Immunology Flashcards
(135 cards)
1
Q
Immune system Primary Organs
A
bone marrow and thymus
2
Q
Immune system Secondary Organs
A
spleen lymph nodes, tonsils, peyer patches
3
Q
Lymph Node
A
has many afferent and efferent. Encapsulated with trabeculae. Nonspecifc filtration by macrophages, circulation of B and T cells and immune response activation.
4
Q
Follicle
A
Site of B cell localization and proliferation. In outer cortex primary follicles are dense and quiescent. secondary follicles have pale central germinal centers and are active
5
Q
Medulla
A
medullary sinuses communicate with efferent lymphatics and contain reticular cells and macrophages
6
Q
Paracortex
A
contains T cells. region of cortex between follicles and medulla. Contains high endothelial venules through with T and B cells enter from blood.
Enlarge in extreme cellular immune response
Not developed in DiGeorge
7
Q
Cervical, supraclavicular LN
A
Drain head and neck
URI, mononucleosis, Kawasaki
8
Q
Mediastinal LN
A
Drain Trachea and esophagus
TB, sarcoidosis, lung cancer, granulomatous disease
9
Q
Hilar LN
A
Drain lungs
TB, sarcoidosis, lung cancer, granulomatous disease
10
Q
Axillary LN
A
Drain upper limb, breast, skin above umbilicus
Mastitis, metastasis (breast cancer)
11
Q
Celiac LN
A
Drain liver, stomach, spleen, pancreas, upper duodenum
Mesenteric Lymphadenitis, typhoid, UC, celiac disease
12
Q
Superior Mesenteric LN
A
Drain lower duodenum, jejunum, ileum, colon to splenic flexure
Mesenteric Lymphadenitis, typhoid, UC, celiac disease
13
Q
Inferior Mesenteric LN
A
Drain colon from splenic flexure to upper rectum
Mesenteric Lymphadenitis, typhoid, UC, celiac disease
14
Q
Para-aortic LN
A
Drains testes, ovaries, kidneys, uterus
Metastasis
15
Q
External Iliac LN
A
Drains Cervix, superior bladder and body of uterus
STI
16
Q
Internal iliac
A
drains lower rectum to anal canal, bladder, vagina, cervix, prostate
STI
17
Q
Superficial inguinal LN
A
drains anal canal, skin below umbilicus, scrotum, vulva
STI, medial foot/leg cellulitis
18
Q
Popliteal LN
A
Dorsolateral foot, posterior calf drainage
Lateral foot/leg cellulitis
19
Q
Spleen
A
LUQ, anterolateral to left kidney, protected by ribs 9-11
Barrel hoop basement membrane
T cells in periarteriolar lymphatic sheath (white pulp)
B cells in follicles in white pulp
Marginal zone- between red and white pulp, contain macrophages and specialized B cells, APCs
Remove encapsulated bacteria
20
Q
Splenic dysfunction
A
decrease IgM –> decrease complement –> increased susceptibility to encapsulated bacteria (SCD)
21
Q
Postsplenectomy blood findings
A
Howell Jolly bodies
Target cells
thrombocytosis
lymphocytosis
22
Q
Thymus
A
Anteriosuperior mediastinum.
Site of T cell differentiation and maturation.
3RD PHARYNGEAL POUCH
Cortex- dense with immature T cells
Medulla- pale with mature T cells and Hassall corpuscles
Neonates: sail shaped on CXR
Hypoplastic thymus in SCID and DiGeorge
Thymoma- neoplasm, MG, SVC syndrome, pure red cell aplasia, Good syndrome
23
Q
Innate Immunity
A
Neutrophils, macrophages, monocytes, DC, NK cells, complement
germline encoded
resistance persists through generations- does not change in lifetime
Nonspecific, fast, no memory
TLRs recognize PAMPs –> activate NFkB
24
Q
Adaptive Immunity
A
T cells, B cells, Ab
VDJ recombination during lymphocyte development
microbial resistance not heritable
Highly specific, refined over time, memory response, fast and robust
25
MHC I
```
HLA A,B,C
bind TCR and CD8
present endogenous antigens
all nucleated cells, APCs, platelets (NOT RBC)
Antigen loaded in RER
```
26
MHC II
```
HLA (DP, DQ, DR)
Bind TCR and CD4
APC's
Present exogenous antigens
antigen loaded after release of invariant chain in endosome
```
27
HLA A3
Hemachromatosis
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HLA B8
Addison disease, MG, Graves
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HLA B27
psoriatic arthritis, ankylosing spondylitis, IBD associated arthritis, reactive arthritis
30
HLA C
psoriasis
31
HLA DQ2/DQ8
Celiac disease
32
HLA DR2
multiple sclerosis, hay fever, SLE, Goodpasture
33
HLA DR3
DM Type 1, SLE, Graves, Hashimoto, addisons
34
HLA DR4
Rheumatoid arthritis, DM Type 1, addison
35
HLA DR5
Hashimoto
36
NK cells
Innate immune system
use perforin and granzymes --> apoptosis of viral infection
enhanced by IL 2, 12, IFN alpha and beta
37
B cells
Humoral immunity
recognize and present antigen
somatic hypermutation
produce Ab (differentiate into plasma cells or memory cells)
38
T cells
Cell mediated immunity
CD4- help B cells make Ab and produce cytokines
CD8- directly kill virus infected and tumor cells via perforin and granzymes
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Differentiation of T cells Positive selection
Thymic cortex
| T cells expressing TCR capable of binding to self MHC on cortical epithelial cells survive
40
Differentiation of T cells Negative Selection
Thymic medulla
| T cells expressing TCRs with high affinity for self antigens undergo apoptosis or become Treg cells.
