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Phase I > Robbins chapter 6 > Flashcards

Robbins chapter 6 Flashcards

1
Q

Chediak Higashi syndrome: what can be seen in the leucocytes at the microscope?

A

giant granules, resulting from aberrant phagolysosome fusion (defective fusion of phagosomes and lyzosomes)

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2
Q

Give one more manifestation of cheddiak higashi syndrome (other than granules in leucocytes)

A

abnormalities in melanocyte (leading to albinism), nervous system (nerve defects), platelets (bleeding disorders)

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3
Q

Explain the pathogeny of chronic granulomatous disease?

A

defect in microbicidal activity: neutrophils are insufficient-> macrophage rich chronic inflammation to control the infection when the initial neutrophil defense is inadequate

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4
Q

Read on complement deficiencies

A

p242

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5
Q

SCID (severe combined immunodeficiency): defects in humoral or/and cell mediated?

A

both (humoral secondarily). Sometimes X linked. Many different causes ex: mutaion in RAG or JAK3 or kinases

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6
Q

In addition to infections, what are people with Iga deficiency more at risk of?

A

autoimmune disease

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7
Q

How does pretein malnutrition cause immunodeficiency? (1 type of leucocyte)

A

metabolic derangement inhibit lymphocyte maturation and function

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8
Q

Is the complement innate or adaptive immunity?

A

Both

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9
Q

what are innate lymphoid cells?

A

lymphocytes that lack T-cell antigen receptors and cannot respond to antigens but instead are activated by cytokines and other mediators produced at site of tissue dammage

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10
Q

Microbial structures that are shared amongst many microbes, often essential for infectivity (cannot be mutated). They are recognized by innate immunity. What are they?

A

PAMPs. Pattern recognition receptors (ex: toll like) are also recognizing molecules released by injured and necrotic cells. These receptors are located in all cellular compartments where microbes may be present (cytosol, endosome, membrane).

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11
Q

Name an example of pattern recognition receptors (other than toll like)

A

NOD-like receptor, cytosolic receptor recognizing products released from necrotic/damaged cells (ATP, uric acid), loss of K+ ions and some microbial products

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12
Q

Differences between the 3 types of amyloid: amyloid light chain, amyloid associated protein, beta amyloid

A

light chain: immunoglobulin
amyloid associated protein: non Ig protein made by the liver, beta amyloid: cerebral plaques (alzheimer)

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13
Q

Different types of amyloidosis (3) and their meanings

A

primary (plasma clonal cells), secondary (complication of chronic inflammation process), hereditary

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14
Q

3 broad causes of metastatic calcification

A

increased secretion of PTH, resorption of bone tissue (ex: tumor of bone marrow), vitamin D excess/sensitivity, renal failure

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15
Q

infections can trigger autoimmune reactions by 2 main processes + others

A
  1. upregulate expression of costimulators on APC
  2. microbes expressing antigens that share amino acid sequences with self antigens

others: certain viruses cause polyclonal B cell activation, which may lead to the production of autoantibodies

others: tissue injury releases and structurally modify self antigens, creating neoantigens able to activate T cells

Others: production of cytokines that recuite lymphocytes, potentionally self reactive

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16
Q

C type lectins are expressed on which cells?

A

dendrocytes and macrophages. They detect fongiha

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17
Q

what are named receptors that are in the cytosol and detect viral nucleid acid?

A

RIG-like.

stimulate the production of antiviral cytokine like interferon alpha(STING pathway)

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18
Q

Which receptor express NK cells? what is it for?

A

IgG coaed target cells

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19
Q

which cytokine does NK cell secretes to activate macrophages

A

Interferon gamma (IFN gamma)

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20
Q

what is the name of the enzyme that mediates recombination of gene segments for antigen receptorss in lymphocytes?

A

RAG

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21
Q

What is alphabeta TCR

A

the most common T cell receptor

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22
Q

What is the antigen binding component of the b cell receptor complex?

A

IgM and IgD. present en the surface of all mature naive B cells

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23
Q

which are the most important antigen presenting cells for intiating t cell response against protein antigens?

