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Lymphocytes Flashcards

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1
Q

Innate vs adaptive immunity according to components

A

innate immunity –> neutrophils, macrophages, monocytes, demdritic cells, NK cells (lymphoid origin), complement
adaptive immunity –> T and B cells, circulating antiboides

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2
Q

Innate vs adaptive immunity according to origin

A

innate immunity –> germline encoded

adaptive immunity –> Variation through V(D)J recombination during lymphocytes development

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3
Q

Innate vs adaptive immunity according to resistance persistence

A

innate immunity –> resistance persists through generations. Does not change within an organisms lifetime
adaptive immunity –> Microbial resistance not heritable

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4
Q

Innate vs adaptive immunity according to type of response to pathogens (specificity)

A

innate immunity –> nonspecific,

adaptive immunity –> highly specific, refined over time

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5
Q

Innate vs adaptive immunity according to time of response to pathogens

A

innate immunity –> rapidly (minutes to hours)

adaptive immunity –> develops over long periods, memory response is faster and more rodust

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6
Q

Innate vs adaptive immunity according to physical barriers

A

innate immunity –> epithelial tight juctions, mucus

adaptive immunity –> no

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7
Q

Innate vs adaptive immunity according to secreted proteins

A

innate immunity –> Lysozyme, complement, C-reactive proteins, defensins
adaptive immunity –> immunoglobulins

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8
Q

Innate immunity - key features in pathogen recognition

A

TOLL-like receptors (TLRs): pattern recognition receptors that recognize pathogen associated molecular patterns (PAMPs)

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9
Q

Innate immunity - example of PAMPs

A
  1. LPS
  2. Flagellin
  3. ssRNA
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10
Q

adaptive immunity - key features in pathogen recognition

A

Memory cells: activated B and T cells –> subsequent exposure to a previously encountered antigen –> stronger, quicker immune response

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11
Q

MHC types / encoded by

A

MHC I and II / encoded by HLA genes

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12
Q

MHC function

A

present antigen fragments to T cells and bind T-cell receptors (TCRs)

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13
Q

TCR vs TLR according to meaning

A

TCR –> T-cell receptor

TLR –> Toll-like receptor

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14
Q

MCH I vs II according to loci

A

MCH I –> HLA-A. HLA-B, HLA-C

MCH II –> HLA-DR, HLA-DP, HLA-DQ

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15
Q

MCH I vs II according to binding

A

MCH I –> TCR and CD8
MCH II –> TCR and CD4
(mnemonic: 4x2=8, 8x1=8)

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16
Q

MCH I vs II according to expression (which cells express them)

A

MCH I –> all nucleated cells (not on RBCs)

MCH II –> antigen presenting cells (APCs)

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17
Q

MCH I vs II according to function

A

MCH I –> present ENDOGENOUSLY synthesised antigens (eg. viral or cytosolic proteins) to CD8 cytotoxic cells
MCH II –> present EXOGENOUSLY synthesised antigens (eg. bacterial proteins) to CD4 helper T cells

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18
Q

MCH I vs II according to antigen loading

A

MCH I –> Antigen peptides loaded onto MHC I in RER after delivery via TAP (transporter associated antigen processing)
MCH II –> antigen loaded following release of invariant chain in an acidified endosome

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19
Q

MCH I vs II according to associated proteins

A

MCH I –> β2-microglobulin

MCH II –> Invariant chains (CD74)

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20
Q

MCH I structure

A

a peptide, β2-microglobulin –> peptide-binding grove

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21
Q

MCH II structure

A

α peptide, β peptide, invariant chain

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22
Q

invariant chain (cd74) - function

A
  1. shape the peptide binding groove and prevent formation of a closed conformation
  2. prevent binding of peptides from the endogenous pathway to the groove
    3 .facilitates MHC class II’s export from the ER in a vesicle
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23
Q

HLA subtypes are associated with (all types and diseases)

