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What the primary lymphoid organs?

Thymus and Bone marrow


What is the function of lymph nodes?

nonspecific filtration by macrophages, storage and activation of B and T cells. Ab production


What does the structure of a lymph node look like?

1. many afferents, one efferent
2. encapsulated w/ trabeculae
3. follicle, medullar, and paracortex


What is found in the follicle of a lymph node?

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 found in the medullar of a lymph node?

- medullary cords (closely packed lymphocytes and plasma cells
- medullary sinuses - communicated w/ efferent lymphatics and contain reticular cells and macrophages


What is found in the paracortex?

1. T cells
2. this is the region btw follicles and medulla
- contains high endothelial venules through which T and B cells enter from blood


What happens to the paracortex in an intense immune response?

becomes greatly enlarged


What happens to the paracortex in DiGeorge pts?

not well developed b/c they don't have T cells


What is the lymphatic drainage from the following areas of the body?
1. Upper limb, lateral breast
2. stomach
3. duodenum, jejunum
4. sigmoid colon
5. rectum (lower portion) of anal canal (above pectinate line)
6. anal canal below the pectinate line
7. testes
8. scrotum
9. thigh
10. lateral side of dorsum of foot

1. axillary
2. Celiac
3. superior mesenteric
4. colonic -- inferior mesenteric
5. internal iliac
6. superficial inguinal
7. superficial and deep plexuses --> para aortic
8. superficial inguinal
9. superficial inguinal
10. popliteal


What is considered to be the largest component of the immune system?

MALT - made up by GALT, NALT, BALT, genitourinary tract, appendix, tonsils, adenoids, M cells


What are M cells?

- found in the mucous membranes of small gut
- flattened epithelial cells lacking microvilli. there are deep pockets on the basilar side that allow Ag presentation to dendritic cells, B and T cells, and macrophages


What are Peyer's patches?

- unencapsulated lymphoid tissue
- found in lamina propria and submucosa of small gut
- B cells make IgA


What does the right lymphatic duct drain?

-right arm, right chest, and right half of head


What does the thoracic duct drain?

everything else


Where does the thoracic duct drain?

junction b/w lespift subclavian and internal jugular vein


Describe the sinusoids of the spleen?

long, vascular channels in red pulp w/ fenestrated barrel hoop basement membrane. Macrophages found nearby


Where are T cells found in the spleen?

Periarterial lymphatic sheath (PALS) within the white pulp


Where are the B cells found in the spleen?

follicles w/in the white pulp


What is the role of the macrophages in the spleen?

remove encapsulated bacteria


What happens when there is splenic dysfunction?

- decreased IgM = decreased complement activation = decreased C3b opsonization
- increases susceptibility to encapusulated organisms


What are some encapsulated organisms that you need to worry about when you have splenic dysfunction?

E coli, pseudomonas, strep pneumoniae, Haemophilus influenzae type B, Nessiera meningitidis, salmonella, klebsiella, cryptococcus neogformans, group B Strep


Where are situations that a splenic dysfunction will take place?

1. sickle cell pts
2. Trauma to spleen
3. hereditary sphereocytosis


What happens after postsplenectomy?

1. Howell Jolly bodies - nuclear remnants
2. Target cells
3. Thrombocytosis


What is important about the thymus?

1. site of T cell differentiation and maturation
2. encapsulated
3. from epithelium of 3rd branchial pouch
4. Cortex is dense w/ immature T cells
2. Medulla is pale w/ mature T cells and epithelial reticular cells containing Hassall's corpuscles.


What is innate immunity?

1. response to pathogens is fast and nospecific
2. no memory
3. consists of neutrophils, macrophages, dendritic cells, natural killer cells, and complement


What is adaptive immunity?

1. receptors that recognize pathogens undergo VDJ recombination during lymphocyte development
2. Response is slow on first exposure but memory response is faster and more robust.
3. Consists of T and B cells and circulating Abs


What is the MHC?

major histocompatibility complex
- encoded by human leukocyte antigen (HLA) genes
- presents Ag fragment to T cells and TCR


What are the genetics for MHC I?

HLA A, B, and C


What cells have MHC I?

expressed on all nucleated cells. not expressed on RBC


What does MHC I bind to?

TCR and CD8


How does MHC I work?

