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Describe the capsular structure of a lymph node; what are the functions of the LN?
Capsule of lymph node is made up of type III collagen (made by reticulin fibers!), extension of this collagen extends into the splenic tissue as trabeculae; nonspecific filtration of lymph by Macrophages, Antibody production (via activation), storage and activation of B and T cells via bringing antigens from lymph by APCs or alone
Describe the interstitial tissue of a spleen including the sinuses. What type of cells are found in the four structures (cortex, paracortex, medulla and sinuses)?
The interstitial tissue of a lymph node is structured into the cortex on the outside which is densely cellular which transitions into the paracortex which is less dense and then the medulla which is least dense. The cells that inhabit these tissues are B cells (in both inactive and active follicles), T cells, and plasma cells respectively. The cells came from the lymph and vasculature. Afferent lymphatics pierce the capsular structure and empty into the subscapular sinuses which are continuous with the cortical sinuses which are then continuous with the paracortical sinuses and then the medullary sinuses. These sinuses are closely adjunct to the cords of the corresponding tissue and allow for interaction between lymph and the lymphocytes in the ln tissue and are lined with macrophages that engulf antigens and present them to the lymphocytes in the adjunct cords. The sinuses empty in the efferent lymphatics.
T/F the secondary follicles found in the cortex of a lymph node are densely colored.
False, secondary follicles have pale central germinal centers; primary follicles are dense
What are HEV? Where are they found? where does the vasculature of the lymph node travel to?
High endothelial venules are post capillary cuboidal endothelial cells that contain specific adhesion molecules for lymphocytes with specific binders that allows for lymphocytes to drain out of the vasculature into the lymph node structure (this is how these lymphocytes get there in the first place!); They are found in the paracortical section of the LN; the vasculature travels through the entire ln, once lymph dont find an antigen to attack they empty back into veins or into efferent lymphatics
What happens in a secondary follicle?
isotype switching (activated by Th2 cell signals and cytokines), somatic hypermutation
What happens when a T helper cell in the paracortical section encounters an antigen? a cytotoxic t cell? a B cell in the cortical section?
An antigen encounter (presented by APC for Th2) with Th2 will result in it to go to the cortical section and help with B cell activation; Cytotoxic T cell will enter vasculature/efferent lymph to go kill; B cell will wait for Th2 for activation and then follicular dendritic cells will select for plasma cell which will go to medulla and secrete Ab
What part of the lymph node specifically expands during a cellular immune response? when would this occur?
Paracortex; viral infection
what can cause a lymph node enlargement?
local infection/inflammation; infection of the ln itself; metastasis
What bugs can actually infect the lymph node itself?
Mycobacterium Tuberculosis, Mycobacterium Avium Intracellulare; Toxoplasmosis Gondii
what are the sinusoids of the spleen? what is the difference between a spleen and a lymph node?
the red pulp of the spleen its where the vasculature channels go through and interact with the parenchyma of the spleen (has macrophages) which empty in the sinuses; they are both encapsulated (with trabeculae) secondary lymphoid organs that trap antigens from local tissue but the spleen also does the same for the blood!
what type of fenestrations are found in the red pulp of the spleen?
barrel hoop basement membrane fenestrations
what is the white pulp of the spleen?
surrounds the red pulp and begins with PALS and then turns into follicles with B cells/follicles
what is the marginal zone of the spleen? what happens there?
found in the red pulp; contains the cords of billroth or the splenic parenchyma that have APCs/Macrophages that closely interact with the basement membrane of the vasculature and where RBCs squeeze through into the parenchyma and interact with Macrophages and those not eaten empty back into venous sinuses
what are the PALS?
periarteriolar lymphatic sheath in the white pulp that surround that dead end of the capillaries in the red pulp, contain T cells
what is the two fates of the RBCs that go through the spleen? what happens eventually to all of them>
closed circuit where go directly to veins and open where squeeze out of capillary sinusoids and interact with either PALS or with macrophages in the cords of Billroth (for antigen immune function or for blood cleaning or for both) and squeeze back into venous sinuses; all end up going through open circuit
what are four results of a splenectomy?
