TABLE OF CONTENTS
Immunology
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
Lymphoid Tissue
Innate vs Adaptive Immunity
Inflammatory Response
Cytokines
T-cells
B-cells
Antibodies
Complement
Vaccinations
Immunodeficiency Syndromes
Hypersensitivities
12.
13.
Blood Transfusion Reactions
Transplant Rejection
OUTLINE
1.
Immunology:
Lymphoid Tissue
Overview
●
A. Types of Lymphoid Tissue
2. Primary Lymphoid Organs
●
A. Bone Marrow
●
B. Thymus
3. Secondary Lymphoid Organs
●
A. Spleen
●
B. Lymph Node
●
C. Peyer’s Patches
●
D. Tonsils
Immunology: Lymphoid Tissue
•
•
Primary
•
Types: Bone marrow, Thymus
•
Lymphocyte formation and development
Secondary
•
Types: Spleen, Lymph node, Peyer’s patches, Tonsils
•
Lymphocyte activation and proliferation
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Immunology: Lymphoid Tissue
•
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Bone Marrow:
•
Hematopoietic stem cells à Lymphoid lineage à B-cells, T-cells, NK cells
•
B-cell proliferation and maturation
GMCSF
IL-7
IL-3
HSC
Lymphoid
B-cells
T-cells
Mature in bone
marrow
Mature in
thymus
Myeloid
NK cells
Erythrocytes
Platelets
Dendritic cells
Macrophages,
Monocytes
Eosinophils
Basophils
Mast cells
Immunology: Lymphoid Tissue
•
Thymus:
•
Derived from 3rd pharyngeal pouch
•
Encapsulated
•
T-cell maturation
•
Cortex: Darker staining (↑ lymphocytes)
•
Medulla: Lighter staining
•
Hassal corpuscles (medulla)
•
DiGeorge Syndrome, SCIDà Thymic aplasia
•
Myasthenia Gravis à Thymoma
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Immunology: Lymphoid Tissue
•
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Spleen:
•
White pulp à Follicles à B-cells
•
White pulp à Periarteriolar lymphatic sheaths à T-cells
•
Marginal zone à Phagocytic cells, antigen presentation from blood
•
•
•
•
•
•
•
•
Red pulp à Arterioles, Sinusoids, Phagocytic cells
Age-dependent RBC removal by macrophages
Asplenia à ↑ Risk of infection w/ encapsulated bacteria à Vaccinate
Trauma à Rupture
Hereditary spherocytosis à Splenectomy
Sickle Cell Disease à Functional asplenia
IgM production
Platelet storage
Big 3 Encapsulated Bacteria
Streptococcus Pneumoniae
Haemophiles influenza type b
Neisseria meningitidis
Immunology: Lymphoid Tissue
•
Lymph Nodes:
•
Cortex à Follicles à B-cells
•
Primary follicles = Dense and dormant
•
Secondary follicles = Activation, isotype switching, ↑ Infection, ↓ X-linked agammaglobulinemia, ↓ SCID
•
•
•
Paracortex à T-cells
High endothelial venules à Lymphocytes enter
↑ Viral and fungal infection, ↓ DiGeorge Syndrome
•
•
Medulla à Plasma cells, lymphocytes, macrophages
Sinuses à Drain lymph out, macrophages
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Immunology: Lymphoid Tissue
•
•
Peyer’s Patches
•
Ileum
•
M-cells à Antigen transport to macrophages
•
B-cells à Identify antigens à Plasma cells à IgA
Tonsils
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Item 1 of 13
Question ID: 0058
Test Your Knowledge
Difficulty Rating: ✪✪
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A 22-day old male with an uncomplicated prenatal history presents to the emergency department with recent seizure activity and failure to
thrive. Vital signs reveal a temperature of 38.3 ℃ (101℉), respiratory rate of 72 breaths/min, and a heart rate of 164 beats/min. Physical
examination reveals a harsh systolic ejection murmur at the left upper sternal border with a single S2. Initial labs are significant for severe
hypocalcemia. Calcium supplementation and broad-spectrum antibiotics are initiated. Chest X-ray reveals cardiomegaly and an absence of a
thymic shadow.
Tracheal aspirate cultures later grow Enterobacter cloacae. Over the following days, the infant develops pancytopenia and multiorgan failure
with disseminated intravascular coagulation. Despite numerous attempts at medical intervention, the infant would later expire. Biopsies are
obtained and reviewed. Mediastinal soft tissue biopsies fail to reveal significant parathyroid and thymic tissues. Lymph node specimens are
most likely to reveal which of the following findings?
⚪ A. Centrilobular necrosis and massive sinusoidal congestion
⚪ B. Underdevelopment of primary and secondary follicles
⚪ C. Paracortical atrophy
⚪ D. Reactive paracortical hyperplasia
⚪ E. Adipose tissue infiltration and hypocellularity
OUTLINE
1.
Immunology:
Innate vs Adaptive
Immunity
Innate Immunity
●
A. General Characteristics
●
B. Innate Response
●
C. Primary Function
●
D. Genetic Considerations
2. Adaptive Immunity
●
A. General Characteristics
●
B. Adaptive Response
●
C. Primary Function
●
D. Genetic Considerations
3. Antigen Presentation
●
A. Antigen Presenting Cells
●
B. Dendritic Cell à Antigen Presentation
●
C. B-cell à Antigen Presentation
Immunology: Innate vs Adaptive Immunity
•
•
•
•
General Characteristics:
•
Nonspecific
•
Speed: Rapid
•
Future Response: Equal to initial
•
Memory: None
•
Antigen ID: Toll-like receptors (TLRs) ß à PAMPs à ↑ NF-kB
•
IgM, Complement, lysozyme, lactoferrin, respiratory burst (superoxide radicals, hydrogen peroxide)
Innate Response:
•
Bone marrow à ↑ Neutrophils and other PMNs
•
Neutrophils à General response, phagocytosis, oxidative burst
•
Eosinophil à Parasitic infection, phagocytosis
•
Basophil à Parasitic infection, allergic reaction
•
Mast cells à Allergic reaction
•
Monocytes à Macrophages à Phagocytosis, antigen presentation
•
Monocytes à Dendritic cells à Phagocytosis, antigen presentation
•
Natural killer cells
Primary Function:
•
Rapid recognition and resolution of new infectious agent
•
Effective vs fungi and parasites
Genetic Considerations:
•
Germline encoded
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Immunology: Innate vs Adaptive Immunity
•
•
•
•
General Characteristics:
•
Specific
•
Speed: Slow
•
Future Response: Heightened
•
Memory: Present after exposure
•
Antigen ID: Previous epitope exposure
•
IgM à IgA, IgG, IgE
Adaptive Response:
•
T-cells à CD8+, CD4+
•
B-cellsà Plasma cells, immunoglobulins
Primary Function:
•
Rapid recognition and resolution of previously encounter infectious agent
•
Effective vs robust or frequently encountered pathogens
Genetic Considerations:
•
VDJ recombination, hypervariation
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Immunology: Innate vs Adaptive Immunity
•
•
•
Antigen Presenting Cells (APCs)
•
Dendritic cells
•
Macrophages
•
Monocytes
•
B-cells
Dendritic Cell à Antigen Presentation:
•
Dendritic cell phagocytosis of pathogen
•
Protein components loaded onto major histocompatibility complex (MHC) receptor I or II
•
Antigen presentation to naïve T-cell with matching T-cell receptor (TCR)
•
T-cell is activated à Cell-mediated Immunity
•
CD4+ TCR binds to MHC II à Cytokine release
•
CD8+ TCR binds to MHC I à Destroys APC
B-cell à Antigen Presentation:
•
B-cell phagocytosis of pathogen
•
Protein components loaded onto major histocompatibility complex (MHC) receptor II
•
Antigen presentation to naïve T-cell in with matching T-cell receptor (TCR)
•
B-cell à Class switching à Plasma cell à Humoral Immunity
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Item 2 of 13
Question ID: 0059
Test Your Knowledge
Difficulty Rating: ✪✪✪
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A researcher is studying the relationship between pattern recognition receptors (PRR) present within host cells and Crohn’s disease. The
PRR, nucleotide-binding oligomerization domain protein 2 (NOD2) has been shown to detect conserved motifs in bacterial peptidoglycans
such as the intracellular muramyl dipeptide and promote activation of host proinflammatory pathways. NOD2 has been known to be highly
expressed in Paneth cells of the small intestine. The researcher attempts to induce mutations to further elucidate the effects of ileal
inflammation on NOD2-deficient mice.
Based on the information above, which of the following would most likely be impaired in NOD2-deficient mice?
⚪ A. NF-κB activity
⚪ B. B7 protein binding to CD28
⚪ C. CD40 membrane receptor activity
⚪ D. Alterations within the heavy chain constant domain of immunoglobulins
⚪ E. Terminal deoxynucleotidyl transferase activity
OUTLINE
1.