41
AIRE deficiency
Tissue restricted self antigens are expressed in the thymus duet to AIRE
deficiency: autoimmune polyendocrine syndrome I (candidiasis, hypoparathyroidism, adrenal insufficiency, recurrent candida infection)
42
Macrophage- lymphocyte interaction
Th1 cells secrete IFNy --> enhance ability of monocytes and macrophages to kill microbes they ingest. Also, interaction of T cell CD40L with macrophage CD40.
43
Cytotoxic T cells
Kill virus infected, neoplastic and donor graft cells via apoptosis. Release cytotoxic granules
CD8
44
Treg cells
Maintain specific immune tolerance by suppressing CD4 and CD8.
Express CD3, CD4, CD25 and FOXP3
Produce anti inflammatory cytokines (IL 10, TGF B)
45
IPEX
deficiency of FOXP3 --> autoimmunity
Enteropathy, endocrinopath, nail dystrophy, dermatitis
Associated with DM in male infants
X linked
46
T cell activation
1. DC samples and processes Ag then migrates to LN
2. T cell activation- exogenous Ag present on MHC II and recognized by TCR on CD4 cell. Endogenous Ag presented on MHC I to CD8
3. Proliferation and survival- DC CD80/86 and naive T cell CD28 interaction
4. Activated Th cell produce cytokines and kill virus infected cell
47
B cell activation
1. Th cell activation
2. B cell receptor mediated endocytosis
3. Exogenous antigen presented on MHC II and recognized by TCR on Th cell
4. CD40 on B cells bind CD40L on Th cell
5. Th cell secrete cytokines that determine Ig class switching
6. B cells are activated and undergo class switching and affinity maturation --> produce Ab
48
Fab Ab structure
Fragment antigen binding.
| Variable/hypervariable regions containing light and heavy chains.
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Fc Ab Structure
```
Constant
Carboxy terminal
Complement binding
Carb side chain
Determine isotype
```
50
Generation of Ab Diversity
1. random recombination of light chain or heavy chain
2. Random addition of nucleotides to DNA during recombination by TdT
3. Random combination of heavy chains with light chains
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Generation of Ab specificity
```
Somatic hypermutation and affinity maturation (variable region)
Isotype switching (constant region)
```
52
IgG
Main Ab in secondary response to Ag
Most abundant
Fix complement, opsonize bacteria, neutralize toxins
CROSS PLACENTA
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IgA
prevent attachment of bacteria and viruses to mucus membranes
Cross epithelial by transcytosis
Most produced Ab overall
Produced in GI tract
54
IgM
Immediate response to Ag.
