Buzzwords 1 Flashcards
Increased synthesis of disorganized collagen (types 1 and 3)
Keloid formation
Primary pathogenesis
Increased synthesis of parallel (non-disorganized) type 3 collagen
Hypertrophic scar formation
Primary pathogenesis
Deficient AIRE (autoimmune regulator)
Autoimmune polyendocrine syndrome 1
Pathogenesis
Expresses tissue-restricted self-antigens in the thymic medulla for negative selection
AIRE
Normal function
Fas mutation leads to impaired negative selection in the thymic medulla and increased self-reacting lymphocytes
Autoimmune lymphoproliferative syndrome
Pathogenesis
Deficient FOXP3 (normally regulates Tregs)
IPEX
Pathogenesis
Increased risk of severe, recurrent pyogenic sinus and respiratory infections, especially with encapsulated organisms
C1-C4 (early complement) deficiencies
Presentation
Increased susceptibility to recurrent Neisseria bacteremia
C5-C9 (late complement) deficiency
Presentation
Prevents complement activation on self-cells
C1 esterase inhibitor
Function
Hereditary angioedema
C1 esterase inhibitor deficiency
Presentation
Defect in the PIGA gene
CD55 (DAF) deficiency
Pathogenesis
Paroxysmal nocturnal hemoglobinuria
CD55 (DAF) deficiency
Presentation
Most common primary immunodeficiency
Selective IgA deficiency
Superlative
Defect in B-cell DIFFERENTIATION
CVID
Pathogenesis
Defect in B-cell MATURATION
Bruton agammaglobulinemia
Pathogenesis
Recurrent bacterial (especially encapsulated) and enteroviral infections PRESENTING AFTER 6 MONTHS
Bruton agammaglobulinemia
Presentation
Increased susceptibility to Giardia
Selective IgA deficiency
Increase susceptibility to what organism?
Increased risk of AI disease, bronchiectasis, lymphoma, sinopulmonary infections USUALLY PRESENTING AFTER AGE 2
CVID
Presentation
Absent B cells in peripheral blood and absent/scanty lymph nodes and tonsils
Bruton agammaglobulinemia
Key lab finding
Decreased plasma cells
CVID
Key lab finding
Deletion of 22q11 leads to aberrant/failed development of third and fourth pharyngeal pouches -> absent (or hypoplastic) thymus and parathyroid glands
Thymic aplasia (DiGeroge syndrome)
Pathogenesis
Decreased Th1 response due to a specific IL-receptor deficiency
IL-12 receptor deficiency
Pathogenesis
STAT3 mutation -> deficiency of Th17 cells -> impaired recruitment of neutrophils to infection sites
Hyper Ig-E syndrome (Job syndrome)
Pathogenesis
Presents after BCG vaccination
IL-12 receptor deficiency
Presents after what inciting event?
Non-inflammed staphylococcal abscesses
Hyper-IgE (Job syndrome)
Unique presenting symptom
Retained primary teeth
Hyper-IgE (Job syndrome)
Unique presenting symptom
Which immunodeficiency requires lifelong antimycobacterial antibiotics?
IL-12 receptor deficiency
Requires treatment with lifelong ___
Adenosine deaminase deficiency
SCID
Autosomal recessive cause
Defective IL-2R gamma chain
SCID
X-linked recessive cause
Defective ATM gene -> failure to detect DNA damage -> failure to halt cell cycle -> accumulation of mutations
Ataxia-telangiectasia
Pathogenesis
Defect in CD40L on Th cells -> class-switching defect
Hyper-IgM syndrome
Pathogenesis
Mutated WASp gene -> abnormal cytoskeleton function in leukocytes and platelets -> defective antigen presentation
Wiskott-Aldrich syndrome
Pathogenesis
DDx - absent or hypoplastic thymus
DiGeorge syndrome
SCID
(Both present with what symptom?)
Deficient ADA -> increased dATP -> toxic to lymphocytes
ADA deficiency ( autosomal recessive cause of SCID)
Pathogenesis
Cytokines that mediate cachexia secondary to chronic diseases like cancer, AIDS, HF, COPD, etc.