-mediates viral immunity
- pairs w/ Beta 2 microglobulin (aids in transport to cell surface)
- Ag is loaded in RER w/ mostly intracellular peptides


What genes are associated w/ MHC II?

HLA DR, DP, and DQ


What receptors does MHC II bind to?

binds TCR and CD4


what cells have MHC II?

expressed only on APCs


How does MHC II work?

Ag is loaded following release of invariant chain in an acidified endosome


What are the following HLA genes associated with?
1. A3
2. B27
3. DQ2/8
4. DR2
5. DR3
6. DR4
7. DR5

1. hemochromatosis
2. Psoriatic arthritis, ankylosing spondylitis, inflammatory bowel disease, reiter's syndrome -- (PAIR)
3. Celiac disease
4. MS, hay fever, SLE, goodpasture's
5. DM type 1, Grave's disease
6. RA, DM type 1
7. Pernicious anemia --> B12 deficiency, Hashimoto's thyroiditis


How do natural killer cells work?

they use perforin and granzyme to induce apoptosis of virally infected cells and tumor cells.
- it's the only lymphocyte member of innate immune system


What cytokines enhance natural killer cells?

IL2, IL12, IFN-beta, and IFN -alpha


When are natural killer cells induced to kill?

1. when exposed to a nonspecific Ag signal on target cells
2. an absence of class I MHC on target cell surface


What are the surface makers for natural killer cells?

CD 16, CD 56


What does CD16 do?

it binds to constant region of Abs
- found on NK cells and phagocytes to help them recognize and kill Ig coated cells by Ab dependent cell mediated cytotoxicity (ADCC)


What are the major functions of B cells?

1. make Abs
2. used in hyperacute and humorally mediated acute and chronic organ rejection


What are the roles of Abs?

1. opsonize bacteria
2. neutralize viruses (IgG)
3. activated complement (IgM, IgG)
4. sensitize mast cells (IgE)


What are the major functions of T cells?

1. CD4 T cells help B cells make Ab and produce cytokines to activate other cells of immune system
2. CD8 cell kill virus-infected cells directly
3. involved in cell-mediated HSR (type 4)
4. Acute and chronic cellular organ rejection


What are all the APCs of the body

1. M cells in gut
2. Dendritic cells in the skin
3. Macrophages
4. B cells


What are the steps of T cell differentiation?

1. immature T cells in bone marrow travel to the thymus
2. Positive and negative selection takes place in corticomedullary junction
4. the matured cells like in the lymph nodes and wait to be activate


What happens during positive selection of T cells?

T cells expressing TCRs capable of binding surface self MHC molecules survive


What happens during negative selection of T cells?

T cells expressing TCRs / high affinity for self Ag undergo apoptosis


What cytokines help differentiate Helper T cells to become either Th1 or Th2 cells?

1. to make Th1 cells, you need IL 12
2. to make Th2 cells, you need IL 4


What cells are capable of activating T and B cells?

- 2 signals are required to activate these cells


What are the steps of T cell activation

1. Foreign body is phagocytosed by dendritic cells
2 Forgeign Ag is presented on MHC II and recognized by TCR on T helper cells. Ag is presented on MHC I to cytoxic cells --- this is the 1st signal
3. Costimulatory signal is given by interaction of B7 and CD28 ( signal 2)
4. T helper cells activates and produces cytokines
Cytotoxic T cells activates and is able to recognize and kill virus infected cells


How are B cells activated?

1. First you need to get helper T cell activated so remember that process (TCR binds to Ag on MHC II, and B7 binds to CD28 for co-stimulation)
2. B cell receptor mediated endocytosis, foreign Ag is presented on MHC II and recognized by TCR on T helper cells (signal I)
3. CD 40 receptor on B cell binds CD40 ligand on Th cells (signal 2)
4. Th cell secretes cytokines that determine Ig class switching of B cell. B cell activates and undergoes class switiching, affinity maturation, and Ab production


What do Th1 cells do?

1. secrete IFN-gamma and IL2
2. activated macrophages and cytotoxic T cells


What cytokines inhibit Th1 cells?

by Il 4 and 10 from Th2 cells


What do Th2 cells do?

1. secrete Il 4, 5, 10, and 13
2. Recruit eosinophils for parasite defense and promote IgE production by B cells


What cytokines inhibt Th2 cells?



