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Immunity, Autoimmune disease, Immunodeficiency Flashcards

PBVD Ch. 5, R&C Ch. 6 (96 cards)

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1
Q

What antimicrobial molecules do epithelia produce?

A

Defensins

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2
Q

What is the role of Innate Lymphoid Cells? Example?

A

Tissue resident lymphocytes that are activated by cytokines and are a source of cytokines in early immune reactions; NK cell

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3
Q

Which complement pathways are part of innate immunity? adaptive?

A

Lectin and alternative; classical (Ab-Ag complexes)

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4
Q

What proteins of innate immunity coat microbes and promote phagocytosis (not complement)

A

Mannose binding lectin and C-reactive protein

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5
Q

Receptor for IgG coated cells that stimulate Antibody dependent cellular cytotoxicity

A

Fc receptor (CD16) on NK cells

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6
Q

Two transcription factors activated by TLRs

A

NF-kappaB that stimulate release of cytokines and expression of adhesion molecules
IRFs (interferon regulatory factors) that stimulate production of type I interferons

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7
Q

Cytosolic receptors and their signals

A

NOD-like receptors- damaged cell products, microbial products
RIG-like receptors- viral RNA

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8
Q

How do NOD-like receptors work?

A

Bind to caspase 1, forms the inflammasome, activates caspase 1, which cleaves precursor IL-1

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9
Q

Role of IL-1

A

Recruits leukocytes and induces fever

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10
Q

Cell membrane receptors and their signals

A

C-type lectin- fungal glycans
TLRs- many

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11
Q

What molecule do neutrophils use G protein-coupled receptors to chemotax toward bacteria?

A

N-formylmethionine

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12
Q

What do NK cells produce upon activation? What inhibits their activation?

A

IFN-gamma- activates macrophages
Inhibitory receptors recognize MHC I

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13
Q

What cytokines stimulate NK cell proliferation?

A

IL-2 and IL-15

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14
Q

What cytokine stimulates NK cells to kill and secrete IFN gamma

A

IL-12

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15
Q

Enzyme in lymphocytes involved in somatic recombination and antigen receptor diversity

A

RAG1 and RAG2

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16
Q

What are the components of a T cell receptor; what is it linked to? Other two parts of the complex?

A

Alpha and beta chain heterodimer, each with a variable region
Linked to CD3 complex- 6 invariable proteins
CD4 or 8- coreceptors (binds MHCII or I)
CD28- 2nd signal (binds CD80 or CD86/B7)

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17
Q

What makes up the B cell receptor? Other parts of the complex?

A

IgM and IgD membrane bound antibodies
Heterodimer of two invariant proteins (Igalpha and Igbeta) aka CD79 a and b
Type 2 complement receptor (CR2 aka CD21)- recognize complement
CD40- bind CD40L on T helper cell

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18
Q

Features of follicular dendritic cells

A

In germinal centers
Bear Fc receptors for IgG and receptors for C3b
Present antigens to B cells, become plasma or memory cells

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19
Q

Most important APC for T cell response

A

Dendritic cells

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20
Q

Three jobs of macrophages

A

APC for T cell response
Activated by T cells to kill infected cells?
Phagocytose and destroy microbes opsonized by IgG or C3b (humoral)

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21
Q

Which cells express CD40?

A

Macrophages and B cells

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22
Q

What molecules stimulate IgM production?

A

Polysaccharides and lipids

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23
Q

What molecules stimulate IgG, IgA, or IgE production?

A

Proteins via CD40L and helper T cells (isotype switching)

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24
Q

What induces isotype switching of antibodies?

