-
Lymph drainage sites:
Axillary
Celiac
Superior Mesenteric
Colic -> Inferior Mesenteric
Internal Iliac
Superficial inguinal
Para-aortic
Popliteal
- Axillary - upper limb, lateral breast
- Celiac - stomach
- Superior Mesenteric - duodenum, jejumum
- Colic -> Inferior Mesenteric - sigmoid colon
- Internal Iliac - rectum
- Superficial inguinal - anal canal, scrotum, thigh
- Para-aortic - testes
- Popliteal - dorsum of foot
-
Macrophages in the spleen remove what?
- Encapsulated Bacteria - "even some killers have pretty nice capsules"
- E. coli
- S.pneumoniae
- Klebsiella pneumoniae
- H. influenzae
- Psuedomonas aeruginosa
- N. meningitidis
- Cryptococcus neoformans
-
Innate immune cells
- neutrophils
- macrophages
- dendritic cells (APCs)
- NK cells
- complement made by hepatocytes
-
Adaptive immune cells
T cells, B cells, circulating antibodies
- VDJ recombination
- responds to vaccines
-
MHC I
expressed on all cells except RBCs
binds TCR on CD8 cells to present antigen
HLA-A, B and C (one digit, MHC I)
-
MHC II
expressed ONLY on APCs!!
binds TCR on CD4 (T Helpers)
HLA-DR, DQ, DP (two digits, MHC II)
a doctor goes to dairy queen to get a doctor pepper
-
HLA Subtypes:
A3
B27
DR3
DR4
- A3 - hemochromatosis
- B27 - Psoriasis and arthritis, Ankylosing spondylitis, IBD, Reiter's syndrome
- DR3 and 4 - Diabetes Mellitus
- DR4 - RA
-
Have CD16 and 56
respond to IL-12, IFN-B and IFN-a
binds to constant region of antibodies on phagocytes presenting antigens
Natural Killer Cells
-
Mast Cell found in tissues
mediates Type I Hypersensitivity
degranulate histamine, heparin, eosinophil chemotactic factors
-
Lymphocyte - can be a T or B cell
-
Dendritic cell
professional APC, expresses MHC II, CD 80 and 86
also have MHC I and Fc Receptors
-
Plasma cell - antibody machine
"Clock face" chromatin, abundant RER
If you see a ton of monoclonal antibodies - consider multiple myeloma
-
multiple myeloma is a neoplasm of what?
plasma cells
-
Neutrophils
multilobe nucleus
acute response cell
most numerous in WBCs
-
Monocyte
- kidney shaped nucleus
- becomes macrophage in tissues, monocyte in blood
-
Macrophage
CD 14 is specific marker
also has CD40 (as an APC), B7
activated by INFy
-
Eosinophil
Bilobed nucleus, very pink cell
Good for helminthic infections
produces histaminase to calm things down after mast cell degranulation
-
Basophil
found in blood only
mediates allergic reaction
very dark spotty cell
-
Carries markers CD 19, 20, 21
IgM and IgD on surface, as well as CD40, MHC II
B cell
-
Carries CD3 on cell surface
both T cells
-
Self cells present with this type of MHC
MHC I - to cytotoxic T cells
-
Blood types: universal donor? universal recipient?
-
If you transfuse the wrong type of blood, what type of hypersensitivity reaction will you get?
Type II
-
Dendritic cells in the skin are called Langerhans cells. What do you see histologically in these cells on electron microscopy?
Tennis rackets - Birbeck Granules
-
what 3 cell types are known for presenting antigen to T cells?
- Dendritic cells
- Macrophages
- B cells
-
what hematologic changes would you see in a patient without a functional spleen?
- howell-jolly bodies
- target cells
- thrombocytosis
-
T cell differentiation:
What cell markers appear in which stage?
T cell precursor
Primoridal T cell
Cytotoxic
Helper1
Helper2
- T cell precursor - none
- Primordial - all (CD4 and CD8)
- Cytotoxic - CD8
- Helpers - CD4
-
IL2 and INFy are made by _ which activate what cells?
Th1 cells
activate macrophages and CD8's
-
IL4, IL5 and IL-10 are made by _ which activate what cells?
Th2 cells
help B cells make antibodies
-
Th1 cells are INDUCED by what cytokines? INHBITED by what cytokines?
