Immunology Flashcards
primary lymphoid organs
bone marrow
thymus
Secondary lymphoid organs
spleen, lymph nodes, MALT
Peyer patches
only found in the lamina propria and submucosa of the ileum, made of unencapsulated lymphoid tissue and containing M cells, which sample ans present antigens to immune cells.
Peyer patch germinal center B cells make IgA.
LN
where macrophages filter lymph, B and T cells are stored, and where immune response activation/ proliferation/ differentiation take place.
LN- follicle
B cell localization
Medulla (middle, medial to paracortex)
Medullary sinuses house macrophages
Paracortex
Paracortex houses T cells (between follicles and medulla. high endothelial venules through which T and B cells enter from blood, not well developed in patient with DiGeorge, expands when cellular immune reponse (viral infection)
arm, lateral breast
axillary nodes
lateral dorsum of foot
popliteal nodes
thighs
superficial inguinal nodes
stomach
celiac nodes
duodenum, jejunum
superior mesenteric nodes
sigmoid colon
inferior mesenteric
upper rectum
pararectal
lower rectum above pectinate line
internal iliac nodes
lower rectum below pectinate line
superficial inguinal nodes
testes
para-aortic lymph nodes. testes descend from within the body cavity and are not a superficial structure
scrotum
superficial inguinal nodes
right arm, right half of head
right lymphatic duct
everything besides the right arm and right half of the head
thoracic duct, which joins in at the branch of the left IJ and brachiocephalic veins
sigmoid colon
inferior mesenteric nodes
upper rectum
pararectal lymph nodes
lower rectum above pectinate line
internal iliac nodes
lower rectum below pectinate line
superficial inguinal nodes
HLA B27 associated with disease
psoriatic arthritis, ankylosing spondylitis, arthritis of inflammatory bowel disease, reactive arthritis (formerly Reiter syndrome) seronegative arthropathies
DR3
diabetes mellitus type I, SLE, Goodpasture syndrome
DR4
rheumatoid arthritis, DM1 (4 walls in a rheum)
DR5
pernicious anemia > B12 deficiency, Hashimoto thyroiditis
DR2
MS, hay fever, SLE, Goodpasture syndrome
DQ2/DQ8
celiac disease
A3
hemochromatosis
IL2
T cell proliferation
IL4
B cell proliferation, Th0 stimulated to become Th2
IL5
B cell proliferation
IL10
Th1 and macrophage inhibition
IL12
Th0 is stimulated to become Th1
IFN-gamma
macrophage activation, Th2 inhibition
cytokines produced by Th1
IL2, IFN-gamma
cytokines produced by Th2
IL2, IL4, IL5, IL10
B cell surface markers
CD19, 20 21, IgM, IgD, MHCI, MHC II, B7 protein (80 or 86), CD40
The differential diagnosis for eosinophilia
Collagen vascular disease (PAN, dermatomyositis)
Atopic diseases (allergy, asthma, churg- strauss, bronchopulmonary asperfillosis)
Neoplasm
Adrenal insufficiency (Addison disease)
Drugs (NSAIDs, PCN, cephalosporin)
Acute interstitial nephritis
Parasites (Strongyloides, Ascaris > Loeffler eosinophilic pneumonitis)
Other: HIV, hyper IgE, coccidiomycosis, etc.