TNF-alpha, IL-1, IL-6, IFN-gamma
Defective LFA-1 integrin (CD18) protein on phagocytes -> impaired phagocyte migration and chemotaxis
Leukocyte adhesion deficiency type 1
Pathogenesis
Decreased Sialyl-Lewis ligands -> impaired margination and rolling of leukocytes
Leukocyte adhesion deficiency type 2
Pathogenesis
Impaired beta-3 integrins on platelets
Leukocyte adhesion deficiency type 3
Pathogenesis
Absent pus
Leukocyte adhesion deficiency type 1
Unique presenting symptom
Which type of leukocyte adhesion deficiency does not present with delayed separation of the umbilical cord?
Leukocyte adhesion deficiency type 2; milder, less severe and fewer infections
Increased neutrophils in the blood + absence of neutrophils at infection sites
Leukocyte adhesion deficiency type 1
Key lab finding
Defective LYST gene -> microtubule dysfunction in neutrophil phagosome-lysosome fusion
Chediak-Higashi syndrome
Pathogenesis
Giant granules in granulocytes and platelets (blood smear)
Chediak-Higashi syndrome
Blood smear finding
Partial oculocutaneous albinism
Chediak-Higashi syndrome
Unique presenting symptom
Defective NADPH oxidase -> decreased generation of ROS in phagolyosomes -> decreased respiratory burst in neutrophils -> decreased intracellular killing
Chronic granulomatous disease
Pathogenesis
Abnormal dihydrorhodamine test (decreased green fluorescence)
Chronic granulomatous disease
(Diagnostic test)
*This test measures neutrophil superoxide production
Ataxia, telangiectasia (spider angioma), IgA deficiency
Ataxia-telangiectasia
Triad
Thrombocytopenia, eczema, recurrent pyogenic infections that WORSEN WITH AGE
Wiskott-Aldrich syndrome
Presenting symptoms
NO T-cells on flow cytometry
SCID
Key lab finding
Increased AFP (+ decreased IgA, IgE, IgG)
Ataxia-telangiectasis
Key lab finding
Increased (or normal) IgM (+very decreased IgA, IgE, IgG)
Hyper-IgM syndrome
Key lab finding
Increased IgA, IgE (+normal or decreased IgG, IgM)
Wiskott-Aldrich syndrome
Decreased T-cell receptor excision circles (TRECs)
SCID
Key lab finding
Curative treatment for SCID?
Bone marrow transplant
Curative treatment for which immunodeficiency?
Recurrent bacterial and fungal infections of the lungs, skin, lymph nodes, and liver, especially with CATALASE POSITIVE ORGANISMS
Chronic granulomatous disease
Presentation
SEVERE recurrent infections with bacteria, fungi, viruses, protozoa; chronic diarrhea, thrush, and failure to thrive
SCID
Presentation
Severe recurrent pyogenic sinopulmonary and GI infections “early,” including OPPORTUNISTIC INFECTIONS WITH PJP, CRYPTOSPORIDIUM, AND CMV
Hyper-IgM syndrome
Presentation
Which 2 immunodeficiencies involve recurrent bacterial infections with encapsulated bacteria?
C1-C4 complement deficiency (pyogenic sinopulmonary)
Bruton agammaglobulinemia (also see enterovirus recurrence)
(Shared feature?)
Recurrent disseminated mycobacterial infection (and fungal infection)?
IL-12 receptor deficiency
Presentation
Recurrent skin and mucous membrane infection with Candida albicans
Chronic mucocutaneous candidiasis
(Presentation)
Remember, this is a T-cell deficiency
T-cells are affected in which 2 immunodeficiencies? What happens to them?
DiGeorge syndrome - decrease in mature T cells
SCID - absent T cells
B-cells are affected in which 2 immunodeficiencies? What happens to them?
Bruton - no B cells in the periphery
CVID - decreased plasma cells
Which two immunodeficiencies involve a decrease in IFN-gamma?
IL-12 receptor deficiency
Hyper-IgE syndrome (also has increased IgE and eosinophils)
(Shared feature?)