1) susceptibility to encapsulated organisms 2) Howell Jolly Bodies 3) Target cells 4) Thrombocytosis
what bacteria are a splenectomy patient most susceptible to? why?
N. meningitidis, H. influenzae, S. pneumonia, Salmonella d/t lack of C3b opsonization for MAC d/t lack of complement activation d/t lack of IgM; MAC is needed by encapsulated avoid by humoral and cell mediated through their capsule
what are howell jolly bodies?
nuclear remnants that are usually taken out of RBC before complete maturation by Macrophages
what are target cells?
cells that stil have weird parts of their membrane that macrophages usually bite off
what is the thymus ? where is it located? is it encapsulated? how many lobes does it have?
the place of T cell diff and maturation; ant mediastinum above heart; yes; 2
T/F the thymus and its comp derived from 3rd branchial pouch
false- the lymphocytes are mesenchymal origin
how is the thymus organized? what happens in each section?
Into cortex and medulla; cortex is where immature T lymphocytes enter, at the corticomedullar junction is where positive and negative selection occur; and at the medulla is where the mature T lymphs, reticulin cells and hassalls corpuscles are (dead reticular cells)
in thymic development, what is the positive selection? negative selections?
when you select for which MHC it will have; take out the lymphs that self react
What are MHC Class molecules (ie what macromolecule are they made out of)? what gene are responsible for MHC?
What is MHC I made out of? where is it found? What does it bind to? What type of antigens does it present?
an alpha chain and a B2 microglobulin; on all nucleated cells; TCR and CD8; intracellular antigens
What is MHC II made out of? where is it found? what does it bind to? What type of antigens does it present?
an alpha and beta chain; only on APCs; TCR and CD4; extracellular (phagocytosed by APCs)
how is the antigen loaded onto a MHC II?
an acidified endosome with the antigen fuses with the MHC which causes the release of the invariant chain which is sitting in spot of antigen and stabilizing the MHC II
which MHC presents intracellular peptides? how so?
MHC I; from RER with help of the B2 microglobulin
which disease is associated with B27?
(PAIR) Psoriasis, Ankylosis Spondylitis, IBD, Reiters; all seronegative spondylopathies
What type of cells do NK cells attack? with what tools? by necrosis or apoptosis?
tumor cells and virally infected cells; perforin pore to secrete granzymes through it; apoptosis
which interleukin receptor is required for NK development? activation?
IL 12, interferon Beta and interferon alpha
what are the two signals to kill for NK cells?
lack of MHC class I constant region which it binds or a nonspecific activation signal (TLR)
what prevents NK cells from killing normal cells if their default is to kill?
MHC class molecules bind to KIRS or CD94 to prevent killing
What are the major functions of Antibodies?
opsonize bacteria (for enhanced phagocytosis), neutralize viruses (igG), activate complement (igM and igG), sensitize mast cells (igE)
What are the function of B cells?
Make antibody, allergy type 1 (IgE), Cytotoxic and immunecomplex hypersensitivity type II and III (igG); hyperacute organ rejection is Ab mediated
What are the T cell functions?
CD4+ T cells help B cells make Ab, produce gamma interferon to activate Macrophages, CD8+ T cells kill viruses directly, delayed cell mediated hypersensitivity, acute and chronic rejection
Often bacteria are associated with being killed by humoral immunity. Name some bugs that require cell mediated immunity because they evade humoral response
Legionella, N. gonorrhea, L. monocytogenes, viruses, protozoa (leismaniasis)
what are the two signals required for Th1 cells? what happens after then activated?
MHC II/CD4 and B7 (on APC) and CD28 (on Th cell); releases cytokines to kill those extracellular buggers!
What are the two signals required for T cells? what happens after?
