUS.
Self-antigen presented to T cell |
|
|
Term
| Central T cell Tolerance - Regulatory T cells |
|
Definition
| A subset of self-reactive T cells become Reg T cells. These are allowed to migrate to the peripheral lymphoid organs. |
|
|
Term
| Peripheral T lymphocyte Tolerance |
|
Definition
Occurs in the peripheral lymphoid organs.
Due to either incomplete central tolerance
or
no self-antigen was presented to the cell in the thymus while it was there, so the cell is permitted to leave thymus even though it DOES recognize self-antigen |
|
|
Term
| Peripheral T cell tolerance - anergy |
|
Definition
Anergy is the functional inactivation of T cells.
-Occurs when primary signal (MHC/Peptide-TCR binding) happens without secondary signal (B7-CD28 binding).A useless T cell that cannot respond to antigen is now neutralized. |
|
|
Term
| Peripheral T cell tolerance - Activation-induced cell death |
|
Definition
Activated T lymphocytes will die by apoptosis if they are repeatedly stimulated with antigen.
Fas and Fas ligand expressed, results in apoptosis.
Expression of pro-apoptotic proteins resulting in apoptosis. |
|
|
Term
| Peripheral T cell tolerance - Reg T cells |
|
Definition
Develop in response to recognition of self-antigen.
CD4, CD25 T cells suppress or inhibit the activation of other T cells (probably due to inhibitory cytokine production). Il-10 inhibits macrophages, TGF-beta inhibits CD4 T cells |
|
|
Term
| B cells only undergo ______ tolerance |
|
Definition
|
|
Term
| T cells undergo ______ tolerance and ______ tolerance |
|
Definition
|
|
Term
| Induction of Auto-immunity - Molecular mimicry - Ankylosing spondylitis |
|
Definition
Antibodies against antigens from Klebsiella cross-react with antigens in the spine resulting in a chronic inflammation, fibrosis and ossofication of the articulations of the spine. (HLA-B27 positive is common among 90% of patients)
Basically our cells have similar epitope to bacteria. |
|
|
Term
| Induction of autoimmunity - Molecular mimicry - Rheumatic fever |
|
Definition
| Antibodies from antigens against streptococcus cross-react with heart valve antigens resulting in myocarditis |
|
|
Term
| Induction of auto-immunity - molecular mimicry - Guillan Barre Syndrome |
|
Definition
| Antibodies against LPS from Campylobacter cross-react with gangliosides of the motor neurons resulting in paralysis and polyneuritis. |
|
|
Term
Myasthenia Gravis
1. Systemic or organ specific?
2. Antibody mediated, T cell mediated, or both?
3. HLA association?
4. Mechanism?
5. Type of hypersensitivity? |
|
Definition
1. Organ specific (to skeletal muscle)
2. Antibody Mediated
3. HLA-DR3
4. Antibodies produced against acetylcholin receptors at neuromuscular junctions thus blocking the impulse.
5. Type II |
|
|
Term
Systemic Lupus Erythematosus (SLE)
1. Systemic or organ specific?
2. Antibody mediated, T cell mediated, or both?
3. HLA association?
4. Mechanism?
5. Type of hypersensitivity? |
|
Definition
1. Systemic
2. Antibody Mediated
3. HLA-DR3 and DR2
4. Antibodies produced against dsDNA and ANA. Get butterfly rash and photosensitivity, heart (pericarditis), kidneys (nephritis), joints (arthritis), lymph nodes (lymphadenopathy).
5. Type III |
|
|
Term
SLE pathogensis.
____________________
Ocular symptoms |
|
Definition
ANA form soluble immune complexes with antigens and get deposited in tissues which causes inflammation.