DDx - absent germinal centers in lymph nodes (3)
SCID
Bruton agammaglobulinemia
Hyper IgM syndrome
(Shared feature?)
Chediak-Higashi syndrome is most commonly diagnosed in ___.
Childhood
Which immunodeficiency is most commonly diagnosed in childhood?
Avoid live vaccination in these two immunodeficiencies
Bruton
SCID
(Shared feature?)
Lymph node cluster draining the head and neck?
Cervical
Drains?
Lymph node cluster draining the dorsolateral foot and posterior calf?
Popliteal
Drains?
Lymph node cluster draining the trachea and esophagus?
Mediastinal
Drains?
Lymph node cluster draining the anal canal below the pectinate line, skin below the umbilicus except the popliteal area, scrotum, and vulva
Superficial inguinal
Drains?
Lymph node cluster draining the lungs
Hilar
Drains?
Lymph node cluster draining the lower rectum to the anal canal above the pectinate line, bladder, middle 1/3 of vagina, cervix, prostate
Internal iliac
Drains?
Lymph node cluster draining the upper limb, breast, skin above the umbilicus?
Axillary
Drains?
Lymph node cluster draining the testes, ovaries, kidneys, uterus?
Para-aortic
Drains?
Lymph node cluster draining the liver, spleen, pancreas, stomach, upper duodenum?
Celiac
Drains?
Lymph node cluster draining the lower duodenum, jejunum, ileum, colon to the splenic flexure?
Superior mesenteric
Drains?
Lymph node cluster draining the colon from the splenic flexure to the upper rectum?
Inferior mesenteric
Drains?
What lymph node cluster is a primary lung cancer associated with?
Primary lung cancer
Which two lymph node clusters are associated with granulomatous disease?
Mediastinal and hilar
What lymph node cluster drains the skin above the umbilicus? Below the umbilicus?
Above - axillary
Below - superficial inguinal (except the popliteal area)
Track drainage to lymph node clusters through the GI tract, beginning with the esophagus.
Esophagus - Mediastinal
Stomach - Celiac
Small intestine - Celiac (upper duodenum), Superior mesenteric (lower duodenum through the ileum)
Large intestine - Superior mesenteric (colon to the splenic flexure), Inferior mesenteric (colon from the splenic flexure to the upper rectum)
Rectum - Inferior mesenteric (upper), Internal iliac (lower rectum to the anal canal, aka above the pectinate line), Superficial inguinal (anal canal below the pectinate line)
Which lymph node cluster drains the gonads?
Para-aortic (testes, ovaries, uterus)
Compare the superficial and deep lymphatic drainage of the lower extremities.
Superficial - follow venous system, drain directly to the superficial inguinal nodes via long saphenous vein (medial extremities)
Deep - follow arterial system, drain into popliteal, then inguinal nodes (lateral extremities)
Explain lymph node drainage of the reproductive organs.
Para-aortic - testes, ovaries, uterus
Internal iliac - vagina (middle 1/3), cervix, prostate
Superficial inguinal - scrotum, vulva
Deep inguinal - glans penis, penile urethra
Remove encapsulated bacteria
Splenic macrophages
Unique role
Which cell does not express MHC I?
RBCs
Structure of MHC I?
1 long chain (A1, A2, A3)
1 short chain (B2)
Structure of MHC II?
2 equal chains (A1, A2, B1, B2)
HLA-A3? (1)
Hemochromatosis
HLA subtype
HLA-B8 (3?)
Addison disease
Myasthenia gravis
Graves disease
(HLA subtype)
Mnemonic for HLA-B8?
Don’t B late(8), Dr. ADDISON, or else you’ll send MY patient to the GRAVE
(Addison disease, Myasthenia gravis, Graves disease)
HLA-B27?
Psoriatic arthritis
Ankylosing spondylitis
IBD-associated arthritis
Reactive arthritis
(HLA subtype)
HLA-DQ2/DQ8?
Celiac disease
HLA subtype
HLA-DR2?
MS, Hay fever, SLE, Goodpasture syndrome
HLA-DR3?
DM1, SLE, Graves disease, Hashimoto thyroiditis, Addison disease
(HLA subtype?)
HLA-DR4?