MHC I/CD8 and IL2/IL 2 Receptor (IL 2 is from Th1!); cytoxicity!
What are the two signals required for B cell class switching? which is the second signal?
CD40 (on b cell) CD40 ligand on Th2 cell; and interleukins (4,5,6) from Th2 cell; CD40 is actually the second signal
Which helper T cells' development is induced by IL 4? IL 12?
(remember, IL4/Th2/CD40 ligand; IL12/Th1/IL2 receptor)
Which T helper cell activated Macrophages? by secreting what? what else does Th1 secrete? for what?
Th1; interferon gamma; IL 2 for cytotoxic T cell activation
Which cytokines do Th2 release and for what?
IL 4,5,6 for B cell class switching, IL 10 to inhibit TH1
T/F the two constant parts of the light chains of an antibody contribute to the Fc region
FALSE. only the heavy chains contribute to the Fc region
T/F the Fab (antigen binding) determines the isotype
false! idiotype; the Fc portion determines the isotype
So antibodies are the effectors for the humoral response. List some of their functions.
cross link antigens which increases their phagocytability; activate complement for MAC attack; opsonization; neutralization
Name 5 ways Antibody diversity is generated?
1) VJ light chain random creation 2) VDJ (heavy chain) random creation 3) random combination of light with heavy 4) somatic hypermutation (high frequency mutating that occurs on activation) 5) terminal deoxynucleotidyl transferase (TDT) random addition of nucleotides at the end of the chains
where do somatic hypermutation and class switching occur?
in the germinal center of secondary follicles (In the paler center)
what happens in order for class switching to occur (after being activated by IL and cd40 L)?
alternative splicing of mRNA
T/F IgM can both fix complement and cross the placenta
false! can fix complement but cant cross placenta
What does it mean if there are igM in the serum at birth?
since cant cross placenta most likely means that child was forced early to produce due to an infection (most likely CMV)
What does IgE do on the surface of the mast cell to induce inflammatory mediator release?
If an antigen lacks a peptide component how does the adaptive immunity attack it? what type of response is this called. give an example of bugs that do this. what implications does this have on splenectomy?
This means that MHC can not recognize it and thus will not be phagocytosed. The humoral response rescues- IgM is the primary response attack. Since there is no class switching (without MHC activation no CD40 L and interleukins to activate!) then there is memory and igE attack is all we get; this is called Thymus independent antigens; Bugs that do this are bugs with lipopolysaccharide from envelope of gram negative or polysaccharide capsular antigen. Since spleen is where all igM are housed and produced, then there will be increased risk for infection by these types of organisms that lack a peptide component.
how do we use thymus dependent antigens to prevent infection from organisms that lack a peptide component?
give a vaccine with a peptide comp from it that the cell mediated immunity otherwise cant get to! like h.influenzae vaccine. then class switching and memory response can occur
what ensure that a memory response is generated?
if there is class switching and plasma cell production (that is when memory cells are produced)
what are complements in the complement system? what activates them? there seems to be different ones, what are these pathways called?
proteins; IgG, IgM, endotoxin (microbial surfaces in general- nonspecific ones also), mannose binding Lectin; classic, alternative, MB pathway (resp)
how does complement link innate and adaptive?
adaptive uses classic pathway to kill; innate uses alternative pathway to kill
What is the end result of complement activation? what bugs are this important for? through what pathway and why?
MAC (membrane attack complex) which is activated by C5b-C9 and results in lysis and cytoxicity by creating pores in the target membrane; encapsulated organisms (S. pnuemonia, H.influenzae, B perfussis for example) and other organisms with non peptide antigens because IgM coats these and through the classic pathway these can then be killed
what part of the complement system also acts as an opsonin? what is opsonization? can you name two other opsonins?
