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Immunology, Block 5
Diseases and key points
94
Immunology
Graduate
02/24/2011

Additional Immunology Flashcards

 


 

Cards

Term
What tactic of immune evasion does S. pneumoniae utilize?
Definition

Antigenic Variation

 

Has 84 different Serotypes, each with a differnt, antigenically distinct polysaccride capsule.

 

Clearing an infection of one of the serotypes does not protect against future infection by different serotypes.

Term
What tactic of immune evasion does the Infulenza virus employ?
Definition

Antigenic Variation

Antigenic Drift: point mutations in the genes encoding the surface proteins hemagglutinin and neuramidase yeilds a variant of the virus that can evade utilization by antibodies and/or destruction by CTLs.

 

Antigenic Shift: in some circumstances there can be a reassortment of the segmented RNA genome of the virus during co-infection of an animal host. Results in major changes to the hemagglutanin protein which renders a virus that is highly pathogenic.

Term
What tactic of immune evasion does the African Trypanosome use?
Definition

Antigenic Variation

Programmed rearrangement of DNA by the pathogen.

Trypanosomes have only a single type of surface protien (VSG) which is encoded by a cassette gene system that allows one of over 1000 distinct VSGs to be expressed at a time.

Paracites that are expressing a variant VSG on their surface can escape immune detection and replicate rapidly causing a recurrence of the disease.

 

Can happen over and over causing tissue damage (African Sleeping Sickness)

Term
What tactic of immune evasion does Herpes Simplex Virus use?
Definition

Viral Latency

Virus infects epithelial cells and then spreads to nearby sensory neurons, persisting after the immune response in sensory neurons by integrating into host cell episomal DNA.

Viral reactivation can be triggered by a number of stimuli causing a return of the epithelial infection.

Term
Varicella zoster
Definition

Virus, causes chicken pox

 

A good example of Viral Latency

Remains latent in the dorsal root ganglia of the host and is reactivated by stress at which point it spreads down the nerve and infects the skin causing shingles.

Reactivation of Varicella typically only occurs once.

Term

Epstein-Barr Virus

(EBV)

Definition

Causes cold symptoms in children and Mono in adults upon inital infection.

 

Mononucleosis form: B cell is infected with EBV and then proliferates making lots of new virus and activating T cells. Here the infection is controlled by CD8+ effectors that kill the infected B cells.

 

EBV becomes latent by inserting its genome into host DNA, however reactivation rarely causes disease.

Term
Mycobacterium tuburculosis
Definition

Subverts host cell immune responses

 

TB is taken up by macrophages but the bacterium is able to prevent phagosome-lysosome fusion and is therefore able to survive inside the phagocyte host.

Term
Listeria monocytogenes
Definition

Subverts host cell immune responses

 

Can escape from the phagosome and repilcate freely in the cytoplasm  of th emacrophage.

Spread via cell-cell contact so once it is in the cell the cell it can spread intracellularly.

 

Cleared by CTLs.

Term
Toxoplasm gondii
Definition

Subverts host cell immune responses

A protozoan parasite

 

Is able to generate its own vessicle following phagocytosis to isolate itself from the cell and the MHCs that would present it.

Remains invisible to the immune system.

Term
Staphylococcal bacteria
Definition

ex: Staphylococcal enterotoxins and TSS toxin-1

Staph bacteria produce toxins that are Superantigens.

 

Superantigens are capable of binding the outer surface of MHC II and the V-beta region of a TCR tricking the TCR into becoming stimulated and producing massive amounts of cytokines causing toxicity.

 

Because superantigens are specific for one type of V-beta region they can only activate TCRs with this beta chain (up to 20% of the T cell population)

Term
Mycobacterium leprae
Definition

Causes suppression of cell-mediated acquired responses. Bacteria is highly infectious and replicates freely in macrophages. (Lepromatous leprosy) Elevated levels of Ig/Abs. Low or absent T cells and the host cell in an anergic state, unable to respond to any antigens.

 

OR

Induces a potent cell-mediated antibacterial response via macrophage activation (Tuberculoid leprosy) which controls but does not eradicate infection.

Normal Ig levels in serum and normal T cell response (granulomas and local inflammation)

Term
Bruton's X-linked agammaglobulinemia
Definition

Deficiency in Ab production

 

Defective Btk gene=failure to produce tyrosine kinase that is vital for transducing cell-surface signals that allow for B cell development, halting B cells at the pre-B stage.

 

No Btk = No B-Cells

Succeptibility to extracellular bacteria that produce polysaccride capsules (that are resistant to phagocytosis) and enteroviruses that are sensitive to neutralizing Abs.