A

HLA-A3 –> hemochromotosis
HLA-B8 –> Addison disease, myasthenia gravis
HLA-B27 –> seronegative arthritis
HLA-DQ2/DQ8 –> celiac disease
HLA-DR2 –> Multiple sclerosis, Hay fever, SLE, Goodpasture syndrome
HLA-DR3 –> DM1, SLE, Graves disease, Hashimoto thyroditis, Addisson
HLA-DR4 –> RA, DM1, Addison disease
HLA-DR5 –> Pernicious anemia, Hashimoto

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24
Q

seronegative arthritis - types and genetics

A

genetics: B27
types 1. Psoriatic arhtritis 2. Ankylosing spondylitis
3. arthritis of Inflammatory bowel disease
4. Reactive arthritis (Reiter syndrome)

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25
Hay fever - definition/causes/manifestations
an allergy caused by pollen or dust in which --> mucous membranes of the eyes and nose are inflamed --> causing running at the nose and watery eyes
26
HLA - SLE
DR2 | DR3
27
HLA - Hashimoto
DR3 | DR5
28
HLA - diabetes mellitus
DM1 --> DR3, DR4
29
Natural Killer cells - type of cell and immunity
Lymphocyte member of innate immune system
30
Natural Killer cells - mechanism of action
1. Use perforin and granzymes to induce apoptosus if virally infected cells and tumor cells 2. Kills via antibody-depended cell-mediated cytotoxicity (CD16 binds FC region of bound IG, activating NK cells) Their activity is enhanced by IL-2, IL12, INF-α, INF-β
31
Natural Killer cells - their activity is enhanced by
1. IL-2 2. IL-12 3. INF-α 4. INF-β
32
NK cells - antibody-depended cell-mediated cytotoxicity - mechanism
CD16 binds FC region of bound IG, activating NK cells
33
NK cells induced to kill when
1. exposed to a nonspecific activation signal on target cell and/or 2. to an absence of class I MHC on target cell surface
34
Major B-cell functions (and mechanism)
1. Recognize antigen --> undegro somatic hypermutation to optimize antigen specificity 2. Produce antibody --> differentiate into plasma cells to secrete specific immunoglobins 3. Maintain immunologic memory --> memory cells persists and accelerate future response to antigen
35
Major T-cell function (CD4 and CD8)
1. CD4 help B cells make antibodies and produce cytokines to recruit phagocytes and activate other leukocytes 2. CD8 directly kill virus-infected cells (and neoplastic) 3. Delayed cell-mediated hypersensitivity 4. Acute and chronic cellular organ rejection
36
Differentiation of T-cells (and location)
T cell precursor (no CD4,8, no T-cell receptor) in bone marrow --> T cell with CD4, CD8 (both) and T-cell receptor (cortex of thymus) --> T cells with T-cell receptor and either CD8 or CD4 (medulla of Thymus) -->: CD8: Cytotoxic T cells (lymph node) CD4: Helper T cells (lymph node) --> a. IL-12: Th1 b. il-4: Th2 c. TGF-β + IL-6: TH 17
37
CD4: Helper T cells (lymph node) --> ....(differentiate to, and how)
a. IL-12 + INF-γ: Th1 | b. il-4: Th2 c. TGF-β + IL-6: Th17
38
Central tolerance is the
mechanism by which newly developing T cells and B cells are rendered non-reactive to self
39
Central tolerance - T cells - types (and location)
1. positive selection --> thimic cortex | 2. negative selection --> thimic medulla
40
T cells positive selection - location and mechanism
location: thymic cortex | T cells expressing TCRs capable of binding surface self-MHC molecules survive
41
T cells negative selection - location and mechanism
location: thymic medulla T cells expressing TCRs with high affinity for self antigens undergo apoptosis --> Tissue restricted self antigens are expressed in thymus due to the action of autoimmune regulator (AIRE) AIRE --> transcriptio factor --> major proteins from elsewhere in the body (tissue-restricted antigens)
42
autoimmune regulator (AIRE) mutation
autoimmune polyendocrine syndrome-1
43
Helper T cells - types
1. Th1 2. Th2 3. Th17