C3b; coating of a pathogen with molecules that promotes phagocytosis; IgG and CRP
How does the alternative pathway lead to MAC activation?
soluble C3 spontaneously hydrolyzes spontaneously to C3b and opsonizes microbial and host cell surfaces and accumulates on surfaces; C3b activates C5 convertase which leads to MAC activation
If the alternative pathway is constitively active, how come normal cells don't get attacked with MAC?
DAF and C1 esterase inhibitor on cells prevent complement activation on their surfaces (microbial surfaces lack this)
after C3 spontaneously hydrolyzes to C3b and C3a, what happens to C3a?
its involved in inflammation and results in anaphylaxis and neutrophil chemotaxis.
Describe the Mannose Lectin pathway
some microbial surfaces (only) have mannan binding lectin which activates a protease that cleaves C2 and C4 which combine to make C3. the rest follows the alternative pathway
describe the classic complement pathway.
IgG and IgM bind to pathogens activating C1 convertase and leads to C2 and C4 and then C3 convertase activated
What happens in a deficiency of C3?
severe recurrent pyogenic sinus and resp tract AND increased susceptibility to type III hypersensitivity like SLE
what happens in a deficiency of C5-C8? why dont you get recurrent pyogenic infections like in C3 def?
septicemia with neisseria; because at least you have C3 to act like a neutrophilic chemotactic and an acute phase reactant
what is hereditary angioedema? What are the C3 levels?
Aut. Dominant; C1 esterase inhibitor deficiency resulting in continued C1 which results in increased C2 and C4 cleavage products which have anaphyltoxic activity and result in swelling of face and oropharynx
In order to produce Antibodies, does the antigen have to be phagocytosed? give an example with a bug and an autoimmune (type II hypersensitivity for example).
no! That is why they are different from T cells- they can recognize antigens in free solution; if a bug has a peptide fragment that a mature naive B cell recognizes it will bind to it and cause activation, it then gets activated into a plasma cell! same for type II or III hypersensitivity except the antigen is usually harmless (like an RBC cell slight altered with penicillin on it).
explain the process from beginning (ie phagocytosis of the peptide) to end of how Abs are formed in Goodpasteurs.
for some reason a mature naive B lymphocyte got away from tolerance and the result was a production an Ab on its surface with an Fab region that recognized the alpha 3 collagen subunit on the BM as non self. It then gets activated by a Th2 cell (entire immune system recognizes it as non self)
Name three things that IL 1 does as a cytokine. other than the liver, who secretes IL 1
induces fever, chemokine secretion to recruit, activates adhesion molecules; macrophages
Other than stimulating fever, what else does IL 6 do?
stimulate the liver to release acute phase reactants
what is the main function of IL 12? other than macrophages who else can release IL 12?
induce differentiation of T cells into Th1 helper cells and activates NK cells also; B cells
what is the main function of TNF alpha? how does it do this?
mediates septic shock; activates the endothelium for adhesion and dilation and leukocyte recruitment results in vascular leak
other than mediating shock, what else does TNF alpha do? who releases it mainly?
activates Th1 helper cells; Macrophages
What cytokines do macrophages release? who else can secrete IL 6? IL 12?
IL 1, IL 6, IL 12, TNF alpha; IL 6- Th2 cells; IL 12- B cells
what is the main cytokine released by T cells? what does it do
IL 3; supports growth and differentiation of bone marrow stem cells
What does interferon gamma do? what two type of cells does it attack mostly?
activates Macrophages and Th1 cells; suppresses Th2 cells; antiviral and antitumor
what does IL 5 do?
acts as second signal on B cells to induce class switching to IgA; also stimulates eosinophils
what does IL 10 do? who is secreted by?
suppresses immune response (also specifically Th1 cells) and activates Th2; regulatory T cells
what is the main function of interferons?
antiviral for uninfected cells (for future protection) and kills virally infected cells (NK activation)
what does Interferon alpha and beta do? how?
antiviral by inducing ribonuclease which degrades only viral mRNA (prevents protein synthesis) and activates NK cells to kill virus infected cells
what does interferon gamma do to be antiviral?
increases expression of MHC I and MHC II and also activates NK cells
what else does interferon gamma do other than inducing ribonuclease production, activating NK cells, inducing increased MHC expression?
what are the main Cell surface proteins on T cells?