 

 

Term
λ5 Deficiency
Definition

A form of Ab deficiency

 

The λ5 chain is a vital 'place holder' during the development of the BCR. After the mu HC has rearranged, the λ5 chain holds the place of the light chain while it undergoes somatic recombination.

Without the λ5 chain many of the B cells cannot produce a pre-BCR and undergo apoptosis.

 

Results in a profound B cell deficiency and succeptibility to both extracellular bacteria and many viral pathogens.

Term
Selective IgA Deficiency
Definition

Realtively common in caucasians (1 in 500)

Only a problem when parasites are an issue. IgM can mostly compensate.

People with IgA deficiency make higher levels of other Ab isotypes.

Term
Selective IgG Deficiency
Definition

Deficiency of each subtype is possible.

IgG1 is the most abundant subtype and the most severe deficiency. Very rare. Succeptibility to many bacterial and viral pathogens.

IgG2: most common in kids, succeptibility to encapsulated bacteria.

IgG3: most common in adults

IgG4 dont' worry about it

Term
X-linked Hyper-IgM Syndrome
Definition

Geneterc disorder charactarized by high serum levels of IgM but very low concentrations of other isotypes.

Due to CD40L defect means that Thelper cells cannot deliver the second signal of activation to B cells expressinc CD40 and that Th1 cells cannot activate macrophages.

Results in a profound immunodeficiency and a failure to form germinal centers as a diagnostic feature.

Some other Ab isotypes are present but in very low amts.

Due to a defect in Activation-induced cytidine deaminase (AID): Without the enzyme that carries out isotype switching there can be no other isotypes produced!

Term
Properdin P defect
Definition

Properdin P is a control protein that enhances the activity of the alternative complement pathway.

 

Defects in properdin P leads to heightened sensitivity to Nisseria (just like MAC failure)

Term
Paroxysmal nocturnal hemoglobulinuria
Definition

Caused by deficiency in DAF and/or CD59 (which protect host cells from being activated in the alternative pathway) causes patients to destroy their own RBCs.

 

Term

Hereditary Angioneurotic Edema

(HANE)

Definition

Caused by defects in the C1-inhibitor leading to an inappropriate activation of the classical complement cascade and the uncontrolled cleavage of C2.

 

Continual C2 cleavage allows generation of lots of the vasoactive fragment C2a which causes fluid accumulation in the tissues and epiglottal swelling that can lead to suffocation.

Term
Chronic granulomatous disease
Definition

Defect in phagocytic cells.

X-linked Recessive

Defect in the gp91 protein (PHOX gene)

 

Phagocytes cannot produce ROS (especially superoixide) which impairs their ability to kill bacteria.

Term
Chedak-Higashi Syndrome
Definition

Defect in phagocytic vessicles

Due to a defect a protein involved in intracellular vessicle fusion.

Causes a fialure of phagosome:lysosome fusion (like the TB virus can cause) which impairs the ability of phagocytes to kill bacteria.

 

Charactarized by partial albinism, abnormal platelets and severe immunodeficiency.

Term
Adenosine demainase (ADA) and purine nucleotide phosphorylase (PNP) deficiencies
Definition

T cell defects/SCID phenotype

 

Lead to accumulation of nucleotide catabolites that are toxic to developing T and B cells.

Term
Bare lymphocyte syndrome
Definition

Classical: A lack of expression of all MHC class II molecules which results in an inability of CD4T cells to be postively selected in the Thymus.

The end result is a complete absence of T cells and a SCID phenotype.

 

Lack of MHC class I also called bare lymphocyte syndrome.

Two chief causes: TAP1/2 deficiency or a deficiency of the beta2-microglobulin. Same phenotype.

Term
Complete DiGeorge Syndrome
Definition

In addition to the congenital heart disease, palatal abnormalities and hypocalcemia that accompanies traditional DiGeorge, these patients also have an underdeveloped or non-functional thymus (=no T cells=SCID).

 

Can be treated with a thymic transplant.

Term
Common gamma chain deficiency/Jak3 deficiency
Definition

The common gamma chain (X-linked) is a vital signaling component of key cytokine receptors (such as the receptors for IL2, 4, 7, 9, 15).

The gamma chain on the cytokine receptor interacts with Jak to initiate the signaling cascade.

No gamma chain and/or no Jak=inability to initiate signaling in response to binding of any of the aforementioned cytokines.

Results in a SCID phenotype.

Term
Omenn Syndrome
Definition

Caused by a missense mutation in RAG (Recombination Activating Gene) enzyme genes which leaves them only partially active and unable to mediate somatic recombination of BCR.

 

The result of lack of RAG is NO B cells and low numbers of oligoclonal, autoreactie T cells.