RA, DM1, Addison disease
HLA subtype?
HLA-DR5?
Hashimoto thyroiditis
HLA subtype?
Addison disease - HLA subtypes
B8, DR3, DR4
Graves disease - HLA subtypes
B8, DR3
SLE - HLA subtypes
DR2, DR3
Hashimoto thyroiditis - HLA subtypes
DR3, 5
“Hashimoto is an ODD DoctoR”
DM1 - HLA subtypes?
DR3, 4
What activates an NK cell to kill? (3 major things)
- Non-specific activation signal on target
- ABSENCE of MHC 1 on target
- CD16 (on NK) binds Fc region of bound Ig
Enteropathy, endocrinopathy, nail dystrophy, dermatitis, other AI dermatologic conditions
IPEX
General symptoms
Associated with DM in male infants
IPEX
2 cell signals required for T-cell activation?
- MHC II (w/Ag) + TCR (CD4) or MHC I (w/Ag) + TCR (CD8)
2. Costimulatory B7 protein (CD80/86) + CD28 (T cell)
2 cell signals required for B-cell activation?
- TCR (activated Th cell) + MHC II (w/Ag)
2. CD40L (Th cell) + CD40 (B cell)
Ab in breast millk?
IgA
Role of C3b?
Opsonization (also IgG)
Roles of C3a, C4a, C5a?
Anaphylaxis
Roles of C5b-9?
Cytolysis by MAC
Fever and sepsis?
IL-1, IL-6, TNF-alpha
Maintains granulomas in TB?
TNF-alpha
Cause of green sputum?
Myeloperoxidase (blue-green heme-containing pigment)
NK cells:
Activated by?
Secrete?
Activated by IL2, IL12, IFN-alpha, IFN-beta
Secrete IFN-gamma
Th1 cells:
Activated by?
Inhibited by?
Secrete?
Activated by IL-12, IFN-gamma
Inhibited by IL-4, IL-10
Secrete IFN-gamma
Th2 cells:
Activated by?
Inhibited by?
Secrete?
Activated by IL-2, IL-4
Inhibited by IFN-gamma
Secreted IL-4, 5, 6, 10, 13
Th17 cells:
Activated by?
Inhibited by?
Secrete?
Activated by IL1, IL-6, TGF-beta
Inhibited by: IL-4, IFN-gamma
Secrete IL-17, IL-21, IL-22
Treg cells:
Activated by?
Inhibited by?
Secrete?
Activated by IL-2, TGF-beta
Inhibited by IL-6
Secrete IL-10, IL-35, TGF-beta
Macrophages secrete?
IL-1, IL-6, IL-8, IL-12, INF-alpha
What do all T-cells secrete?
IL-2, IL3
Purpose of IL-17, 21, 22?
Activate neutrophils to attack extracellular microbes
Stimulates production of acute phase proteins
IL-6
Stimualtes vascular leak?
TNF-alpha
Class switching to IgG and IgE?
IL-4
Class switching to IgA?
IL-5
CD25?
Treg
CD19, CD20, CD21, CD40?
B cells
Macrophage CDs?
CD14 (PAMP receptor), CD40, CCR5, MHC II, B7 (CD 80/86), Fc and C3b receptors
NK cell CDs?
CD16, CD56
Hematopoietic stem cells CD?
CD34
Passive vs. active - anti-toxin vs. toxoid?
Passive - anti-toxin
Active - toxoid
When are patients given preformed antibodies (passive)?
After exposure to Tetanus toxin, Botulinum toxin, HBV, Varicella, Rabies virus, or diphtheria toxin
“To Be Healed Very Rapidly or Die”
When are patients given combined passive and active immunization?
Hepatits B and Rabies
2 toxoid vaccines?
C. tetani
C. diphtheriae
Ab-mediated HSN rxns? Which Ab?
I - IgE
II - IgG/IgM
III - Ag-Ab complexes (mostly IgG)
Complement-mediated HSN rxns?
II, III
Which hypersensitivity reactions involve neutrophils?
II, III
Which hypersensitivity reaction involves T cells?
IV
Which hypersensitivity reactions involve macrophages?
II, IV
