Immuno FA - part I 96-108 Flashcards
1
Q
Primary lymphoid organs and function
A
Bone marrow—immune cell production, B cell maturation Thymus—T cell maturation
2
Q
Secondary lymphoid organs and function
A
Spleen, lymph nodes, tonsils, Peyer patches Allow immune cells to interact with antigen
3
Q
What happens in a lymphoid follicle? Loc where in a lymph node?
A
Site of B-cell localization and proliferation. , in outer cortex
4
Q
Diff between primary and 2ndary follicle?
A
1° follicles are dense and dormant. 2° follicles have pale central germinal centers and are active
5
Q
What do medullary sinuses contain?
A
reticular cells and macrophages.
6
Q
What is in the paracortex?
A
T cells
7
Q
What disease has under developed paracortex?
A
DiGeorge syndrome
8
Q
What part of the lymph node enlarges during viral infections?
A
Paracortex - Paracortex enlarges in an extreme cellular immune response (eg, EBV and other viral infections paracortical hyperplasia lymphadenopathy).
9
Q
What is contained in the white pulp of a spleen?
A
T cells are found in the periarteriolar lymphatic sheath (PALS) within the white pulp (white arrows in A). B cells are found in follicles within the white pulp.
10
Q
What’s in the marginal zone?
A
The marginal zone, in between the red pulp and white pulp, contains macrophages and specialized B cells, and is where antigen presenting cells (APCs) capture blood-borne antigens for recognition by lymphocytes.
11
Q
Which bacteria are cleared by the spleen? ex/
A
encapsulated bacteria - Pseudomonas aeruginosa, Streptococcus pneumoniae A, Haemophilus influenzae type b, Neisseria meningitidis, Escherichia coli, Salmonella, Klebsiella pneumoniae, and group B Strep (S. agalacticae)
Please SHiNE my SKiS
12
Q
How does splenic dysfunction lead to inc susceptibility to encapsulated organisms?
A
dec IgM –> dec complement activation –> dec C3b opsonization
13
Q
Blood finding post splenectomy?
A
Howell-Jolly bodies (nuclear remnants) Target cells Thrombocytosis (loss of sequestration and removal) Lymphocytosis (loss of sequestration)
14
Q
Which vaccines do splenectomy patients need?
A
N meningitidis S pneumoniae H influenzae
15
Q
Embryonic origin of thymic lymphocytes and epithelium?
A
Thymus epithelium is derived from Third pharyngeal pouch (endoderm), whereas thymic lymphocytes are of mesodermal origin
16
Q
What is in the cortex and medulla of the thymus?
A
Cortex is dense with immature T cells;
Medulla is pale with Mature T cells and Hassall corpuscles containing epithelial reticular cells
17
Q
Neoplasm of thymus assoc with which diseases?
A
Associated with myasthenia gravis, superior vena cava syndrome, pure red cell aplasia, Good syndrome.
18
Q
How to innate immune cells recognize pathogens?
A
Toll-like receptors (TLRs): pattern recognition receptors that recognize pathogen-associated molecular patterns (PAMPs) and lead to activation of NF-κB.
19
Q
Ex of PAMPs?
A
Examples of PAMPs include LPS (gram ⊝ bacteria), flagellin (bacteria), nucleic acids (viruses), dectin1 (fungi)
20
Q
MHCs are encoded by which genes?
A
HLA genes
21
Q
Fxn of MHC?
A
Present antigen fragments to T cells and bind T-cell receptors (TCRs).
22
Q
Loci of MHC I and MHC II?
A
HLA-A, HLA-B, HLA-C MHC I loci have 1 letter HLA-DP, HLA-DQ, HLA-DR MHC II loci have 2 letters
23
Q
What binds to MHC I and II?
A
MHC I - TCR and CD8 MHC II - TCR and CD4
24
Q
Structure of MHC I and II?
A
MHC I - 1 long chain, 1 short chain MHC II - 2 equal-length chains (2 α, 2 β)
25
Where is MHC I and II expressed?
MHC I - All nucleated cells, APCs, platelets (except RBCs) MHC II - APCs
26
Function of MHC I and MHC II?
MHC I - Present **endogenous** antigens (eg, viral or cytosolic proteins) to **CD8+ cytotoxic T cells**
MHC I - **In** - endogenous
MHC II - Present **exogenous** antigens (eg, bacterial proteins) to **CD4+ helper T cells**
27
How are antigens loaded on to MHC I and MHC II?
MHC I - Antigen peptides loaded onto MHC I in RER after delivery via TAP (transporter associated with antigen processing) MHC II - Antigen loaded following release of invariant chain in an acidified endosome
28
Proteins associated by MHC I and MHC II?
MHC I - B2 microglobulin MHC II - invariant chain
29
Disease assoc w/ HLA subtype A3
Hemochromatosis HA3mochromatosis.