44
Th1 vs Th2 according to secretions
Th1 secretes IFN-γ | Th2 secretes IL-4, IL-5, IL-10, IL-13
45
Th1 vs Th2 according to function
Th1 activates macrophages and cytotxic T cells | Th2 recruits eosinophils for parasite defense and promotes IgE production by B cells
46
Th1 vs Th2 according to activation by
Th1 is activated by INF-γ and IL-12 | Th2 is activated by IL-4
47
Th1 vs Th2 according to inhibition
Th1 is inhibited by il-4 and il-10 (from Th2) | Th2 is inhibited by INF-γ (from Th1)
48
Helper T cells - vs cytotoxic T cells according to CD (CD4 or CD8)
Helper T cells --> CD4 | cytotoxic T cells --> CD8
49
T cell differentiation to Th1 - the whole mechanism
macrophage-lymphocyte interaction - macrophage release IL-12, which stimulates T-cells to differentate into TH1 cells. Th1 Ccells release IFN-γ to stimulate macrophages
50
Cytotoxic T cells kill ..... by ....
virus-infected, neoplastic and donor graft cells by inducing apoptosis
51
Cytotoxic T cells - mechanism of apoptosis
release cytotoxic granules containing performed proteins (perforinm granzyme B)
52
Regulatory T cells - function
Help maintain specific immune tolerance by suppressing CD4 and CD8 t cell effector functions activated regulatory cells produce anti-inflammatory cytokines (eg. IL-10, TGF-β)
53
Regulatory T cells - identified by
expression of CD3, CD4, CD25, FOXP3
54
Regulatory T cells? (everything)
Help maintain specific immune tolerance by suppressing CD4 and CD8 t cell effector functions activated regulatory cells produce anti-inflammatory cytokines (eg. IL-10, TGF-β identify by CD3, CD4, CD25, FOXP3 expression
55
Antigen-presenting cells - cells?
1. B-cells 2. marcophages 3. dendritic cells
56
Naive T-cell activation - steps
1. Dendritic cell (specialized APC samples and processes antigen 2. Dendritic cell migrates to the draining lymph node 3. Foreign antigen is presented on MHCII and recognized by TCR on Th (CD4) cell. Antigen is presented on MHCI to Tc (CD8) cell (SIGNAL 1) 4. Constimulatory signal is given by interaction of B7 (CD80/86) and cd28 (t cell) (SIGNAL 2) 5. Th cell activates and produces cytokines. Tc activates and is able to recognize and kill virus-infected cells
57
B cell activation and class switching - steps
1. Th-cell activation (the 5 steps) 2. B-cell receptor-mediated endocytosis. foreign antigen is presented on MHC II and recognized by TCR on Th cell 3. CD40 receptor on B cell binds CD40 ligand (CD40L) in Th cell 4. Th cell secretes cytokines that determine Ig class switching of B cell --> B cell activates and undergoes class, affinity maturation, and antibody production (plasma cells)
58
Naive T-cell activation - constimulatory signal
interaction of B7 and cd28
59
B cell activation and class switching - constimulatory signal
CD40 receptor on B cell binds CD40L in Th cell
60
Antibody - structure - divided to
1. Fab | 2. Fc
61
Antibody - Fab part structure and function
consists of light (L) and heavy (H) chains and recognizes antigens --> determines idiotype: unique antigen binding pocket only 1 antigenic specificity expressed per B cell
62
idiotype is the
distinctive sequence and region that makes any immunoglobulin/TCR unique from others of the same type which is its variable region
63
antibody - hinge region
flexible amino acid stretch in the central part of the heavy chains of the IgG and IgA immunoglobulin classes, which links these 2 chains by disulfide bonds
64
Antibody - Fab part structure and function
``` constant complement binding Caroxyl terminal carbohydrate side chains Determines isotype (IgM, IgD etc) ```
65
antibody - L and H chains are binded through
S-S
66
antibody - parts of heavy chain
from fab to fc: VH - CH1 - HINGE (Fab) CH2 - CH3 (Fc)
67
antibody - parts of light chain