Patients develop the viral, fungal, and bacterial infections typical of SCID.

 

Same phenotype as common gamma chain deficiency.

Erythroderma, alopecia, chronic diarrhea, failure to thrive, lymphadenopaty and hepatosplenomegaly.

Term
Zap-70 deficiency
Definition

ZAP-70 is a tyrosine kinase that associates with phosphorylated ITAMS during TCR complex signaling. It is vital for proper TCR signaling.

 

No ZAP-70 = No CD8+ T cells but normal numbers of nonfunctional CD4+ T cells.

Term
APECED
Definition

Caused by a defect in the gene that encodes the autoimmune regulator AIRE (a transcription factor that regulates expression of host tissue proteins on the epithelial cells in the thymic medulla to allow negative selection to take place).

No AIRE=no negative selection=Autoimmune issues

 

Hypoparathyrodisim, hypogonadisum, DM, hypothyrodism, alopecia, candidiasis, pernicious anemia, and malabsorption/diarrhea.

Term
IPEX
Definition

Caused by a genetic deficiency in the gene encoding FoxP3 which is key in the function of Treg cells.

 

No FoxP3→no Treg cells→no control/destruction of self-reactive T cells→symptoms of autoimmunity.

 

Presentation is with the clinical triad*

Watery diarrhea, eczmatous dermatitis and endocrenopaty (DM, type 1)

Anemia, neutropenia, and tubular nephropathy also.

Treatment is with immunosuppresion or BM transplant.


Coombs Positive Anemia: Patient RBC can be bound by anti-human Ab which causes agglutination because patient RBC have auto Ab and Complement on them!

Term

Autoimmune Lymphoproliferative Syndrome

(ALPS)

Definition

Genetic disease caused by lack of expression of Fas/FasL, or Caspase 10 resulting in a failure of immune cells to undergo apoptosis following an immune response leading to an overpopulation of immune tissues.

 

Shows autoimmune hemolytic anemia, neutropenia, thrombocytopenia, lymphadenopathy, splenomegaly.

Patients often have lots of CD4-CD8- T cells*

 

Treat with IV Ig and immunosuppression.

Term

Graft-vs-Host Disease

GVHD

Definition

A major complication of BM transplant. Occurs when mature T cells from the donor/transplanted marrow attack the tissues of the recipient.

Successful transplantation is dependent on good HLA matching between the donor and the recipient. Because all BM-derrived cells will be of the donor's haplotype they must be able to present to other cell types that are of the recipient's HLA haplotype.

Term
HIV
Definition

A retrovirus whose envelope complex gp120:gp41 engages in high affinity binding to CD4 molecules on T cells, interacts witha  co-receptor chemokine and gains entry into the cell.

Seroconversion is the process whereby infected patients convert all their CD8 T cells to become active and specific for HIV antigens; occurs 2-6 weeks post-infection.

Latency phase of the disease begins when seroconversiont akes place and during this phase 50% of the normal number of CD4+ T cells are in circulation and the patient is asymptomatic.

AIDS/Symptomatic Phase occurs when CD4 levels become very low (below 200 per microL). Results in death.

 

HIV is a master of immune response evasion.

Reverse Transcriptase enzyme, used to convert HIV's RNA genome to cDNA for insertion into the host to allow latency, is faulty. Results in antigenic variation via point mutations (drift). CHnages in the envelope lead to evasiono fthe immune system and to resistance to anti-viral drugs.

Term
Type 1 Hypersensitivity reactions
Definition

IgE

Response to a soluble Ag

Effector: Mast cell activation

 

Key examples=allergic rhinitis, asthma, systemc anaphylaxis.

Term
Type 2 hypersensitivity reactions
Definition

IgG

Reaction to altered self Ag's

(Cell or matrix-associated Ag or cell-surface receptor)

 Mediated by complement and FcR+ cells (phagocytes and NK cells or via the alteration of a signal by an Ab.

 

Examples inculde some drug allergies (penicillin) and chronic uticaria (hives).

 

Term
Type 3 hypersensitivity reactions
Definition

IgG

Soluble antigen in Immune Complexes!

Effectors: complement phagocytes

 

Examples include serum sickness and the Arthus reaction (involves the deposition of ICs on vascular walls)

Term
Type 4 hypersensitivity reactions
Definition

T cell-mediated

Soluble (Th1 and Th2) and cell-associated (CTL) Ag's

Effectors: Complement/phagocytes, activation of macrophages, IgE production, cytotoxicity.

 

Examples include: Contact dermatitis and the tuberculin reaction (Th1), Chronic asthma and chronic allergic rhinitis (Th2), and graft rejection (CTL)

Term
Allergic asthma
Definition

A condition where allergic to reactions to commonly inhaled llergens cause brethaing difficulties by triggering degranulation of submucosal mast cells in the lower respiratory tract and bronchial constriction.