A

Dendritic cells

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24
Q

3 processes/causes of amyloidosis

A

mutation, misfolding and aggregation, incomplete proteolytic degradation of extracellular proteins

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25
does amyloidosis evoke an inflammatory response?
No
26
Qu'est ce que la reconnaissance directe et indirecte des antigène lors d'une transplantation d'orgne?
directe: antigens du doneur présentés par les cellules présentatrices d'antigène du doneur aux cellules T du receveur. Rôle dans la rejection aigue indirecte: antigene captés par les cellules présentatrices d'antigène du receveur, puis présentés aux cellules T de l'hôte Rôle dans la rejection chronique
27
acute vs chronic rejection of transplant mecanism (in a few words)
acute: T cell and mediated, direct dammage with CD8 and dammage with CD4 inflammation OR anibody mediaed: antibodies bind to endothelium-> classical complement pahway Chronic: T cells secrete cytokines that activate fibroblasts-> interstitial fibrosis and narrowing of graft blood vessels
28
3 factors contibute to autoimmune diseases: defective tolerance/regulation (inherited), abnormal display of self antigens, inflammation or an initial innate immune response. Name 2 causes for the second one
increase expression and persistence of self antigens, or structural change in antigens (post translation)
29
30
2 reasons for why autoimmune disease tend to be chronic?
1. epitope spreading (dammage of tissue-> release of epitope (antigens) 2. intrinsic amplification loops (normal mecanism present for normal exernal antigens)
31
3 conditions to call a autoimmune disease
1. Not secondary to tissue dammage 2. specific immune reaction to self antigen or self tissue 3. absence of another cause
32
Central immunologic tolerance : what is negative selection or clonal deletion?
immature T cells expressing TCRs for self antigens encounter these antigens in the thymus-> killing by apoptosis OR become regulatory T cells
33
What is the use of the protein AIRE? (central immunity)
(autoimmune regulator) its job is to stimulates the expression of some peripheral tissue-restricted self antigens in the thymus (important for deletion of T cells specific for these antigens)
34
what happens if B cell encounter a self antigen in peripheral tissues, especially in the absence of specific Helper T cell?
B cell is unable to respond tu subsequent antigenic stimulaiton and may be excluded from lymphoïd follicules, resulting in death
35
Where does central tolerance takes place?
Thymus and bone marrow
36
T cell becomes anergic if an anigen is presented to her without adequate levels of _______
costimulators, like CD28. These are not or weakly expressed on resting DC in normal tissues Other receptor that are useful to create anergy are two coinhibitor (so opposie of CD28 but same ulttimate function): CTLA-4 and PD-1
37
What are the 2 other mecanisms, aside from anergy, that allows peripheral tolerance?
suppression by regulatory T cells and depletion by apoptosis
38
Name the receptor and the transcription factor that are imporant for development and maintenance of CD4+ regulatory T cell
Receptor IL-2, with his alpha chain CD25, and trancription factor FOXP3
39
name two cytokines that are secreted by regulatory T cells
IL10 and TGFbeta
40
what are immune privileged sites?
brain, eye, testis. Little to no reaction to antigens. Self antigens do not communicate with blood and lymph. if self antigens are released though, chronic inflamamtion
41
how much time later does the kate phase reaction of type 1 hypersensitivity occurs?
2-24 hours later
42
which are the signature cytokines produced by Th2? (3)
IL4, IL5, IL13 Their effects are in order chronololgically with their number
43
these complement proeins bind to mast cells receptors
C5a and C3a (Anaphylatoxins)
44
name one similarity and one difference of basophils and mastocytes
similarity: IgE Fc receptor on surface and cytoplasmic granules difference: basophail not normally present in tissues bu rather are in circulation in small number
45
Mastocytes granules include vasoacive amins, enzymes and proteoglycans. What is the role of the enzymes? And proteoglycans?