Tell me about macrophage-lymphocyte interaction

Activated lymphocytes release IFN-gamma and macrophages release IL1 and TNF alpha stimulating each other


What do helper T cells and cytotoxic T cells have in terms of CD and what receptors do they bind to in terms of MHC?

1. Th cells have CD4 bind to MHC II
2. Tc cells have CD8 bind to MHC I


What are the roles of cytotoxic T cells?

1. kill virus-infected, neoplastic, and donor graft cells by inducing apoptosis


How do cytotoxic T cells work?

they release cytotoxic granules containing preformed proteins
1. perforin - makes holes in membranes
2. granzyme - serine protease that activates apoptosis inside target cells
3. granulysin - antimicrobial, induces apoptosis


what are regulatory T cells?

help maintain specific immune tolerance by suppressing CD4 and CD8 T cell effector functions


What surface markers do regulatory T cell express?

1. CD3, CD4, CD25 (alpha chain of IL 2 receptor)


What cytokines do regulatory T cell produce?

anti-inflammatory cytokines like IL10 and TGF beta


What is the structure of Abs?

1. 2 light chains (lambda or kappa)
2. 2 heavy chains ( Mu, Delta, Gamma, Alpha, Epsilon)
3. Variable part of L and H chains recognize Ags
4. Heavy chain contributes to Fc and Fab fractions
5. Light chain contributes to Fab fractions


What holds the structure of Abs together?

Disulfide bonds - the exist within the heavy and light chains. They hold the heavy chains together. They hold the heavy and light chains together as well.


What is the role of the Fab portion of the Ab?

- Ag binding fragment
- determines idiotype: unique antigen binding pocket; only 1 antigenic specificity expressed per B cell


What is the role of the Fc portion of the Ab?

- constant chain
- carboxy terminal of Ab
- complement binding at Ch2 (IgG and IgM only)
- carbohydrate side chains
determines isotype of Ab


How is Ab diversity generated?

by random recombination of VJ (light chain) or VDJ (heavy chain) genes
- random combination of heavy chains w/ light chains
- somatic hypermutation (following Ag stimulation)
- Addition of nucleotides to DNA during recombination (see 1st entry in this list) by terminal deoxynucleotidy transferase
- rearrangement begins w/ break in dsDNA at recombination signal sequences (RSS) that flank the VDJ coding regions - RAG 1 and 2 recognize the RSS


What what happens there are mutations in the RAG genes?

inability to initiate VDJ rearrangement and an arrest of B and T cells


What is the normal ratio of lambda to kappa light chains?



What is the role of IgG

- main Ab in the delayed response to an Ag
- fixes complement and crosses the placenta (provides passive immunity to infant)
- opsonizes bacteria, neutralizes bacterial toxins and viruses


What is the most abundant Ab?



What is the role of IgA?

-prevents attachment of bacteria and viruses to mucous membranes
- does NOT fix complement
- crosses epithelial cells by transcytosis
- picks up secretory component from epithelial cells before secretion


What are the forms that IgA can be found in?

- in circulation = monomer
- when secreted = dimer


Where can IgA be found?

in secretions (tears, saliva, mucus) and early breast milk (colostrum)


What is the role of IgM?

- produced in the immediate response to an Ag
- Fixes complement but does NOT cross the placenta
- Ag receptor on the surface of B cells
- monomer on B cell or pentamer


Why does IgM exist in a pentamer form>

allow it to efficiently trap free antigens out of tissue while humoral response evolves


What is the role of IgD?

unknown; found on surface of many B cells and in serum


What is the role of IgE?

-binds mast cells and basophils
- cross -links when exposed to allergens, mediating immediate (type I) HSR through release of inflammatory mediators such as histamine
- mediates immunity to worms by activating eosinophils
- lowest concentration in serum


What is thymus independent Ag?

Ag lacking a peptide component
- can't be presented to MHC to T cells
- stimulates release of Abs and don't result in immunologic memory


What are examples of thymus independent Ag?

LPS from cell envelope of gram - negative bacteria and polysaccharide capsular ag


What are thymus dependent Ag?

Ags containing a protein component
- class switching and immunologic memory occur as a result of direct contact of B cells w/ Th cells


What is the role of complement?

a system of interacting proteins that play a role in innate immunity and inflammation. MAC of complement defends against gram-negative bacteria


How are the various complement pathways activated?