Leads to trapping of air in the lungs making breathing difficulty.

 

Note that the condition of chronic asthma is the result of generalized hypersensitivty in the airways and inflammation that can be perpetuated in the absence of further antigen. Chronic asthma is considered a type IV hypersensitivtiy reaction.

Term
Bird Breeder's disease
Definition
A common form of type II hypersensitivity of the lungs that is caused by inhillation of avian antigens that elicit IgG responsenes leading to the accumulation of immune complexes in the lung alveoli.
Term
Allergic rhinitis
Definition

aka Hay Fever

A type I hypersensitivity reaction

 

A milde allergic response to inhaled allergens mediated by IgE/mast cells.

Causes bursts of sneexing and runny nose. Local edema in the mucosa causes nasal discharge of eosinophil-rich mucous. Histamne release by the mast cells causes general irritation.

Term
Antihistamines
Definition
Block the bindign of histamine to H1 receptors on vascular endothelum and reduce the impact of allergic reaction by blocking an effector pathway that causes hrinitis and urticaria.
Term
Corticosteroids
Definition

Suppresses the function of leukocytes.

 

Used to treat chronic inflammation caused by asthma, rhinitis, or eczema.

Term
Cromolyn sulfate
Definition
Used as a prophylactic inhalent to prevent the decranulation of activated mast cells and granulocytes.
Term
Epi Pen
Definition

Used to reverse anaphylaxis.

 

Epinephrine helps to reseal the tight junctions in vascular endothelium which reduces edema and swelling and raising blood pressure.

Epi also relaxes constricted bronchial smooth muscle and stimulates the heart.

Term
Serum Sickness
Definition

A Type III hypersensitivity reaction.

Results from immune responses to non-self material in the bloodstream (systemic reaction to IV treatments) causing chills, fever, rash, vasculitis, and glomerulonephritis.

 

Symptoms are caused by the systemic accumulation of immune complexes and the systemic inflammatory responses that follow.

Term
Farmer's Lung
Definition

Type III immune hypersensitivity reaction

 

Caused by repeated inhalation of hay, dust, mold spores, and other allergens that trigger IgG responses and lead to the  deposition of immune complexes in the walls of lung alveoli leading to inflammatory immune responses.

Term
Tuburculin reaction
Definition

A Type IV (delayed type) Hypersensitivity reaction.

 

Injection of protein extracted from M. tuberculosis subQ.

If an individual has previously produced an immune response to TB they will produce an inflammatory reaction around the site of injection in 1-3 days.

Term
penadecacatechol
Definition

The antigen that produces the type IV hypersensitivity reaction to poison ivy (Contact Sensitivity).

 

Initial contact allows this protien to form covalent bonds with excell proteins and skin proteins which form new antigens that are recgonized by local APCs as non-self and taken to the secondary lymphoid tissues where they are presented to naive CD4+ T cells on MHC II (can also be presented on class I to CTL).

 

Subsequent exposure results in rash due to action of antigen-specific CTLs and Th1 cells that produce macophage activation and inflammation.

Term
SCID
Definition

Severe Combined Immune Deficiency

The phenotype shown by individuals who have defects in T cell function.

Hilights the central role of T cells in the adaptive immune response to all antigens.

Without T cells, hosts cannot produce T-dependent Ab responsenes, cannot mount cell-mediated responses and therefore cannot mount protective or memory responses.

Term
Type II Autoimmunity
Definition

Auto-antibody against cell-surface or matrix antigens.

 

Includes autoimmune hemolytic anemai, autoimmune thrombocytopenia purpura, Goodpastyre's, Pemphigus vulgaris, acute rheumatic fecer, Graves', Myastenia gravis, Type II DM, and hypoglycemia.

Term
Type III Autoimmunity
Definition

Immune complex autoimmune disease.

 

Includes subacute bacterial endocarditis, mixed essential cryoglobulinemai, and SLE.

Term
Type IV Autoimmunity
Definition

T-cell mediated autoimmune diseases.

 

Inculdes IDDM, rheumatoid arthritis and MS.

Term
Autoimmune hemolytic anemia
Definition

Autoantigen: Rh blood group antigens, I antigen

Consequence: Destruction of RBC by complement and phagocytes resulting in anemia.

 

IgG and Igm bind to the surface of erythrocytes, activate the classical complement pathway leading to destruction of RBC either by MAC formation or by their clearence via C3b-mediated phagocytosis in the speen.

 

Gives a postive direct Coomb's hemagglutination test.

Term
Neutropenia
Definition

Occurs when WBC are targeted for autoimmune destruction.