30
Disease assoc w/ HLA subtype B8
Addison disease, myasthenia gravis, Graves disease Don't Be late(8), Addison, or else you'll send my patient to the grave.
31
Disease assoc w/ HLA subtype B27
Psoriatic arthritis, Ankylosing spondylitis, IBD-associated arthritis, Reactive arthritis PAIR. Also known as seronegative arthropathies.
32
Disease assoc w/ HLA subtype C
Psoriasis
33
Disease assoc w/ HLA subtype DQ2/DQ8
Celiac disease I ate (8) too (2) much gluten at Dairy Queen.
34
Disease assoc w/ HLA subtype DR2
Multiple sclerosis, hay fever, SLE, Goodpasture syndrome Multiple hay pastures are TWO dirty (DR2).
35
Disease assoc w/ HLA subtype DR3
DM type 1, SLE, Graves disease, Hashimoto thyroiditis, Addison disease 2-3, S-L-E.
36
Disease assoc w/ HLA subtype DR4
Rheumatoid arthritis, DM type 1, Addison disease There are 4 walls in 1 “rheum” (room).
37
Disease assoc w/ HLA subtype DR5
Hashimoto thyroiditis Hashimoto is an odd Dr (DR3, DR5).
38
How do NK cells induce apoptosis?
using perforins and granzymes or by antibody-dependent cell-mediated cytotoxicity (CD16 binds Fc region of bound IgG, activating the NK cell).
39
NK cell activity activated by ?
enhanced by IL-2, IL-12, IFN-α, and IFN-β.
40
How is NK cell induced to kill?
Induced to kill when exposed to a nonspecific activation signal on target cell and/or to an absence of MHC I on target cell surface.
41
Functions of B cells
Humoral immunity. Recognize antigen—undergo somatic hypermutation to optimize antigen specificity. Produce antibody—differentiate into plasma cells to secrete specific immunoglobulins. Maintain immunologic memory—memory B cells persist and accelerate future response to antigen.
42
Functions of T cells
Cell-mediated immunity.
CD4+ T cells help B cells make antibodies and produce cytokines to recruit phagocytes and activate other leukocytes.
CD8+ T cells directly kill virus-infected cells.
Delayed cell-mediated hypersensitivity (type IV).
Acute and chronic cellular organ rejection.
43
Explain where/how positive selection in the thymus happens
Thymic cortex. T cells expressing TCRs capable of binding self-MHC on cortical epithelial cells survive.
44
Explain where/how negative selection in the thymus happens?
Thymic medulla. T cells expressing TCRs with high affinity for self antigens undergo apoptosis or become regulatory T cells
45
Issue with tissue restricted self antigen expression def?
Deficiency leads to autoimmune polyendocrine syndrome-1.
46
How are self antigen expressed in the thymus?
action of autoimmune regulator (AIRE)
47
What do Th1 cell secrete?
IFN-γ, IL-2
48
Function of Th1 cell?
Activates macrophages and cytotoxic T cells to kill phagocytosed microbes
49
Stimulation/Inhibition of Th1 cell?
**Th1:**
(+) by IFN-γ, IL-12
IFNy - from Th1 cells, so self stimulation
IL12 - from mac, T cells --\> Th1 thru IL 12
(-) by IL-4, IL-10 (from Th2 cell)
Th2 (-) Th1
50
Th2 cells secrete?
IL-4, IL-5, IL-6, IL-10, IL-13
51
Function of Th2 cells?
Activates eosinophils and promotes production of IgE for parasite defense
52
Stimulation/Inhibition of Th2 cell?
(+) by IL-2, IL-4 (-) by IFN-γ
53
Secreted by Th17 cell?
IL-17, 1L-21, IL-22
54
Fxn of Th17 cell?
Immunity against extracellular microbes, through induction of neutrophilic inflammation
55
Stimulation/Inhibition of Th17 cell?
T17:
(+) by TGF-β, IL-1, IL-6
TGF-B - from Treg?
IL-1 & IL-6 - start of neutrophilic inflammation --\> (+) T17
(-) by IFN-γ, IL -4
IFN-y - from Th1
IL 4 - from Th2
56
Immunodef of Th17 leads to?
Hyper IgE syndrome
57
Treg secretes?
TGF-β, IL-10, IL-35
58
Fxn of Treg?
Prevents autoimmunity by maintaining tolerance to self antigens
59
Stimulation/Inhibition of Tregs?
(+) by TGF-β, IL-2 (-) by IL-6
60
Immunodef of Treg?
IPEX
61
How do T cells and macrophages interact?
Th1 cells secrete IFN-γ, which enhances the ability of monocytes and macrophages to kill microbes they ingest. This function is also enhanced by interaction of T cell CD40L with CD40 on macrophages.
