Immunology III Flashcards

Question

Tolerance vs. Tolerogen

Answer 1

Tolerence: The acquisition of a specific nonresponsiveness to a molecule recognized by the immune system as nonself Tolerogen: An otherwise immunogenic substance that, because of its chemical composition, dose, or route of introduction, induces immunologic tolerance rather than immunity; a foreign Ag that suppresses the immune response or produces immune tolerance

Answer 2

An absence of cell-mediated immune reaction in supposedly sensitized animals or individuals T or B cells are indifferent towards Ag In advanced cases of TB, infections with Mycobacterium tuberculosis, the tuberculin test becomes negative

Answer 3

Tolerance is unresponsiveness of the adaptive immune system to Ags as a result of inactivation or death of Ag-specific lymphocytes (T & B cells) Induced by exposure to Ag (Tolerogen) Conditions that influence tolerance induction: The immunologic maturity of an animal & its immune cells The dose of Ag The physicochemical nature of the Ag The immunogenicity of an Ag The route of Ag administration The kind of recipient It is easiest to induct tolerance using a neonate with an undeveloped immune system

Answer 4

Physical elimination or clonal deletion Functional inactivation, anergy Regulated inhibition of Ag-reactive T and B cells Induction of self-tolerance can occur at 3 levels: 1. The T-cell level 2. The B-cell level 3. The T-cell-B-cell cooperative level

Answer 5

1. Clonal abortion: multivalent antigen can, when given in appropriate concentrations, cause immature B cells to abort by preventing their further differentiation because B cells are only supposed to react with one epitope, not many (multivalent); tolerizability of pre-B cells is high 2. Clonal deletion: very strong negative signals can cause deletion of mature B cells (B cells do not react to Ag when supposed to) 3. Clonal anergy: intermediate concentrations of multivalent antigen allows pre-B cells to develop into morphologically normal B cells, with normal numbers of immunoglobulin receptors, but renders them profoundly anergic; will not bind any epitopes, and will not produce Ab

Answer 6

CTLA-4 is a CD28 homologue that is synthesized after the activation of T cell When CTLA-4 ligates B7 on the APC blocking activation signals so no more IL-2 is synthesized leading to T cell death TCR (t cell receptors) and MHC with peptide we need the CD4 that binds to it… these are the essential requirements Sometimes need costimulatory signals on B cells, macrophages, or any of the APCs must have these costimulators; if this is done and the costimulators are bound, then we see that the T cell will produce IL-2 which will bind to IL-2 receptor and activate the T cell to proliferate and produce more cells If we don’t have costimulators, like CTLA-4 binding to B7 = cannot transmit a signal to the T cell to make IL-2… this means no stimulation so the cell will most likely die via apoptosis

Answer 7

Left side: If the self Ag is present in the body, it can bind to the Ab but cannot activate the cell because in order to activate it, we need a T helper cell, but in this case there is no T cell; therefore the B cell is a ticking time bomb if the right side doesn’t happen Right side: bacterial infection has an Ag that is different from the self Ag, but they are similar enough to bind (similar epitopes usually) the Ab; when this infection occurs, this Ag will be broken down by the B cell and it will be presented with the MHC II to the T helper cell, which is present!; The T helper cell wants to help the B cell produce an Ab against the bacteria.. But once the Ab is released it does not differentiate against either the self or bacterial Ag since they are similar; once the bacteria is killed, the Ag will continued to be produced and this infection induced the autoimmune reaction because the Ab will recognize anything with this epitope

Answer 8

Advantages: Self-tolerance is essential for the function of the immune system Tolerance to foreign tissue grafts Control of damaging immune responses such as: i. Hypersensitivity ii. Autoimmune diseases Disadvantages: Tolerance to certain foreign antigens that cause disease such as bacterial infections Anergy- unresponsiveness to Ags Tolerance to some self-antigens associated with cancer

Answer 9

The immune response of the body with antibodies or cell-mediated immunity to self-tissues or antigens, resulting in pathological consequences and autoimmune disease 1. No auto reactive T cell (no help) + auto reactive B cell= No auto antigen or Disease 2. T helper cell (help) + Auto reactive B cell =Auto Ab and Autoimmune Disease 3. No auto reactive T cell (no help) + Polyclonal activated auto reactive B cell (from virus) = Auto antibody + Autoimmune Disease