A

T cells producing IFNgamma and IL4

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25
What do IgG and IgM do? What else does IgG do?
Activate classical complement; opsonize microbes for recognition by APCs with Fc receptors for IgG
26
What special thing does IgA do? IgE? IgG?
Mucosal immunity; mast cell and eosinophil activation (allergy); newborn immunity
27
Who expresses MHC Class I? Components? What two components bind antigen? What site binds CD8?
Nucleated cells and platelets; Alpha heavy chain (1, 2, 3) and beta2 microglobulin; alpha1 and alpha 2; alpha3
28
Who expresses MHC Class II? Components? What two components bind antigen? What site binds CD4?
APCs, B lymphocytes; alpha (1 and 2) and beta (1 and 2) heavy chains; alpha 1 and beta 1; beta2
29
Main source of cytokines in adaptive immunity
CD4+ T lymphocytes
30
Cytokines that serve to terminate immune response
TGF-beta and IL-10
31
What stimulates affinity maturation?
Helper T cells, follicular type, in germinal centers
32
What type of T cell response causes Type I hypersensitivity? Cells and molecules involved; example?
Th2; IgE, mast cells; allergy, anaphylaxis
33
What sensitizes mast cells? What activates mast cells? Other causes of mast cell activation
IgE; Crosslinking of IgE; C5a, C3a, IL-8, drugs (codeine, adenosine, bee venom), physical stimuli (heat, cold, sunlight)
34
What from eosinophils contributes to type I HS
Major Basic Protein
35
Most sensitive species to anaphylaxis?
Guinea pigs
36
Immediate type I hypersensitivity features; late-phase features
Vasodilation, congestion, edema; inflammatory infiltrate of eos, neutrophils, T cells
37
What receptor does IgE bind to on mast cells?
FcepsilonRI
38
How is ADCC different from opsonization and phagocytosis via IgG and IgM
No phagocytosis, NK cells and macrophages kill cells coated in antibody whereas opsonization activates complement and phagocytosis
39
What mediates Type II HS?
Secreted IgG and IgM antibodies then ADCC, opsonization, phagocytosis,
40
Examples of Type II HS?
IMHA, pemphigus, drug reactions, transfusion reactions
41
Example of Type II HS due to cellular dysfunction, not inflammation
Myasthenia gravis- Abs interfere with function of Ach receptors
42
What mediates Type III HS?
Ab-Ag complexes, IgG and IgM, activate complement, phagocytosis, platelet aggregation, coag factors
43
Examples of Type III HS?
SLE, glomerulonephritis, vasculitis, arthritis
44
What mediates Type IV HS?
Cytokines produced by CD4+ T cells, aka cell-mediated, Th1 (macrophage dominated) and Th17 (neutrophil dominated) cells; can also be CD8 direct cytolysis
45
Examples of Type IV HS?
Tuberculosis, Equine recurrent uveitis, rheumatoid arthritis, poison ivy, allergic contact dermatitis (haptens)
46
Link between type III HS and coag cascade
Complexes activate factor XII (Hageman factor), which activates kinins and causes vasodilation and edema
47
How do CD8+ T cells kill cells?
Release granzymes, perforins into immunologic synapse, and express Fas ligand to also induce apoptosis
48
Where does central tolerance occur for T cells? B cells?
Thymus; bone marrow
49
What is central tolerance for T cells?
Positive selection for T cells that recognize MHC; Negative selection of T cells that recognize self antigen bound to MHC
50
What protein mediates expression of self-antigens in the thymus for negative selection?
Autoimmune regulator (AIRE)
51
What happens to T cells that are self-reactive in the thymus?
Undergo apoptosis via Fas-FasL Become Treg cells Escape
52
What happens to B cells that are self-reactive?
Antigen receptor gene rearrangement- receptor editing Apoptosis
53
What is peripheral tolerance?
Back up system in case self-reactive cells escape central tolerance
54
What three mechanisms of peripheral tolerance are there?
Anergy Treg suppression Deletion by apoptosis
55
What causes anergy of T cells (2)? B cells?
Self-reactive T cell presented with self-antigen, and does not receive second signal, or receives inhibitory signal from CTLA-4; No CD40L from Th cells
56
Features of regulatory T cells
CD4+ Express CD25 (IL-2 receptor)- require IL-2 FOXP3 Secrete IL-10 and TGFbeta
57
Mechanisms of apoptosis in peripheral tolerance
Unopposed Bim expression Activation induced cell death- if persistently activated, express Fas
58
What is the hallmark of SLE?
Production of autoantibodies (ANAs, IgGs)
59
What type of HS is SLE?
Type III
