chapter 6 Flashcards
1
Q
What are features of innate immune
A
nonspecific
no memory
does not change with antigenic exposure
2
Q
What does the innate immune system manifest as
A
inflammation
3
Q
What are the 6 PRR?
A
- TLL
- Nod-like receptors
- GCPRs
- C-type lectin receptors
- Mannose-binding lectin receptors
- ROD-like receptors
4
Q
Where are the following receptors located?
- TLL
- NOD-like receptor
- C-type lectin receptors (CLR)
- GCPRs
- ROD-like receptors
A
- plasma membrane and endosome
- Cytosol of necrotic cells
- Plasma membrane of MO and DCs**
- neutrophils, MO and most leukocytes
- Cytosol
5
Q
What are the 3 responses of the innate immune system?
A
- inflammation
- protect against viruses using Type-1 interferons
- the adaptive immune respronse
6
Q
Adaptive immunity develops later and is stronger. It is mediated by lymphocytes, which have specific receptors for antigens, and antibodies. Consists of 2 types:
what types of microbes do they respond to?
A
- Humoral immunity; mediated by B cells and anitbodies and respond to EXTRACELLULAR microbes
- Cell-mediated immunty is mediated by T-cells and responds to INTRACELLULAR microbes
7
Q
What is clonal selection?
A
B4 lymphocytes respond to an antigen, they are already specific for certain antigens.
Lymphocytes will then bind to that antigen and activate/ make more that are specific that that antigen.
8
Q
What are our generative (primary/central) lymphoid organs?
A
- BM
2. Thymus
9
Q
What occurs in BM and thymus
A
BM: hematopoiesis (BM, leukocytes and plasma cells are made) and B-cells mature (become naive)
Thymus: T -cel mature (become naive)
10
Q
What is located in peripheral organs (secondary) and what occurs?
A
lymphocytes, APC and antigens
immune response
11
Q
What are 3 examples of peripheral organs
A
LN
spleen
MALT
12
Q
What occurs in LN
A
lymphocytes interact with antigens in circulation and undergo clonal expansion
13
Q
what occurs in spleen
A
lymphocytes interact with blood borne antigens
14
Q
MALT is made up of tonsils, adenoids and peyers patches) and is located where?
What is the purpose of it?
A
under the epithelial of skin, resp, GI tract
Allows lymphocytes to be near antigens of the mouth and GI tract
15
Q
How are B cells organized in LN?
What happens when B cells are activated
A
In follicles located peripherally with follicular DC, which present the antigen to them
A germinal center is created in the middle
16
Q
How are T cells located in the LN
A
Paracortex around follicles.
DC in the paracortex present antigen
17
Q
Lymphocyte recirculation is important for what cells?
A
T cells.
Mature the thymus into naive T-cell => peripheral lymphoid organ, where they will meet up with antigen => become effector T-cell which then goes to the site of infection
18
Q
why is lymphocyte less important to B-cells
A
Plasma cells stay in the lymphoid organ.
Follicular DCs present antigen to them and then they make AB that are secreted to go tothe site of infection
19
Q
Where are antigens concentrated
A
lymphoid organs
20
Q
in the case of immunization with a protein antigen, microbial mimics, called _____, are given with the antigen and these stimulate the ____ immune response
A
adjuvents
innate
21
Q
When does a lymphocyte stop being naive?
A
when an antigen binds
22
Q
When antigen binds, what happens
A
becomes:
- effector cell
- memory cell
23
Q
Lymphocytes can respond to multiple antigens, but what is the catch?
A
They can only be of 1 type!
24
Q
CD4+ Helper T cells
recognize what?
that are presented on what MHC, causing what to happen?
What is the action of what aoocured
A
Extracellular antigens (bacterial and allergens)
MHC Class II, located ONLY on APC=> release of cytokines
- Activate MO => phagocytose
- T and B cells
- Recruit leukocytes => inflammation
25
CD8+ CTLs
recognize what?
that are presented on what MHC, causing what to happen?