1. Classical = IgG or IgM mediated --> C1 mediated to make a C4b2a C3 convertase
2. Alternative = microbe surface molecules --> C3 deposition and C3b interacts w/ Bb to make C3bBb C3 converatse. Bb comes from D
3. Lectin = mannose of other sugars on microbe surface


What's the function of the following complement proteins?
1. C3b
2. C3a, C5a
3. C5a
4. C5b-9

1. opsonization
2. anaphylaxis
3. neutrophil chemotaxis (LTB4, IL8)
4. MAC formation


What are the main opsonins?

C3b and IgG are two primary opsonins in bacterial defense; C3b also helps clear immune complexes


What are the inhibitors of the complement pathway?

1. DAF
2. C1 esterase inhibitor
* both help prevent complement activation on self cells


What happens when you have a C1 esterase inhibitor deficiency?

hereditary angioedema.
- ACE inhibitors are contraindicated


What happens w/ a C3 deficiency?

severe, recurrent pyogenic sinus and respiratory tract infections. Increased susceptibility to type III HSR rxns esp GN in kidneys due to complex deposition


What happens w/ C5-9 deficiency?

recurrent Neisseria bacteremia


What happens w/ a DAF (GPI anchored enzyme) deficiency?

complement mediated lysis of RBCs and paroxysmal nocturnal hemoglobinuria (PNH)


What are all the cytokines secreted by the macrophage?

IL 1, 6, 8, 12, and TNF alpha


What is the role of IL 1?

-endogenous pyrogen
- causes fever, acute inflammation
- activates endothelium to express adhesion molecules
- induces chemokine secretion to recruit leukocytes


What is the role of IL 6?

- endogenous pyrogen
- also secreted by Th2 cells
- causes fever and stimulates production of acute phase proteins


What is the role of IL 8?

- major chemotactic factor for PMN


What is the role of IL 12?

- induces differentiation of T cells into Th1 cells
- activates NK cells
- also secreted by B cells


What is the role of TNF alpha?

- mediates septic shock
- activates endothelium
- causes leukocyte recruitment, vascular leak


What are cytokines secreted by all T cells?

IL 2 and IL 3


What is the role of IL2?

stimulates growth of helper, cytotoxic, and regulatory T cells


What is the role of IL 3?

supports growth and differentiation of bone marrow stem cells
- functions like GM-CSF


What is the role of IFN gamma?

activates macrophage and Th1 cells
- suppresses Th2 cells
- has antiviral and antitumor properties
- increase MHC I and II expression and Ag presentation in all cells


What is the role of IL 4?

induces differentiation into Th2 cells
- promotes growth of B cells
- enhances class switching to IgE and IgG


What is the role of IL 5?

- promotes differentiation of B cells
- enhances class switching to IgA
- stimulates the growth and differentiation of eosinophils


What is the role of IL 10?

- modulates inflammatory response
- inhibits actions of activated T cells and Th1
- also secreted by regulatory T cells


What are interferons?

proteins that place uninfected cells in an antiviral state
- induce the production of a ribonuclease that inhibits viral protein synthesis by degrading viral mRNA (but not host mRNA)


What do IFN alpha and beta do?

inhibit viral protein synthesis
- activate NK cells to kill virus infected cells


What are the cell surface proteins for T cells?

TCR - binds ag-MHC complex
CD3 - associated w/ TCR for signal transduction
CD28 (binds B7 on APC)


What are the cell surface proteins for helper T cells?

CD4, CD40 ligand


What are the cell surface proteins for Tc cells?



What are the cells surface markers of B cells?

- Ig (binds Ag)
- CD19, 20, 21 (receptor for EBV), CD 40
- MHC II, B7


What are the cell surface markers for macrophages?

- CD 14, 40, 16
- Fc and C3b receptors


What CD binds to LPS or endotoxin of gram negative bacteria?

CD 14


What are the cell surface markers of NK cells?

CD 16, CD 56


What is anergy?

self reactive T cells become nonreactive without costimulatory molecule. B cells also become anergic, but tolerance is less complete than in T cells


How do superantigens work?

- cross link the Beta region of the TCR to the MHC class II on APCs. Can activate any T cell, leading to massive release of cytokines


how do endotoxins/LPS work?

directly stimulate macrophages by binding to endotoxin receptor CD14; Th cells are not involved


What are some infectious agents that can undergo antigenic variation?