This usually occurs via phagocytosis as nucleated cells are less succeptible to MAC.

Neutropenia refers to the resulting condition of too few neutrophils.

 

Commn treatment for neutropenia and hemolytic anemia is splnectomy which reduces rates of blood cell destruction.

Term
Goodpasture's Syndrome
Definition

Type II autoimmune disease

Caused by antibodies specific for ECM autoantigens.

Ab's are specific for the common α chain of type IV collagen (in BM of membranes throughout the body).

Leads to the deposition of Ab along the BM of renal glomeruli and tubules which causes inflammatory response and eventually glomulonephritis and kidney failure.

Treatment is plasma exchange (to remove self-reactive antibodies) and immnosuppressive drug treatemtn to prevent new autoantibodies from forming.

Term
Autoimmune/Idiopathic thrombocytopenic purpura
Definition

Type II, IgG-mediated autoimmune response.

 

IgG-mediated inhibition of the nezyme responsible for the cleavage of the von Willdebrand factor (which links platelets and blood vessels with clots).

Causes thromocytopenia (low platelets), brusing (pupura) neurological issues and microangioplastic hemolytc anemia (when RBC are damaged when being pushed through micro clots).

 

Diagnosis is made based on the presence of microangioplastic helolytic anemia.

Treatment is Plasmapheresis (an exchange transfusion with plasma from healthy donors).

Term
Schleroderma
Definition

Type II autoimmune disease

 

Caused by inflammatory destruction of endothelial cells and replacement with collagen and other fibrous materials.

Causes local and systemic, symmetric thickening of the skin with ivory-colored areas of hardened skin.

 

Diagnosis made based on the presence of anti-nuclear, anti-topoisomerase and anti-centromere Ab's (IgG)

Treatment (no cure) is patient-specific and usually includes drugs that increase blood flow to the extremities.

Term
Acute rheumatic fever
Definition

Type II autoimmune disease

 

Caused by IgG Ab which are initially produced in response to bacterial infection (group A streptococcal cell wall components) but, via Molecular Mimicry are cross-reactive with self antigens in the human heart.

Binding of streptococcal antibodies to heart tissue components causes an inflammatory response that can cause tissue damage to the heart including scarring of the valves and myocarditis.

Term
Pemphigus vulgaris
Definition

A type II autoimmune disease.

 

Mediated by IgG Ab's specific for Desmoglein 1 and 3 wich results in loss of cohesion in the keratinocytes in the epidermis.

 

Causes painful, chronic blistering of the skin.

Diagnosis is made via punch biopsy of the skin lesion followed by immunoflourescent staining for IgG4.

Treatment is with Corticosteroids and other anti-inflammatory drugs.

Rituximab is a monocolnal antibody (mAb) to CD-20, a cell surface marker for B cells.

Term
Graves' Disease
Definition

Hyperthyroidism

Type II autoimmune disease

 

Caused by antibodies that bind to the TSH receptor and mimic binding of the ligand (Ab's act as agonists) resulting in the chronic overproduction of thyroid hormone independant of feedback regulation by TSH levels.

Causes hyperthyrodisim which causes heat intolorance, weightloss, thyroid enlargement, bulging eyes and a charactaristic stare (imparied fuction of eye muscles).

Treatment includes drug therapy to reduce thyroid functionor thyroidectomy.

 

*IgG autoantibodies that cause Graves' and many other autoimmune diseased can be transported across the placenta by Brambell's receptors confering the disease onto the child for the first months of life. A plasma exchange can be used to clear autoantibodies from the baby's system if needed.

Term
Myasthenia gravis
Definition

Type II autoimmune disease.

 

Caused by IgG antibodies specific for acetylcholine receptors on muscle cells. Antagonist autoantibodies cause their receptors to be endocytosed and degraded.

With lower numbers of Ach receptors in the NMJ, muscles are much less sensitive to neuronal stimulation leading to muscle weakness. Presents with ptosis.

 

Treatment is with anti-inflammatory drugs and also with Pyridostigmine a drug that inhibits cholinesterase activity (enzymatic degredation of Ach) which allows Ach to stay around in the NMJ longer and to better compete for binding to the remaining Ach receptors.

Term

Systemic Lupus Erythematosis

(SLE)

Definition

Type III autoimmune disease

 

Mediated by autoantibodies specific for self macromolecules (DNA, histones, ribosomes)

Abs bind to cell surface components which causes inflammation leading to tissue destruction.

Cyclic and escalating nature of the disease results because tissue destruction results in the release of more macormolecules which forms immune complexes whih are deposited leading to more inflammation (further priming of immune responses).