Fixes complement
Ag receptor on surface of B cell
Pentamer --> avid binding to Ag while humoral response evolves
55
IgE
bind to mast cells and basophils
cross links when exposed to allergen --> histamine release
TYPE 1 HYPERSENSITIVITY
Parasites
56
Thymus independent Ag
Lack peptide component
cannot be presented to MHC to T cells
weakly immunogenic
booster vaccines
57
Thymus dependent Ag
contain peptide component. Class switching and immunologic memory occur as a result of direct contact of B cells with Th cells
58
Complement
```
Innate immunity and inflammation
Synthesized in liver
MAC - defend against Gram (-)
Classic- IgG IgM
Alternative- microbial surface molecules
Lectin- mannose
```
59
Complement opsonization
C3b
60
Complement Anaphylaxis
C3a, C4a, C5a
61
Complement Neutrophil chemotaxis
C5a
62
Complement cytolysis
C5b-9 = MAC
63
Opsonins
C3b and IgG in bacterial defense
| enhance phagocytosis
64
Inhibitors
DAF (CD55) and C1 esterase help prevent complement activation on self cells
65
Early Complement Deficiencies
C1-4
| Increased risk of severe, recurrent pyogenic sinus and URI. Increased risk of SLE
66
Terminal Complement deficiencies
C5-9
| Increased susceptibility to recurrent Neisseria bacteremia
67
C1 esterase inhibitor deficiency
Causes hereditary angioedema due to unregulated activation of kalikrein --> increase braykinin
low C4
ACEi contraindicated
68
Paroxysmal Nocturnal Hemoglobinuria
defect in PIGA gene --> prevent formation of GPI anchors for complement inhibitors (DAF or MIRL)
Intravascular hemolysis --> low haptoglobin, dark urine
69
IL1
cause fever, acute inflammation,
activates endothelium to express adhesion molecules.
induce chemokine secretion to recruit WBCs
osteoclast activator
Secreted by macrophages
70
IL6
cause fever and stimulate production of acute phase protiens
| secreted by macrophages
71
TNFa
```
activates endothelium
Cause WBC recruitment
vascular leak
causes cachexia in malignancy
maintains granulomas in TB
mediate fever and sepsis
Secreted by macrophages
```
72
IL8
Major chemotactic factor for neutrophils
| Secreted by macrophages
73
!L12
Induce differentiation of T cells into Th1
activate NK cells
secreted by macrophages
74
IL2
stimulate growth of helper, cytotoxic, regulatory T cells and NK cells
secreted by T cells
75
IL3
Supports growth and differentiation of bone marrow stem cells
like GM CSF
secreted by T cells
76
IFNy
secreted by NK ells and T cells in response to Ag or IL12 from macrophages
stimulates macrophages to kill pathogens
inhibit Th2 differentiation
77
IL4
induce differentiation of T cells into Th2 cells.
Promote growth of B cells
Enhance class switching to IgE and IgG
Secreted by Th2
78
IL5
promote growth and differentiation of B cells
Enhance class switching of IgA
stimulate growth and differentiation of eosinophils
Secreted by Th2
79
IL10
Attenuate inflammatory response
Decrease MHC class II and Th1 cytokines
Inhibit activated macrophages and DC
Secreted by Treg and Th2 cells
80
Respiratory burst
activate NADPH oxidase complex --> rapid release of ROS.
| Create and neutralize ROS
81
Chronic Granulomatous Disorder
can utilize H2O2 --> ROS --> decrease oxidative burst. increased risk of infection by catalase (+) species
Defect in NADPH oxidase
abnormal dihydrorhodamine test
82
Interferons
interfere with RNA and DNA viruses
downregulate protein synthesis to resist potential viral replication and upregulate MHC expression
Activate anti-tumor immunity
Adverse: flu-like symptoms, depression, neutropenia, myopathy, autoimmunity
83
Anergy
state when cell cannot be activated by exposure to Ag.
| When B or T cells exposed to their Ag without costimulatory signal
84
Passive immunity
receive performed Ab
Rapid onset
short span of Ab
breast milk, maternal IgG
85
Active immunity
exposure to exogenous antigens
slow onset
long lasting protection
natural infection, vaccines, toxoid
86
Live attenuated vaccines
microorganism loses its pathogenicity but retains capacity for transient growth within inoculated host. Induce cellular and humoral responses
Contra in pregnancy and immunodeficiency
87
Killed or inactivated vaccine
pathogen is inactivated by heat or chemicals. Maintain epitope structure on surface Ag. Induce humoral response