- induced:
- IL-12 (viruses secrete)
- inhibited:
- IL-10 (from Th2 cell)
-
Th2 cells are INDUCED by what cytokines? INHIBITED by what cytokines?
Induced: IL-10
Inhibited: IFNy produced by Th1 cells
-
Helper T cell activation
- APC presents antigen on MHC II to TCR on T cell
- B7 on APC interacts with CD28 (costimulation)
- Th cells produce cytokines
-
Cytotoxic T cell activation:
- Any cell presents antigen on MHC I to TCR on cytotoxic t cell
- IL-2 from nearby Th1 cell activates cytotoxic T cell
-
B cell activation and class switching
- Helper T is activated (MHC II) and releases IL4,5,6 and 10.
- CD40 on B cell binds CD40L on Th2 cell
- B7 CD28 costimulation
-
Regulatory T cells
suppress CD4 and CD8 function
express CD3, CD4 and CD25 ono surface - produce IL-10 and TNFb (anti-inflammatory cytokines)
protect from autoimmune disease
-
Different types of monocytes:
blood, alveoli, intestines
CT
liver
kidney
brain
bone
joints
- blood, alveoli, intestines - macrophages
- CT - histiocytes, dendritic cells
- Liver - Kupffer Cells
- Kidney - mesangial cells
- Brain - microglia
- Bone - Osteoclasts
- Joints - A cells
-
Important cytokines - function: IL-1
Hot T Bone StEAK
mediates fever
-
Important cytokines - function: IL-2
Hot T Bone StEAK
stimulates t cell function
-
Important cytokines - function: IL-3
Hot T Bone StEAK
stimulates bone marrow
-
Important cytokines - function: IL-4
Hot T Bone StEAk
stimulates IgE and IgG production
-
Important cytokines - function: IL-5
Hot T Bone StEAk
stimulates IgA and eosinophil production
-
Important cytokines - function: IL-6
general - fever
-
Important cytokines - function: IL-8
Neutrophil Chemotaxis (remember CILK)
-
Important cytokines - function: IL-10
Th2 cell activation
shuts down Th1 cells
-
Important cytokines - function: IL-12
Induces Th1 cells and activates NK cells
-
Important cytokines - function: TNFa
Mediates septic shock!
-
Antibody structure
2 light chains, 2 heavy chains, together by S-S (disulfide) bond
2 regions - Fab (antigen binding) *light chains only contribute to Fab* and Fc (constant)
-
Complement and Macrophages bind to which part of the antibody structure?
Fc - constant region
-
Name 5 types of heavy chains seen in antibodies
- Mu - IgM
- Delta - IgD
- Gamma - IgG
- Alpha - IgA
- Epsilon - IgE
-
Name 2 types of light chains seen in antibodies
Lambda and Kappa
2 Kappa to every Lambda is normal - if not, consider multiple myeloma
-
What are three functions of antibodies?
- Opsonization - like sugar on bugs for APC's
- Neutralization - blocks binding regions on bugs
- Complement activation
-
Antibody diversity
Recombination of VJ (light chains) or VDJ (heavy chains) genes
initiated by recombination of RAG1 and RAG2 - recombination activating gene complexes.
-
What happens if RAG genes mutate?
No T or B cells!
-
Name the live attenuated vaccines
- Smallpox
- Yellow Fever
- MMR
- Chickenpox
- Sabin's polio
-
Name the killed vaccines
- Rabies
- Salk Polio (K for killed)
- Influenza
- HAV
-
do you need a booster for live attenuated vaccines?
NO
-
Mature B lymphocytes express what immunoglobulins on their surfaces?
