HLA type A3 is associated with what disease?
(=excess iron absorption from diet)
Don't confuse with HLA D3 (assoc'd w/ SLE, T1DM, Graves)
HLA type B27 is associated with what disease?
arthritis of Inflammatory Bowel Disease
HLA type DQ2/DQ8 is associated with what disease?
(if you have Celiac, you should go to Dairy Queen DQ not McD's)
HLA type DR2 is associated with what disease?
Mult sclerosis, hay fever, SLE, Goodpasture
HLA type DR3 is associated with what disease?
Type I DM, SLE, Graves
("I got DR3 and I can't see": T1DM -> diabetic retinopathy; Graves -> exopthalmos; SLE -> photosensitivity)
HLA type DR4 is associated with what disease?
Rheumatoid arthritis, Type I DM
(4 walls in a "rheum")
HLA type DR5 is associated with what disease?
Pernicious anemia --> B12 deficiency
MHC I and II: present antigens to what cells?
Present antigen fragments to T cells and bind TCRs.
MHC I presents what kind of antigens to what cells?
Presents endogenously synthesized antigens (ie viral) to CD8+ cytotoxic T cells
MHC II presents what kind of antigens to what cells?
Presents exogenously synthized proteins (ie bacterial proteins and viral capsid proteins) to CD4+ T helper cells
NK cells: what do they do
use perforin and granzymes to induce apoptosis of virally infected cells and tumor cells.
(only lymphocyte member of the innate/acute immune system)
what cytokines/proteins enhance the activity of NK cells? (5)
IL-2 from all T cells
IL-12 from macrophages & B cells
interferon-α, interferon-β from viral-infected cells
interferon-γ from Th1 cells
NK cells: 3 ways they are induced to kill target cells?
1. when exposed to a nonspecific activation signal on target cell
2. and/or the absence of MHC I on a target cell surface
3. Fc region of a bound Ig binds CD16 on surface of NK & activates it. "antibody-dependent cell-mediated"
(all nucleated cells except RBCs express MHC I)
Major functions of B cells?
-undergo somatic hypermutation to optimize antigen specificity
-produce antibody (differentiate -> plasma cells to secrete immunoglobulins)
-maintain immuno memory (memory B cells)
Major functions of T cells?
-CD4+ T cells (HELPER) help B cells make antibody and produce cytokines
-CD8+ T cells (KILLER) kill virus-infected cells directly
-Delayed cell-mediated hypersensitivity (Type IV)
-Acute and chronic cellular organ rejection
for the differentiation of T cells, where does the T cell precursor come from?
what happens in the thymus in terms of differentiation of T cells?
-T cells that are positive for both CD4+ and CD8+ are separated into groups that are EITHER CD4+ OR CD8+
-Positive selection (cortex)
-Negative selection (medulla)
what is positive selection? where does it occur?
in the Thymic cortex
T cells that express TCRs capable of binding surface self MHC molecules survive.
what is negative selection? where does it occur?
T cells expressing TCRs with high affinity for self antigens undergo apoptosis
what happens to CD4+ T cells in the lymph nodes?
differentiate into Th1 cells, Th2 cells, Th17 cells, and Treg cells
(based on the influence of IL-12, IL-4, TGF-beta/IL-6, and TGF-beta)
what does IL-12 do in the lymph node?
induces CD4+ T cells to differentiate into Th1 cells
what does IL-4 do in the lymph node?
influences CD4+ T cells to differentiate into Th2 cells
what does the combination of TGF-beta and IL-16 do in the lymph node?
induces CD4+ T cells to differentiate into Th17 cells
what does TGF-beta do in the lymph node?
induces CD4+ T cells to differentiate into:
Th17 cells (if IL-6 is present)
what are the 3 types of antigen-presenting cells?
1. B cells
3. Dendritic cells (Langerhans cell in skin = example of dendritic)
Process of activation for CD4+ T cell?
-Foreign body phagocytosed by dendritic cell
-Foreign antigen presented on MHC I and recognized by TCR on T helper cell. (signal 1)
-Costimulatory signal is given by the interaction of B7 and C28 (signal 2)
-Th cell activates and produces cytokines.
Process of activation for CD8+ T cell?
-Foreign body phagocytosed by dendritic cell
-Foreign antigen presented on MHC II and recognized by TCR on T killer cell. (signal 1)
-Costimulatory signal is given by the interaction of B7 and C28 (signal 2)
-Tc cell activates; recognizes & kills virus-infected cells
Process of B cell activation and class switching?
-Helper T cell is activated
-B cell endocytoses foreign antigen; presents it on MHC II. Recognized by TCR on Th cell. (signal 1)
-B cell's CD40 receptor binds the T cell's CD40 ligand (signal 2)
-Th cell secretes cytokines. --> determines Ig class switching of the B cell. B cell activates, undergoes class switching, affinity matulration and antibody production.