What is the action of what aoocured
Intracellular antigens (viral and tumors)
MHC Class I, located on all nucleated cells => secrete cytokines
Cytokines released will kill intracellular antigen
26
T-REG CELLS AXN
SUPRESS IMMUNE RESPONSE AND PREVENT SELF ANTIGEN
27
where are mature T-cells located?
1. blood (bc recirculate; 60-70% of lymphocytes)
| 2. T cell zone of peripheral lymphoid organs
28
Describe the TCR
1. TCR heterodimer: binds the antigen; 95% is ab
2. CD3 and zeta chains: noncovalently linked and are signal transducer; identical in all T-cells
3. CD4 ORRRR CD8+
29
How much of circulating lymphocytes are mature B=cells ?
10-20%
30
Where are mature B-cells located?
LN, spleen and MALT
31
What receptors and ligands are involved in CD4+ helper T-cells activating B-cells?
CD40 on B cell
CD40L on helper T-cell
32
How can the compliment system that occured in innate immunity activate B-cells?
Compliment products made during innate immunity will bind to CR2/CD21 receptors on the B cells.
33
What part of the BCR is relavant in hyper IgM syndrome?
CD40
34
DCs are the MOST IMPORTANT cells for initiating a ___-cell response.
What features of it allow it to do so?
T-cell
1. Expresses many receptors to recognize antigens
2. Expresses high levels of MHC
3. Go to peripheral LN in response to microbes
4. Located in epithelium and intersitium, where many antiges are made
35
Follicular DCs are found in _________ of lymphoid follicles in what peripheral lymphoid organs, where they do what
germinal center
spleen and LN
present to B-cells
36
Follicular DCs ahve receptors for which receptors that bind antigens
IgG
C3b
37
What are the 3 important actions of MO?
How are they important in cell-mediated immunity?
What about humoral-mediated immunity?
1. Phagocytosize and present to T-cell
2. kill ingested microbes
3. important in humoral immunity bc that phagocytosize and destroy microbes that were opsinized by IgG and C3b.
38
What is GM makes Classic cards mean?
IgG and IgM coat pathogens => activate the classical compliment pathway
39
Function of CD16 found of NK cells?
ADCC (antibody-dependent cell-mediated cytotoxicity)
NK cells have CD16, a Fc receptor for IgG.
1. NK cell uses CD16 to recognize cells coated in IgG => kills them
40
How do we control whether a NK cell will kill
Has activating and inhibiting receptor
+ receptor: NKG2D will recognize a damaged cell with virus/tumors that do NOT have class I receptor
- receptor: + of NK cell is inhibited if a cell has Class I MHC, which is present on all nucleated cells
41
actions of NK cells (3)
1. Recognize damaged cells (virus or tumor) and release perforin to kill => MO will then eat it up
2. Release IFN-y => + M1 macrophages to destroy intracellular microbe
3. ADCC: uses CD16 receptor to rexognize and kill antigens coated with IgG
42
What activates NK cells?
What do NK cells rlease nad what does it do?
IL2 and IL15
IL12 => + TH1 cells => IFN-y => + M1 MO
43
What does IL12 do?
+ TH1 cells => IFN-y => activate M1 MO to destroy intracellular microbe
44
Innate lymphoid cells?
what was the first defined ILC
actions
lack TCRs, but secrete cytokines
look like lymphocytes, but act like cells in innate imunity
NK cells
1. early defense in infection
2. Stress survailence
3. release cytokines to help with T -cell differnetiation
45
MHC are encoded on Chromosome 6 and they're HIGHLY polymorphic
do they function primarily in adaptive or innate immunity?
adaptive
46
MHC class 1 is made up of what?
Where are they located?
______ is encoded by what 3 genes?
heterodimer: a heavy chain and B2 microglobulin
on all nucleated cells and platelets
alpha heavy chain is encoded by HLA A/B/C
47
MHC Class 1 displays what antigens?
Binding groove?