62
Fxn of Tc cells?
Kill virus-infected, neoplastic, and donor graft cells by inducing apoptosis. Release cytotoxic granules containing preformed proteins (eg, perforin, granzyme B). Cytotoxic T cells have CD8, which binds to MHC I on virus-infected cells.
63
Fxn of Treg cells?
Help maintain specific immune tolerance by suppressing CD4 and CD8 T-cell effector functions.
64
Genetic def of FOXP3 leads to?
IPEX (Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked) syndrome
65
Sx of IPEX?
Characterized by enteropathy, endocrinopathy, nail dystrophy, dermatitis, and/or other autoimmune dermatologic conditions. Associated with diabetes in male infants.
Sx/ severe watery diarrhea, mult exczematous rashes, born w/ hyperglycemia
66
Give Ex of APCs?
B cells, dendritic cells, Langerhans cells, macrophages
67
List the two signal req for T cell activation after an APC presents an Ag?
T-cell activation (signal 1): antigen is presented on MHC II and recognized by TCR on Th (CD4+) cell. Endogenous or cross-presented antigen is presented on MHC I to Tc (CD8+) cell. Proliferation and survival (signal 2): costimulatory signal via interaction of B7 protein (CD80/86) on dendritic cell and CD28 on naïve T cell.
68
Two signal req for B cell activation/class switching?
B-cell receptor–mediated endocytosis; foreign antigen is presented on MHC II and recognized by TCR on Th cell. CD40 receptor on B cell binds CD40 ligand (CD40L) on Th cell.
69
Fab region of Ab - what parts and fxn?
Fab (containing the variable/hypervariable regions) consisting of both light (L) and heavy (H) chains ;recognizes antigens.
70
Fc region of Ab - what parts and fxn?
Fc region of IgM and IgG fixes complement, and where macrophages bind. only heavy chain
71
What region of Ab determines idiotype?
Fab region
72
Each B cell expresses specficity for how many Ag?
1 Ag
73
What region of Ab determines isotype?
Fc region
74
4 Cs of Fc region?
Fc: Constant Carboxy terminal Complement binding Carbohydrate side chains
75
How do we form diverse Ab without an Ag binding?
1. Random recombination of VJ (light-chain) or V(D)J (heavy-chain) genes 2. Random addition of nucleotides to DNA during recombination by terminal deoxynucleotidyl transferase (TdT) 3. Random combination of heavy chains with light chains
76
How do we make Ab specific to an Ag?
4. Somatic hypermutation and affinity maturation (variable region) 5. Isotype switching (constant region)
77
What Ab do B cells express prior to activation?
All isotypes can exist as monomers. Mature, naïve B cells prior to activation express IgM and IgD on their surfaces.
78
When do B cells produce other Ab?
They may differentiate in germinal centers of lymph nodes by isotype switching (gene rearrangement; induced by cytokines and CD40L) into plasma cells that secrete IgA, IgE, or IgG.
79
What is the main Ab that responds to Ag - primary and secondary response?
primary - IgM secondary - IgG
80
Most abundant isotype in serum?
IgG
81
Fxn of IgG?
Fixes complement, opsonizes bacteria, neutralizes bacterial toxins and viruses.
82
Which isotype of Ab crosses through the placenta? What type of immunity does it convey?
IgG ; passive immunity
83
How does IgA help fight bacteria and virus infection?
Prevents attachment of bacteria and viruses to mucous membranes;
84
What forms of IgA are there?
Monomer (in circulation) or dimer (with J chain when secreted)
85
IgA is formed where (ex/) in the GI tract, fxn there?
Produced in GI tract (eg, by Peyer patches) and protects against gut infections (eg, Giardia).
86
Where is IgA released?
Released into secretions (tears, saliva, mucus) and breast milk.
87
Where does IgA pick up its secretory component? Fxn?
Picks up secretory component from epithelial cells, which protects the Fc portion from luminal proteases
88
Which two Ig fix complement?
IgM, IgG
89
Forms of IgM?
Monomer on B cell, pentamer with J chain when secreted
90
What types of cells does IgE bind to ?
mast cells and basophils
91
What does IgE do in an allergic rxn?
cross-links when exposed to allergen, mediating immediate (type I) hypersensitivity through release of inflammatory mediators such as histamine
92
Which Ig is in lowest conc in serum?
IgE
93
Difference between thymus independent and dependent antigens?
Independent Ag lacks a peptide component and can't be presented by MHC to T cells, dependent Ag have a protein component
94
Complement derived membrane attack complex defends against what organisms?
MAC defends against G - bacteria
95
Function of C3b?
Binds to lipopolysaccharides on bacteria (as an opsonin), also helps clear immune complexes
96
Function of different complement proteins
C3b—opsonization. C3a, C4a, C5a—anaphylaxis. C5a—neutrophil chemotaxis C5b-9—cytolysis by MAC.