Th1 cells secrete what? activate what? inhibited by what?
Secrete IFN-gamma & IL-2
Activate macrophages and cytotoxic T cells
Inhibited by IL4 and IL10 (from Th2 cell)
Th2 cells secrete what?
inhibited by what?
secrete IL-4, IL-5, IL-6, IL-13
Recruit eosinophils for parasite defense, and promote IgE production by B cells
Inhibited by IFN-gamma (from Th1 cell)
what is the overall interaction between macrophages and lymphocytes?
Macrophages release IL-12, which stimulates T cells to differentiate into Th1 cells.
Th1 cells release IFN-gamma to stimulate macrophages
what do cytotoxic T cells kill? generally, how do they do it?
Kill virus-infected, neoplastic, and donor graft cells
induce apoptosis by releasing proteins: Perforin, Granzyme, Granulysin
Cytotoxic T cells release cytotoxic granules containing what? what do the components of these granules do?
Cytotoxic granules contain preformed proteins:
-Perforin: helps deliver content of granules into target cell
-Granzyme B: serine protease; activates apoptosis inside target cell
Granulysin: antimicrobial; induces apoptosis
Lymph node: functions?
secondary lymph organ; functions are nonspecific filtration by macrophages, storage of B and T cells, immune response activation
what occurs in the Follicle of the lymph nodes?
B cell localization and proliferation.
located in outer cortex of node.
what are the 2 parts of the LN Medulla?
what does each part contain/do?
Medulla consists of medullary cords and medullary sinuses.
-Medullary cords contain packed lymptocytes and plasma cells.
-Medullary sinuses contain reticular cells and macrophages. Communicate with efferent (outgoing) lymphatics.
What does the Paracortex of LNs do? Where is it located?
Not well developed in what syndrome?
-Houses T cells. Contains high endothelial venules through which T and B cells enter from blood (paracortex = pathway)
-Located between follicles and medulla
-Not well developed in patients with DiGeorge syndrome
during an extreme cellular immune response such as a viral infection, which part of the LN will enlarge?
Paracortex (contains endothelial venules for T and B cells to enter; houses T cells)
what structure drains lymph from the R side of the body above the diaphragm?
what does it drain into?
Right lymphatic duct.
Drains into junction of R internal jugular and R subclavian v
what structure drains lymph from everything except the R side of the body above the diaphragm?
what does it drain into?
Drains into Left Subclavian
what are the three main parts of a splenic sinusoid, and what is found at each place?
1. Periarterial lymphatic sheath within white pulp: T cells
2. Follicies within the white pulp: B cells (germinal centers)
3. Marginal zone (btwn red pulp and white pulp): APCs and specialized B cells.
within a splenic sinusoid, where do APCs present their antigens?
in the marginal zone, between red pulp and white pulp
macrophages in the spleen remove what type of organisms?
2 reasons for splenic dysfunction?
how does splenic dysfunction lead to increased susceptability to encapsulated organisms?
splenectomy; sickle cell disease
Decreased IgM -> decreased complement activation -> decreased C3b opsonization -> increased susceptability to encapsulated organisms
what are the encapsulated bacteria that we worry about with asplenic patients?
H influenza type B
Neisseria meningitidis (polysaccharide capsule: LOS)
E coli (K capsule)
Salmonella (Vi capsule)
Klebsiella (K capsule)
Group B Strep
what occurs in the Thymus?
from what embryonic structure does it derive?
T cell differentiation and maturation
From epithelium of 3rd pharyngeal pouches
(lymphocytes of mesenchymal origin)
Thymus: 2 parts? what cells are in each?
-Cortex: dense, holds immature T cells
-Medulla: pale, mature T cells & Hassall corpuscules containing epithelial reticular cells
T reg cells: what do they do?
what do they secrete?
what surface markers do they express? (4)
-help maintain specific immune tolerance by suppressing CD4 and CD8 T cell functions
-Secrete IL-10 and TGF-beta (anti-inflammatory cytokines)
-Surface markers: CD3, CD4, CD25 (alpha chain of the IL-2 receptor), & tsn factor FOXP3
What do activated Treg cells do?
Produce anti-inflammatory cytokines (such as IL-10 and TGF-beta)
what parts of antibodies recognize antigens? heavy chain or light chain?
where is the antigen-binding site?
The variable parts of both Light and Heavy chains recognize antigens. (outermost portion of each chain)
antigen binding site is between the two chains on each side.
what portion of antibodies fixes complement?
The Fc portion. binds both complement and macrophages.
what part of an antibody determines its idiotype?
the Fab portion.
contains antigen-binding site, determines idiotype.
only one antigenic specificity expressed per B cell.
What are the 4 C's of the Fc portion of an antibody? what is the 5th thing that the Fc portion does?