Binding co-receptor
TM domain
Intracellular viral/tumors that were derived from proteins and presented as peptides
binding groove: a1 and a2
binding co-receptor: a3 (nonpolymorphic) has a binding spot for CD8+
tm domain: B2-microglobulin
48
MHC class 2 is made up of what?
Where are they located?
encoded by?
a-chain and b-chain
located on all APC: B cells, DCs and MO
HLDA-D has 3 subregions: DR/DQ/DP
49
MHC Class 2 displays what antigens?
Binding groove?
Binding co-receptor
TM domain
extracellular antigens (bacterial and allergy) and soluble proteins that were internalized into vesicles
binding site: a1 and B1
binding co=receptor: B2 has a binding site for spot for CD4+
50
How are MHC class I and 2 complexes different in how they preesnt their antigens?
MHC Class I (intracellular)
1. Intracelullar proteins => proteosomes, where they are broken down into peptides
2. => ER, where they load onto a1/a2 binding groove of HLA-A/B/C
3. HLA combines with B2 globilin to form a stable trimer => moves to surface
MHC Class II (extracellular bacteria and allergies and ingested proteins)
1. taken up into vesicles
2. go to endosome, where they are broken down into peptides by endosomal enzymes
3. combine with HLA-DQ/R/P and form a vesicle
4. go to surface
51
Main function of innate immune system is: inflammation and - viral replication
Cytokines are released mainly by what cells?
What are these cytokines?
MO, DC and neutrophils
IL1, 12, type IFN, IFN-y and TNF
52
Main function of adaptive immune system is: increase lymphocytes, differentiation and activation
Cytokines are released mainly by what cells?
What are these cytokines
CD4+ T cells
IL2, 4, 5, 17, IFN-y
53
Main function of hematopoeisis is to increase leukocytes and replace them
What releases what cytokines to stimulate hemotopoeiss?
Marrow, stroma, T cells and MO
GM-CSF and IL-7
54
which Igs have the shortest and longest half life
shortest: IgE
longest: IgG
55
Which IgG goes across placenta
IgG
56
IgE does what
binds to mast cells, eso, basophils with high affinity => kill parasites
57
when are mast cell sensitized in type 1 reactions
when IgE binds to the surface
58
Besides the second exposure of the allergen to mast cell in Type 1, what else can + the mast cell
C3a
C5a
==> mimic anaplaxais
59
Immediate phase of type I occurs minutes after d/t the release of what
1. vasoactive amines (histamine, enzymes and proteoglycans)
| 2. lipid mediators (leukotriene B4-E4, prostaglandin D2, PAF)
60
What does Leukotriene B4 do
recruit eosinphils, neutrophils and monocytes
61
What are the most potent VASOACTIVE and BRONCHIOSPASMIC AGENTS?
Leukotriene C4, D4, E4,
62
What is the most abundant mediator made by mast cells? what does it do?
prostaglandin D2
causes bronchospasm and increase mucus secretions
63
What lipid mediator is released in immediate type I reactions, but is the only one not made from AA?
Platelet activating factor
64
Sx in early phase response of type 1 reaxtion
vasodilation
edema
smooth muscle contraction
mucus secretion
65
why do local immediate phase reactions occur at the sites that they do?
Mast cells are located IN tissue NEAR BV, nears and subepithelial tissues.
66
How are basophils and mast cells different?
similar (both have IgE receptors and granules in cytplasm,
, but they are NOT in tissue, they circulate in blood.
67
What found inside Mast cells helps us to visualize them histologically?
Acidic proteoglycans which bind basic dyes such as touidine blue
68
Late phase occurs 2-24 hours later and is d/t the release of what?
cytokines and leukotrienes
69
What is the late phase characterized by
infiltration of the tissue with
```
eosinphils*****
neutrophils**
basophils*
monocytes
CD4+ T cells
```
and epithelial tissue damage
70
What do eosphilis do?
release
major basic protein,
proteolytic enzymes,
cationic protein
THAT DAMAGE MUCOSAL EPITHELIAL TISSUE
71
Which cytokines released by Mast cells and their functions?