Immunology:
Inflammation
Acute Inflammatory Response
●
A. Toll-Like Receptors
●
B. Arachidonic Acid
●
C. Bradykinin, Hageman Factor XII
●
D. Inflammatory Cytokines
●
E. Damaged Endothelial Cells
2. Neutrophil Migration
●
A. Margination
●
B. Rolling
●
C. Tight Adhesion
●
D. Transmigration
3. Disorders of Leukocyte Migration
●
A. Leukocyte Adhesion Deficiency
●
B. Chediak-Higashi Syndrome
4. Chronic Inflammatory Response
●
A. Chronic Inflammation
●
B. Granulomas
Immunology: Inflammation
•
•
•
•
•
•
Toll-Like Receptors (TLRs):
•
PRRs recognize PAMPs and DAMPs à Triggers inflammatory response
•
Ex. TLR4 à LPS
•
Co-receptor for TLR4: CD14
•
Expressed in phagocytes of innate immune system
•
NF-kB nuclear translocation
Arachidonic Acid:
•
Lipooxygenase pathway à Leukotrienes à LTB4 à ↑ Neutrophil chemotaxis
•
Cyclooxygenase pathway à ↑ Prostaglandins à ↑ TXA2
Complement:
•
C3a, C4a à ↑ Histamine release from mast cells à ↑ Vasodilation
•
C3b à Opsonization
•
C5a à ↑ Neutrophil chemotaxis and ↑ Histamine release from mast cells à ↑ Vasodilation
•
C5b-9 Membrane Attack Complex à Pathogen cell lysis
Bradykinin, Hageman Factor XII:
•
↑ Vasodilation
•
↑ Vascular permeability
•
↑ Pain sensitivity
Inflammatory Cytokines:
•
IL-1, TNF-⍺, IL-6 à Acute Inflammatory process
•
IL-8 à ↑ Neutrophil chemotaxis, ongoing inflammation
•
IL-1, TNF à ↑ T setpoint, ↑ E-selectin, ICAM-1 on endothelium
Damaged Endothelial Cells:
•
↑ Nitric oxide à ↑ Vasodilation
•
↑ Adhesion proteins à ↑ Neutrophil extravasation
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Immunology: Inflammation
•
•
•
•
Margination:
•
↑ Vascular permeability à Hemoconcentration à ↑ Neutrophil contact with endothelium
Rolling:
•
Neutrophil: Sialyl LewisX
•
Endothelium: E-selectin, P-selectin
Tight Adhesion:
•
Neutrophil: LFA-1 (CD11a/CD18), Mac1 (CD11b/CD18)
•
Endothelium: ICAM-1 (CD54)
Transmigration:
•
Neutrophil: PECAM-1 (CD31)
•
Endothelium: PECAM-1 (CD31)
•
Driven by chemotaxis (LTB4, IL-8, C5a)
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Immunology: Inflammation
•
•
Leukocyte Adhesion Deficiency:
•
LAD type 1: Absence of LFA-1 (CD18) (or Mac-1 on macrophages)
•
Unable to have tight adhesion
•
Presentation: Recurrent infections with absence of pus
•
Impaired wound healing
•
Umbilical cord delayed detachment
Chediak-Higashi Syndrome:
•
Impaired microtubule polymerization à ↓ Neutrophil chemotaxis
•
Lysosomal dysfunction à Enlarged vesicles, non-functioning lysosomes
•
Autosomal recessive, LYST gene defect
•
Presentation: Recurrent infections, partial albinism, peripheral neuropathy
•
Giant cytoplasmic granules
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Immunology: Inflammation
•
•
Chronic Inflammation:
•
Fibrosis, Angiogenesis
•
Tuberculosis classic
•
IFN-ɣ: Secreted by Th1 cells, activates macrophages to ↑ inflammatory response
•
IL-4, IL-13: Secreted by Th2 cells, activate macrophages to ↓ inflammatory response
•
FGF, VEGF: ↑ Angiogenesis
•
TGF-β: ↑ Angiogenesis, Fibrosis
•
PDGF: ↑ Fibroblast collagen synthesis
Granulomas:
•
APC à Th cells (CD4+) + IL-12 à Th1 cells
•
Th1 cells à IFN-ɣ, TNF-⍺ à Macrophage activation
•
Macrophages à TNF-⍺
•
Granuloma maintained by IL-12 and TNF-⍺
•
Multinucleated giant cells, fibroblasts, lymphocytes, epithelioid cells
•
Caseating: Central necrotic core (TB, fungal infections)
•
Non-caseating: Absence of necrotic core (Sarcoidosis, Beryllium)
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Item 3 of 13
Question ID: 0060
Test Your Knowledge
Difficulty Rating: ✪✪
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A 1-month-old male presents with family to a pediatric ward in rural Chile for irritability. Physical examination reveals tenderness and
erythema at the umbilical stump with serosanguinous drainage. Notably, the umbilical cord remains attached from birth. Induration is also
noted along the surrounding tissues. Otoscopic examination demonstrates a bulging right tympanic membrane with opacification and a loss
of light reflex. Initial laboratory evaluation is shown below.
Hemoglobin: 16.5 g/dL
Leukocyte count: 45,500/mm3
Platelet count: 185,000/mm3
C-reactive protein: Elevated
Nitroblue tetrazolium dye reduction test: Positive
Which of the following are most likely linked to the underlying condition in this infant?
⚪ A. LYST gene defect
⚪ B. Impaired microtubule polymerization
⚪ C. Impaired superoxide production
⚪ D. Absence of CD18 (LFA-1)
⚪ E. HAX1 gene defect
OUTLINE
1.
Immunology:
Cytokines
Proinflammatory Cytokines
●
A. Acute Inflammatory Response
●
B. Proliferative Response
●
C. Th1 Response
2. Additional Cytokines
●
A. Th2 Response
●
B. Class Switching Cytokines
●
C. Allergic and Parasitic Response
●
D. Treg and Th17 Response
Immunology: Cytokines
•
•
•
Acute Inflammatory Response:
•
PRRs à PAMPs, DAMPs
•
↑ NF-kB
•
Initial Response: IL-1, IL-6, TNF à Acute reactants
•
↑ Expression of endothelial adhesion molecules
•
Neutrophil Chemotaxis à IL-8, LTB4, C5a
Proliferative Response:
•
IL-2 à ↑ Proliferation of immune cells
•
Ag binds to TCR à IL-2 à Autocrine action
•
IL-3 à ↑ Hematopoiesis
Th1 Response:
•
Th1 response à Cell-mediated response
•
Macrophage à Th1 stimulation via IL-12
•
Th1 cells à Macrophage stimulation via IFN-ɣ
•
IFN-⍺, IFN-β à Released from virally infected cells
•
IFN-ɣ à Activation of macrophages and CD8+ Tcells
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Immunology: Cytokines
•
•
•
•
Th2 Response:
•
Th2 response à Humoral-mediated
•
IL4, IL-5, IL-10, IL-13
•
Secreted by Th2 cells, Treg cells, and macrophages
Class Switching Cytokines:
•
IL-4 à Th2 à ↑ IgE, IgG
•
IL-5 à ↑ IgA, Eosinophils
•
IL-13 à ↑ IgE
Allergic and Parasitic Response:
•
IL-4, IL-5, IL-10, IL-13, IL-17
•
Eosinophils, Basophils, Mast cells
Treg, Th17 Response:
•
TGF-β, IL-10 à Treg à Prevent autoimmunity à ↓ Immune response
•
TGF-β à Th17 à IL-17 à ↑ Neutrophil function
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Item 4 of 13
Question ID: 0061
Test Your Knowledge
Difficulty Rating: ✪✪
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A 74-year-old female presents to the emergency department with acute onset diplopia and severe unilateral right-sided headache. Her past
medical history is significant for hypertension, hyperlipidemia, and osteopenia. The patient reports that she has had 10 lbs (4.5 kg) of weight
loss over the past 3 months and has also had increased fatigue and symmetric bilateral shoulder, hip, and neck pain that is worse in the
evening. Physical examination demonstrates right temporal artery distention and tenderness to touch over the right temporal region.
Laboratory evaluation reveals a significantly elevated erythrocyte sedimentation rate. Intravenous methylprednisolone is administered, and
her symptoms improve.
Two weeks later the patient returns to the emergency department reporting worsening jaw claudication and visual loss in the right eye.
Funduscopic examination is shown in the image below. Urgent treatment with intravenous tocilizumab and methylprednisolone is initiated.
Based on the vignette, which of the following are most likely inhibited by the pharmacologic management utilized in the treatment of this
patient?
⚪ A. Interleukin-6
⚪ B. Interleukin-10
⚪ C. Receptor activator of nuclear factor κB ligand
⚪ D. Transforming growth factor-β
⚪ E. ⍺4 integrin
OUTLINE
1.
Immunology:
T-cells
T-cell Development
●
A. Lymphoid Progenitor Cells
●
B. Precursor T-cell
●
C. Naïve T-cell Pre-selection
●
D. Positive Selection
●
E. Negative Selection
●
F. Naïve T-cell Post-selection
2. Major Histocompatibility Complex
●
A. MHC Class I
●
B. MHC Class II
3. T-cell Activation
●
A. Cytotoxic T-cell Activation
●
B. Helper T-cell Activation
●
C. Th1 Activation
●
D. Th2 Activation
●
E. Regulatory T-cell Activation
Immunology: T-cells
•
•
•
•
•
•
Lymphoid Progenitor Cells:
•
Originate from the bone marrow
Precursor T-cell:
•
Leave bone marrow à Thymus
•
CD4-/CD8Naïve T-cell Pre-selection:
•
TCR created using RAG1 and RAG2
•
CD4+/CD8+
Positive Selection:
•
CD8+ binds with MHC I
•
CD4+ binds with MHC II
•
If binding is not adequate, naïve T-cell à Apoptosis
Negative Selection:
•
Self-antigens presented on MHC I and MHC II receptors
•
If strong binding to self-peptides, naïve T-cell à Apoptosis
•
Exception: T-regulatory cells (small percentage)
•
AIRE protein (Autoimmune regulator protein)
Naïve T-cell Post-selection (Immunocompetent):
•
CD4+/CD8-, TCR à T-helper cell
•
CD4-/CD8+, TCR à Cytotoxic T-cell
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Immunology: T-cells
•
MHC Class I:
•
Most nucleated cells
•
Allows recognition of healthy vs infected cells
•
HLA-A, HLA-B, HLA-C
•
Receptor contains β2-microglobulin
•
MHC I antigen complex developed in RER
•
Intracellular pathogens à CD8+ T-cells à Cell-mediated
•
Absence of MHC I à NK cell-mediated destruction
•
Upregulated by IFN-⍺, IFN-β
2
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•
MHC Class II:
•
Antigen presenting cells
•
HLA-DP, HLA-DQ, HLA-DR
•
Receptor has chains of equal length
•
Invariant chain prevents premature antigen binding
•
Extracellular pathogens à CD4+ T-cells à Humoral
Immunology: T-cells
•
Cytotoxic T-cell Activation:
•
Nucleated cell presents Ag (endogenous) via MHC I
•
CD8+ T-cells bind to MHC I on nucleated cell
•
Effective vs intracellular pathogens
•
Perforin, granzyme B released by CD8+ T-cell
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•
•
•
•
Regulatory T-cell Activation:
•
CD4+, CD25+, FOXP3+
•
Protective vs self-antigens
•
Prevent autoimmunity
•
Stimulated by TGF-β, inhibited by IL-6
•
Release TGF-β and IL-10 à ↓ Immune response
Helper T-cell Activation:
•
APC presents Ag via MHC II
•
CD4+ T-cells bind to MHC II on APC
•
B7-CD28 co-stimulatory signal
Th1 Activation:
•
Effective vs intracellular pathogens
•
APC stimulates Th1 response via IL-12
•
Th1 cells à IFN-ɣ, IL-2, TNF
•
Granuloma formation
Th2 Activation:
•
Effective vs extracellular pathogens
•
APC stimulates Th2 response via IL-4
•
Th2 cells à IL-4, IL-5, IL-13
≣
Item 5 of 13
Question ID: 0062
Test Your Knowledge
Difficulty Rating: ✪✪
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A 10-month-old female presents with family to her pediatrician with a 4-day history of irritability and decreased appetite. Her mother reports
that her symptoms were accompanied by a fever that resolved yesterday. Shortly after the fever subsided, a generalized erythematous rash
on the trunk was noted by family. Since that time, the rash has spread to the face, neck, and lower extremities. Immunizations are current
and the family denies any recent illnesses or sick contacts. On examination the infant is well appearing with stable vital signs and a blanching
maculopapular rash extending from the trunk to the bilateral lower extremities.
CD56 positive lymphocytes in this patient most likely target infected cells through which process?
⚪ A. Interleukin-5 release
⚪ B. Interleukin-10 release
⚪ C. Absence of MHC I receptor
⚪ D. Presence of MHC II receptor
⚪ E. IL-4 release
OUTLINE
1.