BOOSTER SHOTS NEEDED
88
Subunit vaccine
induce only the Ag that best stimulate the immune system
89
Toxoid Vaccine
Denatured bacterial toxin with an intact receptor binding site. stimulates the immune system to make Ab without potential for causing disease
90
Type 1 Hypersensitivity
Anaphylactic
Immediate phase: antigen crosslinks preformed IgE on presensitized mast cells --> immediate degranulation --> release of histamine and tryptase
Late phase: chemokines and other mediators from mast cells --> inflammation and tissue damage
91
Type 2 Hypersensitivity
Antibodies bind to cell surface antigens --> cellular destruction, inflammation and cellular dysfunction
cell is opsonized by Ab --> phagocytosis or NK kill
binding of Ab to cell surface --> complement and inflammation
Ab bind to cell surface receptor --> abnormal blockade or activate downstream process
Autoimmune hemolytic anemia, transfusion reaction, goodpastures, rheumatic fever, MG, graves, pemphigus vulgaris
92
Type 3 Hypersensitivity
Immune complex activate complement which attracts neutrophils --> release lysosomal enzymes
SLE, PAN, poststrep glomerulonephritis
Serum sickness (Ab produced 1-2 weeks later and deposit in tissue)
Arthus reaction (injection of Ag --> immune complex formation in skin)
93
Type 4 Hypersensitivity
1. Direct cell cytotoxicity (CD8) kill target cells
2. inflammatory reaction- CD4 recognize Ag and release inflammation inducing cytokines
contact dermatitis, Graft vs host
94
Blood Transfusion reaction: allergic
Type 1 hypersensitivity against plasma proteins in transfused blood. IgA deficient individuals should not receive blood products without IgA
Within minutes to 2-3 hours
urticaria, anaphylaxis
95
Blood Transfusion reaction: acute hemolytic
Type 2 hypersensitivity
causes intravascular hemolysis ABO
during transfusion or within 24 hours
fever, hypotension, tachy, flank pain
96
Blood Transfusion reaction: febrile hemolytic
Cytokines created by donor WBCs accumulate suring stoarge of blood. reaction prevented by leukoreduction
within 1-6 hours
fever, HA, chills, flushing
Children
97
Transfusion related acute lung injury
Neutrophils are sequestered and primed in pulmonary vasculature and neutrophils are activated by a product in the transfused blood and release inflammatory mediators --> pulm edema
within minutes to 6 hr
Resp distress, pulm edema
98
Blood Transfusion reaction: Delayed hemolytic
Anamnestic response to a foreign Ag on donor RBC. Cause extravascular hemolysis
Onset >24hrs
self limited, mild fever, hyperbilirubinemia
99
X linked agammaglobulinemia
```
defect in BTK --> no B cell maturation
X linked recessive
recurrent bacterial and enteroviral infections after 6 months
(-) B cell, decreased Ig
absent LN and tonsils
Contra- live vaccines
```
100
Selective IgA deficiency
Asymptomatic
can see airway and GI infections, autoimmune, atopy, anaphylaxis to IgA products
decrease in IgA only, increased susceptibility to giardia
False (+) B-hCG test
101
Common variable immunodeficiency
Defect in B cell differentiation
may present in childhood
increase risk of autoimmune disease, bronchiectasis, lymphoma, sinopulm infections
decrease plasma cells and Ig
102
Thymic Aplasia
22q11 microdeletion, failure to develop 3rd and 4th pharyngeal pouches --> absent thymus and parathyroid
DiGeorge: thymic, parathyroid, cardiac defect
Velovardiofacial syndroms: palate, facial, cardiac disease
CATCH-22
decrease T cells, PTH and Calcium
Thymic shadow absent on CXR
103
IL12 deficiency
decreased th1 response AR
Disseminated mycobacterial and fungal infections
decreased IFNy
104
AD hyper-IgE syndrome
Deficiency of Th17 cells due to STAT3 mutation --> impaired recruitment of neutrophils to sites of infection
Cold staph abscesses, retained baby teeth, coarse facies, eczema, increased IgE, bone fractures
increased IgE, eosinophils
105
Chronic mucocutaneous candidiasis
T cell dysfunction, impaired cell mediated immunity against Candida via defect in AIRE
persistent Candida albicans infection
absent T cell proliferation
106
Severe combined immunodeficiency
IL2R gamma chain defect (X linked), adenosine deaminase deficiency (AR) or RAG mutation --> VDJ recombination defect.