from Fab to Fc: | VL - CL
68
Generation of Antibody diversity
antigen independent 1. Random recombination of VJ (light) or V(D)J (heavy) genes 2. Random combinations of heavy chains with light chains 3. random addition of nucleotides to DNA during recombination by terminal deoxynucleotidyl transferase
69
generation of antibody specificity
antigen depended 1. Somatic hypermutation and affinity maturation (variable region) 2. Isotype switching (constant region)
70
antibody function according to area (and definition)
1. opsonization (CH2 and CH3) --> antibody promotes phagocytosis 2. Neutroalization (FAB) prevents bacterial adherence 3. Complement activation (CH2) --> activates complement --> enhances lysis (Membrane attack complex (MAC)) and opsonization
71
Mature B cell surface
IgM and IgD
72
Mature B cell - differatnitation into .... (and location)
plasma cells that secrete IgA, IgE, IgG | location: germinal centers of lymph nodes
73
main antibody in 2ry (delayed) response to an antigen
IgG
74
Most abundant isotype in serum
IgG
75
IgG function
1. Fixes complement 2. crosses placenta (passive immunity in infants) 3. opsonizes bacteria 4. neutralizes bacterial toxins and varuses
76
IgG structure
monomer
77
IgA - function
prevents attachment of bacteria and viruses to mucous membranes
78
IgA structure
monomer in circulation | dimer when secreted (WITH J CHAIN)
79
IgA release into
secretions (tears, saliva, mucus) and breast milk
80
IgA - complement
does no to fix it
81
IgA crosses epithelial cells by (also during secretion)
transcytosis | picks up secretory component from epithelial cells before secretion --> protect the Fc portion from luminal proteases
82
Most produced antibody overall
IgA - but lower serum concentrations
83
IgD - function and location
unclear | found on surface of many B cells and in serum
84
antibody that produced in the primary immediate response to an antigen
IgM
85
IgM - complement and placenta
fixes complement but does not crosses the placenta
86
Beside in the blood, IgM is also found in
the surface of B cells (as a receptor)
87
IgM - structure
Monomoer in B cells Pentamer when secreted (J CHAIN)
88
special feature of pentamer IgM
pentamer enables avid binding to antigen while humoral response involves
89
antibody with the lowest concentration in serum
IgE
90
IgE - function
1. Binds mast cells and basophils --> cross links when exposed to allergen mediating immediate (type 1) hypersensitivity through release of inflammatory mediators such as histmamine 2. immunity to worms by activating eosinphils
91
Antigen type and memory
1. Thymus-independent antigens | 2. Thymus-dependent antigens
92
Thymus-independent antigens (structure, mechanism etc)
Antigens lacking a peptide compoment (eg. LPS) --> cannot be presented by MHC to T cells --> Weakly or nonimmunogenic
93
Thymus-dependent antigens (structure, mechanism etc)
Antigens containing a protein component (eg diphteria vaccine) --> class switching and immunologic memory occur as a result of direct contact of B cells with Th cells (CD40-CD40L)
94
which antibodies are not monomeric (and how the are binded
IgM (pentameric, monomer at B cell) IgA (dimer when secreted, monomer in circulation) binded with J chain
95
Addisson - HLA
B8, DR3, DR3
96
autoimmune polyendocrine syndrome-1 is due to mutation in
autoimmune regulator (AIRE)
97
Defective Fas-FasL interaction ->
autoimmune lymphoproliferatice syndrome
98
B7 protein is AKA
CD80/86
99
antibodies that fix complements (and the region)
IgM, IgG | CH2 of Fc
100
GI IgA is produced by (example)
Peyer Patches
101
CD54
ICAM-1
102
CD106
VCAM-1
103
ICAM-1 (CD54) is the receptor of
Rhinovirus

Immunology (10 decks)

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