Immunology:
B-cells
B-cell Overview
●
A. Lymphoid Progenitor Cells
●
B. Precursor B-cell
●
C. Naïve Mature B-cell
●
D. Proliferation
●
E. Plasma Cell
2. B-cell Activation
●
A. Th-Dependent
●
B. Th-Independent
●
C. Affinity Maturation
●
D. Isotype Switching
Immunology: B-cells
•
•
•
•
•
Lymphoid Progenitor Cells:
•
Originate from the bone marrow
Precursor B-cell:
•
Stay in bone marrow to mature
Naïve Mature B-cell:
•
BCR: Membrane-bound IgM and IgD
•
BCR generated from somatic recombination
•
CD19, CD20, CD21
•
MHC II receptor
Proliferation:
•
Lymphoid follicles à Germinal centers
Plasma Cell:
•
Produce and secrete antibodies
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Immunology: B-cells
•
•
•
•
Th-Dependent:
•
Peptide Ag
•
T-cell activation via APC
•
Naïve B-cell binds Ag to BCR
•
B-cell receptor-mediated endocytosis of Ag
•
Ag displayed on B-cell MHC II
•
Activated Th-cell binds to B-cell
•
CD40L-CD40 co-signal à Isotype class switching
•
B-cell becomes activated à Proliferation à Plasma cell
Th-Independent:
•
Non-peptide conserved Ag
•
Ex: Flagellin, LPS
•
Cross-linking of surface IgG (BCR)
•
Leads to production of IgM
Affinity Maturation:
•
B-cell à Lymph node à Secondary follicles
•
Proliferation in germinal centers
•
Random mutations of BCR à strongest affinity survives
Isotype Switching:
•
B-cell à Lymph node à Secondary follicles
•
IL-4 à IgE, IgG
•
IL-5 à IgA
•
IL-13 à IgE
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Item 6 of 13
Question ID: 0063
Test Your Knowledge
Difficulty Rating: ✪✪✪
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A 32-year-old male with a past medical history of microscopic polyangiitis and end-stage renal disease presents to the emergency
department with a fever of 39.1 ℃ (102.4℉), abdominal pain, and general malaise over the past 6 hours. The patient states that he is on
home peritoneal dialysis and recently had his catheter replaced 5 days earlier without complication. Tenderness is noted over the abdomen
at the peritoneal catheter insertion site. The patient states his recently adopted dog playfully bit the insertion site of the dialysis tubing
causing a small puncture in the material just prior to symptom onset. Relevant laboratory studies are shown below. Intravenous antibiotics
are initiated. Blood cultures later grow Pasteurella multocida.
Hemoglobin: 11.1 g/dL
Leukocyte count: 3,200/mm3
Immunoglobulin M: 922 mg/dL (reference range: 40-345 mg/dL)
Immunoglobulin A: 88 mg/dL (reference range: 76-390 mg/dL)
Immunoglobulin G: 770 mg/dL (reference range: 650-1,500 mg/dL)
B-cells producing high quantities of immunoglobulin M in this patient are most likely responding to which antigen?
⚪ A. Lipoteichoic acid
⚪ B. Lipopolysaccharide
⚪ C. Exogenous bacterial peptide
⚪ D. Endogenous bacterial peptide
⚪ E. Host peptide
OUTLINE
1.
Immunology:
Antibodies
Antibody Structure
●
A. Fc Region
●
B. Fab Region
2. Antibody Properties
●
A. V(D)J Recombination
●
B. Somatic Hypermutation
●
C. Affinity Maturation
●
D. Isotype Switching
●
E. Primary Response
●
F. Secondary Response
3. Immunoglobulin Isotypes
●
A. IgM
●
B. IgG
●
C. IgA
●
D. IgE
●
E. IgD
Immunology: Antibodies
•
•
Fc Region:
•
Consists of CH
•
Determines isotype
•
C-terminus
•
Site of complement binding (IgM, IgG)
•
Site of binding to phagocytes à Opsonization
•
Carbohydrate side chains
Fab Region:
•
Consists of CL, VL, and VH
•
Determines idiotype
•
Binds antigens via epitope
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Immunology: Antibodies
•
•
•
•
•
V(D)J Recombination:
•
Heavy chain à VDJ
•
Light chain à VJ
•
Random recombination of genes à Fab
Somatic Hypermutation à Affinity Maturation:
•
Random variations of the variable region
•
Activated B-cell à Lymph node à Secondary follicles
•
Proliferation of B-cell in germinal centers
•
Random mutations of BCR à Strongest affinity survives
Isotype Switching:
•
Activated B-cell à Lymph node à Secondary follicles
•
Changes occur in CH domain (Fc)
•
CD40-CD40L (B-cell – T-cell)
•
IL-4 à IgE, IgG
•
IL-5 à IgA
•
IL-13 à IgE
Primary Response:
•
IgM initially released
Secondary Response:
•
Significantly larger IgG response
•
IgM response is relatively unchanged
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Immunology: Antibodies
•
•
•
•
•
IgM:
•
•
•
•
•
•
IgG:
•
•
•
•
•
•
•
•
IgA:
•
•
•
•
IgE:
•
•
•
•
IgD:
•
Pentamer or monomer
Pentamer linked by J-chain
Early response to infection (vs IgG)
Similar response on repeated exposure (vs IgG)
Activate complement
Acts as a BCR
Most abundant immunoglobulin in blood
Monomer
Delayed response to infection (vs IgM)
↑↑ response on repeated exposure (vs IgM)
Activate complement
Opsonization
Acts as a BCR
Passive immunity to fetus (from mother) via placenta
Located primarily in MALT, breastmilk, sweat, saliva
Monomer (circulation) à Dimer
Dimer linked by J-chain
Passive immunity to infant (from mother) via breastmilk
Monomer
Fc binding to mast cell receptor à Crosslink allergen à degranulation
Effective vs helminths à Eosinophils
Type I Hypersensitivity reaction à Anaphylaxis
Monomer
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Monomer
IgD, IgE, IgG
Dimer
IgA
Pentamer
IgM
≣
Test Your Knowledge
Difficulty Rating: ✪✪✪
Item 7 of 13
Question ID: 0064
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A researcher conducts an experiment to measure the effects of thymic tissue in adult mice. A control group and two additional groups of mice
are studied. Group 1 mice undergo a placebo surgical intervention, omitting thymectomy. Group 2 mice undergo surgical thymectomy. XX77,
a primary immunization is given 11 days prior to surgical intervention and a booster immunization is subsequently given 21 days later.
The data below is collected at 30 days after surgical intervention. Which of the following can the researcher most reasonably assume based
on the results of this experiment?
CD19+CD21+
(106 cells)
XX77-specific heavy chain
variable region mutation
frequency
XX77-specific
IgM (µg/mL)
XX77-specific
IgG (µg/mL)
Control
24.3
4.7%
274
764
Group 1
21.1
2.1%
278
758
Group 2
22.1
2.2%
271
767
⚪ A. Impaired somatic hypermutation after surgery
⚪ B. Impaired isotype switching after thymectomy
⚪ C. Impaired V(D)J recombination after thymectomy
⚪ D. Marginal zone B-cell hyperplasia after surgery
⚪ E. Impaired CD40/CD40L binding after surgery
OUTLINE
1.
Immunology:
Complement
Complement Overview
●
A. General Properties
●
B. Functional Components
2. Complement Pathways
●
A. Classical
●
B. Lectin
●
C. Alternative
●
D. Common
●
E. Inhibitory
3. Disorders of Complement
●
A. Early Complement Deficiency
●
B. Terminal Complement Deficiency
●
C. C1 Esterase Inhibitor Deficiency
●
D. Paroxysmal Nocturnal Hemoglobinuria
Immunology: Complement
•
•
General Properties:
•
Synthesized in liver (inactive state)
•
Activation à Immunoglobulin, enzymes à C3b, MAC
•
Inhibition à DAF (CD55), C1 esterase inhibitor
Functional Components:
•
C3a, C4aà ↑ Histamine release from mast cells à ↑ Vasodilation
•
C5a à ↑ Neutrophil chemotaxis and ↑ Histamine release from mast cells à ↑ Vasodilation
•
C3b à Opsonization
•
C5b-9 Membrane Attack Complex (MAC) à Pathogen cell lysis
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Immunology: Complement
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Functional Components of Complement
•
Classical:
•
•
•
•
•
Lectin:
•
•
•
•
•
•
Activation à Microbial cell surface
C3b bound to surface à binds factor B
C3bBb forms C3 convertase
C3b2Bb forms C5 convertase
Common:
•
•
•
•
Activationà Mannose
MBL binding to mannose forms C1-like complex
C1-like complex à splits C4 and C2 à C4a, C4b, C2a, C2b
C4b2b forms C3 convertase
C4b2b3b forms C5 convertase
Alternative:
•
•
•
•
•
Activation à IgM or IgG
C1 complex à splits C4 and C2 à C4a, C4b, C2a, C2b
C4b2b forms C3 convertase
C4b2b3b forms C5 convertase
C3 convertase à C3a (chemotaxis), C3b (C5 convertase formation)
C5 convertase formation à C5a, C5b
C5b à Binds C6-C9 à Forms MAC
Inhibitory:
•
•
•
C1-esterase inhibitor prevents cleavage of C2 and C4
DAF (CD55) prevents formation of C3 convertase
MIRL (CD59) prevents formation of MAC
C3a, C4aà ↑ Histamine release from mast cells
C5a à ↑ Neutrophil chemotaxis and ↑ Histamine release from mast cells
C3b à Opsonization
C5b-9 Membrane Attack Complex (MAC) à Pathogen cell lysis
Immunology: Complement
•
•
•
•
Early Complement Deficiency:
•
Pathophysiology: Deficiency of C1-C4
•
Presentation: Recurring respiratory/sinus infections
•
↑ Risk of developing SLE
Terminal Complement Deficiency:
•
Pathophysiology: Deficiency of C5-C9 (MAC)
•
↑ Risk of Neisseria sp. infections
C1 Esterase Inhibitor Deficiency:
•
Autosomal dominant
•
Pathophysiology: ↑ Kallikrein à ↑ Bradykinin
•
Presentation: Recurring angioedema (precipitated by trigger)
•
Diagnostics: ↑ Bradykinin, ↓C4
•
Avoid ACE inhibitors
Paroxysmal Nocturnal Hemoglobinuria:
•
Hemolytic anemia +/- pancytopenia
•
Pathophysiology: Complement destruction of RBCs due to loss GPI proteins
•
CD55/DAF and CD59/MIRL
•
Presentation: Fatigue, pallor, intermittent jaundice, hemoglobinuria
•
Venous thrombus in atypical locations à Budd-Chiari syndrome
•
Diagnostics: Direct coombs negative
•
Management: Eculizumab, Ravulozumab (Anti-C5 Ab)
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Test Your Knowledge
Difficulty Rating: ✪✪✪
Item 8 of 13
Question ID: 0065
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A 37-year-old female presents to the emergency department with a 3-day history of worsening severe left lower quadrant abdominal pain.