-Carbohydrate side chains
-Determines Isotype (IgM, IgD, etc)
How is antibody diversity generated? (4 ways)
-random recombination of VJ (light chain) or VJ/VDJ (heavy chain) genes
-random combination of heavy chains with light chains
-somatic hypermutation following antigen stimulation
-addition of nucleotides to DNA during recombination by terminal deoxynucleotidyl transferase
what are the 5 immunoglobulin isotypes
IgG, IgA, IgM, IgD, IgE
mature B lymphocytes express what on their surface?
how do we get cells that express the other immunoglobulin isotypes?
Express IgM and IgD.
they differentiate into plasma cells that secrete IgA, IgE, IgG in germinal centers (LNs) by isotype switching.
what mediates the isotype switching of mature B lymphocytes?
isotype switching = gene rearrangement
mediated by cytokines and CD40 ligand
main AB in the delayed response to an antigen.
fixes complement, crosses placenta (gives fetus passive immunity), opsonizes bacteria, neutralizes bacterial toxins and viruses.
prevents attachment of bacteria and viruses to mucus membranes. does not fix complement.
crosses epithelial cells by transcytosis. released into secretions (tears, saliva, mucus, early breast milk/colostrum).
IgA: what form is it present in in circulation? in secretions?
Circulation - Monomer
secretions - dimer
produced in the immediate response to an antigen. Fixes complement
does not cross placenta
antigen rceptor on the surface of B cells (along with IgD).
IgM: what forms is it present in?
on B cell: monomer
in secretions: pentamer. shape of pentamer allows it to trap free antigens out of tissue while humoral response evolves (remember IgM = part of immediate response to antigen)
IgD: function? located where?
found on the surface of many B cells and in serum
-Binds mast cells and basophils; cross links when exposed to allergen
-mediates Type I/immediate hypersensitivity reaction thru release of inflammatory mediators such as histamine.
-Mediates immunity to worms by activating eosinophils.
which immunoglobin isotype is most abundant in serum? least?
most abundant: IgG
lowest concentration: IgE
what are thymus-independent antigens?
-antigens lacking a peptide component. cannot be presented by MHC to T cells.
-weakly- or non-immunogenic; vaccines often require boosters (ex pneumococcal polysaccharide vaccine)
what are thymus-dependent antigens?
-antigen containing a protein component.
-class switching and immunologic memory occur as a result of direct contact of B cells with Th cells (remember the CD40-CD40L interaction)
what are acute phase reactants? where are they produced? what induces them?
-factors whose serum concentrations change significantly in response to inflammation
-produced by the liver in both acute and chronic inflammatory states.
-Induced by IL-6, IL-1, TNF-alpha, IFN-gamma
what acute phase reactants are upregulated in response to inflammation?
Serum amyloid A
Each of these acute phase reactants is upregulated in response to inflammation: what does each do?
Serum amyloid A
Serum amyloid A: function not given. (prolonged elevation can lead to amyloidosis)
CRP: Opsonin; fixes complement, facilitates phagocytosis. Measured clinically as a sign of inflammation.
Ferritin: Binds and sequesters iron to inhibit microbial iron scavenging
Fibrinogen: coagulation factor: promotes endothelial repair; correlates with ESR
Hepcidin: Prevents release of iron bound by ferritin -> anemia of chronic disease
what are the 2 acute phase reactants that are downregulated with inflammation? what does each do?
-Albumin: reduction of albumin conserves amino acids for the reactants that are upregulated with inflammation
-Transferrin: internalized by macrophages to sequester iron
Complement: what is a general overview?
system of interacting plasma proteins that play a role in innate immunity and inflammation.
MAC defends against gram-neg bacteria.
Complement system: three methods of activation?
-Classic pathway: IgG or IgM mediated (GM makes Classic cars)
-Alternative pathway: microbe surface molecules
-Lectin pathway: mannose or other sugars on microbe surface
(See FA'14 p204 for extensive diagram)
Describe the functions of each of these parts of the complement cascade:
C3a, C4a, C5a
C3b: Opsonization (C3b binds bacteria)
C3a, C4a, C5a: anaphylaxis (aaaa)
C5a: neutrophil chemotaxis
C5b-C9: cytolysis by Membrane Attack Complex (Big MAC attack)
describe this complement disorder: C1 esterase inhibitor deficiency.
causes hereditary angioedema.
ACE inhibitors are contraindicated
(C1 is part of both the Lectin and Classic activation pathways)
describe this complement disorder: C3 deficiency.
Increases risk of severe, recurrent pyogenic sinus and resp tract infections.
Increases susceptibility to Type III hypersens reactions.
describe this complement disorder: C5-C9 deficiencies.
Increased susceptibility to recurrent Neisseria bacteremia
(recall C5-C9 --> MAC/membrane attack complex which causes cytolysis)
describe this complement disorder: DAF (GPI anchored enzyme) deficiency.