TCR, CD4/8, CD28 (binds B7), CD3 (for intracellular transduction), CD40L
what is the receptor for EBV? on what cells is that located?
CD21 on B cells (although there is T cell lymphocytosis in EBV)
What are the cell surface proteins for Macrophages? which two are for opsonins?
MHC II, B7, CD40 and CD14; CD40 and D14 for FcG and C3b resp
what will NK cells do to cells covered in IgG Ab? why?
kill them because they have CD16 on them that recognize the FcG portion
what is anergy? why does this occur?
lack of response from lymphocytes when activated; because they are self reactive, this is a form of tolerance
what are superantigens? give two examples.
CROSS LINK Beta region on TCR of CD4 cells to the MHC class II on APCs this results in uncoordinated release of Interferon gamma from CD4 Th1 cells and subsequent release of IL1, IL6 and TNF alpha from Macrophages --> toxic shock syndrome; s. pyogene and s. aureus both have this toxin
how do endotoxin/LPS of gram negative bacteria stimulate the immune system if they do not have a peptide fragment?
they directly stimulate Macrophages by binding CD14; also the alternative complement pathway binds to these host surfaces and induces MAC complex; also TLRs exist for endotoxins; also IgM though not an opsonin can act as a pentamer and trap the antigen which can activate classical pathway complement activation
Give three examples of bacteria that use antigenic variation and how.
Salmonella- 2 flagellar variants; Borrelia (relapsing fever); and Neisseria gonorrhoaea- pilus protein
give an example of a virus that uses antigenic variation. what does a major variation result in? minor?
influenza; antigenic shift; antigenic drift
what is an example of a parasite showing antigenic variation?
trypanosomes with programmed rearrangement (results in recurring fever-- sleeping sickness!)
which type of immunity is slow but long lasting? as opposed to...
active; passive- fast but short half life (3 weeks!)
what is a type I hypersensitivity reaction? what is atopic?
an anaphylactic immediate reaction; atopy refers to the inherited propensity to develop asthmatic or allergic reactions
what is the pathogenesis of a hypersensitivity reaction?
first a B cell gets sensitized to an allergen, after sensitization, it gets induce by Th2 secreting IL4 to class switch from IgM to IgE, next time blood stream is exposed to allergen these antigens cross like IgEs on mast cells and result in chemical mediator release
what amine is the main chemical mediator released by mast cells? where does it act what does it result in?
histamine; post capillary venules- vasodilation
what is the late phase reaction of anaphylaxis allergy? what mediates it?
hours later (instead of minutes); instead of release of preformed mediators, mast cells synthesize PGs and LTs that mediate the late phase reaction (edema, inflammation, decreased airflow)
what are the mediators that mast cells release?
histamine (causes vasodilation), leukotrienes (causes bronchoconstriction), chemotaxins for eos, and heparin (increased blood flow needs to be anticoagulated!)
what two ways do you test for a type 1 hypersensitivity reaction? what will you see?
scratch test - histamine mediated wheal; radioimmunosorbent assay (detects specific IgEs in serum)
what mediates the type II hypersensitivity? what are the two different methods?
Antibody mediated cytotoxicity; either complement dependent or complement independent
Describe complement dependent Type II hypersensitivity. Give an example.
IgM or IgG antibodies coat the antigen and result in activation of MAC complex via the classical pathway OR fixed macrophages in the spleen phagoctyose the opsonized (C3b or igG) antigens- ex penicillin reaction; IgM AIHA, anti B IgMs in a group A blood donor to a group B recipient
Describe the complement independent Type II hypersenstivity reaction. Give an example.