The patient states that she ordered a hamburger from a fast-food restaurant for dinner the day prior to onset of symptoms. The patient’s past
medical history includes allergies to dust, pollen, and numerous medications. Additionally, the patient was started on lisinopril by her primary
care physician one week prior for essential hypertension. Vital signs are stable. Physical examination reveals significant edema in the
bilateral upper extremities. When questioned regarding the swelling, the patient appears unconcerned and states “everyone in my family has
this happen from time to time.” Abdominal CT scan reveals significant diffuse bowel wall edema.
Which of the following sets of laboratory data are most consistent with this patient’s presentation?
Kallikrein
Bradykinin
Serum
C2 level
Serum
C4 level
C1inhibitor
function
⚪ A.
A.
↑
↑
↑
↑
↑
⚪ B.
B.
↑
↑
↑
↑
↓
⚪ C.
C.
↓
↓
↑
↑
↑
⚪ D.
D.
↓
↑
↑
↑
↓
⚪ E.
E.
↑
↑
↑
↓
↓
⚪ F.
F.
↑
↑
↓
↓
↓
⚪ G.
G.
↑
↑
↓
↓
↑
OUTLINE
1.
Immunology:
Vaccinations
Active vs Passive Immunity
●
A. Active Immunity
●
B. Passive Immunity
2. Vaccine Types
●
A. Live Attenuated
●
B. Whole Inactivated
●
C. Subunit Protein Inactivated
●
D. Subunit Polysaccharide Inactivated
●
E. Subunit Polysaccharide + Conjugate Inactivated
●
F. RNA
Immunology: Vaccinations
•
•
Active Immunity:
•
Host generates Abs in immune response
•
Delayed humoral response
•
Repeated exposures à ↑ Ab response over time
•
Natural à Infection
•
Artificial à Immunization
Passive Immunity:
•
Preformed Abs administered
•
Rapid humoral response
•
t1/2 ~ 3 weeks à ↓ Ab response over time
•
Natural à Mother IgG in fetal serum
•
Artificial à Tetanus immunoglobulin (TIG)
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Immunology: Vaccinations
•
•
•
•
•
•
Live Attenuated:
•
Replicating live pathogen, less pathogenic, does not usually cause disease
•
Compares to infectious immune response
•
Avoided in immunocompromised (infants, elderly, pregnant, transplant, AIDS)
•
Strong immune response à Humoral IgG and Cellular
•
Less safe à Acquisition of virulence factor(s) à ↑ Pathogenicity
•
Exception: Rotavirus vaccine
•
Classic Examples: Varicella, MMR, Rotavirus, Yellow fever, Intranasal influenza, Oral polio (Sabin), BCG, Smallpox
Whole Inactivated:
•
Non-replicating, non-pathogenic virus/bacteria
•
Moderate immune response à Humoral IgG
•
Classic Examples: Influenza (IM), Hepatitis A, Polio (Salk), S. typhi (IM)
Subunit Protein Inactivated:
•
Antigenic (protein) components of pathogen
•
Moderate immune response à Humoral IgG
•
Classic Examples: Pertussis (acellular), Hepatitis B, HPV
•
Toxoid vaccines use bacterial toxin à Tetanus, Diphtheria
Subunit Polysaccharide Inactivated:
•
Polysaccharide component of pathogen or Conjugate (polysaccharide + protein)
•
Polysaccharide only à Th-Independent Response à Humoral IgM only
•
Classic Example: PPSV23 (Strep pneumo)
Subunit Polysaccharide + Conjugate Inactivated:
•
Conjugate (polysaccharide + protein)
•
Conjugate à Th-Dependent Response à Humoral IgG
•
Classic Examples: PCV13 (Strep pneumo), Meningococcal, Hib
RNA:
•
mRNA à Ag production by host cells
•
Classic Example: COVID-19
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Test Your Knowledge
Difficulty Rating: ✪✪✪
Item 9 of 13
Question ID: 0066
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A research group attempts to identify the effectiveness of “SSVK”, a vaccination against Shigella sonnei bacteria. Isolated S. sonnei were
grown in broth containing deoxycholate. Formalin was added to the vaccination sample for complete inactivation of pathogenicity. In preclinical trials, the vaccine demonstrated immunogenicity against various strains of S. sonnei infected mice. Response per participant was
recorded as “strong” or “poor” utilizing cutoff serum values of specific immunoglobulins. Data collected is shown below.
Which of the following most likely describes the SSVK vaccine?
⚪ A. Live-attenuated
⚪ B. Whole inactivated
SSVK-specific
serum IgG
SSVK-specific
serum IgA
SSVK-specific
fecal IgA
SSVK-specific CD8+
Cytotoxic
T-lymphocyte Assay
⚪ C. Subunit polysaccharide
Strong
Response
71
71
72
0
⚪ D. DNA sequence
Poor
Response
2
2
1
73
⚪ E. RNA sequence
Total
Participants
73
73
73
73
OUTLINE
Immunology:
Immunodeficiency
Syndromes
1.
B-cell and T-cell Variants
●
●
●
●
A. Severe Combined Immunodeficiency
B. Bruton (X-linked) Agammaglobulinemia
C. Common Variable Immunodeficiency
D. Thymic Aplasia
2.
Immunoglobulin Variants
A. Selective IgA Deficiency
B. Hyper-IgM Syndrome
C. Hyper-IgE (Job) Syndrome
D. Wiskott-Aldrich Syndrome
Additional Variants
A. IL-12 Receptor Deficiency
B. Chronic Mucocutaneous Candidiasis
C. IPEX Syndrome
●
●
●
●
3.
●
●
●
Immunology: Immunodeficiency Syndromes
•
•
•
•
Severe Combined Immunodeficiency (SCID):
•
Pathophysiology: Defective IL-2Rɣ receptor (MC mutation, XLR), Adenosine deaminase deficiency (AR), RAG mutations
•
Presentation:
1. Normal newborn à Failure to thrive, recurring infections (thrush, diarrhea)
2. Absent lymphoid tissue (lymph nodes, tonsils)
•
Diagnostics:
1. ↓ TRECs
2. Absent thymic shadow (CXR)
3. ↓↓↓ T-cells (Flow cytometry)
4. ↓↓↓ Serum Ig (all isotypes)
Bruton (X-linked) Agammaglobulinemia:
•
Pathophysiology: Defective BTK (XLR)
•
Presentation:
1. Normal newborn à Failure to thrive, recurring infections (thrush, diarrhea)
2. Absent lymphoid tissue (lymph nodes, tonsils)
•
Diagnostics:
1. ↓↓↓ B-cells [CD19, 20, 21] (Flow cytometry)
2. ↓↓↓ Serum Ig (all isotypes)
Common Variable Immunodeficiency:
•
Pathophysiology: Defective B-cell differentiation
•
Presentation: Normal newborn à Recurring infections post-puberty
•
Association: ↑ Risk of lymphoma and autoimmune disease
•
Diagnostics: ↓ Ig (all types), plasma cells
Thymic Aplasia:
•
Pathophysiology: Defective 3rd and 4th pharyngeal pouch development à Thymic hypoplasia (or aplasia) à ↓↓↓ T-cells
•
Presentation: DiGeorge à Hypocalcemia
•
Association: ↑ Risk of lymphoma and autoimmune disease
•
Diagnostics: ↓↓↓ T-cells (flow cytometry), ↓ PTH, ↓ Calcium, CXR: Absent thymus
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Immunology: Immunodeficiency Syndromes
•
•
•
•
Selective IgA Deficiency:
•
Pathophysiology: ↓↓↓ IgA
•
Presentation: Less severe, respiratory illness, diarrhea (Giardia)
•
Association:
1. Anaphylaxis with transfusion à Anti-IgA IgE
2. Celiac Disease (tTG-IgA à False negative)
•
Diagnostics: ↓ Serum IgA, Normal IgM and IgG
Hyper-IgM Syndrome:
•
Pathophysiology: Defective CD40L (XLR)
•
Presentation: Childhood opportunistic infections à Pneumocystis, Histoplasma, Cryptosporidium
•
Diagnostics: Normal/↑ IgM, ↓↓↓ Serum IgA, IgG, IgE
Hyper-IgE Syndrome (Job Syndrome):
•
Pathophysiology: STAT3 mutation (AD) à ↓ Th17 à Impaired chemotaxis
•
Presentation: Abscess without inflammation, coarse facies, eczema
•
Diagnostics: ↑ IgE and eosinophils, ↓ IFN-ɣ
Wiskott-Aldrich Syndrome
•
Pathophysiology: WASp mutation (XLR) à Impaired antigen presentation
•
Presentation: Eczema, purpura, encapsulated organism and opportunistic infections
•
Association: ↑ Risk of lymphoma and leukemia
•
Diagnostics:
1. ↑ IgA and IgE, Normal/↓ IgG and IgM
2. Thrombocytopenia (small platelets)
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Immunology: Immunodeficiency Syndromes
•
•
•
IL-12 Receptor Deficiency:
•
Pathophysiology: ↓ IL-12 receptor
•
Presentation: Disseminated tuberculosis (Mycobacteria)
•
Diagnostics: ↓IFN-ɣ
Chronic Mucocutaneous Candidiasis:
•
Pathophysiology: ↓ AIRE proteinà Defective IL-17/IL-17R à ↓ Response to Candida antigens
•
Presentation: Recurring and/or refractory Candida infections
•
Diagnostics: Absent cutaneous reaction to Candida antigens
IPEX Syndrome:
•
Pathophysiology: Mutation in FOXP3
•
Presentation: Infancy
•
Diagnostics: ↓↓↓ FOXP3, CD4+ CD25+ T-cells, Normal other T-cell lines
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Immunology: Immunodeficiency Syndromes
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Disorder
Pathophysiology
Problem
Classic Presentation
SCID
Defective IL-2R (XLR)
ADA Deficiency (AR)
RAG mutation
Absent T-cells
+/- B-cell dysfunction
Bruton Agammaglobulinemia
Defective BTK gene (XLR)
Absent mature B-cells
(Normal T-cells)
CVID
Defective B-cell differentiation
Present dysfunctional B-cells
(Normal T-cells)
Presents later (20-40y/o)
↓↓ Serum Igs (all)
↓↓ Plasma cells
Lymphoma
Autoimmune disease
Selective IgA Deficiency
Anti-IgA antibodies
↓↓↓ IgA
Respiratory illness
GI illness (Giardia)
Anaphylaxis to blood transx
↓↓↓ IgA
Celiac Disease
(False negative tTG-IgA)
Hyper IgM Syndrome
Defective CD40L (XLR)
Impaired class switching
Childhood opportunistic
infections
-/↑ IgM
↓↓↓ IgA, IgE, IgG
Hyper IgE Syndrome
STAT3 mutation (AD)
Impaired
neutrophil/macrophage
chemotaxis
Abscess w/o inflammation
Coarse facies
Eczema
↑ IgE, eosinophils
↓ IFN-ɣ
Wiskott-Aldrich Syndrome
WASp mutation (XLR)
Impaired antigen presentation
Purpura
Eczema
Recurring infections
Thrombocytopenia
Unusually small platelets
↑ IgA, IgE
-/↓ IgM, IgG
IL-12R Deficiency
----
↓ IL-12R
Disseminated TB
↓ IFN-ɣ
Chronic Mucocutaneous
Candidiasis
↓ AIRE protein à Defective
IL-17/IL-17R
Poor response to candida Ag
Recurring/refractory candida
infections
Absent cutaneous rxn to
candida antigens
Autoimmune disease
IPEX Syndrome
Mutation in FOXP3 (X-linked)
↓ regulatory T-cells
Enteropathy, dermatitis,
polyendocrinopathy
↓↓↓ FOXP3, CD4+ CD25+
Normal other T-cell lines
Autoimmune disease
Enteropathy
Normal newborn
Failure to thrive
Recurring, opportunistic
infections
Diagnostics
Key Associations
↓ TRECs
Absent thymus
↓↓↓ CD3+
↓↓↓ Serum Igs (all)
↓↓↓ CD19+, CD20+, CD21+
↓↓↓ Serum Igs (all)
Lymphoma
Leukemia
≣
Item 10 of 13
Question ID: 0067
Test Your Knowledge
Difficulty Rating: ✪✪
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A 21-year-old male presents to his primary care physician to establish care. He states that he has been suffering from rhinorrhea, intermittent
headaches, and cough for the past 2 weeks. He reports that this is his seventh illness this year and states that he recently recovered from a
prolonged course of watery diarrhea. He states that he has recently had multiple episodes of prolonged nose bleeds. Vaccinations are up to
date. The patient denies any sick contacts. Past medical and birth history are insignificant. Physical examination reveals increased nasal
mucus secretions and maxillary sinus pressure to percussion. Multiple ecchymoses are noted on the upper and lower extremities. The
patient is subsequently referred to a hematologist and immunologist for further evaluation. Diagnostic serum studies and flow cytometry
results are shown below. Lymph node biopsy reveals reactive follicular hyperplasia.