60
What MHC allele is SLE associated with in dogs? ANAs usually against?
DLA-A7; Histones
61
Arms of immunity involved in SLE
Humoral and cellular- Too many CD4 cells and too many self-reactive B cells
62
Clin path findings with SLE
Lymphopenia with high CD4:CD8 ratio
63
What are LE cells?
Phagocytes that have engulfed an LE body, which are ANAs on free nuclei
64
What is Sjogren-like syndrome? Presentation in cats? In dogs?
KCS, xerostomia, sialoadenitis; Lymphoplasmacytic sialoadenitis with primarily B cells; KCS with primarily CD4+ T cells and hypergammaglobulinemia
65
What type of HS is juvenile polyarteritis?
Beagle pain syndrome- type III
66
Immunologic features with beagle pain syndrome?
IL-6 (stimulates B cells) and IgA elevated, ANA negative
67
Direct transplant rejection
Donor APCs present antigen to recipient T cells- CD8+ response, acute
68
Indirect transplant rejection
Recipient APCs present antigen to recipient T cells- antibody production, chronic
69
Three examples of innate immunodeficiencies
Leukocyte adhesion deficiency Chediak-Higashi Syndrome Complement deficiencies
70
What is Type I LAD?
Mutations in Beta2 chain subunits of CD18/CD11 integrins (on LFA-1, MAC-1, CR-2), so can't bind ICAMs on endothelium
71
What is Type II LAD?
Can't synthesize sialyl-Lewis X, so can't interact with E- or P-selectins on endothelium
72
Cause of Chediak-Higashi
Autosomal recessive LYST gene mutation, so can't fuse lysosomes and phagosomes
73
Clinical presentation of Chediak- Higashi
Enlarged granules, impaired immunity, hypopigmentation, coagulopathy
74
Most common complement deficiency; least severe one? Associated with what?
C2; C2; SLE- can't clear immune complexes
75
Most severe complement deficiency; what breed?
C3; Brittany spaniels get autosomal recessive deficiency
76
What happens with a Factor H deficiency? Who gets it?
C3b excess accumulation; Norwegian Yorkshire pigs, end up with type II membranoproliferative glomerulonephritis
77
SCID heritability; cells affected
X-linked or autosomal recessive; T or B cells, or both
78
Who is predisposed to X-linked SCID; pathogenesis
Males, Bassett hounds, Welsh corgis; Mutation in gamma subunit of cytokine receptors, so no mature T lymphocytes, and then no B cells activated
79
Who is predisposed to autosomal recessive SCID?
Arabian foals, CB-17 mice Can't produce variable region of antibody or antigen receptor, so no functional T or B cells
80
Other causes of autosomal recessive SCID?
Deficiency in adenosine deaminase (ADA), so accumulate deoxyadenosine, which is toxic to T cells Deficiency in RAG gene, so can't do somatic gene rearrangement
81
What is agammaglobulinemia? Who gets it? Heritability?
B cell precursors can't mature; Horses; X-linked
82
What is DiGeorge Syndrome?
Thymic hypoplasia, failure of development of 3rd and 4th pharyngeal pouch, so no T cells
83
Who gets an IgA deficiency?
GSDs, Shar-peis, Irish setters, beagles
84
Who gets a hyper-IgM syndrome? Cause?
Humans, dogs, horses; Mutation in CD40L, preventing class switching
85
What does HIV target?
CD4+ T cells
86
What are the two HIV glycoproteins? Where are they and what do they do?
gp120- surface, binds CD4, then CCR5 gp41- transmembrane, membrane fusion and release of RNA into cell
87
How does HIV work once viral genome enters cell?
viral RNA uses it's own reverse transcriptase to form cytoplasmic DNA, which chills until the cell divides, then enters the genome. Chills there until cytokine activation, then replication and shedding, cell lysis
88
Why can't HIV infect naive T cells?
APOBEC3G enzyme mutates viral DNA
89
gag gene function
Polyprotein that forms matrix protein (p17), capsid protein (p24), nucleocapsid protein (p7)
90
pol gene function
Polymerase that forms protease, reverse transcriptase, etc.
91
env gene function
gp160 envelope protein, cleaved into gp120 and gp41
92
What transcription factor stimulates transcription of virus upon activation of T cells; how?
NFkappaB; HIV genome has NFkappaB binding sites
92
How does HIV cause recruitment of other inflammatory cells?
Inflammasome activation and pyroptosis
93
Why does HIV cause syncytia?
gp120 expression on infected cells
94
What other cells does HIV infect, but doesnt kill?
Macrophages/monocytes, microglia, dendritic cells
95
What cell types are not infected by HIV
Neurons, B cells, CD8+ T cells

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