Activate complement, attract leukocytes (PMNs)
_________________________
Dry eye, keratitis sicca (keratoconjunctivitis sicca), due to secondary sjogren's syndrome, retinopathy (cotton wool spots) |
|
|
Term
Scleroderma
1. Systemic or organ specific?
2. Antibody mediated, T cell mediated, or both?
3. HLA association?
4. Mechanism?
5. Type of hypersensitivity? |
|
Definition
1. Systemic
2. Antibody
3. Not sure
4. Antibodies against nuclear antigens are present (topoisomerase, RNA polymerase, centromere antigens)
5. not sure |
|
|
Term
Sjogren's Syndrome
1. Systemic or organ specific?
2. Antibody mediated, T cell mediated, or both?
3. HLA association?
4. Mechanism?
5. Type of hypersensitivity? |
|
Definition
1. Systemic
2. Antibody
3. not sure
4. Inflammatory destruction of exocrine glands.
5. not sure |
|
|
Term
| Sjogren's Syndrome - pathogenesis |
|
Definition
Can result in dry eye (lacrimal gland) which is keratoconjunctivitis sicca. Also can result in dry mouth (salivary gland).
Antibodies against cytoplasmic RNA-protein complex, SS-A (Ro) and SS-B (La). Associated with SLE, RA, and scleroderma. |
|
|
Term
Graves Disease
1. Systemic or organ specific?
2. Antibody mediated, T cell mediated, or both?
3. HLA association?
4. Mechanism?
5. Type of hypersensitivity? |
|
Definition
1. Organ (tissue) specific (thyroid gland) (exophthalmos)
2. Antibody Mediated
3. HLA - DR3
4. Antibodies against TSH receptor (induces hyperthyroidism). Women 7x more likely.
5. Type II |
|
|
Term
|
Definition
| Symptoms can be transferred (IgG) from mothrt to child. |
|
|
Term
Hashimoto's Thyroiditis
1. Systemic or organ specific?
2. Antibody mediated, T cell mediated, or both?
3. HLA association?
4. Mechanism?
5. Type of hypersensitivity? |
|
Definition
1. Organ-specific
2. T cell mediated
3. HLA - DR5 and DR3 (MHC II) as well as HLA - B8 (MHC I) alleles
4. hypothyroidism
5. Type IV (Cell mediated) |
|
|
Term
Multiple Sclerosis
1. Systemic or organ specific?
2. Antibody mediated, T cell mediated, or both?
3. HLA association?
4. Mechanism?
5. Type of hypersensitivity? |
|
Definition
1. Organ specific? Neurons?
2. T cell mediated (primarily CD4 but also CD8)
3. HLA - DR2
4. demyelinated neurons, less NT to muscles
5. Type IV (cell mediated)
3. |
|
|
Term
Type I DM
1. Systemic or organ specific?
2. Antibody mediated, T cell mediated, or both?
3. HLA association?
4. Mechanism?
5. Type of hypersensitivity? |
|
Definition
1. Organ specific (pancreas)
2. T cell mediated
3. HLA - DR3 and secondarily DR4 and relative risk is 100% in those carrying DR3 AND DQw8
4. Its diabetes, antibodies against insulin
5. Type IV (T cell mediated) |
|
|
Term
Rheumatoid Arthritis
1. Systemic or organ specific?
2. Antibody mediated, T cell mediated, or both?
3. HLA association?
4. Mechanism?
5. Type of hypersensitivity? |
|
Definition
1. Systemic
2. Both antibody and T cell mediated
3. HLA-DR4
4. Molecular mimicry, pannus formation (increase osteoclast activity, decrease joint flexibility)
5. Type III and Type IV |
|
|
Term
|
Definition
| Inflammation initiated by deposition of IC and sustained by chronic inflammatory cells. Chronic inflammation of the synovium and other connective tissues. Rheumatoid factor produced by B cells. Anti-IgG in high % of patients. RF binds IgG to form ICs. |
|
|
Term
Laws of Transplantation
-Allogenic |
|
Definition
| Grafts exchanged between members of the same species |
|
|
Term
Laws of transplantation
-Xenogenic |
|
Definition
| Grafts exchanged between members of different species |
|
|
Term
| Allogenic and Xenogenic transplants are ______ rejected |
|
Definition
| ALWAYS. They require immunosuppressant |
|
|
Term
Laws of Transplantation
-Autograph |
|
Definition
| Grafts from one body part to another on the same person |
|
|
Term
Laws of transplantation
-Isograph |
|
Definition
| Grafts exchanged between monozygotic twins |
|
|
Term
|
Definition
| Principle antigens of graft rejection. MHC Class II DR is common in auto-immune diseases. |
|
|
Term
Role of T cells in rejection
(4 different mechanisms) |
|
Definition
Graft MHC interacts weakly with TCR may generate a signal for T cell activation.