The antibodies (igM or IgG) either neutralize the target directly (cytoxic!) or recruit leukocytes (Neutrophils and Macrophages!) to incite tissue damage
what are the three types of Type III hypersensitivity ? what is the common mechanism between them?
Immune complex, Arthus reaction and Serum sickness; they are all a result of antibody-antigen complex deposition resulting in complement activation
what is immune complex disease? give an example.
type III hypersensitivity where an internal antigen antibody complexes activate classical complement pathway resulting in C3a neutrophilic chemotaxis and neutrophilic lysosomal death. SLE
what is serum sickness? give an example.
type III hypersensitivity where an exogenous antigen results in a systemic antigen antibody complex disease (takes around 5 days after exposure for the Abs to develop); immune complexes then fix in tissue and activate complement resulting in tissue damage; horse antithymocyte globulin Ab
what are the symptoms of serum sickness?
fever, urticaria, arthralgias, proteinuria, lymphadenopathy
what is the arthus reaction? what is the difference between arthus and serum sickness? give an example. how do you test for it?
it is a localized type III hypersensitivity reaction to an external antigen; localized instead of systemic; ?; intradermal injection of the antigen results in antibody production and antigen antibody complexes deposit in the skin
describe the pathogenesis of delayed type IV hypersensitivity
T cells react to the angtigen and activate leukocyted (macrophage acitivation)
what is the pathogenesis of IgG AIHA ABO hemolytic disease of a newborn? describe what happens.
Type II hypersensitivity, complement dependent resulting in phagocytosis of RBCs coated with C3b by fixed macrophages in the spleen; Group O mother has anti A,B, IgG Abs that cross placenta and attach to fetal blood group A or B RBCs
what is the difference of IgE AIHA and IgG AIHA if they are both complement dependent type II hypersensitivities?
in IgE AIHA- it results in MAC attack (remember IgE is not an opsonin!), in IgG AIHA C3b (and IgG) opsonization results in phagocytosis by fixed macrophages in the spleen
what results in symptoms of shock in an acute hemolytic transfusion reaction?
since it is a comp dependent type II hypersensitivity reaction; C3a brings anaphylotoxins that bring in mediators of shock
what is the autoantibody for SLE that is nonspecific? Specific?
Anti nuclear Antibodies (ANA); Anti dsDNA, anti Smith
what are the autoantibodies for scleroderma (CREST)? scleroderma diffuse?
anticentromere; anti Scl-70 (anti DNA topoisomerase I)
what are the autoantibodies for Celiac disease?
Antigliadin, antiendomysial (both are IgAs- anti tissue transgluataminase igA)
what are the autoantibodies for goodpastures syndrome?
Anti alpha subunit 3 of collagen on type IV bm
what are the autoantibodies for type I diabetes mellitus?
anti glutamate carboxylase and anti insulin
what are the autoantibodies for wegeners granulomatosis?
c-ANCA (antiproteinase); in neutrophil; c= cytoplasmic
what are the autoantibodies for other vasculitides?
p-ANCA (antimyeloperoxidase); in neutrophil; p= perinuclear
what are the three immune privileged sites? why are they called that? what happens after infection in these areas?
brain, eyes, placenta/fetus, testicles; because they can have an antigen in there and not get attacked by immune system because dont have contact with immune system via blood and lymph; if an infection occurs such that trauma results in exposure to immune response- takes a long time time- prolonges uveitis and orchitis
what is the defect in Brutons agammaglobulinemia? what is its effect on B cells? what is its inheritance pattern?
defect in BTK a tyrosine kinase gene; failed maturation of B cells; X linked recessive
with failed maturation of B cells in Brutons agammaglobulinemia, what is its effect on immune pathways and why?
its main effect is a defect in Ab opsonization for killing
what is the presentation of Brutons agammaglobulinemia?
recurrent sinopulmonary bacterial infections after 6 months (d/t mothers igGs transplacental) due to opsonization defect
what are the labs in brutons agammaglobulinemia?
normal pro B (CD 19 +), no mature B cells results in decreased total B cell level, and decreased amount of immunoglobulins in each class
what is the defect in hyper IgM syndrome? what are the lab results?
defect in CD40L results in inability to class switch; a lot of IgM and no IgG, A, E
What is the most common selective Ig deficiency? what is the presentation?