 

More common in women (3:1), presents with butterfly rash, varaible progression/severity.

Treatment is with anti-inflammatory drugs.

Term

Guillain Barre Syndrome

(GBS)

Definition

Type II autoimmune disease

Molecular mimicry

 

Mediated by IgG Ab specific for gangliosides (in nerural tissues) which mediates acute inflammatory demylenating polyneuropathy (AIDP).

Typically follows infection (Campylobacter jejuni which causes diarrhea).

 

Causes weakness of the lower limbs which rapidly ascends to the upper limbs and face leading to loss of control of facial muscles.

Treatment is with plasma exchange + immunosuppressive drug treatment.

Term

Insulin-Dependant Diabetes Mellitus

(IDDM)

Definition

Type IV autoimmune disease that results int eh destructiono f insulin-producing cells in the pancreas by CTL that have specificitiy for a component of pancreatic beta cells.

Common in individuals of European descent (1 in 300)

Many symptoms, can be deadly.

 

Treatment with injection of pig/bovine insulin (human recombinant if patient forms a response against the animal insulin).

Term
Miller-Fisher Syndrome
Definition
An alternate form of GBS.
Begins in the eyes and descends (rather than ascending as in GBS).
Term
Wegener's Granulomatosis
Definition

Type II autoimmune disorder

Caused by anti-neutrophil cytoplasmic antibodies (ANCA) which are IgGs most commonly to the Ag Proteinase-3.

ANCAs bind neutrophils causing them to become activated and upregulate expression of adhesin which allows neutrophils to bind to endothelial cells, degranulate and cause vasculitis.

Typically follows an infection where the pathogen triggers production of cross-reactive IgG.

Presenting symptom is often Rhinitis but upper airway infection, nose stuffiness, nosebleeds, and conjunctivitus of the eyes, arthritis, skin nodules, and progressive glomulonephritis occur.

 

Treatment is with plamsa exchange +anti-inflammatory drug treatement.

Term

Rhumatoid arthritis

(RA)

Definition

Type IV autoimmune disease

 

An inflammatory disease of the joins caused by autoreactive T cells that initiate inflammatory response.

A feature if the disease is the production of rheumatoid factor an IgM antibody against the Fc region of IgG.

 

Treatment can be via anti-TNF-alpha Ab (Infliximab) or by using ADCC to deplete B cells using an anti-CD20 Ab called rituximab.

Term

Multiple sclerosis

(MS)

Definition

Type IV autoimmune disease

 

Mediated by Th1 CD4+ cells, directed agians thte myelin sheath of nerve cells causing sclerotic plaques of white matter int eh CNS and demylination.

Motor weakness, spasticity and impaired vision result with variable progression.

 

Diagnostic lab result=Presence of oligoclonal bands of IgG in CSF.

 

Treatment includes immunosuppressive drugs and IFN-beta1 which reduces the incidence of attack.

Term
Sjogren's syndrome
Definition

aka Mikulicz Disease, a Type IV autoimmune disease, the second most common rheumatic disease.

 

Causes the inflammatory destruction of exocrine glands that produce tears and saliva by autoreactive T cells.

Causes dry eyes, mouth, skin, nose, and vagina.

 

Diagnosis is via the Schirmer test for tear output and ANA/RF tests (this often occurs secondary to RA).

No known cure, artifical tears and goggles used by patients as well as punctual plugs.

Term
Hyperacute transplant rejection
Definition

Occurs in 12-48 hours

Triggered by failure to cross-match the blood type of the donor tissue/organ with that of the recipient.

 

Triggers complement activation throughout the vasculature of the graft (remember that endothelial cells of the recipient express the blood group antigens).

 

Can also be mediated by preformed Ab's to allogenic HLA antigens generated in the recipient as a result of a previous pregnancy, transfusion, or graft (accelerated form of an acute rejection because the memory T cells have already been formed).

 

Panel-Reactive Ab (PRA) is a measeure of the degree to which a patient seeking transplant has been sensitized to potential donors. Involves testing patient sera against a pannel of individuals and seeing what percentage of the wells show a positive reaction.

Term
Acute graft rejection
Definition

11-15 days post-transplant

 

Mediated by host effector T cells that respond to HLA differences between the donor and the recipient.

Is the result of a newly-formed acquired immune response against alloAgs floowing a graft (there has been no previous response and there are therefore no preformed Ag's hence it taking longer to develop).

Term
Minor histocompatability antigen-mediated rejection
Definition

Results from immune responses to minor HC Ag's (when the donor and recipient are HLA matched).

Minor HC Ag's are other polymorphic genes (often encoded by MHC gene) that can play a role in transplant rejection.