Causes complement-mediated lysis of RBCs and paroxymal nocturnal hemoglobinuria
Macrophages secrete 5 impt cytokines. what are they?
IL-1, IL-6, IL-8, IL-12, TNF-alpha
briefly, what are the functions of IL-1 through IL-6?
(hints: generally they stimulate things. also there is an acronym)
HOT T-bone stEAK:
IL-1: Hot (fever)
IL-2: stimulates T cells
IL-3: stimulates bone marrow
IL-4: stimulates IgE production
IL-5: stimulates IgA production
IL-6: stimulates aKute-phase protein production
IL-1: secreted by what cell? what is it also called? causes what?
what does it activate?
Secr by macrophages.
endogenous pyrogen; also called osteoclast-activating factor.
Causes fever & acute inflammation (the HOT in HOT T-bone stEAK)
activates endothelium to express adhesion molecules; induces chemokine secretion to recruit leukocytes
IL-6: secreted by what cell? causes what?
Endogenous pyrogen (as is IL-1)
Secreted by both macrophages and Th2 cells
Causes fever and stimulates production of acute-phase proteins (aKute phase proteins... the K in "Hot Tbone stEAK")
IL-8: secreted by what cell? what does it do?
secreted by macrophages
major chemotactic factor for neutrophils
"Clean up on aisle 8" (neutrophils recruited by IL-8 to clear infections)
IL-12: secreted by what cell?
what does it do?
secreted by macrophages and B cells
induces differentiation of T cells into Th1 cells
Activates NK cells
TNF-alpha: what secretes it? what does it do?
secr by macrophages
mediates septic shock. activates endothelium. causes leukocyte recruitment, vascular leak.
what two cytokines are secreted by ALL T cells?
IL-2 and IL-3
IL-2: secreted by what? what does it do?
secr by all T cells
stimulates growth of helper, cytotoxic and regulatory T cells
IL-3: secreted by what? what does it do?
secr by all T cells
supports growth and differentiation of bone marrow stem cells. functions like GM-CSF.
Interferon-gamma: secreted by what? what does it do?
secreted by Th1 cells.
has antiviral and antitumor properties.
Activates NK cells to kill virus-infected cells; increases MHC expression and antigen presentation on all cells
what 3 cytokines are secreted by Th2 cells?
IL-4, IL-5, IL-10
IL-4: secreted by what? what does it do?
secr by Th2 cells
Induces differentiation into Th2 cells.
Promotes growth of B cells. Enhances class switching to IgE and IgG
IL-5: secreted by what? what does it do?
secr by Th2 cells
promotes differentiation of B cells; enhances class switching to IgA.
Stimulates the growth and differentiation of eosinophils
IL-10: secreted by what? what does it do?
secr by Th2 cells and Treg cells.
Modulates inflammatory response. Inhibits actions of activated T cells and Th1.
(similar to TGF-beta; both involved in inhibiting inflammation)
what are interferons? (interferon alpha and beta)
part of innate host defense against both RNA and DNA viruses
(Interferons INTERFERE with viruses)
glycoproteins synthesized by viral-infected cells. act locally on uninfected cells, priming them for viral defense.
what happens to cells that have been primed by interferon when they are infected with a virus?
viral nucleic acid (can be viral RNA or DNA) activates RNAaseL (degrades viral/host mRNA) and Protein kinase (inhibits viral/host protein synthesis).
Essentially results in apoptosis --> interrupts viral amplification in host.
all T cells: what cell surface proteins do they have?
TCR (binds antigen-MHC complex)
CD3 (assoc'd with TCR for signal transduction)
CD28 (binds B7 on APC)
Th cells: what cell surface proteins do they have?
MHC I, CD4, CD40L
Tc cells: what cell surface proteins do they have?
MHC I, CD8
B cells: what cell surface proteins do they have?
Ig (binds antigen)
CD19, CD20, CD21 (receptor for EBV), CD40
MHC II, B7
"Drink Beer at the Barr when you're 21" -- B cells/Epstein Barr virus/CD21
Macrophages: what cell surface proteins do they have?
MHC II, B7
Fc and C3b receptors (enhanced phagocytosis)
NK cells: what cell surface proteins do they have?
CD16 (binds Fc of IgG)
CD56 (unique marker for NK)
what cells does it apply to?
the body fails to react to an antigen. applies to both T cells and B cells.
-T cells become non-reactive without costim molecule
-B cells also become anergic but tolerance is less complete than in T cells
what are superantigens?
what bacteria have them?
bacterial toxins that can cross-link the beta region of the T cell receptor to the MHC II on APCs. Can thus activate any T cell --> massive release of cytokines!
S pyogenes and S aureus have superantigens.
what are endotoxins/lipopolysaccharides? what bacteria have them?