Graft MHC can present the graft's own peptides.
Graft MHC can present processed antigens of host molecules. Host will not tolerate the difference of the MHC/antigen combination.
Different graft molecules can be taken up by host APCs and processed and presented on self MHC molecules. |
|
|
Term
|
Definition
| DONOR APC presents GRAFT peptide to recipient T cells. Direct activation is more powerful stimulus for graft rejection |
|
|
Term
|
Definition
| Recipient APC presents graft peptide to recipient T cells. |
|
|
Term
|
Definition
| Minutes to hours. Host needs pre-existing antibodies. Reason why animal (xenograph) transplants don't work well because we eat meat. |
|
|
Term
|
Definition
| Days to weeks. Due to primary activation of T cells against alloantigens in the graft. CD8 T cell mediated. Normal RXN. |
|
|
Term
|
Definition
| CD8 directly destroys graft cells. |
|
|
Term
|
Definition
| Months to years. Genetic disparity between donor and recipient. Also caused by immunosuppressive treatment. Like a delayed RXN. |
|
|
Term
|
Definition
| Walls of graft blood vessels thicken and get blocked. Interstitial fibrosis (scar formation) |
|
|
Term
|
Definition
| CD4 mediated. Low-grade cell mediated rejection. |
|
|
Term
Immunodeficiencies
Primary |
|
Definition
| Congenital or hereditary (mostly hereditary). |
|
|
Term
Immunodeficiencies
Secondary |
|
Definition
| Acquired. Caused by environmental factors. Infections, neoplasia, malnutrition, pathophysiological causes (diabetes), medical intervention (chemotherapy, surgeries, NSAIDs, corticosteroids). Secondary is more common than primary. |
|
|
Term
| Deficiencies in phagocytosis |
|
Definition
| Characterized by infections with opportunistic extracellular pathogens. |
|
|
Term
Deficiencies in phagocytosis
-Quantitative (reduced cell number)
-Primary |
|
Definition
Congenital granulocytopenia or agranulocytosis.
G-CSF deficiency - this hormone stimulates neutrophil production |
|
|
Term
| Secondary deficiency in phagocytosis |
|
Definition
Induced neutropenias.
-Chemotherapy, radiation
-Leukemia |
|
|
Term
Deficiencies in Phagocytosis
Qualitative |
|
Definition
| Defective phagocytic function |
|
|
Term
Deficiencies in Phagocytosis (qualitative)
Adherence defects |
|
Definition
Leukocyte adherence deficiency (no firm adhesion)
Due to a deficiency in beta chain of the CD18 molecule. |
|
|
Term
Humoral Immune Deficiencies
(Quantitative) |
|
Definition
Bruton's X-linked disease
No light chains produced, no B cells to full maturation stage |
|
|
Term
Humoral Immune deficiencies
(qualitative) |
|
Definition
X-linked hyper IgM syndrome
-Defective isotype switching. (no class switch due to mutation is CD40L)
Makes almost exclusively IgM. |
|
|
Term
Humoral Immune Deficiencies
Selective IgA deficiency |
|
Definition
-Qualitative
low or not IgA
Effects similar to Bruton's (few mature B cells) |
|
|
Term
Primary T Cell Deficiency
DiGeorge Syndrome |
|
Definition
| Defect in thymus development. Low CD3 counts in blood. No place for T cells to mature. |
|
|
Term
| SCID (sever combined immunodeficiency) |
|
Definition
X linked. (Bubble boy). Affects B and T cell development.
IL-7 receptor mutation affects T cell development.