Answer 10

i. Genetic factors: Monozygotic twins, dizygotic twins and family members have increased predisposition for certain diseases. Such inheritance is polygenic. Examples: 1. SLE (anti-dsDNA Abs) aka Lupus 2. Type 1 diabetes (>14 genes are involved) 3. HLA genes ii. Environmental factors: trigger autoimmune diseases There are Ags that are sequestered from the lymphoid system. Examples: Lens and uveal proteins of the eye; spermatozoa; accidents might end the sequestration of such Ags leading to autoimmunity iii. Upset control mechanisms such as: Suppressor T cells: Impairment can lead to autoimmune response as result of primary immunodeficiency or anti-Ts Abs Absence of MHC II, but if MHC becomes an APC = autoimmune response Absence of TH cells: [means tolerance], but any mechanism that causes bypassing TH absence leads to autoimmunity

Answer 11

1. Providing altered determinant capable of activating TH 2. Polyclonal activation of B cells (many B cells and their Ab against one antigen) 3. Bacterial & viral infections: streptococcal infections elicit Ab that cross-reacts with human heart Ags leading to autoimmune disease (rheumatic heart disease) Bacteria and EBV act as adjuvant = polyclonal activation = autoimmune response

Answer 12

Type II Hypersensitivity: myasthenia gravis – disease that effects the signal transmission around the synapses the nerve cell, neuron, and muscle cell Normal: ACh will activate the muscle cell Autoimmune: some people produce an Ag (IgG) and is directed against the receptor of the ACh, and it blocks the receptor from binding to the ACh; Sometimes the reaction is so severe and they will remove the receptors from the membrane of the muscle cell= lose innervation of muscle cell; ACh will not bind so no signal goes to the muscle cell so it remains uncontracted and leads to muscle atrophy; IgG can cross the placenta, so if woman has MG, then baby will too, but must be treated early or the infant will not last long= transient congenital MG

Answer 13

Ab Mediated: Myasthenia Gravis, Graves' Disease, Autoimmune Hemolytic Anemia Immune complex-mediated autoimmunity: Systemic lupus erythematosus (SLE) T-Cell-mediated autoimmunity: Multiple sclerosis, Type I diabetes mellitus, Hashimoto's thyroiditis Antibody- & T-cell-mediated autoimmune disease Rheumatoid arthritis

Answer 14

Chronic, inflammatory joint disease. Young women are usually involved. Serum and synovial fluid of patients contain "Rheumatoid factor"(IgM and IgG antibodies bound to Fc fragment of normal IgG.) Synovial membranes and blood vessels contain rheumatoid factor and normal IgG, which attract PMNs causing inflammation In active disease the patients have low titers (amount of Ab in blood) of complement and high titers of rheumatoid factor

Answer 15

Develops several weeks after group A beta-hemolytic streptococcal infection aka S. pyogenes pharyngitis Complement level is low Ag-Ab complexes deposit on glomeruli, fix/activate complement, attract PMN, and initiate the inflammatory process Heavy deposits of immunoglobulin and C3 along glomerular membrane can be shown by immunofluorescence Symptom: blood in the urine

Answer 16

Autoimmune diseases that can form lumpy deposits- combination of autoimmune disease + infectious disease Viral infections: Hepatitis B, Dengue hemorrhagic fever Infective endocarditis Serum sickness Systemic lupus erythematosus (SLE) nephritis- lumpy deposits contain DNA as antigen

Answer 17

For the B cell, it can recognize Ag and be activated to produce Ab without the help of the T cells (T cell independent) These Ag are LPS & nucleic acids (RNA and DNA), anything other than proteins (protein Ag require T cells) The B cells do not produce memory cells, only IgM ``` T-cell dependent route: recognizes protein antigens resulting in long term immunity IgG is produced by class switching T and B memory cells produced ```

Answer 18

Antigen that causes allergy: The term is used to refer to the antigen molecule itself or its source, such as pollen grain, animal dander, and insect venom or food products. Many naturally occurring and synthetic chemicals have been considered allergens Any foreign substance, which can elicit an immune response, is a potential allergen

Answer 19

Harmful exaggerated immune response to a harmless Ag Sensitization (necessary): first contact of Ag with host induces Ab formation Allergic response: result of second contact of same Ag and patient; hypersensitivity established/ patient allergic/Ag = allergen Clinical manifestation and symptoms vary