GN bacterial toxins that directly stimulate macrophages by binding to CD14 on macrophages; Th cells not involved
what is antigenic variation?
give examples of Bacteria (3), Viruses (1), and Parasites (1)
mechanisms for variation of the organism. includes DNA rearrangement and RNA segment re-assortment
Bacteria: Salmonella (flagellar variants); Borrelia (relapsing fever); Neisseria gonorrhoeae (pilus protein)
Virus: influenza (minor variation = drift, major variation = shift)
Parasite: Trypanosomes (programmed re-arrangement)
Means of acquisition?
Means of acquisition: receiving pre-formed antibodies
duration: short span of antibodies (half-life = 3 weeks)
examples: IgA in breast milk, maternal IgG crossing placenta, antitoxin, humanized monoclonal ab.
Passive immunity via delivery of preformed antibodies are given to patients with what exposures?
"To Be Healed Rapidly!"
Means of acquisition?
Means of acquisition: exposure to foreign antigens
duration: long-lasting protection (memory)
examples: natural infection, vaccines, toxoid
For Hep B or Rabies exposure, we can give Passive immunity via preformed antibodies; what else can we offer?
can also give combined passive and active immunizations for HBV or Rabies exposure. why not.
Live attenuated vaccine: how does the vaccine work?
microorganism loses its pathogenicity, but retains capacity for transient growth within inoculated host.
Induces a cellular response.
Live attenuated vaccine: Pros and cons?
Pros: induces strong, often lifelong immunity
Cons: may revert to virulent form. often contraindicated during pregnancy and for immunocompromised pts.
Live attenuated vaccine: Examples?
Measles, Mumps, Rubella (MMR)
Inactivated or killed vaccine: how does it work?
pathogen is inactivated by heat or chemicals; maintaining epitope structure on surface antigens is impt for immune response.
induces humoral immunity
Inactivated or killed vaccine: Pros/cons?
Pros: stable, safer than live vaccines
Cons: weaker immune response. booster shots usually required.
Inactivated or killed vaccine: examples?
Hep A (series of shots)
Influenza (injection; tell immunocompromised pts to get flu injection rather than intranasal)
Rabies (don't want to give a live-attenuated vaccine for such a bad disease)
Type I hypersensitivity reaction: describe the process.
what immune system components are involved?
Antibody-mediated reaction. IgE.
-Anaphylactic and atopic - free antigen cross-links IgE on presensitized mast cells and basophils.
-Triggers immediate release of vasoactive amines that act at postcapillary venules (ie histamine).
-Reaction develops rapidly after antigen exposure due to preformed antibody.
-Delayed response follows due to production of arachidonic acid metabolites (eg leukotrienes)
Type II hypersensitivity reaction: describe the process.
what immune system components are involved?
Antibody mediated; cytotoxic (Cy-2-toxic). Antibody and complement lead to MAC.
IgM/IgG bind to antigen on enemy cell, leading to cellular destruction. Three mechs:
-opsonization leading to phagocytosis or complement activation
-antibody-dependent cell-mediated cytotoxicity, usually due to NK cells or macrophages.
Test for Type II hypersens reaction?
Direct and Indirect Coombs' test
Direct: detects antibodies that have already adhered to patient's RBCs (test an Rh+ infant of an Rh- mom).
Indirect: detects antibodies that can adhere to other RBCs (test an Rh- woman for antibodies to Rh)
Test for Type I hypersens reaction?
Skin test for specific IgE
Type III hypersensitivity reaction: describe the process.
what immune system components are involved?
Immune complex reaction. (type III: 3 things stick together. antigen/antibody/complement)
Antigen-antibody complexes activate complement, which attracts neutrophils. Neutrophils release lysosomal enzymes.
Serum sickness: describe. what type of hypersens reaction is it?
Type III/immune complex reaction
antibodies to foreign proteins are produced (5d). Immune complexes form, are deposited in membranes. There they fix complement -> tissue damage.
Serum sickness: what causes it? what is presentation?
most serum sickness is caused by drugs acting as haptens (rather than serum).
Presentation: pt will have fever, urticaria, arthralgias, proteinuria, lymphadenopathy 5-10d post exposure to an antigen.
Arthus reaction: describe. what type of hypersens reaction?
how is it tested for?
local subacute antibody-mediated hypersensitivity Type III reaction.
intradermal injection of antigen induces antibodies, which form antigen-antibody complexes in the skin.
Characterized by edema, necrosis, complement activation.
Test via immunofluorescence staining.
Type IV hypersensitivity reaction: describe the process.
what immune system components are involved?
Delayed, T cell mediated type. (therefore cannot be transferred by serum)
Sensitized T lymphocytes encounter antigen and release lymphokines
Leads to macrophage activation. no antibody involved.
Type IV hypersens reaction: what are some examples when this reaction occurs?
How is it tested for?
the 4 Ts:
TB skin tests
Touching (ie contact dermatitis)
Test: patch test, PPD
Very briefly, what is the main characteristic of each type of hypersensitivity reaction?