1. TNF, IL-1 and chemokines => recruit leukocytes (which is key in late phase response)
2. IL4 => increases TH2
72
Sx in late phase:
mucosal epithelial cell damage allergic rhinits and asthma
73
[Q:] Which mediators are responsible for the intense immediate reactions characterized by edema, mucus secretion, and smooth muscle spasm?
histamine
leukotrienes
74
[Q:] Which mediators set the stage for the late-phase response by recruiting additional leukocytes?
cytokines and chemokines
75
Patient comes in with a type I hypersensitivity rxn. how do we treat?
early phase: anti-histamines (EPI)
late phase: anti-inflammtory drugs
76
[Q:] What molecule is chemotactic for eosinophils?
• eotaxin
77
Genetics and environment are big players in our predispostion to allergies. describe them
Genetics
1. Atopy: increased propensity to devvelop immediate hypersensitivity reactions: high IgE and IL-4
2. Mut on Chr 5, which encode cytokines in reaction
3. Mut on Chr 6, located near HLA complex
Evn: may be more imp?
Non-atopic allergy: allergy caused by non-antigenix stimuli that do NOT involve IgE or TH2: it is through that we get these bc our mast cells are ABNORMALLY SENSITIVE to non-immune stimuli
78
Systemic anaphlaxis key sz
1. Vascular shock
2. widespread edema
3. diff breathing
A. itching, hives, uticaria
B. bronchoconstriction and laryngeal edema (hoarse)
C. V/D, cramps and laryngeal obstruction
D hypotensive shock and death can occur in min- hours
79
Type 3 reactions (other name)
Reactions tend to be what? Although, what?
D/t:
SYSTEMIC -immune complex mediated
systemic, although, immune complexes seen to accumulate in the [kidney, lungs, skin and joints].
1. too many exogenous antigens present (acute serum sickness)
2. endogenous antigens (lupus)
3. infectios diseases
80
Type III Hypersensitivity preferentially involve what 3 organs/sites?
causing what?
1. Kidneys => glomerulonepritits
2. small BV => vasculitis
3. Joints => arthritis
81
What AB are usually involved in type 3
IgG
IgM
82
In step 3 of Type 3 sensitivity;
Inflammation and tissue injury
1. About 10 days after antigen introduction --> classical compliment system is activated => producing anaphylatoxins (C3a, 4a and 5a), attracting leukocytes (neutrophils) to immune complex, which release enzymes and causes what?
acute inflammatory rxc =>
1. fever
2. joint pain (arthralgia)
3. proteinuria
4. lymphadenopthy
5. uticaria
83
What is the difference between serum sickness and arthus reaction?
Serum sickness => systemic reaction
Arthus reaction=> local reaction
84
When single large non-protein antigen is introduced to the body, it caues a acute, self-limited diseases that goes away as the antigen is elimianted. When the antigen is removed, it is it goes away. What is this caused and what are examples
acute serum sickness
diptheria anti-toxin and post-strep glomerulonephritis
85
When single large non-protein antigen is introduced to the body, but the exposure is prolonged and causes chronic recurrent tissue injury. What is this called and what are examples
chronic serum sickness
lupus; a persistant AB response to autoantigens
86
inflammatory reaction caused when you inject antigen at a specific site in a previously immunized animal that has AB for the antigen
=> forms local immune complezes => localized necrosis and vasculitis
arthus reaction (experiment)
87
What is the morphology of type 3 mediated diseases
fibrinoid necrosis and nucleophilic infiltration
88
immunofluorescene of type 2 reactions will look how?
smooth and linear d/t deposits of immunoglobulin and compliment
89
immunofluorescene of type 2 reactions will look how?
grainy and lumpy
90
How will post-streptococcal differ in the <3 and kidney?
How will this differ on immunoflurosences
Post-step in the HEART => is a type 2 reaction => look smooth and linear
Post-strep in the KIDNEY => type 3 reaction and will look grainy