Which of the following immunologic disorders is most consistent with this patient’s presentation and diagnostic evaluation?
⚪ A. Common variable immunodeficiency
⚪ B. Acquired immunodeficiency syndrome
⚪ C. Interleukin-12 receptor deficiency
⚪ D. Severe combined immunodeficiency
⚪ E. X-linked agammaglobulinemia
Hemoglobin: 16.1 g/dL
Leukocyte count: 8,200/mm3
Platelet count: 61,000/mm3
Prothrombin time: Normal
Partial thromboplastin time: Normal
Bleeding time: Prolonged
Immunoglobulin A: 4 mg/dL (reference range: 76-390 mg/dL)
Immunoglobulin G: 37 mg/dL (reference range: 650-1500 mg/dL)
Immunoglobulin M: 32 mg/dL (reference range: 50-170 mg/dL)
CD3+: 1,398 cells/mm3(reference range: 928-2,371 cells/mm3)
CD3+CD4+: 770 cells/mm3(reference range: 501-1,401 cells/mm3)
CD19+ cells: 78 cells/mm3(reference range: 218-745 cells/mm3)
OUTLINE
Immunology:
Hypersensitivity
Reactions
1.
Type I Hypersensitivity
●
●
●
●
●
●
A. Classic Etiology
B. Early-Phase Mechanism
C. Late-Phase Mechanism
D. Presentation
E. Diagnostics
F. Non-IgE Mediated Histaminergic Reactions
2.
Type II Hypersensitivity
●
●
●
A. Destructive Mechanism
B. Receptor Binding Mechanism
C. Diagnostics
3.
Type III Hypersensitivity
●
●
●
●
A. Mechanism
B. Serum Sickness
C. Serum Sickness-Like Reaction
D. Arthus Reaction
4.
Type IV Hypersensitivity
●
●
●
●
A. Mechanism
B. CD8+ Cytotoxicity
C. Diagnostics
D. Skin Differential
5.
Summary Table
Immunology: Hypersensitivity Reactions
•
•
•
•
•
•
Classic Etiology:
•
Foods (peanuts, shellfish)
•
Medications (sulfa drugs)
•
Insect sting
Early-Phase Mechanism:
•
Preformed IgE from previous sensitization
•
IgE Fc portion bound to FcεRI on mast cells and basophils
•
IgE Fab portion bound to antigen (allergen)
•
Crosslinking à Degranulation à Histamine, tryptase release
•
Bronchoconstriction, vasodilation, ↑ vascular permeability
Late-Phase Mechanism:
•
Prostaglandins, leukotrienes, and eosinophils à Inflammation
Presentation:
•
Mild: Bronchospasm, pruritis, urticaria, edema
•
Severe: Anaphylaxis
Diagnostics:
•
Clinical in acute setting
•
Serum tryptase
•
Skin testing
Non-IgE Mediated Histaminergic Reactions:
•
Vancomycin à Rapid infusion
•
Radioiodine contrast
•
Low potency opioids
Bootcamp.com
Immunology: Hypersensitivity Reactions
•
•
•
Destructive Mechanism:
•
Cytotoxic Destruction Examples: AIHA, ITP, Acute hemolytic transfusion reaction, Erythroblastosis fetalis
•
Inflammatory Examples: Goodpasture syndrome, Rheumatic fever, Hyperacute transplant rejection
•
Ab binds to antigen on host cell surface (or graft)
1. MAC activated to destroy host cell
2. C3b à Opsonization à Phagocytosis of host cell
3. C5a à Neutrophil chemotaxis à Destruction of host cell
4. Antibody-dependent cell mediated cytotoxicity (NK cells)
Receptor Binding Mechanism:
•
Examples: Myasthenia gravis, Graves disease, Pemphigus vulgaris, Bullous pemphigoid
•
Ab binds to receptor à Alteration of downstream signaling
•
Myasthenia gravis à Blockade of AChR at NMJ
•
Graves disease à Stimulation of TSHR
Diagnostics:
•
Direct Coombs Test: Tests for Ab bound to host cells
•
Indirect Coombs Test: Tests for Ab present in host serum
Bootcamp.com
Immunology: Hypersensitivity Reactions
•
•
•
•
Mechanism:
•
Examples: Polyarteritis nodosa, PSGN, SLE, IgA nephropathy, Hypersensitivity pneumonitis
•
Ag binds to IgG à Immune complex
•
Deposited in tissues (Blood vessels, joints, kidney)
•
Complement activation (↑↑↑ vs T2HS)
1. C3a, C4a, C5a à ↑ Vascular permeability à Edema
2. C5a à Neutrophil chemotaxis à Lysosomal destruction of tissue
•
Vasculitis, arthritis, glomerulonephritis
Serum Sickness:
•
Etiology: Antitoxin/Antivenom, monoclonal antibodies
•
Anti-Antivenom IgG created after initial exposure
•
Re-exposure to Antivenom Ab à Immune complex formation (systemic)
•
↓ C3, C4 levels
Serum Sickness-Like Reaction:
•
Etiology: PCN, cephalosporins
•
Not considered to be a Type III HS
•
No immune complex formation
•
Less systemic symptoms compared to Serum Sickness
•
Normal complement levels
Arthus Reaction
•
Complication of vaccination (Tdap)
•
Pre-sensitized host w/ preform antigen IgG
•
Re-exposure via vaccine à Immune complex formation (local)
Bootcamp.com
Immunology: Hypersensitivity Reactions
•
•
•
•
Mechanism:
•
Examples: Allergic Contact Dermatitis
•
Initial exposure to Ag/hapten
•
APC presents Ag to naïve T-cells
•
CD4+ T-cell binding to MHC II
•
IL-12 stimulates Th1 differentiation
•
IL-2, IFN-ɣ released by Th1 cells
•
Re-exposure à Pre-formed T-cells
•
↑↑ IFN-ɣ released by Th1 cells
•
Macrophage activation à Inflammatory response
•
CD8+ T-cells target keratinocytes expressing Ag/hapten
CD8+ Cytotoxicity:
•
Examples: Multiple Sclerosis, IBD, T1DM, Hashimoto Thyroiditis
•
CD8+ T-cell binding to MHC I
•
Presenting cell lysis via perforins and granzymes
Diagnostics:
•
Tuberculin skin test
•
Candida skin test
Skin Differential:
•
Allergic Contact Dermatitis à Poison Ivy (Urushiol), latex, nickel
•
DRESS Syndrome à Allopurinol
•
SJS/TEN à Lamotrigine, Phenytoin, Carbamazepine
Bootcamp.com
Immunology: Hypersensitivity Reactions
Bootcamp.com
Hypersensitivity Type
Mechanism
Presentation
Diagnostics
Key Components
Key Examples
Type I Immediate
Early phase:
Mast cell and basophil
Preformed IgE
Crosslinks after Ag binding
Degranulation
Histamine release
Urticaria, edema
Bronchospasm
Anaphylaxis
Serum tryptase
Skin testing
IgE
Mast cells
Basophils
Eosinophils
Food allergy
Insect stings
Late Phase:
Prostaglandins, Leukotrienes
Eosinophils
Type II Cytotoxic
Ab bind to host cell surface
Ag binds to Ab
MAC-induced cytolysis
C3b-induced opsonization
C5a-induced chemotaxis
NK ADCC
Variable depending on
cells destroyed
(i.e., AIHA, RBCs)
Type II Receptor Binding
Ab binds to receptor
Downstream signaling
Variable depending on
receptor
Type III Immune Complex
Ag-Ab immune complex
Deposits in tissues
C3a, C4a, C5a à Edema
C5a-induced chemotaxis
Vasculitis
Arthritis
Glomerulonephritis
(among others)
↓ Serum C3, C4
IgG
Complement
Neutrophils
Polyarteritis nodosa
PSGN
SLE
Serum sickness
Arthus reaction
Type IV Delayed (Cell-mediated)
APCà Ag to CD4+ T-cell
IL-12 stimulates Th1
IL-2, IFN-ɣ release by Th1
Variable depending on
tissue and cells destroyed
(i.e., T1DM, pancreas)
Tuberculin skin test
Candida skin test
CD4+ T-cells
CD8+ T-cells
Neutrophils, Macrophages
Allergic contact dermatitis
Multiple Sclerosis
Inflammatory Bowel Disease
Type 1 Diabetes Mellitus
Hashimoto Thyroidtis
Type II Inflammatory
MHC Ià Ag to CD8+ T-cell
Destruction of host cell
Direct Coombs Test
Indirect Coombs Test
Serum antibody
IgG and/or IgM
Complement
Neutrophils
Natural killer cells
AIHA, ITP
Acute hemolytic reaction
Erythroblastosis fetalis
Goodpasture syndrome
Rheumatic fever
Hyperacute transplant rej.