Anaphlactic & Atopic (Type I)
Cytotoxic, antibody-mediated (Type II)
Immune complex (Type III)
Delayed, cell-mediated (Type IV)
Type I hypersensitivity disorders: presentation?
immediate, anaphylactic, atopic
1. Anaphylaxis due to bee sting, food/drug allergy
2. Allergic and atopic disorders (rhinitis, hay fever, eczema, hives, asthma)
Type II hypersensitivity disorders: presentation?
Presentation: specific to tissue or site where antigen is found.
1. Autoimmune hemolytic anemia
2. pernicious anemia
3. idiopathic thrombocytopenic purpura
4. erythroblastosis fetalis (Rh mediated hemolytic dz of newborn)
5. Acute hemolytic transfusion reactions
6. Rheumatic fever
8. Bullous pemphigoid
9. Pemphigus vulgaris
Type III hypersensitivity disorders: presentation?
Presentation: vasculitis, systemic manifestations
2. Polyarteritis nodosa
3. Poststrep glomerulonephritis
4. Serum sickness
5. Arthus reaction (swelling and inflammation following tetanus vaccine)
Type IV hypersensitivity disorders: presentation?
Presentation: response is delayed, does not involve antibodies (Types I, II, III all involve antibodies)
1. Multiple sclerosis
3. Graft v Host disease
4. PPD (test for TB)
5. Contact dermatitis (eg poison ivy, nickel allergy)
Allergic reaction to a blood transfusion: pathogenesis? clinical presentation? treatment?
Pathogenesis: Type I hypersens rxn against plasma proteins in transfused blood.
Presentation: urticaria, pruritis, wheezing, fever.
Anaphylactic reaction to a blood transfusion: pathogenesis? clinical presentation?
Severe allergic reaction. IgA-deficient pts must receive blood products that lack IgA.
Presentation: dyspnea, bronchospasm, hypotension, resp arrest, shock
Febrile nonhemolytic transfusion reaction: pathogenesis? clinical presentation?
Pathogenesis: Type II hypersens reaction. Host antibodies against donor HLA antigens and leukocytes.
Presentation: fever, headaches, chills, flushing
Acute hemolytic transfusion reaction: pathogenesis? clinical presentation?
Type II hypersens reaction. Intravascular hemolysis (ABO blood type incompatibility)
or extravascular hemolysis (host antibody reaction against foreign antigen on donor RBCs)
Presentation: fever, hypotension, tachypnea, tachycardia, flank pain, hemoclobinemia (intravascular), jaundice (extravascular hemolysis)
What is the disorder associated with this autoantibody: Anti-ACh receptor
What is the disorder associated with this autoantibody: anti-basement membrane
What is the disorder associated with this autoantibody: anti-cardiolipin, lupus anticoagulant
SLE, antiphospholipid syndrome
What is the disorder associated with this autoantibody: anticentromere
Limited scleroderma (CREST syndrome)
What is the disorder associated with this autoantibody: anti-desmoglein
What is the disorder associated with this autoantibody: anti-dsDNA, anti-Smith
What is the disorder associated with this autoantibody: anti-glutamate decarboxylase
What is the disorder associated with this autoantibody: anti-hemidesmosime
What is the disorder associated with this autoantibody: anti-histone
What is the disorder associated with this autoantibody: anti-Jo-1, anti-SRP, anti-Mi-2
What is the disorder associated with this autoantibody: antimicrosomal, antithyroglobulin
What is the disorder associated with this autoantibody: antimitochondrial
1' biliary cirrhosis
What is the disorder associated with this autoantibody: antinuclear antibodies
What is the disorder associated with this autoantibody: anti-Scl-70 (anti-DNA topoisomerase I)
What is the disorder associated with this autoantibody: anti smooth muscle
What is the disorder associated with this autoantibody: anti-SSA, anti-SSB (anti-Ro, anti-La)
What is the disorder associated with this autoantibody: anti-TSH receptor
What is the disorder associated with this autoantibody: anti-UI RNP (ribonucleoprotein)
Mixed connective tissue disease
What is the disorder associated with this autoantibody: c-ANCA (PR3-ANCA)
Granulomatosis with polyangiitis (Wegeners)
What is the disorder associated with this autoantibody: IgA antiendomysial, IgA anti-tissue transglutaminase
What is the disorder associated with this autoantibody: p-ANCA (MPO-ANCA)
Microscopic polyangiitis, Churg-Strauss syndrome
What is the disorder associated with this autoantibody: Rheumatoid factor (antibody, most commonly IgM, specific to IgG Fc region), anti-CCP
If a patient has no T cells, what problems will they have with Bacterial pathogens? Viral? Fungi/parasites?