ADA mutation affects both B and T cell development. |
|
|
Term
Secondary Acquired Immunodeficiency
-HIV |
|
Definition
| RNA Virus. Causes AIDS. Depletion of CD4 T cells leading to opportunistic infections and neoplasms. |
|
|
Term
|
Definition
| CD-SIGN found on dendritic cells and macrophages. HIV infects only CD4 cells which include helper T cells, macrophages, and dendritric cells. |
|
|
Term
|
Definition
| Virus attachment (binding is not sufficient to infect. Needs CD4 and/or cytokines to infect.) |
|
|
Term
|
Definition
| CD4 binding. GP120 binds directly to CD4 on cell surface. Or it can bind to CD4 after first binding to the cell surface via another molecule such as DC-SIGN. CD4 binding induces structural changes in gp120 that allows it to bind a cytokine co-receptor. |
|
|
Term
|
Definition
|
|
Term
|
Definition
| Conformational changes and membrane fusion. GP41 undergoes conformational change and inserts into cellular membrane. It injects genes and reverse transcriptase acts. |
|
|
Term
|
Definition
|
|
Term
|
Definition
Primary Infection in blood or mucosa.
Infection established in lymph node.
Viremia (virus spreads through body).
Immune response (Anti HIV antibodies, HIV specific CTLs.
Chronic infection (virus trapped in dendritic cells, low-level virus production.
Stimulus to replicate (cytokines, other infections).
AIDS |
|
|
Term
|
Definition
IgE Ab mediated
Allergic, anaphylactic.
Mast cell - histamine |
|
|
Term
|
Definition
IgG or IgM Ab mediated.
HDN, transfusion RXNs and autoimmune.
Rh factor, ABO |
|
|
Term
| Type I, II, and III are all mediated by |
|
Definition
|
|
Term
| Type III Hypersensitivity |
|
Definition
Immune complex mediated (IgG and IgM bound to soluble complexes)
IgG or IgM IC. |
|
|
Term
|
Definition
T Cell mediated.
Activation of CD4 and CD8 T cells.
Macrophage activation. |
|
|
Term
Ocular Immune Privilege
-Passive factors |
|
Definition
Blood-ocular barriers (capillaries of iris and retina), RPE
Corneal Endothelium
Lack of lymph drainage
Decreased MHC class I and II expression
APC without Class II MHC - Deficient in CD40 expression so they can't activate CD4 T cells |
|
|
Term
Ocular Immune Privilege
-Active factors |
|
Definition
Inhibitory cytokines
TGF beta (specific to EYES)
IL-10 inhibits T cells
MIF keeps NK Cells out |
|
|
Term
| Anterior Chamber Associated Immune Deviation (ACAID) |
|
Definition
| Antigen enters chamber and is phagocytosed by APC. APC travels to spleen and stimulates regulatory T cell formation. (inhibits Th1 and Th2 formation) |
|
|
Term
| Immune Privilege due to ACAID |
|
Definition
Selective suppression of effectors of immunogenic inflammation.
Delayed hypersensitivity (Type IV) T cells (CD4)
Complement-fixing Ab (IgG and IgM)
Preservation of other effector cells such as CD8 and non-complement fixing IgA |
|
|
Term
|
Definition
Whole organism vaccines
-Killed/Inactivated
-Live ettenuated
-Live heterologous species
Purified macromolecules
-Toxoid
-Polysaccharides
-Naked DNA |
|
|
Term
Antibody Based Diagnostics
-Primary Binding tests
-Elisa |
|
Definition
Must know Ag or Ab.
Plated antigens. Wash away free Antigen. Block unbound sites.
Add patient serum.
Was away unbound Ab.
Add fluorescent Ab. Was away unbound Ab.
Add enzyme, read via spectrophotometry. |
|
|
Term
| Direct Fluorescent Ab Test |
|
Definition
prepare tissue specimen.
Add fluorescein Ab against antigen.
Was away unbound Ab and view specimen under UV microscope |
|
|
Term
| Immunoblotting (aka Western Blot) |
|
Definition
Dissociate proteins with detergent. Separate proteins on gel. Blot on paper. Block excess protein binding sites.
Overlay patent serum with blot. Wash away unbound Ab. Develop as Elisa. |
|
|