IgA; sinus and lung infections from lack of secretory defense, milk allergies and diarrhea from giardiasis; Anaphylasix on exposure to blood products with igA
what is the common variable immunodeficiency ? how is it different from Brutons?
defect in B cell maturation; idiopathic, presents at older age and normal number of B cells and hyperplastic germinal centers because B cells can be activated but can not produce Abs
what is the presentation of common variable immunodef? and what are the labs?
can be acquired in 20s-30s; increased risk of autoimmune disease, lymphoma, Sp infections; normal number of B cells and no plasma cells and immunoglobulin
what are the main symptoms of T cell immunodeficiencies?
intracellular pathogens (acute and chronic viruses and virally induced cancers)
what is the cause of thymic aplasia? what is its presentation? what are the labs?
Digeorge syndrome- 22q11 deletion resulting in failure to develop 3rd and 4th pharyngeal pouches; cardiac and great vessel congenital defects, tetany from hypocalcemia, recurrent viral/fungal infections from T cell deficiency; hypoPTH, hypoCa, and absent thymic shadow on CXR
what is the result of an IL 12 deficiency? what is the presentation? what are the labs?
decreased Th1 response; disseminated mycobacterial infections; decreased interferon gamma
what is the pathogenesis of HyperIgE syndrome? what are the labs?
Th cells fail to produce interferon gamma; a lot of IgE
what is the presentation of Jobs syndrome or Hyper IgE?
coarse Faces, cold (noninflamed d/t inability to attract neutrophils) staph abscesses, retained primary teeth, high igE, dermatologic problems (eczema)
what is three common causes of severe combined immunodef? what is the result of all three?
adenosine deaminase deficiency (AR), defective IL 2 receptor (X linked), and failure to synthesize MHC II; both humoral and cell mediated deficiency
what is the presentation of scid? treatment?
recurrent infections to every type of antigen; bone marrow transplant (be weary of GVH disease!)
what is ataxia telangectasia? what is it caused by? what is the triad of presentation? and its labs?
a B and T cell disorder; defect in DNA repair enzymes; ataxia, telangactasia and IgA def; igA def. and increased AFP
what is wiskott aldrich syndrome? what is its mode of inheritance? what is the pathogenesis of disease? what is its triad of presentation? what labs does it present with?
a B and T cell disorder; X linked recessive; progressive deletion of B and T cells; thrombocytopenic purpura, infections, eczema; high IgE and IgA but low IgM
what are the four steps in phagocytosis? what are the four disease that correspond to each step?
opsonization (Brutons agammaglobulinemia), adhesion (Leukocyte adhesion defect), phagocytosis (chediak higashi syndrome), respiratory burst (chronic granulomatous disease)
what is the defect in Leukocyte adhesion defect? what is the presentation? what are the labs?
defect in LFA 1 integrin (CD 18) protein on phagocytes (neutrophils!); recurrent bacterial infections, severe gingivitis, poor wound healing, absent pus formation, and delayed separation of the umbilicus; neutrophilia
which immunodeficiency presents with delayed separation of the umbilicus? ataxia? telangiectasia?albinism? anaphylaxis on exposure to blood products with IgA? tetany?retained primary teeth? peripheral neuropathy?
Leukocyte adhesion defect; ataxia telangietasia; ataxia telangiectasia; chediak higashi syndrome; IgA def; Digeorge syndrome; Jobs; Chediak Higashi
what is the mode of inheritance of Chediak Higashi syndrome? what is the disease d/t? what does it result in? what is the presentation?