secreted by all T cells
IL2, IL3
secreted by Th1 cells
IL2, IL3, IFN gamma
secreted by Th2 cells
ILe, IL3, IL4, IL5, IL20
secreted by macrophages
IL1, IL6, TNFa ramp up immune response and generate fever, IL6, IL8, Il12 (promotes Th2 from Th0
hyperacute transplant rejection
within minutes, type 2 hypersensitivity reaction by host abs that activate complement, features widespread thrombosis of graft vessels leading to ischemia/necrosis, treat by removing the graft
acute transplant rejection
weeks to months, CD8 T cells activate against foreign MHC, humoral is also possible, with abs developing after the transplant. reversible, features vasculitis of graft vessels with dense interstitial lymphocytic infiltrate. reverse with IL2 blockers and other immunosuppressants
chronic transplant rejection
months to years, translplant cells present antigens to the hosts’ T cells, this is a cellular and humoral response, featuring vascular smooth muscle proliferation and parenchymal fibrosis, lots of cytokines, arteriosclerosis
graft versus host disease
variable amount of time. new transplanted immune system attacks that host, as if the host is non- self, features maculopapular rash, jaundice, diarrhea, hepatosplenomegaly, bone marrow and liver transplants are most prone, potentially benefital in bone marrow transplant for leukemia (graft- versus- tumor)
cyclosporine side effects
binds cyclophilins in cysotol of T cells. cyclophilin binding inhibits calcineurin and this prevents IL2 transcription,
transplant rejection, psoriasis, severe RA, other severe autoimmune
NEPHROTOXICITY because it constricts both afferent and efferent kidney arterioles, hypertension, hyperlipidemia, neurotoxicity, gingival hyperplasia, hirsutism
Tacrolimus (FK506) and pimecrolimus
calcineurin inhibitor that binds FK506 binding protein, the complex blocks T cell activation by inhibiting calcineurin and transcription of IL2,
used for transplant rejection prophylaxis and topical application for eczema
nephrotoxity, increased risk of diabetes and neurotoxicity, HTN
Sirolimus (Rapamycin)
Binds FK binding protein 12 (FKBP12), inhibiting mammalian target of rapamycin (mTOR). This blocks T cell activation and B cell differentiation by preventing T cell response to IL2
NOT NEPHROTOXIC
so it can be used to prevent kidney transplant rejection
synergistic with cyclosporine
can be used in drug- eluting stents
side effects include anemia, thrombocytopenia, leukopenia, insulin resistance, hyperlipidemia
Azathioprine
precursor of 6-mercaptopurine (6MP), interferes with nucleic acid synthesis so that the immune cells can’t divide and proliferate
used in kidney transplants, autoimmune disorders
side effects include bone marroq suppression. It is metabolized by xanthine oxidiase. Toxic effecst are increased by allopurinol, which inhibits xanthine oxidase.
Mycophenalate
Mechanism: inhibits synthesis of guanine by inhibiting inosine monophosphate dehydrogenase (IMP) and thereby prevents lymphocyte proliferation
this is how it prevents humoral response. used in transplant patients and off- label for lupus nephritis
side effects include hyperglycemia, hypercholesterolemia, hypertension, infection, LYMPHOMA, infection, teratogenic
Thalidomide
sedative given to pregnant women, causes phocomyelia. mechanism is that is suppresses TNFa, increases NK cells and IL2 both suppressing and inhibiting immune response. Used for erythema nodosum leprosum (Hansen disease), multiple myeloma where it stmulates cancer cells to kill the cancer cells.
infliximab and adalimumab
bind TNFa
Rituximab
anti CD20 mAb that binds B cells and induces complement to lyse the B cells
useful for B cell non-Hodgkin lymphoma, CLL, RA, ITP
Eculizumab
complement protein C5, mimics TNFalpha receptor decoy receptor.
use for paroxysmal nocturnal hemoglobinuria
Adalimumab, infliximab
binds soluble TNFa, used for IBD, RA, ankylosing spondylitis, and psoriasis
Abciximab
platelet glycoproteins IIb/IIIa. Antiplatelet agent for prevention of ischemic complications in patient undergoing percutaneous coronary intervention.
Thymic aplasia
DiGeorge
90% have a chr 22q11 del (FISH)
3rd and 4th pouches fail to develop
no thymus so no mature T cells, so recurrent viral, fungal, protozoal infections
congenital defects in heart/ great vessels
no parathyroid so no PTH so tetany 2/2 hypocalcemia
Hypocalcemia signs
Chvostek sign- tap on the cheep to cause a muscle spasm
Trousseau sign- tightening the BP cuff yields carpo- pedal spasm
chronic mucocutaneous candidiasis
T cell dysfunction leading to problems specifically with c. albicans.
give prophylactic ketoconazole
IL12 receptor deficiency
Th0 cells without IL12 R.