IgM or IgD
-
Main antibody in delayed antigen response
IgG
-
Most abundant antibody in blood
IgG
-
antibody that fixes complement, crosses the placenta
IgG
-
antibody that fixes complement but does NOT cross placenta
IgM
-
antibody secreted as monomer or dimer
IgA
-
antibody that is in secretion, mucous membranes, and breast milk
IgA
-
antibody produced in immediate response to antigen
IgM
-
antibody secreted as pentamer
IgM
-
antibody that binds mast cells and basophils
IgE
-
antibody that mediates Type I hypersensitivity, lowest concentration in serum
IgE
-
Antinuclear (ANA) antibodies
SLE, nonspecific
-
Anti-ds DNA, Anti-Smith antibodies
SLE
-
Antihistone antibodies
Drug-induced lupus
-
Anti-IgG
Rheumatoid Arthritis
-
Anticentromere
Scleroderma (CREST)
-
Anti-Scl70 (anti DNA topoisomerase I)
Diffuse Scleroderma
-
Antimitochondrial (AMA)
Primary Biliary Cirrhosis
-
antiendomysial
Celiac disease
-
Anti-basement membrane
Goodpasture's Syndrome
-
Anti-desmoglein
Pemphigus Vulgaris
-
Antihemidesmoglein
Bullous Pemphigus
-
Antimicrosomal, antithyroglobulin
Hashimoto's Thyroiditis
-
Anti-Jo-1
Polymyositis, Dermomyositis
-
Anti Ro or Anti La
Sjogren's Syndrome
also anytime you see Anti-SS A or B
-
Anti-U1 RNP (ribonucleoprotein)
Mixed Connective Tissue Disease
-
Anti-smooth muscle
Autoimmune hepatitis
-
Anti-glutamate decarboxylase, anti-glutamic acid
Type I diabetes mellitus
-
c-ANCA
Wegener's Granulomatosis
-
p-ANCA
Microscopic Polyangitis, Churg-Strauss Disease
-
mpo-ANCA
pauci immune crescentic glomerulonephritis
-
anti TSH receptor
Graves Disease
-
anti ACh receptor
Myasthenia Gravis
-
Amyloidosis
B pleated sheets - too much protein, deposited in tissues and vasculature
-
Which cellular organelles are particularly important to plasma cell function?
Golgi and RER - protein synthesis
-
Drug: inhibits Calcineurin which acts as
IL-2 Inhibitor
used for Transplant Rejection
Nephrotox (Mannitol diuresis prevents)
Cyclosporine
-
Drug:
XFK -> IL-2 secretion
used for Organ transplants and eczema
Tox: peripheral neuropathy, nephropathy
Tacrolimus
-
Drug: XFK -> MTOR -> IL-2
Used for kidney transplants with cyclosporine
Rapamycin (sirolimus)
-
Drug:
monoclonal antibody against IL-2 receptors on t cells
used in kidney transplants
Daclizumab
-
Drug:
Inhibits nucleic acid synth
precursor of 6-mercaptopurine
used for glomerulonephritis and hemolytic anemia
metabolized by xanthine oxidase
tox: aplastic anemia
Azathioprine
-
Drug:
MAB against CD3 on T cells
used for kidney transplant
Muromonab
-
Drug:
inhibits inosine monophosphate dehydrogenase
prevents production of GUANINE
Used for Transplants, lupus nephritis
Mycophenolate
-
Drugs:
Targets TNFa
Crohn's, RA, psoriatic arthritis and HLA-B27 seronegative arthropathies, ankylosing spondylolysis
- Infliximab
- Etanercept
- Adalimumab
-
Drug:
platelet activity
targets glycoprotein IIb/IIIa
used for unstable angina
Acliximab
-
Drug: HER2+ breast cancer
Trastuzumab
-
Drug:
CD20 on B cell non-Hodgkins Lymphoma
Rituximab
-
Drug:
used for Type I hypersensitivity, IgE type, asthma
Omalizumab
-
What are the three most "acute" cytokines?
IL-1, IL-6 and TNFa
-
What drug affects TNFa and causes phocomelia?
Thalidomide
-
Complement Pathway: mediated by IgM or IgG, antigen/antibody complexes. Starts with C1.
Classic Pathway
-
Complement Pathway: starts spontaneously with C3 from microbial surface endotoxins.