Myasthenia gravis
Graves’ Disease
•
•
•
•
•
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Item 11 of 13
Question ID: 0068
Test Your Knowledge
Difficulty Rating: ✪✪
Bootcamp.com
A 44-year-old African American female with a past medical history of childhood asthma presents to the emergency department with
worsening dyspnea over the past 4 days. She states that she was initially treated for a presumed asthma exacerbation with oral steroid
medication. She also reports difficulty sleeping at night due to night sweats and worsening anxiety. She has approximately 9.1kg (20 lbs) of
unintentional weight loss over the past month. Additionally, she reports cramping, non-specific abdominal and diffuse joint pain that started
insidiously months earlier. Chest computed tomography imaging reveals a large left lower lobe mass and significant hilar lymphadenopathy.
Subsequent biopsy of the hilar lymph node is conducted and shown below. Bronchoscopy revealed granulomatous inflammation without
evidence of malignancy or infectious etiology. A regimen of high-dose prednisone is initiated.
Which of the following best describes the mechanism of this patient’s underlying disease?
⚪ A. Fc-receptor mediated immune cell activation
⚪ B. IgG mediated inhibition of signaling pathways
⚪ C. IgE mediated mast cell degranulation
⚪ D. Th1-cell mediated interferon-gamma release
⚪ E. Deposition of antigen-antibody complexes
OUTLINE
Immunology:
Transfusion
Reactions
1.
Acute Hemolytic Reaction
4.
TRALI
●
●
●
●
●
A. Classic Etiology
B. Mechanism
C. Presentation
D. Diagnostics
E. Management
●
●
●
●
●
A. Classic Etiology
B. Mechanism
C. Presentation
D. Diagnostics
E. Management
2.
Delayed Hemolytic Reaction
5.
Anaphylactic Reaction
●
●
●
●
●
A. Classic Etiology
B. Mechanism
C. Presentation
D. Diagnostics
E. Management
●
●
●
●
●
A. Classic Etiology
B. Mechanism
C. Presentation
D. Diagnostics
E. Management
3.
Febrile Non-hemolytic Reaction
●
●
●
●
●
A. Classic Etiology
B. Mechanism
C. Presentation
D. Diagnostics
E. Management
Immunology: Transfusion Reactions
•
•
•
•
•
Classic Etiology:
•
Incompatibility RBC antigens (ABO)
Mechanism:
•
Destruction of donor RBCs by recipient preformed Abs (RBC transfusion)
•
Destruction of recipient RBCs by donor preformed Abs (FFP transfusion)
•
Type II hypersensitivity
•
During or hours after transfusion
Presentation:
•
Symptoms of hemolysis: Jaundice, chills, hemoglobinuria
•
Pain at IV site
•
Hypotension, tachycardia
Diagnostics:
•
Positive Direct Coombs Test
•
↑ LDH, ↑ bilirubin, ↓ haptoglobin
Management:
•
Stop transfusion
Red Blood
Cell Txn
Fresh Frozen
Plasma Txn
Universal
Donor
Type O
Type AB
Universal
Recipient
Type AB
Type O
Bootcamp.com
Immunology: Transfusion Reactions
•
•
•
•
•
Classic Etiology:
•
Incompatibility RBC antigens (Kidd, D)
Mechanism:
•
Destruction of donor RBCs by recipient preformed Abs (RBC transfusion)
•
Anamnestic response
•
Type II hypersensitivity
•
Weeks or months after transfusion
Presentation:
•
Mild symptoms
•
Classic presentation: Recurring blood transfusions
Diagnostics:
•
Positive Direct Coombs Test
•
↑ LDH, bilirubin, ↓ haptoglobin
Management:
•
Self-limited
•
Transfusion generally completed at time of reaction
Bootcamp.com
Immunology: Transfusion Reactions
•
•
•
•
•
Classic Etiology:
•
Donor WBC cytokines and antigens
Mechanism:
•
WBC cytokines leak
•
Donor WBCs targeted by recipient preformed antibodies
•
During or hours after transfusion
Presentation:
•
Generally, milder than acute hemolytic reaction
•
Classic vignette: Pediatric patient
Diagnostics:
•
Negative Direct Coombs Test
•
Normal LDH, bilirubin, haptoglobin
Management:
•
Stop transfusion
•
Future occurrences à Leukoreduced blood products
Bootcamp.com
Immunology: Transfusion Reactions
•
•
•
•
•
Classic Etiology:
•
Neutrophil and/or pulmonary endothelial activation
Mechanism:
•
↑ Neutrophil priming and activation à Proinflammatory cytokine release
•
↑ Pulmonary vascular permeability
•
Pulmonary edema (Noncardiogenic)
•
During or hours after transfusion
Presentation:
•
Dyspnea
•
Classic vignette: FFP or platelet transfusion
Diagnostics:
•
Interstitial infiltrates on CXR (transient)
•
Negative Direct Coombs Test
•
Normal LDH, bilirubin, haptoglobin
Management:
•
Stop transfusion
•
Respiratory support à O2 supplementation, intubation
•
Resolves spontaneously
Bootcamp.com
Immunology: Transfusion Reactions
•
•
•
•
•
Classic Etiology:
•
Recipient IgA deficiency
Mechanism:
•
Recipient has preformed anti-IgA IgE antibodies on mast cells
•
Donor IgA in blood sample
•
IgE-mediated degranulation à Histamine
•
Type I hypersensitivity
•
During or hours after transfusion
Presentation:
•
Hypotension, tachycardia
•
Wheezing, urticaria
Diagnostics:
•
Negative Direct Coombs Test
•
Normal LDH, bilirubin, haptoglobin
Management:
•
Stop transfusion à Epinephrine
•
Respiratory support
•
Future occurrences à IgA deficient blood products
Bootcamp.com
Immunology: Transfusion Reactions
Bootcamp.com
Mechanism
Presentation
Diagnostics
Management
Key Vignette Associations
Acute Hemolytic Reaction
Donor RBC destroyed
Recipient Abs
Type II HS
During (or hours after)
Symptoms of
hemolysis
Pain at IV site
Hypotension
Tachycardia
Positive Direct Coombs
↑ LDH, ↑ bilirubin
↓ Haptoglobin
Type and screen
ABO incompatibility
Delayed Hemolytic Reaction
Donor RBC destroyed
Recipient Abs
Anamnestic response
Type II HS
Weeks (or months) after
Mild symptoms
Positive Direct Coombs
↑ LDH, ↑ bilirubin
↓ Haptoglobin
Self-limited
Frequent blood transfusions
IVDU
Febrile Non-hemolytic
Reaction
Donor WBC cytokine
leak
Recipient Abs
Hours after (or during)
Mild symptoms
Negative Direct Coombs
Normal LDH, bilirubin
Normal haptoglobin
Leukoreduced blood
Transfusion Related Acute
Lung Injury (TRALI)
↑ Neutrophil priming and
activation
↑ Pulmonary vascular
permeability
Pulmonary edema
Hours after (or during)
Dyspnea
Increasing O2 req.
Negative Direct Coombs
Normal LDH, bilirubin
Normal haptoglobin
Respiratory support
Resolves spontaneously
Anaphylactic Reaction
Donor IgA
Recipient anti-IgA IgE
Mast cell degranulation
Type I HS
During (or hours after)
Urticaria
Wheezing
Hypotension
Tachycardia
Negative Direct Coombs
Normal LDH, bilirubin
Normal haptoglobin
Respiratory support
IgA-deficient blood
Immediate cessation of transfusion
Transfusion Reaction
Pediatric patient
FFP or platelet transfusion
IgA deficiency
≣
Item 12 of 13
Question ID: 0069
Test Your Knowledge
Difficulty Rating: ✪✪✪
Bootcamp.com
A 34-month-old male with no significant past medical history presents to a pediatric hospital for difficulty standing for the past three days. Two
weeks prior he was noted to have diarrhea and a mild fever and was treated with a short course of trimethoprim-sulfamethoxazole. His
parents report first noticing difficulty with toe clearing when walking in the bilateral lower extremities approximately one day after completing
the antibiotic medication. Birth history reveals that the patient was born at 39 weeks gestation via Cesarean section without complications.
According to his parents, the patient has also achieved normal motor milestones. Vaccinations are currently up to date. Physical examination
reveals distal, flaccid weakness of the lower extremities and areflexia at L4 and S1 bilaterally. Lumbar puncture is performed revealing a
normal cell count and significantly elevated protein. An initial dose of intravenous immunoglobulin is administered. Within seconds, the
patient begins wheezing and demonstrating increased work of breathing. The patient quickly becomes hypotensive and intramuscular
epinephrine is administered.
Which of the following pathophysiologic mechanisms most likely describes the cause of this patient’s reaction to treatment?
⚪ A. Anti-A IgG mediated response
⚪ B. Anti-Kidd IgG mediated response
⚪ C. Anti-GM1 antibody mediated demyelination
⚪ D. IgA mediated enzymatic destruction
⚪ E. Anti-IgA IgE antibody mediated response
OUTLINE
Immunology:
Transplant
Rejection
1.
Transplantation Principles
5.
Graft vs Host Disease
●
●
●
A. Transplant Terminology
B. Graft Terminology
C. Human Leukocyte Antigen
●
●
●
●
●
●
A. Classic Etiology
B. Mechanism
C. Presentation
D. Histopathology
E. Management
F. Additional Considerations
6.
Transplant Rejection Summary
Immunosuppressants
2.
Hyperacute Rejection
●
●
●
●
●
A. Classic Etiology
B. Mechanism
C. Presentation
D. Histopathology
E. Management
3.
Acute Rejection
●
●
●
●
●
A. Classic Etiology
B. Mechanism
C. Presentation
D. Histopathology
E. Management
4.
Chronic Rejection
●
●
●
●
●
A. Classic Etiology
B. Mechanism
C. Presentation
D. Histopathology
E. Management
7.
●
●
●
●
●
●
A. Calcineurin Inhibitors
B. mTOR Inhibitors
C. IL-2 Receptor Inhibitors
D. Recombinant IL-2
E. Glucocorticoids
F. Purine Inhibitors
8.