Failure to thrive, chronic diarrhea, thrush, recurrent viral, bacterial, fungal and protozoal infection
decrease TCRECs, absent thymic shadow
107
Ataxia Telangiectasia
Defect in ATM gene --> failure to detect DNA damage AR
Ataxia, Angiomas, IgA deficiency
increased sensitivity to radiation
increased AFP, decreased IgA, IgG, and IgE, lymphopenia, cerebellar atrophy, increased risk of lymphoma and leukemia
108
Hyper IgM
defective CD40L on Th cells --> class switching defect XR
Severe pyogenic infection, Pneumocystis, CMV, Cryptosporidium
normal or high IgM
low IgG, IgA, IgE
109
Wiskott Aldrich
Mutation in WAS gene, leukocytes and platelets unable to recognize actin cytoskeleton -->defective antigen presentation XR
Thrombocytopenia, eczema, recurrent infections
increase risk of autoimmune disease and malignancy
low to normal IgG and IgM
increased IgE and IgA
110
Leukocyte Adhesion Deficiency
Defect in LFA 1 integrin protein on phagocytes--> impaired migration and chemotaxis AR
late separation of umbilical cord, absent pus, dysfunctional neutrophils
increased neutrophils in blood but not in infection site
111
Chediak Higashi
Defective lysosomal trafficking regulator gene. Microtubule dysfunction in phagosome-lysosome fusion AR
progressice neurodegeneration, lymphohistiocytosis, albinism, recurrent infections, peripheral neuropathy
giant granules, pancytopenia, mild coagulation defects
112
Hyperacute Transplant Rejection
within minutes
Pre-existing recipient Ab react to donor Ag (Type 2) --> activate complement
Thrombosis of graft vessels --> ischemia, necrosis
GRAFT MUST BE REMOVED
113
Acute Transplant Rejection
weeks to months
CD8 and CD4 cells activated against donor MHC (Type 4)
Vasculitis of graft vessel with dense interstitial lymphocytic infiltrate
reverse with immunosuppressants
114
Chronic Transplant Rejection
months to years
CD4 respond to recipient APCs on donor (Type 2 and 4)
proliferation of vascular smooth muscle, parenchymal atrophy, interstitial fibrosis
115
Graft vs. Host
grafted immunocompetent T cells proliferate in the immunocompromised host and reject host cells with foreign proteins --> organ dysfunction
Type 4
Maculopapular rash, jaundice, diarrhea, hepatosplenomegaly
Bone marrow and liver transplants
116
Cyclosporin
Calcineurin inhibitor; bind cyclophilin --> block T cell activation by preventing IL2 transcription
Used in psoriasis, Rheumatoid arthritis
Tox: nephrotoxicity
117
Tacrolimus
Calcineurin inhibitor binds FK506 binding protein --> block T cell activation by preventing IL 2 transcription
Used in psoriasis, Rheumatoid arthritis
Tox: nephrotoxicity, increased risk of diabetes
118
Sirolimus
mTOR inhibitor binds FKBP --> block T cell activation by preventing IL2 transcription
Used in kidney transplant rejection prophylaxis
Tox: pancytopenia, insulin reisstance, hyperlipidemia
119
Basiliximab
Monoclonal Ab blocks IL 2R
Used in kidney transplant rejection prophylaxis
Tox: edema, HTN, tremor
120
Azathioprine
anti 6-mercaptopurine --> block nucleotide synthesis
Used in Rheumatoid arthritis, crohns, glomerulonephritis
Tox: pancytopenia
121
Mycophenylate Mofetil
Reversibly inhibit IMP dehydrogenase --> no purine synthesis in B and T cells
Use in lupus nephritis
Tox: GI, pancytopenia, HTN, hyperglycemia
122
glucocorticoids
inhibit NFkB --> suppress B and T cells
Used in autoimmune diseases, inflammatory disorders, adrenal insufficiency, asthma, CLL, NHL
Tox: cushings, oseoporosis, hyperglycemia, DM, amenorrhea, adrenocortical atrophy, peptic ulcers, avascular necrosis, cataracts
123
Alemtuzumab
Anti CD52
| Use in CLL, multiple sclerosis
124
Bevacizuman
Anti VEGF
| used in colorectal cancer, RCC, non small cell lung cancer
125
Rituximab
anti CD 20
used in B cell NHL, CLL, rheumatoid arthritis, ITP, multiple sclerosis
Risk of PML in patients with JC virus
126
Trastuzumab
anti HER2
| used in breast cancer, gastric cancer
127
adalimumab, infliximab
anti TNFa
| used in IBD, rheumatoid arthritis, ankylosing spondylitis, psoriasis
128
Eculizumab
anti C5
| used in paroxysmal nocturnal hemoglobinuria
129
Ixekizumab, seclukinumab
anti IL17A
| used in psoriasis, psoriatic arthritis
130
Natalizumab
anti a4-integrin
| used in multiple sclerosis, crohns
131
Ustekinumab
anti IL12 and IL23
| used in psoriasis and psoriatic arthritis
132
abciximab
anti platelet gp IIb/IIIa
| used in prevention of ischemic complication in patients undergoing percutaneous coronary intervention
133
Denosumab
anti RANKL
| used in osetoporosis, inhibit osteoclast maturation
134
Omalizumab
anti IgE
| used in refractory allergic asthma
135
Palivizumab
anti RSV F protein
| used in RSV prophylaxis for high risk infants.