Macrophages still make IL12 but the Th0 don’t differentiate correctly into Th1 the way they would under normal circumstances
Increased susceptibility to mycobacterial and fungal infections
Bruton agammaglobulinemia
X- linked (boys)
B-cell deficiency leading to defective tyrosine kinase gene, low levels of all immunoglobulins results, and therefore recurrent bacterial infections after 6 months (after passive immunity)
Selective immunoglobulin deficiencies
Selective IgA is most common. Patient appears healthy, even unaware.
Recurrent sinus and lung infections
1/6 people of European descent, associated with atopy, asthma
important to diagnose because possible anaphylaxis to blood transfusions and blood products.
not much you can do to treat this, but you can give prophylactic treatment before blood products.
Severe combined immunodeficiency
defect in early stem cell differentiation, can be caused by at least 7 different gene defects leading to Adenosine deaminase deficiency Last line is NK cells Presentation triad: I Failure to thrive II chronic diarrhea III recurrent infections: 1 .chronic mucocutaneous candidiasis 2. fatal or recurrent RSV, VZV, measles, flu, parainfluenza 3. pneumocystis jirovecii (PCP), PNA
No thymic shadow on newborn CXR (ddx DiGeorge)
Ataxia telangiectasia
IgA deficiency and T cell deficiency leading to sinus and lung infections
Cerebellar ataxia
Poor smooth pursuit of moving target with eyes
Telangiectasias on face (after 5 yrs age)
Radiation sensitivity (avoid x- rays)
increased risk of lymphoma and acute leukemias
elevated AFP after 8 months of age
Average oge of death is 25yo
ATAXIA: Ataxia Telangiectasia Acute leukemia and lymphoma X- ray sensitivity IgA deficiency AFP
Wiskott Aldrich
WAITER Wiskott Aldrich Immunodeficiency Thrombocytopenia and purpura Eczema (truncal) Recurrent pyogenic infections
X- linked
No IgM against bacterial capsular polysaccharides
Low IgM, high IgA
Hyper IgM syndrome
Increased IgM; other antibody isotypes decreased
The 2 most important variants include AR where there is no CD40 on B cells
More common is the X- linked version where there is no CD40L on the helper T cell
Chronic granulomatous disease
X- linked (65- 70%)
Lack of NADPH oxidase so the phagocytes cannot destroy catalase- positive microbes
Patient is especially susceptible to catalase- positive pathogens, especially
staph aureus and aspergillus infections
Diagnosis is based on negative nitro- blue tetrazolium test (impotent phagocytes)
Treatment: prophylactic TMP- SMX
IFN- gamma is also helpful (mechanism unclear)
Chediak Higashi
phagosome can ingest but can’t transport to lysosome for digestion due to missing LYST gene.
Defective phagocyte lysosomes leads to giant cytoplasmic granules in PMNs
Presentation triad:
- partial albinism
- recurrent respiratory tract and skin infections
- neurologic disorders
HyperIgE syndrome
Job syndrome
Mutation in STAT3 Jak/Stat signaling pathway gene leading to
- impaired PMN recruitment
- impaired Th17 differentiation (mucosal, recruit PMN)
Patient with high levels of IgE and eosinophilia
Presents with eczema
recurrent cold s. aureus abcesses (biblical Job with boils); PMNs can’t be recruited so they stay cold
Coarse facial features: broad nose, prominent forehead, deep- set eyes, and doughy skin
Retains primary teeth resulting in 2 rows of teeth
Leukocyte adhesion deficiency syndrome
abnormal integrins leads to inability of phagocytes to exit circulation
delayed separation of umbilical cord
X- linked immunodeficiencies: WATCH
Wiskott- Aldrich
Agammaglobulinemia (Bruton)
Chronic granulomatous disease
Hyper- IgM syndrome
evidence of asplenia in the blood
thrombocytosis
Howell- Jolly bodies
Target cells
autoabs in type 1 and type 2 autoimmune hepatitis
Type 1:ANA, anti-smooth muscle ab
Type 2: anti- liver- kidney microsomal ab
Anti- liver cytosol ab