Viral: CMV, EBV, JCV, VZV, chronic infection with resp/GI viruses
Fungi/parasites: candida, PCP
If a patient has no B cells, what problems will they have with Bacterial pathogens? Viral? Fungi/parasites?
Bacteria: Encapsulated (SHiNE SKiS)
Viral: Enteroviral encephalitis, poliovirus (live vaccine contraindicated)
Fungi/parasites: GI giardiasis (no IgA)
If a patient has no granulocytes, what problems will they have with Bacterial pathogens? Viral? Fungi/parasites?
Bacteria: Staphylococcus, Burkholderia cepacia, Serratia, Nocardia
Fungi/Parasites: Candida, Aspergillus
If a patient has no complement, what problems will they have with Bacterial pathogens? Viral? Fungi/parasites?
Bacteria: Neisseria (no MAC)
In general, B cell deficiencies produce what kinds of infections?
T cell deficiencies produce what kinds of infections?
B cell deficiencies: -> recurrent bacterial infections
T cell deficiencies: -> fungal/viral infections
Defect in BTK (a tyrosine kinase gene) leads to what problem with immuno cells?
Name the disorder?
Defect in BTK -> no B cell maturation. X linked recessive.
Disorder: X-linked (Bruton) agammaglobulinemia
Presentation: Recurrent bacterial and enteroviral infections after 6 mo (covered by maternal IgG until then)
Findings: Absent CD19+ B cell count, decreased pro-B, decreased Ig (all classes).
Exam: absent/small lymph nodes and tonsils
Most common primary immunodeficiency (B cell disorder) - name the disorder?
Disorder: Selective IgA deficiency (specific defect is unknown)
Presentation: majorly Asymptomatic. may be airway and GI infections, autoimmune disease, atopy, anaphylaxis to IgA-containing products
Findings: IgA < 7 mg/dL with normal IgG and IgM levels
Defect in B cell differentiation (from many causes) - name the disorder?
Disorder: common variable immunodeficiency
Presentation: acquired in 20s-30s. incr risk of autoimmune disease, bronchiectasis, lymphoma, sinopulm infections
Findings: decr plasma cells, decr immunoglobulins.
22q11 deletion; failure to develop 3rd/4th pharyngeal pouches - name the disorder?
Disorder: Thymic aplasia (DiGeorge syndrome). absence of thymus and parathyroids
Presentation: Tetany (due to hypocalcemia), recurrent viral/fungal infections (T cell deficiency), conotruncal abnormalities (tetralogy of Fallot, truncus arteriosus)
Findings: decr T cells, decr PTH, decr Ca2+. 22q11 deletion detected by FISH
Autosomal recessive, decreased Th1 response - name the disorder?
Disorder: IL-12 receptor deficiency.
Presentation: disseminated mycobacterial and fungal infections; may present after BCG vaccine
Findings: decr IFN-gamma
deficiency of Th17 cells due to STAT3 mutation -> decr recruitment of neutrophils to sites of infection - name the disorder?
Disorder: Autosominal dominant hyper-IgE syndrome (Job syndrome)
Presentation: FATED - coarse Facies, cold (not inflammed) staph Abscesses, retained primary Teeth, incr IgE, Dermatologic problems (eczema)
Findings: incr IgE; decr IFN-gamma
T cell dysfunction due to many causes - name a possible disorder?
Disorder: Chronic mucocutaneous candidiasis
Presentation: noninvasive Candida infection of skin and mucous membranes
Findings: absent in vitro T cell prolif in response to Candida antigens, absent cutaneous reaction to Candida antigens
defective IL-2R gamma chain or adenosine deaminase deficiency - name the disorder?
Disorder: Severe Combined Immunodeficiency (SCID) - deficiency in both B cells and T cells
Presentation: Failure to thrive, chronic diarrhea, thrush, recurrent viral,bacterial, fungal, protozoal infections
Treatment: bone marrow transplant (note no concern for rejection)
Findings: decr T cell receptor excision circles (TRECs), absence of thymic shadow on CXR, absence of germinal centers on LN biopsy, absence of T cells on flow cytometry
Defects in ATM gene -> DNA double strand breaks -> cell cycle arrest - name the disorder?
Disorder: Ataxia-telangiectasia (ATM = Ataxia-Telangiectasia Mutated). Bottom line: IgA deficiency causes defect in DNA repair enzymes
Presentation: Triad: cerebellar defects (Ataxia), spider Angiomas (telangiectasia), IgA deficiency
Findings: Incr AFP, decr IgA, decr IgG, decr IgE
Lymphopenia, cerebellar atrophy
defective CD40L on Th cells - name the disorder?
Disorder: Hyper-IgM syndrome (class switching defect)
Presentation: severe pyogenic infections early in life; opportunistic infections with Pneumocystis, Cryptosporidium, CMV
Findings: Incr IgM, decr IgG/IgA/IgE
Mutation in WAS gene -> T cells unable to recognize actin cytoskeleton - name the disorder?