Alternative Pathway
-
Complement: C3b
Opsonization
-
Complement: C3a
anaphylaxis
-
Complement: C5a
anaphylaxis, neutrophil chemotaxis
-
Complement: C5b - 9
Membrane Attack Complex
-
Complement deficiencies: hereditary angioedema
C1 esterase inhibitor deficiency (can't stop classical pathway)
-
Complement deficiencies: severe recurrent pyogenic infections, glomerulonephritis, increased type III reactions
C3 deficiency
-
Complement deficiencies: recurrent Neisseria bacteremia
(C5b-C9) MAC deficiency
-
Complement deficiencies: Paroxysmal nocturnal hemoglobinuria
DAFdeficiency
RBC's are unprotected from complement
Dx: Ham's Test (RBC's lyse at low pH)
-
Erythroblastosis Fetalis
Rh- Mom, Rh+ babies
jaundice, kernicterus, hydrops fetalis
-
Type I Hypersensitivity
Anaphylactic and Atopic (allergies)
IgE, Mast Cells, Basophils
-
Type II Hypersensitivity
Antibody mediated
IgM, IgG
Direct/Indirect Coombs tests
-
Type III Hypersensitivity
Immune complex mediated
antigen+antibodies+complement
Serum sickness and Arthrus reaction
Immunofluorescence test
-
Type IV Hypersensitivity
T cell mediated
Delayed
-
Hypersensitivity Reaction: Wheal and Flare
I
-
Hypersensitivity Reaction: hay fever
I
-
Hypersensitivity Reaction: hemolytic or pernicious anemia
II
-
Hypersensitivity Reaction: Idiopathic Thrombocytopenic Purpura (ITP)
II (antibodies to platelets)
-
Hypersensitivity Reaction: Erythroblastosis Fetalis
II
-
Hypersensitivity Reaction: Transfusion reactions
II
-
Hypersensitivity Reaction: Rheumatic Fever
II
-
Hypersensitivity Reaction: Goodpasture's
II
-
Hypersensitivity Reaction: Bullous Pemphigus or Pemphigus Vulgaris
II
-
Hypersensitivity Reaction: Graves Disease and Myasthenia Gravis
II
-
Hypersensitivity Reaction: SLE
III
-
Hypersensitivity Reaction: RA or polyarteritis nodosum
III
-
Hypersensitivity Reaction: Post-strep glomerulonephritis or pneumonitis
III
-
Hypersensitivity Reaction: Serum sickness, arthrus reaction
III
-
Hypersensitivity Reaction: Type I Diabetes Mellitus
IV
-
Hypersensitivity Reaction: Multiple Sclerosis
IV
-
Hypersensitivity Reaction: Guillain Barre
IV
-
Hypersensitivity Reaction: Hashimotos Thyroiditis
IV
-
Hypersensitivity Reaction: Graft vs Host
IV
-
Hypersensitivity Reaction: PPD or contact dermatitis (poison ivy)
IV
-
Immune Disease:
X linked recessive (boys)
BTK (tyrosine kinase) gene defect
Recurrent bacterial infections
decreased immunoglobins
Brutons Agammaglobulinemia
-
Immune Disease:
Defective CD40L - no class switching
Severe infections at young age
Hyper IgM Syndrome
-
Immune Disease:
defect in isotype switching - deficient in one Ig
lung infections, diarrhea, dairy allergy
IgA deficiency
-
Immune Disease:
22q11 deletion, failure of 3rd and 4th pharyngeal pouches
No T's, PTH
Tetany, Troussaus (tighten cuff), Chevsteks (cheek)
DiGeorge Syndrome
-
Immune Disease:
No IFNy production
2 rows of teeth, doughy skin, excess cold absecesses
coarse facies, eczema (derm probs), IgE in blood
Job Syndrome (Hyper IgE)
-
What are the X-linked recessive immune diseases?
- Brutons
- Wiskott Aldrich
- Chronic Granulomatous Disease
-
Immune Disease:
adenosine deaminase deficiency
No thymus, failure to thrive, recurrent infections, diarrhea
No B or T cells (adenine toxic to these)
SCID
-
Immune Disease:
defect in ATK gene
visual problems with smooth pursuits, ataxia, spider angiomas, increased IgA
Ataxia-Telangiectasia
-
Immune Disease:
X linked recessive
Infections, Eczema, Thrombocytopenic purpura
- WAITER
- Wiskott Aldrich
- Infections, Eczema, Thrombocytopenic purpura, Recessive
-
Immune Disease:
Umbilicus fails to detach, recurrent infections
Defect in LFA-1 integrin
Leukocyte Adhesion Deficiency
-
Immune Disease:
recurrent staph and strep infections
albinism
peripheral neuropathy
microtubule dysfunction in lysosome/phagosome fusion
Chediak Higashi disease
-
Immune Disease:
Lack of NADPH oxidase
increased susceptibility to catalase + organisms (S. aureaus, E. coli, Aspergillus)
Nitroblue tetrazolium dye test - if NEGATIVE test, then you have this disease
Chronic Granulomatous Disease
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