- Salmonella
- Borrelia (relapsing fever)
- Neisseria gonorrhoease (pilus protein)
- Influenza (major = shift; minor = drift)
- Trypanosomes = programmed rearrangment


How does one acquire passive immunity?

- receive performed Abs


What is the onset and duration of passive immunity?

rapid onset but duration is the half life of Abs which is 3 weeks so you have to keep giving them


What are examples of passive immunity?

- IgA in breast milk, antitoxin, humanized monoclonal antibody


How does one acquire active immunity?

- exposure to foreign antigen


What is the onset and duration of active immunity?

- slow onset but long lasting protection due to memory


What are examples of active immunity?

natural infections, vaccines, toxoid


In what clinical exposures are preformed antibodies givens?

- tetanus toxin
- botulinum toxin
- rabies virus
- premature babies get RSV passive vaccine during winter months


What are live attenuated vaccine?

- microorganism loses its pathogenicity but retains capacity fro transient growth within inoculated host


What kind of response doe a live attenuated vaccine induce?

cellular response


What are the pros/cons of a live attenuated vaccine?

1. pros- induces strong often life-long immunity
2. con - may revert to virulent form so don't give to ICPs


What are examples of live attenuated vaccine?

-MMR, polio (sabin - oral), varicella, yellow fever, intrasnasal flu


What are killed vaccines?

pathogen is inactivated by heat or chemicals
- maintains epitope structure on surface antigens
- is a thymus dependent Ag


What kind of response does a killer vaccine induce?

humoral immunity


What are pros and cons of a killed vaccine?

1. pro - stable and safer than live vaccines
2. con - weaker immune response; booster shots usually required


What are examples of killed vaccines?

cholera, Hep A, polio (salk), rabies, IM flu


What are egg based vaccines?

flu, yellow fever


What is a type 1 HSR rxn?

- free Ag cross links IgE on presensitized mast cells and basophils triggering release of vasoactive amines that act at postcapillary venules.
- rxn develops rapidly after antigen exposure b/c of preformed Abs
- anaphylactic and atopic
- wheal and flare


What is a type 2 HSR rxn?

- cytotoxic (antibody mediated) IgM, IgG bind to fixed antigen on enemy cell leading to cellular destruction.
- opsonization leads to phagocytosis or complement activation
- complement mediated lysis
- ADCC usually due to NK cells


What is a why to determine if a type 2 HSR rxn took place?

Direct and indirect Coomb's


What is a type 3 HSR rxn?

Immune complex - Ag-Ab (IgG) complexes activate complement which attracts PMNs. PMNs release lysosomal enzymes


What is serum sickness?

- immune complex disease (type III) in which Abs to the foreign proteins are produced (takes 5 days). Immune complexes form and are deposited in membranes, where they fix complement (leads to tissue damage). More common than Arthus rxn


What is most serum sickness caused by?

drugs acting as a hapten.


What are symptoms of serum sickness?

fever, urticaria, arthralagia, proteinuria, LAD, 5-10 days after antigen exposure


What is an Arthus rxn?

a local subacute Ab mediated HSR (type III) rxn. Intradermal injection of Ag induces complexes in the skin. Characterized by edema, necrosis and activation of complement


What is a type IV HSR?

delayed (T cell mediated) - sensitized T lymphocyes encounter antigen and then release lymphokines (leads to macrophage activation.; no Abs involved)


What are examples of type I HSR?

anaphylaxis; allergic and atopic disorders (rhinits, hay fever, ecezma, hives, asthma)


What are examples of type II HSR?

AIHA, pernicious anemia, ITP, erythroblastosis fetalis, acute hemolytics transfusion reactions, rheumatic fever, Good pastures, Bullous pemphigoid, pemphigus vulgaris, graves, myasthenia gravis


What are examples of type III HSR?

SLE, polyarthritis nodosa, PSGN, serum sickness, Arthus rxn, RA


What are examples of type IV HSR?

MS, GBS, graft verus host disease, PPD, contact dermatitis


What happens when you have an allergic rxn to blood transfusions?

- type I HSR; rxn aganist plasma proteins in transfused blood
- urticaria, pruritus, wheezing, fever
- treat w/ antihistamines


What happens when you have an anphylactic rxn to blood transfusions?

- severe rxn
- IgA deficient pts must receive blood products that lack IgA
- dyspnea, bronchospasm, hypotension, respiratory arrest, shock


What happens when you have a febrile non-hemolytic tranfusion rxn?