Disorder: Wiskott-Aldrich syndrome
Presentation: WATER: Wistott-Aldrich: Thrombocytopenic purpura, Eczema, Recurrent infections
Incr risk of autoimmune dz and malignancy
Findings: decr/nl IgG/IgM. Incr IgE, IgA. fewer/smaller platelets
defect in LFA-1 integrin (CD18) protein on phagocytes - name the disorder?
Disorder: Leukocyte adhesion deficiency (Type 1). Impaired migration and chemotaxis.
Presentation: recurrent bacterial skin and mucosal infections, absent pus formation, impaired wound healing, delayed separation of umbilical cord (>30d)
Findings: incr neutrophils. Neutrophils not present at infection sites.
defective lysosomal trafficking regulator gene (LYST) - name the disorder?
Recurrent pyogenic infections by Staph and Strep, partial albinism, peripheral neuropathy, progressive neurodegeneration, infiltrative lymphohistiocytosis
Giant granules in neutrophils and platlets, pancytopenia and mild coagulation defects.
Chediak-Higashi syndrome (microtubule dysfunction in phagosome-lysosome fusion)
Presentation: Recurrent pyogenic infections by staph and strep; partial albinsm; peripheral neuropathy; progressive neurodegeneration; infoltrative lymphohistiocytosis
Findings: giang granules in neutrophils and platelets; pancytopenia; mild coag defects
Defect of NADPH oxidase causing decr reactive oxygen species and absent resp burst in neutrophils- name the disorder?
Disorder: chronic granulomatous disease
Presentation: incr susc to catalase + organisms (PLACESS: Pseudomonas, Listeria, Aspergillus, Candida, E coli, S aureus, Serratia)
Findings: abnormal dihydrorhodamine test (flow cytometry); nitroblue tetrazolium dye reduction test is -.
Autograft: origin of tissue is ?
Syngeneic graft: origin of tissue is ?
from identical twin or clone
Allograft: origin of tissue is ?
from nonidentical individual of same species (sib, stranger)
Xenograft: origin of tissue is ?
from different species
Transplant rejection within minutes is what type?
Pre-existing recipient antibodies react to donor antigen (Type II reaction) & activate complement
Features: widespread thrombosis of graft vessels -> ischemia/necrosis. Graft must be removed.
Transplant rejection within weeks to months is what type?
Cellular pathogenesis: CTLs activated against donor MHCs.
Humoral pathogenesis: sim to hyperacute rejection, except antibodies develop after transplant (not pre-formed)
Features: vasculitis of graft vessels with dense interstitial lymphocytic infiltrate.
Prevent/reverse with immunosuppressants.
Transplant rejection within months to years is what type?
Pathogenesis: Recipient T cells perceive donor MHC as recipient MHC, and react against donor antigens presented. Both humoral and cellular components.
Features: Irreversible. T cell and antibody-mediated damage.
Organ specific: Heart --> atherosclerosis. Lungs --> bronchiolitis obliterans. Liver --> vanishing bile ducts. Kidney --> vascular fibrosis, glomerulopathy
Graft v Host disease: speed of onset?
Pathogenesis: Grafted immunocompetent T cells proliferate in immunocompromised host and reject host cells with "foreign" proteins -> severe organ dysfunction.
Features: maculopapular rash, jaundice, diarrhea, HSM.
Usually in bone marrow and liver transplants (rich in lymphocytes).
**Potentially beneficial in bone marrow transplant for leukemia (graft v tumor effect)
lymphatic drainge of Left/Right ovary/testis
lymphatic drainage of Distal vagina/vulva/scrotum
superficial inguinal nodes
lymphatic drainage of proximal vagina/uterus
obturator, external iliac and hypogastric nodes.
lymphatic drainage of H&N
lymphatic drainage of lungs
lymphatic drainage of Trachea and esophagus
lymphatic drainage of upper limbs, breast, skin above umbilicus
lymphatic drainage of Liver, stomach, spleen, pancreas, upper duodenum
lymphatic drainag of Lower duodenum -> splenic flexure
superior mesenteric nodes
lymphatic drainage of splenic flexure -> upper rectum
Inferior mesenteric nodes
lymphatic drainages of:
Lower rectum to anal canal (above pectinate line)
bladder, vagina (middle third)
all drains into the internal iliac
lymphatic drainage of Testes, ovaries, kidneys, uterus
lymphatic drainage of Anal canal (below pectinate line), skin below umbilicus
lymphatic drainage of Dorsolateral foot, posterior calf
lymphatic drainage of anal canal above the pectinate line? below the pectinate line?
above the pectinate line = internal iliac
below the pectinate line = superficial inguinal
lympahtic drainage of skin above the umbilicus? below the umbilicus?
above the umbilicus = axillary
below the umbilicus = superficial inguinal (except popliteal territory)