Biologic Immunotherapy
●
●
A. TNF-Inhibitors
B. Monoclonal Antibodies
Immunology: Transplant Rejection
•
•
•
Transplant Terminology:
•
Autologous: Donor to self
•
Isotransplantation: Donor to genetically identical recipient
•
Allogeneic: Donor to another non-genetically identical recipient
Graft Terminology:
•
Autograft: Donor graft to self
•
Isograft: Donor graft to genetically identical recipient
•
Allograft: Donor graft to non-genetically identical recipient
•
Xenograft: Donor graft to different species recipient
Human Leukocyte Antigen:
•
HLA gene cluster codes for MHC
•
HLA-A, HLA-B, HLA-C: Codes for MHC I
•
HLA-DR, HLA-DP, HLA-DQ: Codes for MHC II
Bootcamp.com
Immunology: Transplant Rejection
•
•
•
•
•
Classic Etiology:
•
RBC major antigen (ABO) incompatibility
•
HLA incompatibility
Mechanism:
•
Destruction of donor graft by recipient preformed Abs
•
Type II hypersensitivity
•
Onset within minutes of graft placement
Presentation:
•
Immediate edema to graft tissues
Histopathology:
•
Thrombosis and fibrinoid necrosis of small vessels
•
Necrosis of graft
Management and Preventative:
•
Remove graft
•
Cross matching major RBC (ABO) antigens
•
HLA matching
Bootcamp.com
Immunology: Transplant Rejection
•
•
•
•
•
Classic Etiology:
•
HLA incompatibility
Mechanism:
•
Primarily cell-mediated or humoral rejection only
•
Cell-mediated response (Type IV hypersensitivity) à Macrophage and CD8+ T-cell activation à Cytotoxicity to graft
•
Humoral response (Type II hypersensitivity) à Antibody production à Complement-mediated destruction of graft
•
Onset weeks-months
Presentation:
•
Edema to graft tissues
•
Deterioration of transplanted tissue function
Histopathology:
•
Lymphocytic infiltrate (Cell-mediated)
•
Vasculitis
•
Complement marker + à Consider humoral rejection
•
Complement marker - à Consider cell-mediated rejection
Management and Prevention:
•
HLA matching
•
Immunosuppression
Bootcamp.com
Immunology: Transplant Rejection
•
•
•
•
•
Classic Etiology:
•
HLA incompatibility
Mechanism:
•
Cell-mediated and humoral rejection integrated together
•
Cell-mediated response (Type IV hypersensitivity) à Macrophage and CD8+ T-cell activation à Cytotoxicity to graft
•
Humoral response (Type II hypersensitivity) à Antibody production à Complement-mediated destruction of graft
•
Onset months-years
Presentation:
•
Edema to graft tissues
•
Deterioration of transplanted tissue function
Histopathology:
•
Arteriosclerosis
•
Interstitial fibrosis
•
Vascular smooth muscle proliferation
•
Atrophic graft tissues
Management and Prevention:
•
Remove graft
•
Immunosuppression
Bootcamp.com
Immunology: Transplant Rejection
•
•
•
•
•
•
Classic Etiology:
•
Hematopoietic stem cell transplantation
•
Liver transplantation
Mechanism:
•
Donor T-cells à Cell-mediated response à Host tissue damage
•
Type IV hypersensitivity
•
Onset variable
Presentation:
•
Dermatologic à Maculopapular rash
•
Hepatobiliary à Jaundice, ↑ ALP
•
Intestinal à Non-specific abdominal pain, nausea, emesis, diarrhea
•
Hematologic à Pancytopenia
Histopathology:
•
Lymphocytic infiltration of host specimen
Management and Prevention:
•
Immunosuppression
Additional Consideration:
•
Graft vs tumor effect
Bootcamp.com
Immunology: Transplant Rejection
Bootcamp.com
Rejection Type
Classic Onset
Cell-Mediated
Humoral
Mechanism
Presentation
Histopathology
Hyperacute
Minutes
Humoral
Donor graft destruction
Recipient pre-formed Abs
Type II HS
Immediate edema to graft
tissues
Thrombosis
Fibrinoid necrosis
Necrosis of graft
Acute
Weeks to months
Cell-mediated
Or
Humoral
CM: Recipient T-cell activation
Type IV HS
Edema to graft tissues
Lymphocytic infiltrate
Vasculitis
Chronic
Months to years
Cell-mediated
And
Humoral
Graft vs Host
Variable
Cell-mediated
H: Recipient Ab production vs graft
Type II HS
Donor T-cell activation
Type IV HS
↓ Function of transplanted
tissues
Interstitial fibrosis
Vascular smooth muscle proliferation
Atrophic graft tissues
Maculopapular rash
Jaundice, scleral icterus
Abdominal pain
Pancytopenia
Lymphocytic infiltrate on host specimen (e.g.,
skin)
Immunology: Transplant Rejection
•
Drug Class: Calcineurin Inhibitors
•
Examples: Cyclosporine, Tacrolimus
•
Cyclosporine Mechanism: Binds cyclophilin à ↓ IL-2
•
Tacrolimus Mechanism: Binds FK506BP à ↓ IL-2
•
HY Indications: Transplant rejection prophylaxis, psoriasis
•
HY Adverse Effects: Nephrotoxicity, neurotoxicity
•
Cyclosporine Specifics à Gingival hyperplasia, hirsutism
•
Drug Class: mTOR Inhibitor
•
Examples: Sirolimus (Rapamycin)
•
Mechanism: Binds FKBP
•
HY Indications: Transplant rejection prophylaxis (Renal)
•
HY Adverse Effects: Pancytopenia
•
No nephrotoxicity
•
Drug Class: IL-2R Inhibitor
•
Examples: Basiliximab, Daclizumab
•
Mechanism: Blocks IL-2R receptor
•
HY Indications: Transplant rejection prophylaxis (Renal)
•
HY Adverse Effects: Hypertension, edema
•
Type II hypersensitivity
•
Drug Class: Recombinant IL-2
•
Examples: Aldesleukin
•
Mechanism: Activates lymphoid cells vs malignancy
•
HY Indications: Renal cell carcinoma, metastatic melanoma
Bootcamp.com
Immunology: Transplant Rejection
•
Drug Class: Glucocorticoids
•
Examples: Prednisone, Dexamethasone, Methylprednisolone
•
Mechanism: Inhibit NF-κB and inflammatory cytokine genes
•
HY Indications: AI, asthma, acute inflammatory states
•
HY Adverse Effects: Osteoporosis, Cushing syndrome,
•
HY Adverse Effects: Hyperglycemia, amenorrhea
•
Additional: Leukocytosis, iatrogenic AI with abrupt discontinuation
•
Avascular necrosis of femoral head
Drug Class: Purine Inhibitors
•
Examples: Azathioprine (6-MP), Mycophenolate, Ribavirin, MTX
•
Azathioprine: Indirectly cytotoxic to PRPP Amidotransferase
•
Mycophenolate: Reversible inhibition of IMPDH
•
Methotrexate (MTX): Inhibits dihydrofolate reductase
•
HY Indications: Rheumatoid arthritis
•
HY Adverse Effects: Pancytopenia
•
Additional: ↑↑ 6-MP w/ allopurinol
•
Additional: Mycophenolate à Invasive CMV
Bootcamp.com
Immunology: Transplant Rejection
Bootcamp.com
•
Monoclonal Ab
Target
HY Indication
HY Adverse Effect
Natalizumab
⍺4-integrin
Multiple sclerosis
Reactivation of JC virus
Rituximab
CD20
Many diseases
Reactivation of JC virus
Palivizumab
RSV F protein
RSV prophylaxis
--
Omalizumab
Soluble IgE
Severe/refractory allergic
asthma
--
Trastuzumab
HER2/neu
HER2/neu + breast ca
Dilated cardiomyopathy
Eculizumab
C5
PNH
Encapsulated bacterial
infections
Bevacizumab
VEGF
Many cancers
GI bleeding
Cetuximab
Panitumumab
EGFR inhibitor
Many cancers
--
Denosumab
RANKL
Osteoporosis
Hypocalcemia
Pembrolizumab
PD-1
Many cancers
Abciximab
GP IIb/IIIa receptor
PCI
Bleeding
Alemtuzumab
CD52
CLL
ITP
Ustekinumab
IL-12, IL-23
Psoriasis
Ipilimumab
CTLA-4
Many cancers
Drug Class: TNF-inhibitors
•
Examples: Infliximab, Adalimumab, Golimumab, Certolizumab
•
Infliximab: Chimeric anti-TNF Ab
•
Adalimumab, Golimumab, Certolizumab: Humanized anti-TNF Ab
•
Etanercept: Fusion protein for TNF + IgG1 Fc
•
HY Adverse Effects: Tuberculosis (Screen prior to administration)
≣
Item 13 of 13
Question ID: 0070
Test Your Knowledge
Difficulty Rating: ✪✪✪✪
Bootcamp.com
A 57-year-old male with a past medical history of acute lymphoblastic leukemia previously treated with chemotherapy presents to the
emergency department with abdominal pain and diarrhea. He reports developing acute onset stabbing abdominal pain and chills a few
hours prior to admission. He also endorses two episodes of non-bloody emesis en route to the hospital. He has been hospitalized four
times over the past two months due to numerous infections requiring antibiotics and antifungal medications after receiving a bone marrow
allograft from a family donor. His medications consist of mycophenolate, prednisone, and cyclosporine for immunosuppression. He denies
any history of alcohol, tobacco use, or recent travel. The patient is tachycardic with a heart rate of 108 beats/min, vitals are otherwise
stable. Physical examination reveals jaundice, a maculopapular rash over the dorsum of the hands bilaterally, and tenderness to palpation
in the left and right upper quadrants of the abdomen. Lymphadenopathy is absent. Serum laboratory studies are shown below. CT scan of
the abdomen and pelvis reveals thickening of the ascending colon. A liver biopsy is subsequently performed revealing a moderate
lymphocytic infiltration surrounding vacuolar steatosis with perisinusoidal fibrosis. No neoplastic cells are observed on biopsy. Which of the
following best explains the mechanism for this patient’s pathology?