- type II HSR, host Abs against donor HLA antigens and leukoctyes.
- fever, headaches, chills, flushing


What happens when you have an acute hemolytic transfusion rxn?

- Tyep II HSR,
intravascular hemolysis (ABO blood group incompatibility)
extravascular hemolysis (host Ab rxn against foreign antigen on donor RBCs)
- fever, hypotension, tachypnea, tachycardia, flank pain, hemoglobinema (intravascular), jaundice


What infectious agents are you predisposed to get if you have no T cells?

- sepsis from bacteria
- CMV, EBV, VZV, chronic infection w/ respiratory/GI viruses
- Candida, PCP


What infectious agents are you predisposed to get if you have no B cells?

1. encapsulated bacterial infections
2. enteroviral, encephalitis, poliovirus (live vaccine contraindicated)
3. GI giardiasis (no IgA)


What infectious agents are you predisposed to get if you have no granulocytes?

1. staph, burkholderia cepacia, serratia, nocardia
2. candida, aspergillus


What infectious agents are you predisposed to get if you have no complement?

1. neisseria ( no MAC)


What are the encapsulated bacteria? (SHiN SKiS)

1. Steptococcus pneumoniae
2. Hamephilius infuenzae type B
3. Neisseria meningitidis
4. Salmonella
5. Klebsiella pneumoniae
6. group B Strep


What are B cells disorders?

1. X linked (Bruton's) agammaglobulinemia
2. Selective IgA deficiency
3. Common variable immunodeficiency


What is X linked Brutons agammaglobulinema?

- defect in BTK, a tyrosine kinase gene -> no B cell maturation
- more common in boys


What is the presentation of x linked bruton's agammaglobulinema?

recurrent bacterial infections after 6 months (decreased maternal IgG) as a result of opsonization defect


What are the immune findings for Bruton's agammaglobulinema?

1. normal pro- B
2. decreased maturation
3. decreased number of B cells
4. decrease IgG of all classes


What is selective IgA deficiency?

most common primary immunodeficiency
- most people are Asx
- can get sinopulmonary infections, GI infections, autoimmune disease, Anaphylaxis to IgA containing blood products


What are the immune findings for IgA deficiency?

- IgA < 7mg/dL w/ normal IgG, IgM, and IgG vaccine titers
- false positive Beta hCG tests due to presence of hereophile antibody


What is CVID?

defect in B cell maturation; many causes
- can be acquired in 20s and 30s
- increased risk of autoimmune disease; lymphoma, sinopulmonary infections
- normal number of B cells, decreased plasma cells and Igs


What are T cell disorders?

Digeorge syndrome, IL12 receptor deficiency, Hyper IgE syndrome, chronic mucocutaneous candidiasis


What is DiGeorge syndrome?

-thymic aplasia
- 22q11 deletion
- failure to develop 3rd and 4th pharyngeal pouches


What is the presentation of DiGeorge Syndrome?

- tetant (hypocalcemia)
- recurrent viral/fungal infections
congential heart and great vessel defects
- absent thymic shadow on CXR


What is IL 12 receptor deficiency?

decreased Th1 response
- disseminated mycobacterial infections
- decreased IFN gamma


What is Job's syndrome -- hyper IgE syndrome?

Th1 cells fail to produce IFN gamma --> inability of PMNs to respond to chemotactic stimuli


What is the clinical presentation of Job's syndrome?

1. coarse facies
2. cold (noninflamed) staphylococcal abscesses
3. retained primary teeth
4. increased IgE
5. dermatology problems (ecezma)


What is chronic mucocutaneous candidasis?

T cell dysfunction causing candida albicans infections of skin and mucous membranes


What are B and T cell disorders?

1. severe combined immunodeficiency (SCID)
2. Ataxis telangiectasia
3. Hyper IgM syndrome
4. Wiskott Aldrich syndrome


What is SCID?

several types: defective Il 2 receptor (most common X linked), adenosine deaminase deficiency


What is the clinical presentation of SCID?

- failure to thrive
- chronic diarrhea, thrush
- recurrent viral, bacterial, fungal, and protozoal infections
- absence of thymic shadow, germinal centers (lymph node biopsy) and B cells (peripheral blood smear)


What is the treatment for SCID?

bone marrow transplant


What are the immune findings for SCID?