enzyme: Causing tissue damage and lead to the generation of kinins and activated components of complement by acting on their precursor proteins proteoglycans: heparin and chondroitin sulfate. package and sore the amines
46
On top of granules and cytokine secretion, what does mast cell activation do ? (hint: membrane)
activation on phospholipase A2-> membrane phospholipids become arachidonic acid-> prosaglandine D2 and leukotrienes B4 C4 D4
47
which is the most potent vasoactive agent know?
leukotrienes C4 and D4. Also spasmogenic
48
what does prostaglandin D2 causes?
bronchospasm and mucus production
49
NAme a lipid mediator produced by mastocyte that is not derived from arachidonic acid
platelet activating factor. Causes permeability, vasodilaation, bronchospasm, histamine release and platelet agreggation
50
Atopic individuals have more of what in their blood?
levels of IgE and IL4 producing TH2 lymphocytes
51
what is a non aatopic allergy?
allergy not mediated by Th2 or IgE. ex: heat, exercise. Too sensitive mast cells
52
On top of phagocytosis via antibodies +/- complemet, as well as MAC ( complement), how are cells that are opsonized destroyed?
antibody dependant cytotoxicity: NKs and macrophages binds to the Fc fragment of IgG-> cell lysis without phagocytosis
53
4 clinical categories for type II hypersensitivity:
1. Hemolyic anemia, thrombocytopenia, agranulocytosis 2. Foetus and mom (her antibodies destroys baby-> erythroblastosis foetalis) 3. certain drugs 4. transfusion
54
which sizes of complexes are the most likely to cause disease (hypersensitivity type 3)?
medium size
55
what is arthus reaction?
tissue necrosis resulting from acute immune complex vasculiis.
56
Give 3 clinical example of delayed hypersensitivity (type IV)
tuberculin reaction, drugs, contact dermatitis (poison ivy)
57
name the T cell preformed mediators that serve to kill other cells
perforin and granzyme. Granzymes induces apoptosis Fas ligand is also used by binding to Fas recepor and causing apoptosis
58
Initial cytokine recognized by CD4+ (displayed by dendritic cells) in T cell mediated hypersensitivity (type4) ? And which Th will the lymphocytes differenciate to?
IL2 Th1 and Th17
59
Name 2 other circulating innate immunity plasma proteins
mannose binding lectin avd C reactive protein (coat miicrobes and promote phagocytosis)
60
What are 2 sets of transcription factors that are activated by the toll like receptors?
NF-kappaB (NF-KB): cytokines and adhesion IRF: antiviral cytokine which is interferon type 1
61
what are RIG like receptor (function)?
detect PAMPS of viral DNA
62
macrophages ohagocyte microbes tha are opsonisez by which proteins?
IgG and C3b
63
In the spleen, the lymphocytes concentrated around arterioles are B or T cells?
T cells.. B cells are the white pulp
64
What does it mean tha CD8+ cells are MHC 1 restricted?
they recognize peptides only if presented by MHC 1 MHC1: intracellular antigen (self, tumor, virus) HMC2: extracellular antigen (after internalization). CD4+ are MHC2 restricted
65
Name the cytokines of innate response (5), mostly produces by macrophages
IFN gamma, IFN type 1, IL12, IL1, TNF and chemokines
66
Name the cytokines of adapive immune response (5)
IFN gamma, IL2, IL4, IL5, IL17
67
Which cytokines limite/terminate immune responses?
TGF beta and IL10
68
Name 3 cytokines that are CSF (colony stimulating factors), stimulate production of cells in blood marrow
GM-CSF, IL3
69
How can lymphocytes recognize antigens before adaptive immunity kicks in?
PAMPs
70
which is the main costimulator on antigen presenting cells for T cells?
B7 proteins (CD80 and CD86)-> recognized by CD28 on T cells
71
CD40L role
on Helper T cell, when expressed, it engages CD40 on macrophages or B cells and activate them
72
What is T independant response
when antigens (like polysaccharides or lipid) cant bind to MHC, but have multiple identical antigenic deerminan (isoopes) that are able to engage mnu anigen receptor molecules on each B cell. IgM mainly
73
major site of isotype switching and affinity maturation in lymph node?
germinal center

Phase I (13 decks)

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