⚪ A. Latency associated nuclear antigen binding of p53
⚪ B. Host RNA polymerase transcription of viral proteins
⚪ C. Antibody mediated graft ischemia
⚪ D. Donor T-cell mediated cytotoxicity
⚪ E. Host T-cell mediated cytotoxicity
Leukocyte count: 3,200 mm3
Hemoglobin: 9.2 g/dL
Platelet count: 101,000/mm3
Alanine aminotransferase: 477 U/L
Aspartate aminotransferase: 387 U/L
Total bilirubin: 764 mg/dL
Amylase: 40 U/L
Lipase: 44 mg/dL
Thyroid stimulating hormone: 0.9 µU/mL
Blood cultures: No growth for bacteria or fungi
Anti-double-stranded DNA antibody: Negative
HIV viral load: Undetectable
CMV viral load: Undetectable
Viral hepatitis serologies: Negative
Herpes serologies: Negative
Immunology: Lymphoid Tissue
•
•
•
•
•
•
•
Thymus.JPG
•
https://commons.wikimedia.org/wiki/File:Thymus.JPG
•
Tourbulence at Dutch WikipediaLater versions were uploaded by Siebrand at nl.wikipedia., CC BY-SA 3.0 <http://
creativecommons.org/licenses/by-sa/3.0/>, via Wikimedia Commons
X-ray of an infant with a prominent thymus
•
https://commons.wikimedia.org/wiki/File:X-ray_of_an_infant_with_a_prominent_thymus.jpg
•
Nausheen Khan, Dimakatso C. Thebe, Farhanah Suleman, Irma van de Werke, CC BY 4.0
<https://creativecommons.org/licenses/by/4.0>, via Wikimedia Commons
Thymic corpuscle
•
https://commons.wikimedia.org/wiki/File:Thymic_corpuscle.jpg
•
Nephron, CC BY-SA 3.0 <https://creativecommons.org/licenses/by-sa/3.0>, via Wikimedia Commons
Spleen
•
•
https://commons.wikimedia.org/wiki/File:2208_Spleen.jpg
OpenStax College, CC BY 3.0 <https://creativecommons.org/licenses/by/3.0>, via Wikimedia Commons
Lymphatic immune system lymphnode5-CROPPED
•
https://commons.wikimedia.org/wiki/File:Lymphatic_immune_system_lymph_node5-CROPPED.jpg
•
Chris Sullivan, CC BY-SA 4.0 <https://creativecommons.org/licenses/by-sa/4.0>, via Wikimedia Commons
Progressive transformation of germinal centres -1- very low mag
•
https://commons.wikimedia.org/wiki/File:Progressive_transformation_of_germinal_centres_-1_very_low_mag.jpg
•
Nephron, CC BY-SA 3.0 <https://creativecommons.org/licenses/by-sa/3.0>, via Wikimedia Commons
Peyer’s patch (improved color)
•
https://commons.wikimedia.org/wiki/File:Peyer%27s_patch_(improved_color).jpg
•
User:Plainpaper, CC BY-SA 3.0 <https://creativecommons.org/licenses/by-sa/3.0>, via Wikimedia Commons
Bootcamp.com
Immunology: Innate vs Adaptive Immunity
•
20100825 023736 Neutrophil
•
https://commons.wikimedia.org/wiki/File:20100825_023736_Neutrophil.jpg
•
Hem1Eosinophile
•
https://commons.wikimedia.org/wiki/File:Hem1Eosinophile.jpg
•
Hem1Basophile
•
https://commons.wikimedia.org/wiki/File:Hem1Basophile.jpg
•
Monocytes, a type of white blood cell (Giemsa stained)
•
https://commons.wikimedia.org/wiki/File:Monocytes,_a_type_of_white_blood_cell_(Giemsa_stained).jpg
•
•
•
•
Bob Blaylock, CC BY-SA 3.0 <https://creativecommons.org/licenses/by-sa/3.0>, via Wikimedia Commons
El*Falaf, CC BY-SA 3.0 <https://creativecommons.org/licenses/by-sa/3.0>, via Wikimedia Commons
El*Falaf, CC BY-SA 3.0 <https://creativecommons.org/licenses/by-sa/3.0>, via Wikimedia Commons
Dr Graham Beards, CC BY-SA 3.0 <https://creativecommons.org/licenses/by-sa/3.0>, via Wikimedia Commons
Bootcamp.com
Immunology: Inflammation
Bootcamp.com
•
TLR Signaling Pathway
•
Adapted from “TLR Signaling Pathway”, by BioRender.com (2021). Retrieved from https://app.biorender.com/biorender-templates
•
Leukocyte Migration at Sites of Infection
•
Adapted from “Leukocyte Migration at Sites of Infection”, by BioRender.com (2021). Retrieved from https://app.biorender.com/biorender-templates
•
Neutrophil
•
Adapted from “Endothelial Barrier Inflammation and Leak (Layout)”, by BioRender.com (2021). Retrieved from
https://app.biorender.com/biorender-templates
Leukocyte Adhesion Deficiency
•
Adapted from “Leukocyte Migration at Sites of Infection”, by BioRender.com (2021). Retrieved from https://app.biorender.com/biorender-templates
•
•
•
•
•
Granuloma
•
Adapted from “Granuloma”, by BioRender.com (2021). Retrieved from https://app.biorender.com/biorender-templates
Granulomatous Inflammation Mechanism
•
Created with Biorender.com
Necrogran10x
•
https://commons.wikimedia.org/wiki/File:Necrogran10x.jpg
•
Mutleysmith, Public domain, via Wikimedia Commons
Granuloma mac
•
https://commons.wikimedia.org/wiki/File:Granuloma_mac.jpg
•
Sanjay Mukhopadhyay, Public domain, via Wikimedia Commons
Immunology: Cytokines
•
•
Bootcamp.com
Cytokines
•
Adapted from “Induction of 2nd Order Cytokines”, by BioRender.com (2021). Retrieved from https://app.biorender.com/biorender-templates
T-cell Lines
•
Adapted from “T cell activation and differentiation”, by BioRender.com (2021). Retrieved from https://app.biorender.com/biorender-templates
Immunology: T-cells
Bootcamp.com
•
Thymus T-Cell Development
•
Adapted from “T-Cell Development in Thymus 2”, by BioRender.com (2021). Retrieved from https://app.biorender.com/biorender-templates
•
MHC Class 1.svg
•
https://commons.wikimedia.org/wiki/File:MHC_Class_1.svg
•
User atropos235 on en.wikipedia, CC BY-SA 3.0 <http://creativecommons.org/licenses/by-sa/3.0/>, via Wikimedia Commons
MHC Class 2.svg
•
https://commons.wikimedia.org/wiki/File:MHC_Class_2.svg
•
User atropos235 on en.wikipedia, CC BY-SA 3.0 <http://creativecommons.org/licenses/by-sa/3.0/>, via Wikimedia Commons
Macrophage Activation via MHC II
•
Adapted from “TH1 Cells Help Macrophages Kill Intracellular Bacteria”, by BioRender.com (2021). Retrieved from
https://app.biorender.com/biorender-templates
•
•
•
•
T-cell Activation, CD8+
•
Created with BioRender.com
T-cell Activation, CD4+
•
Created with BioRender.com
Immunology: B-cells
•
•
•
•
Bootcamp.com
B-cell
•
Created with BioRender.com
Figure 42 02 06.jpg
•
https://commons.wikimedia.org/wiki/File:Figure_42_02_06.jpg
•
CNX OpenStax, CC BY 4.0 <https://creativecommons.org/licenses/by/4.0>, via Wikimedia Commons
Steps in B-cell Differentiation
•
Adapted from “Steps in B-cell Differentiation”, by BioRender.com (2021). Retrieved from https://app.biorender.com/biorender-templates
Lymph Node
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Created with BioRender.com
Immunology: Antibodies
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Antibody Structure
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Adapted from “The Variable Region of an Antibody Binds to the Antigen”, by BioRender.com (2021). Retrieved from
https://app.biorender.com/biorender-templates
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Mono-und-Polymere.svg
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https://commons.wikimedia.org/wiki/File:Mono-und-Polymere.svg
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Martin Brändli (brandlee86), CC BY-SA 2.5 <https://creativecommons.org/licenses/by-sa/2.5>, via Wikimedia Commons
Bootcamp.com
Immunology: Complement
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Bootcamp.com
Three Pathways of Complement Activation
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Adapted from “Three Pathways of Complement Activation”, by BioRender.com (2021). Retrieved from https://app.biorender.com/biorendertemplates
Immunology: Vaccinations
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Bootcamp.com
Three Pathways of Complement Activation
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Adapted from “Three Pathways of Complement Activation”, by BioRender.com (2021). Retrieved from https://app.biorender.com/biorendertemplates
Immunology: Immunodeficiency Syndromes
Bootcamp.com
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CD40 Ligand Deficiency
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Adapted from “CD40 Ligand Deficiency”, by BioRender.com (2021). Retrieved from https://app.biorender.com/biorender-templates
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T-cell Activation, CD4+
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Created with BioRender.com
Candida antigen test
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Adapted from “Candida antigen test”, by BioRender.com (2021). Retrieved from https://app.biorender.com/biorender-templates
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Immunology: Hypersensitivity Reactions
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Bootcamp.com
Type I Hypersensitivity Reaction Mechanism
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Created with BioRender.com
EMminor2010.JPG
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https://commons.wikimedia.org/wiki/File:EMminor2010.JPG
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James Heilman, MD, CC BY-SA 3.0 <https://creativecommons.org/licenses/by-sa/3.0>, via Wikimedia Commons
Type II Hypersensitivity Reaction Mechanism
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Created with BioRender.com
Myasthenia MOA
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Adapted from “Myasthenia Gravis – Autoantibodies Against Receptors Cause Disease by Blocking Receptor Function”, by BioRender.com (2021).
Retrieved from https://app.biorender.com/biorender-templates
Graves Disease MOA
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Adapted from “Graves’ Disease”, by BioRender.com (2021). Retrieved from https://app.biorender.com/biorender-templates
Type III Hypersensitivity Reaction Mechanism
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Created with BioRender.com
Churg-Strauss syndrome – high mag.jpg
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https://commons.wikimedia.org/wiki/File:Churg-Strauss_syndrome_-_high_mag.jpg
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Nephron, CC BY-SA 3.0 <https://creativecommons.org/licenses/by-sa/3.0>, via Wikimedia Commons
Churg-Strauss syndrome – very high mag.jpg
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https://commons.wikimedia.org/wiki/File:Churg-Strauss_syndrome_-_very_high_mag.jpg
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Nephron, CC BY-SA 3.0 <https://creativecommons.org/licenses/by-sa/3.0>, via Wikimedia Commons
Type IV Hypersensitivity Reaction Mechanism
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Created with BioRender.com
Poison ivy contact dermatitis.jpg
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https://commons.wikimedia.org/wiki/File:Poison_ivy_contact_dermatitis.jpg
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Britannic124, CC BY-SA 3.0 <https://creativecommons.org/licenses/by-sa/3.0>, via Wikimedia Commons
Poision Ivy 2012
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https://commons.wikimedia.org/wiki/File:Poision_Ivy_2012.jpg
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Alborz Fallah, CC BY-SA 3.0 <https://creativecommons.org/licenses/by-sa/3.0>, via Wikimedia Commons
Immunology: Transfusion Reactions
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Bootcamp.com
ABO blood type.svg
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https://commons.wikimedia.org/wiki/File:ABO_blood_type.svg
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InvictaHOG, Public domain, via Wikimedia Commons
Blood-centrifugation-scheme.png
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https://commons.wikimedia.org/wiki/File:Blood-centrifugation-scheme.png
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KnuteKnudsen at English Wikipedia, CC BY 3.0 <https://creativecommons.org/licenses/by/3.0>, via Wikimedia Commons
RBC Transfusion Reaction
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Created with BioRender.com
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Leukocyte Cytokines
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Created with BioRender.com
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Transfusion-related acute lung injury chest X-ray.gif
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https://commons.wikimedia.org/wiki/File:Transfusion-related_acute_lung_injury_chest_X-ray.gif
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Altaf Gauhar Haji, Shekhar Sharma, DK Vijaykumar and Jerry Paul., CC BY 2.0 <https://creativecommons.org/licenses/by/2.0>, via
Wikimedia Commons
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IgA Deficiency Transfusion
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Created with BioRender.com
Immunology: Transplant Rejection
Bootcamp.com
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Lung transplant rejection – high mag.jpg
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https://commons.wikimedia.org/wiki/File:Lung_transplant_rejection_-_high_mag.jpg
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Nephron, CC BY-SA 3.0 <https://creativecommons.org/licenses/by-sa/3.0>, via Wikimedia Commons
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Glucocorticoid Pathway
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Adapted from “Round Cell Background”, by BioRender.com (2021). Retrieved from https://app.biorender.com/biorender-templates
Calcineurin Inhibitor and mTOR inhibitor Pathway
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Adapted from “Round Cell Background”, by BioRender.com (2021). Retrieved from https://app.biorender.com/biorender-templates
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