- decreased T cell recombinant excision circles
- absence of thymic shadow, germinal centers, and T cells (flow cytometry)


What is Ataxia telangiectasia?

- defects in the ATM gene - codes for DNA repair enzymes
- increased risk of lymphoma and severe leukemia
- poor smooth pursuit
- increased AFP


What is the clinical presentation of ataxia telangiectasia?

- cerebellar defects (ataxia)
- spider angiomas (telangiectasia) after age 5
- IgA deficiency


What is Wiskott Aldrich synrome?

- x linked: in WAS gene on X chromosome -> T cells unable to recognize actin cytoskeleton


What is the clinical presentation of Wisktt Aldrich syndrome?

- thrombocytopenic purpura
- infections
- eczema


What are the immune findings for Wiskott Aldrish syndrome?

- increased IgE, IgA
- decreased IgM


What are some phagocyte dysfunction disorders?

- Leukocyte adhesion deficiency - type 1
- Chediak-Higashi syndrome
- Chronic granulomatous disease


What is leukocyte adhesion deficiency?

- defect in LFA-1 integrin (CD18) protein on phagocytes
-neutrophilia b/c they can't migrate into intersititum


What is the clinical presentation of leukocyte adhesion deficiency?

- recurrent bacterial infxn,
absent pus formation
delayed separation of umbilical cord


What is Chediak Higashi Syndrome?

- AR
- defect in lysosomal trafficking regulator gene (LYST)
- microtubule dysfunction in phagosome-lysosome fusion
- giant granules in neutrophils


What is the clinical presentation of Chediak Higashi Syndrome?

- recurrent pyogenic infections by staph and strep
- partial albinism
- peripheral neuropathy and other CNS problesm


What is chronic granulomatous diease?

lack of NADPH oxidase --> decreased ROS and absent respiratory burst in neutrophils


What is the clinical presentation of chronic granulomatous disease?

increased susceptibility to catalase-positive organism


What is the immune findings of chronic granluomatous diease?

- abnormal dihydrorhodamin (DHR) flow cytometry test
- nitroblue tetrazolium dye reduction test


What is an autograft?

grafts from your own body


What is an syngeneic graft?

graft from identical twin or clone


what is an allograft?

from nonidentical individuals of same species


what is a xenograft?

from different species


What is a hyperacute transplant rejection?

- w/in minutes
- Ab mediated (type II) b/c of presence of preformed anti-donor antibodies in transplant recipient
- occludes graft vessels causing ischemia and necrosis


What is acute transplant rejection?

- weeks later
- cell mediated due to CTL reacting against foreign MHCs
- reversible w/ immunosuppressants
- vasculitis of giant vessels w/ dense interstitial lymphocytic infiltrate


What is chronic transplant rejection?

- months to years
- CLass I MHCnonself is perceived by CTLS as class I MHC self presenting a nonself antigen
- irreversible T cell and Ab mediated vascular damage
- fibrosis of graft tissue and blood vessels


What is graft vs host rejection?

- Grafted immunocompetent T cells proliferate in the irradiated immunocompromised disease hose and reject cells w/ foreign proteins resulting in sever organ dysfunction


What are the features of graft vs host?

- maculopapular rash
- jaundice
- hepatosplenomegaly
- diarrhea
- usually in bone marrow and liver transplant
- potentially beneficial in bone marrow transplant


What is the MOA of cyclosporine?

binds to cyclophilins
complex blocks the differentiation and activation of T cells by inhibiting calcineurin thus preventing production of IL2 and its receptor


ADE of cyclosporine?

Nephrotoxicity, gingivial hyperplasia, hirsutism
HTN, HLD, hyperglycemia, Tremor


What can the nephrotoxicity of cyclosporine be prevented w/

diuresis w/ mannitol


MOA of Tacrolimus

- binds to FK binding protein, inhibits calcineurin and secretion of IL2 and other cytokines


ADE of tacrolimus

HTN, HLD, hyperglycemia, tremor


MOA of Sirolimus

- inhibits mTOR by binding to FK binding protein
- inhibits T cell proliferation in response to IL2


ADE of sirolimus

-HLD, thrombocytopenia, leukopenia


MOA of azathioprine

antimetabolite precurore of 6MP that interferes w/ metabolism and synthesis of nucleic acids. Toxic to proliferating lymphocytes