AR; defect in MT function results in decreased transport and phagocytosis; recurrent pyogenic infections by staphylococci and streptococci, partial albinism, and peripheral neuropathy
what is the pathogenesis of chronic granulomatous disease; what is the presentation? what is the labs?
lack of NADPH oxidase results in a lack of respiratory burst in neutrophils; susceptibility to catalase positive organisms (S. aureus, E. Coli, Aspergillus)
in which immunodef order do you see a lot of pus? no pus?
CGD; Jobs syndrome (defect in Neutrophil chemotactic response)
what is the mechanism for sirolimus? what else it known as?
binds to Mtor which (like tacrolimus and cyclosporine just in a different pathway) inhibits IL 2 production and thus t cell proliferation in response to IL 2 producton
how is sirolimus different from tacrolimus?
both decrease cd8 tcell prolif but one through mtor and the other through calcineurin (resp)
what is the clinical use for sirolimus? what should you combine it with?
immunosuppression after kidney transplantation in combination with cyclosporine and corticosteroids
which of the IL2 inhibitors produce nephrotoxicity? thrombocytopenia/leukopenia?
cyclosporine and tacrolimus; sirolimus (as well as hyperlipidemia)
What is the monoclonal antibody to IL2 on activated T cells? what is it used for?
Daclizumab; prevent ACUTE rejection of renal transplant
what is muromonab- CD3 (OKT3)
monoclonal Ab to CD3- blocks cellular transduction and signaling of T cells
what is the toxicity of muromonab?
cytokine release syndrome due to initial release from initial binding (fever etc) and hypersensitivity reaction
what is filgrastim and sargramostim? and what is it used for?
recomb cytokine of GCSF (granulocyte macrophage colony stimulating factor; for recovery of bone marrow
what is recomb alpha interferon used for?
HBV, HBC, Kaposis, leukemias, malignant melanoma, hairy cell leukemia and condyluma accuminata
what is a factor that is a predictor for a bad transplantation?
patient has had previous exposure to blood products which result in presence of preformed anti HLA cytotoxic Abs
what is an autograft? syngeneic graft? allograft? xenograft? what is an ex of an allograft? xenograft?
from self; from identical twin or clone; from nonidentical individual of same species; from different species; fetus; pig valve
which of the transplant rejections is antibody mediated? why does it occur?
hyperacute; presence of preformed antibodies in the recipient ( to blood groups or HLA )
give an example of someone who could get hyperacute transplant rejection.
previous transfusion; pregnant woman whose fetus had paternal antigens
what is the pathology in hyperacute transplant rejection?
ischemia and necrosis of graft due to occlusion of vessels and fibrinoid necrosis and thrombosis within the vessels
what is the pathogenesis of acute transplant rejection? when does it occur?
cell mediated due to T cell cytotoxicity reacting to foreign MHCs; few weeks after
what is the pathology of acute transplant rejection? is it reversible?
vasculitis of graft vessels with dense interstitial lymphocytic infiltrate; yes! with immunosuppressants
what is the pathogenesis of chronic transplant rejection? when does it occur? is it reversible?
T cell and antibody mediated vascular damage due to MHC non self being recognized as self by self lymphocytes and resulting in attack of the foreign antigens it presents (all of them); months to years after; no :(
what is the pathology seen in chronic transplant rejection?
fibrosis of blood vessels and graft tissue from ischemia; obliterative vascular fibrosis with intimal thickening
when can graft versus host disease? what is the result?
in any situation where immunologically competent cells are transplanted into immunologically crippled recipient; graft rejects all the cells due to foreign proteins resulting in severe organ dysfunction
what is the symptoms involved in graft versus host disease? it what transplant cases does it usually occur? give an example
maculopapular rash (palm, soles, back, neck), jaundice with bile duct necrosis, hepatosplenomegaly, diarrhea; bone marrow and liver transplants (rich with lymphocytes); SCID patient receiving whole blood transfusion
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