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Flashcards in Lymphocytes Deck (103):
1

Innate vs adaptive immunity according to components

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

2

Innate vs adaptive immunity according to origin

innate immunity --> germline encoded
adaptive immunity --> Variation through V(D)J recombination during lymphocytes development

3

Innate vs adaptive immunity according to resistance persistence

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

4

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

innate immunity --> nonspecific,
adaptive immunity --> highly specific, refined over time

5

Innate vs adaptive immunity according to time of response to pathogens

innate immunity --> rapidly (minutes to hours)
adaptive immunity --> develops over long periods, memory response is faster and more rodust

6

Innate vs adaptive immunity according to physical barriers

innate immunity --> epithelial tight juctions, mucus
adaptive immunity --> no

7

Innate vs adaptive immunity according to secreted proteins

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

8

Innate immunity - key features in pathogen recognition

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

9

Innate immunity - example of PAMPs

1. LPS
2. Flagellin
3. ssRNA

10

adaptive immunity - key features in pathogen recognition

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

11

MHC types / encoded by

MHC I and II / encoded by HLA genes

12

MHC function

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

13

TCR vs TLR according to meaning

TCR --> T-cell receptor
TLR --> Toll-like receptor

14

MCH I vs II according to loci

MCH I --> HLA-A. HLA-B, HLA-C
MCH II --> HLA-DR, HLA-DP, HLA-DQ

15

MCH I vs II according to binding

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

16

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

MCH I --> all nucleated cells (not on RBCs)
MCH II --> antigen presenting cells (APCs)

17

MCH I vs II according to function

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

18

MCH I vs II according to antigen loading

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

19

MCH I vs II according to associated proteins

MCH I --> β2-microglobulin
MCH II --> Invariant chains (CD74)

20

MCH I structure

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

21

MCH II structure

α peptide, β peptide, invariant chain

22

invariant chain (cd74) - function

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

23

HLA subtypes are associated with (all types and diseases)

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

24

seronegative arthritis - types and genetics

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

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