ADE of azathioprine

Bone marrow suppression
Active metabolic 6MP is metabolized by xanthine oxidase thus toxic effects may be increased by allopurinol


MOA of muromonab

mab that binds CD3 on surface of T cells.
- blocks cellular interaction w/ CD3 protein responsible for T cell signal transduction


ADE of muromonab

cytokine release syndrome, HSR rxn


thalidomide uses

immunosuppression, anti-angiogenic


MOA mycophenolate

inhibits IMP DH preventing production of guanine


What is aldesleukin

IL 2 used in Renal cell carcinoma and metastic melanoma


What is Epotein Alfa

erythropoietin for anemias (especially in renal failure)


what is filgrastim and sargramostime

granulocyte colony stimulating factor - to help bone marrow recover


What is alpha-interferon used for

Hep B and C, Kaposi's sarcoma, leukemias, malignant melanoma


What is beta interferon used for?



What is gamma IFN used for

chronic granulomatous disease


What is oprelvekin

recombinant IL12 for thrombocytopenia


What is digoxin immune Fab

targets digoxin; antidote for digoxin intoxication


MOA of inflixmab, adalimumab, enteracept

anti TNF alpha
- used for Crohn's , RA, psoriatic arthritis


MOA of abciximab

targets glycoprotein IIb/IIIa to prevent cardiac ischemia in unstable angina and in pts treated w/ percutaneous coronary intervention


MOA of trastuzumab?

targets HER2


MOA of rituximab?

targers CD20; B cell non-Hodgkin's lymphoma


MOA of omalizumab

targets IgE; additional line of treatment for severe asthma


What diseases do the following autoAb associate w/?
1. Antinuclear
2. Anti-dsDNA, anti-Smith
3. Anti-histone
4. Rheumatoid factor, anti CCP
5. Anti-centromere

1. SLE - nonspecific
2. SLE - renal dz
3. Drug induced lupus
4. RA
5. CREST scleroderma


What diseases do the following autoAb associate w/?
1. Anti-Scl70: DNA topo I
2. Antimitochondrial
3. IgA antiendomysial, antiTGminase
4. Anti-basement membrane
5. Anti-desmoglein

1. Scleroderma diffuse
2. Primary biliary cirrhosis
3. Celiac dz
4. Goodpastures
5. Pemphigus vulgaris


What diseases do the following autoAb associate w/?
1. Antimicrosomal, antithyroglobulin
2. Anti-Jo1, anti SRP, anti-Mi2
3. Anti SSA (anti-Ro)
4. Anti-SSB (anti-La)
5. Anti- U1 RNP (ribonucleoprotein)

1. Hashimoto's thyroiditis
2. Polymyositis, dermatomyositis
3. Sjogren's syndrome
4. Sjogren's syndrome
5. Mixed CT disease


What diseases do the following autoAb associate w/?
1. Anti-smooth muscle
2. Anti-glutamate decarboxylase
4. p-ANCA

1. autoimmune hepatitis
2. Type 1 DM
3. Granulomatosis w/ polyangitis (wegner's)
4. Microscopic polyangitis, Churg-Strauss syndrome
5. pauci-immune cresentic GN


What disease do the following autoAb associate w/?
1. Anti-ACH receptor
2. Anti-cardiolipin, lupus anticoagulant
3. Anti-hemidesmosome
4. Anti-TSH receptor

1. Mysathenia gravis
2. SLE, antiphosplipid syndrome
3. Bullous pemphigoid
4. Grave's dz


MOA of Basiliximab

blocks IL2-R, mab
- used for kidney transplant rejection prophylaxis


ADE of basiliximab

edema, HTN, tremor


MOA of glucocorticoids

Inhibits NFkB
- suppresses both B and T cell function and decreases transcription of cytokines


ADE glucorticoids

hyperglycemia, osteoporosis, central obesity, muscle breakdown, psychosis, acne, HTN, cataracts, peptic ulcers


MOA of Alemtuzumab

Ab against CD52, used in CLL


MOA of cetuximab

Ab aginst EGFR, use in stage 4 CRC, head and neck cancer


MOA of Natalizumab

Ab against alpha-4 integrin, used in MS and Crohn's disease
- risk of PML in pts w/ JC virus


MOA of denosumab

Mab against RANKL
- used to treat osteoporosis (inhibits osteoclast maturation - mimics osteoprotegrin)


MOA of Palivizumab

Mab against RSV F protein