97
Major opsonins in bacterial defense?
C3b and IgG
98
What inhibits complement activation on self cells?
DAF (decay accelerating factor CD55) and C1 esterase inhibtor
99
what do opsonins do?
enhance phagocytosis
100
Early complement deficiencies (C1-C4) - inc risk of what?
inc risk of severe, recurrent pyogenic sinus and respiratory tract infections. Increased risk of SLE.
101
Terminal complement deficiencies (C5–C9) - inc risk of ?
susceptibility to recurrent Neisseria bacteremia.
102
cause of hereditary angioedema? what drug causes angioedema due to similar mech?
C1 esterase inhibitor deficiency Causes hereditary angioedema due to unregulated activation of kallikrein --\> inc bradykinin. ACE inhibitors are contraindicated (also inc bradykinin).
103
How to detect c1 esterase inhibitor def/
dec C4 levels
104
Tx for hereditary angioedema?
Danazol
105
Disease with issue forming glycosylphosphatidylinositol (GPI) anchors for complement inhibitors?
PNH (Paroxysmal nocturnal hemoglobinuria)
106
ex of complement inhibitors
decay-acclerating factor (DAF/CD55) and membrane inhibitor of reactive lysis (MIRL/CD59)
107
gene defective in PNH?
PIGA
108
Drug vs PNH? Mech?
Eculizumab - vs. C5
109
Fxn IL 1 - secreted by?
From macrophages
* Causes fever, acute inflammation.
* Activates endothelium to express adhesion molecules.
* Induces chemokine secretion to recruit WBCs.
* Also known as osteoclast-activating factor.
110
IL 2 - secreted by? Fxn? Rx that is an analogue of it?
From all T cells
* Stimulates growth of helper, cytotoxic, and regulatory T cells, and NK cells.
* Aldesleukin - Renal Cell CA, Malignant melanoma
111
IL 3 - secreted by? Fxn?
Rx that functions like GM- CSF?
From **all T cells**
* Supports **growth** and differentiation of **bone marrow stem cells.**
* Functions like GM-CSF. Stimulates the **myeloid cell line** - formation of granulocytes,etc
IL 3 --\> M
* Filgrastim - fxn like GM-CSF
112
IL 4 - secreted by? Fxn?
**From Th2 cells**
* Induces differentiation of T cells into Th (helper) 2 cells.
* Promotes **growth of B cells.**
* Enhances class switching to IgE and IgG.
IL4 = **G**oes 4 **E**ver ==\>Ig**G,** Ig**E**
Ain’t too proud 2 BEG 4 help. 2 - Th2 cells B - B cells EG - IgE IgG
113
IL 5 - secreted by? Fxn?
**From Th2 cells**
* growth and differentiation of B cells.
* Enhances class switching to IgA.
* Stimulates growth and differentiation of eosinophils
114
IL 6 - secreted by? Fxn?
**From Macrophages**
* Causes **fever**
* stimulates production of **acute phase proteins**.
115
IL 7 -
stimulates the lymphoid precursor line
116
IL 8 - secreted by? fxn?
**by macrophages**
Major chemotactic factor for **neutrophils**
117
Interleukin-10 - secreted by? fxn?
**IL10
Secreted by Th2 and Treg cells**
* At**ten**uates inflammatory response.
* **Decreases expression of MHC class II a**nd Th1 **cytokines.**
* **Inhibits activated macrophages and dendritic cells.**
118
Tumor necrosis factor-α - secreted by? fxn?
TNF alpha:
**from macrophages**
* Activates endothelium.
* Causes WBC recruitment, vascular leak.
* Causes cachexia in malignancy.
* Maintains granulomas in TB.
* IL1, IL6 and TNF a all mediate fever, sepsis
119
Interferon-γ - secreted by? fxn?
**From NK and Th1 cells (1 = I (INF))**
* _Secreted by NK cells and T cells_ in response to antigen or IL-12 from macrophages;
* **stimulates macrophages** to kill phagocytosed pathogens.
* **Inhibits** differentiation of **Th2 cells.**
* Also **activates NK cells to kil**l virus-infected cells.
* **Increases MHC expression and antigen presentation** by all cells
120
IL 12 - secreted by? fxn?
**by macrophages**
* Induces differentiation of T cells into Th1 cells.
* Activates NK cells.
121
Which two cytokines attenuate immune response
TGF-B & IL10
TGF-**β** and IL-**10** **b**oth at**ten**uate the immune response.
122
What is produced by Macrophages? (IL, etc)
IL 1 - fever, inflammation
IL 6 - fever, APP
IL 8 - neutrophils
IL12 - T --\> Th1, (+) NK
TNF alpha - endothelium (+)'n, cachexia, granulomas in TB