 

Because these minor HC Ag's are often present in lower concentrations and are less polymorphic than MHC, rejection mediated soely by minor HC Ag's takes ~60 days.

Term
Chronic rejection
Definition

Months to years after transplantation.

Responsible for 50% of failed kidney and heart transplants within 10 years.

 

Chronic rejection is correlated with the presence of antibodies specific for MHC I of the grafted/donor tissue.

Triggers reactions in the vasculature of the graft that result in a thickening of the vessel walls and a gradual reduction of blood flow to the graft.

Mediated by alloreactive MHC I-specific Ab's that bind to the vascular epithelia of the grafted tissue which attracts Fc receptor bearing immune cells (macrophages and neutrophils) which trigger chronic inflammation, tissue damage and death of the grafted tissue.

Term
What are the two ways that HLA molecules can stimulate acquired immune responses (as in acute graft rejection)?
Definition

Directly: Occurs when naive T cells of the recipient recognize donor-self peptides loaded onto donor HLA (on donor APC MHCs). The recgoinize these as foreign and mount a response.

Indirectly: When peptides derrived from the donor HLA molecules themselves are preocessed and presneted by host APCs to naive host T cells.

These HLA proteins typically come from donor APCs which migrate to host lymphoid tissues and undergo apoptosis making their HLA proteins availible for enxocytosis and processing/presentation by resident APCs and then presentation on MHC II to CD4 T cells (most commonly). This can happen in acute rejection but is vital in the development of chronic rejection*

Term
Sympathetic opthalmia
Definition

Trauma to immunologically privileged tissue of the anterior compartment of the eye leads to the release of antigens which are carried to local lymph nodes.

Here immune responses can be mounted to these antigens and an autoimmune response develops and CTL will destroy tissue in both eyes.

Shows that immunological privilege is not a result of physical separation of the eye from the immune system but of other factors that prevent the presentation of eye antigens in the absence of trauma.

 

Note that corneal transplants do not require MHC haplotype matching.

Term
BCG Vaccine
Definition
A widely used (though not in the US) whole, live, bacterial vaccine against the bovine strain of Mycobacterium tuberculosis.
Term
Toxoids
Definition

Bacterial toxins that have been inactivated and can be used as vaccine immunogens.

 

C. diptheriae and C. tetani produce toxins that cause their respective diseases (diptheria and tetanus) which can be purified and deactivated and used as subunit vaccines.

 

The abovementioned toxoids can also be combined with a killedm whole preparation of B. pertussis (whooping cough causal agent) to form the DPT vaccine

Term
DPT Vaccine
Definition
Combination vaccine made from the toxoids of the causal agents of diptheria and tetnus and a killed preparation of the causal agent of whooping cough.
Term
Attenuated
Definition

Describes a particle that has had its ability to cause disease reduced or eliminated but is still able to replicate in the host so that it mimics a real infection.

 

Most anti-viral vaccines are live-attenuated viruses*

Incl Measles, mumps, rubella, Sabin polio, varicella, influenza, Rotavirus (w/ recombinant live), Typhoid fever (with subunit components), Rabies and yellow fever vaccines.

 

Requires identification and mutation/deletion of the virulent portion of a virus.

 

Not 100% safe: can mutate in vivo and revert to the pathogenic strain (especially in immunocomprimised individuals who can't mount a response to the vaccine virus and therefore it sits around and mutates)


Rotovirus Vaccines are an example of a successful recombiant attenuated vaccine. Rotarix has varients of the common VP4 and VP6 coat proteins. RotaTeq has a mixture of cattle rotovirus strains that do not cause diease in humans and each has been engineered to express a different common VD4 and VD7 glycoprotein of the common human serotypes.

Term
Killed Bacterial Vaccines
Definition
Pertussis, Paratyphoid fever, Typhus fever, cholera, plague
Term
Subunit vaccines
Definition

Use a part of the subunit or coat protein of a pathogenic agent to generate a vaccine.

 

Hepatitis A, Hepatits B, human papillomavirus.

Term
Parenternal Immunization
Definition

Immunization that is administered by any route other than by the digestive system.

 

In order of effectiveness, the routes of parenternal immunization are:

SubQ > Intraperitoneal > IM > IV

 

Prenternal Immunization can only prime immune responses against systemic pathogens, not against those that effect the mucosal surfaces of the GI.

Term
Mucosal Immunization
Definition

Immunization to prime mucosal immune responses must be adminstered via a mucosal (digestive) route.

 

Unllike parenteral immunizations, those given by mucosal route protect against systemic and mucosal infections.

 

Ex: vaccine to the mucosal toxin that causes Cholera must be given intranasally or ingested.