Answer 20

used to treat with people allergeries to any drugs, including antibiotics if no replacement drug present Take drug in small doses over 15 minute intervals and this will give the person small reactions and then after doing it for two hours, give the antibiotic that is needed and no reaction will occur- patient was desensitized temporarily because the patient becomes sensitized again within a few days Goals: formation of few Ag-IgE complexes, low release of mediators, and no major allergic reaction

Answer 21

Long-term administration of Ag to allergic patient- weekly Result: production of IgG-blocking Abs in the serum IgG prevent subsequent Ag from binding IgE on mast cells Immediate hypersensitive reaction would not occur Example: those deathly allergic to bee venom

Answer 22

Immediate/ Anaphylactic Hypersensitivity effect is fast: exposure causes immediate Ag activation of Th2 cells and stimulation of IgE class switching B cells IgE binds to surface of mast cell and trigger the release of histamine and other substances that are harmful ex. Bee stings mast cell derived mediators and cytokines mediate inflammatory response Allergen = trigger Mediators include cytokines and vasoactive amines/lipids Vasoactive amines: pre-made and have immediate response Cytokines: late phase after activation of certain enzymes; can take up to 24 hours high cGMP: increases degranulation high cAMP: decreases mediators released *Epinephrine increases cAMP at the expense of cGMP in order to decreases mediator release to decrease inflammation

Answer 23

Cytotoxic Ab-mediated reactions Involved Ab specifically that is directed against one antigen and one cell and causes damage by activating different types of reactions uses IgG and IgM Complement ad Fc receptor mediated recruitment and activation of leukocytes Opsonization and phagocytosis of cells Abnormalities in cellular function If the Fc doesn’t bind the receptor, then complement will and cause production of C5a to attract other neutrophil and get an accumulation of cell and damage the tissue

Answer 24

Immune complex Ab-mediated small blood vessel where Ab binds to antigen and the complex has no problem when in large blood vessels, but when in small ones in kidney or joints or lungs then can precipitate there and attracts lymphocytes and activate complement and cause damage uses IgG and IgM Localized where the Ag is present Complement and Fc receptor mediated recruitment and activation of leukocytes

Answer 25

Delayed-type cell-mediated ex. poison ivy using cytotoxic T cells and helper T cells CD4 cells does not have an effector function that kills/damages things directly- macrophage will do the damage CD8 once activated, it can damage the target cells directly by producing toxic substances Macrophage activation, cytokine mediated inflammation Direct target cell lyses, cytokine mediated inflammation

Answer 26

``` Exposure causes immediate Ag activation of Th2 cells and stimulation of IgE class switching B cells IgE binds to surface of mast cell and trigger the release of histamine and other substances that are harmful ``` Cross-linking of IgE on a mast cell by an allergen initiates multiple signaling pathways from the signaling chains of FceRI including the phosphorylation of ITAMs These signaling pathways stimulate: release of mast cell granule contents (amines & proteases), synthesis of arachidonic acid metabolites (prostaglandins & leukotrienes), and synthesis of various cytokines Mast cell mediators stimulate the various reactions of immediate hypersensitivity

Answer 27

Newly Synthesized: production of phospholipase that eventually act on arachidonic acid coming from cell membranes, so this causes damage to the membranes and contents will be released in the form of the “runny nose” in this case Cyclooxygenase will produce prostaglandins and thromboxanes which will lead to clotting of platelets/thrombocytes Lipooxygenase make leukotrienes- might lead to asthma/anaphylaxis Preformed: histamine, heparin, neutrophil chemotactic factor

Answer 28

Food allergies lead to diarrhea due to increased peristalsis Anaphylaxis: need treatment with epinephrine or blood vessels expand to lower BP and obstruction of airways = edema and death Allergic rhinitis, sinusitis (hay fever): increased mucus secretion, inflammation of upper airways, sinuses Bronchial asthma: bronchial hyper responsiveness caused by smooth muscle contraction; inflammation and tissue injury caused by late phase reaction Bronchial asthma: increase in cAMP and this will stop degranulation via corticosteroids and phosphodiesterase inhibitors Most allergic diseases: the use of anti-IgG so no production of IgE to cure the allergy permanently (anti IgE Ab), antihistamines, cromyln

Immunology III Flashcards

(52 cards)