Term
Extracellular Pathogens
Definition
Ideal response is mediated via Th2 response
Term
Intracellular Pathogens
Definition
Ideal response is via CTL and Th1
Term
Adjuvants
Definition

Substances that enhance the immunogenicity of an antigen, often by ↑ the length of exposure to Ag by slow release (Depot Formation), or by making a soluble Ag into a particulate one (more readily ingested by APCs), may also cause inflammation causing APC uptake of Ag.

Some can speficically elicit mucosal immune responses and others attempt to use cytokines.

 

Freund's Incomplete: Oil-in-water emulsion, delayed release of Ag and ↑ uptake by APCs.

Freund's Complete: Oil-in-water+ dead mycobacteria (which is a costimulator for APCs, intro a danger signal)

Freund's with MDP: Oil-in-water with MDP, a dipeptide consituant of mycobacteria (like Freund's Complete)

Alum: Aluminum hydroxide gell w. killed pertussis (delaywed release + ↑ uptake by APCs+ danger signals)

MF59: Squaline-oil-water emulsion, delayed release.

 

Immune Stimulatory Complexes (ISCOMs): A matrix of lipid micelles that engulf the viral proteins and deliver them to the cytosol of the target cell. Allows the introduction of Ag into the class I pathway and activation of CTLs*

Great for intracellular pathogens that need to be dealt with this way. Typically used with subunit vaccines*

Term
Cytokines and Vaccines
Definition

Cytokines can be used to modulate the immune response to pathogens and vaccine immunogens due to their key role in shaping the acquired immune responses.

 

Cytokines can be administered to alter the outcome of the intracellular parasite Leishmania.

Only mice who mount a Th1 can survive infection (those who mount a Th2 response die). In this case, admnistartion of IL-12 which promotes a Th1 response helps survival.

Anti-IL-4 (a cytokine that promotes Th2 differentiation and inhibits Th1 diff) can also be administered to help the development of a Th1 response that can fight this infection.

 

Cytokines may also be able to be used int he future as adjuvants when co adminstered with an Ag as a vaccine component.

Term
NEMO Deficiency
Definition

X-linked

Defect in a protien required for NF kappa B that acts downstream of the toll-like receptors.

 

Without NFkB you have impaired innate immune responses.

Suffer from recurrent bacterial and viral infections (Myco avium, a common opportunisitc pathogen)

 

Deep-set eyes, sparce hair, skin blistering.

 

Treatment is with a bone marrow transplant and gamma globulin.

Term
Human Cytomegalovirus
Definition

Subversts the immune system by inhibiting TAP and NK cell recoginiton of infected cells

Prevents peptide presentation by MHC I

Term
Asplenia
Definition

Inheritied absence of a spleen or acquired via trauma

 

Elevated suceptibility to encapuslated bacterial pathogens (Strep pneumo, Haemophilus influenzae)

 

Prophalactic antibiotics and vaccines for encapsulated bacterial pathogens is recommended.

 

Vaccines must be given subQ/IV

NOT IV! Because these enter the secondary lympoid tissues throught the spleen and in an asplenic patient this would never occur and the individual would not be vaccinated.

Term

What HLA haplotype that predisposes to diabetes?

To Goodpasture?

To allergies?

Definition

Diabetes: HLA-DQ2 and HLA-DQ8

 

Goodpasture: HLA-DR2

 

Allergy: On chromosome 11 encodes the high affinity IgE receptor and a gene cluster on chromosome 5 encodes IL-3,4,5,9,13 and GM-CSF (key in isotype switching, eosinophil survival and mast cell proliveration.

An inherited sequence variation in the promotor region for the gene encoding IL-4 is correlated with high levels of IL-4 in atopic individuals (more isotype switching to IgE)

Term
Molecular Mimicry
Definition

Rhumatic Fever (Strep A)

 

Wegner's Granulamatosis (unknown trigger, ANCAs/protinase-3)

 

GBS (Camper jeujini)

Term
Corticosterioids
Definition

Anti-inflammatory

Alter patterns of gene expression

Key for inhibiting NFkB (a TF involved in cytokine production)

 

Ex: Prednisone

Term
Cytotoxic Drugs
Definition

Interfere with DNA replication killing proliferating T lymphocytes

 

Azathioprine (solid organ transplant)

Cyclophosphamide (high toxicity)

Methotrexate (used to inhibit GVHD)

Term
Microbial Products as immunosuppresive drugs
Definition

Inhibit signaling pathways for T cell activation.

 

Cyclosporin A (Derrived from a fungis, interferes with IL-2 expression therefore lyphocyte activation and proliferation)

 

Tacrolimus (derived from soil, suprresses T cell activation)

 

Rampamycin (Interferes with IL-2 receptor signaling)

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