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Flashcards in Basics of Immunology Deck (127)
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1
Q

PAMPs

A

Pathogen-associated molecular patterns. On the intruder,. What is recongnized by PRRs on the cell surface of innate immune cells. These are proteins that humans don’t have, so we know they don’t belong (ie a protein of bacterial cell well or dsRNA)

2
Q

PRRs

A

Pattern-recognition receptor. Proteins on the cell surface expressed by cells of innate immune system. PRRs identify the PAMPs expressed on foreign intruders

3
Q

TLRs

A

Toll-like receptors. A type of PRR. There are at least 10 TLRs and are located where infections enter, ie lining blood vessels

4
Q

DAMPs

A

Damage-associated molecular pattern. Stress or damage indicators expressed by body cells (ie paintball example)

5
Q

What are some foreign patters recognized by TLRs?

A
TLR1: Lipopeptide (bacterial)
TLR2: Zymosan (fungal)
TLR3: dsRNA (viral)
TLR4: endotoxin
TLR5: flagellin (bacteria)
TLR6: Lipopeptide (mycoplasma)
TLR7: ssRNA (Influenza)
TLR8: ssRNA (viral)
TLR9: Unmethylated CpG (herpes)
TLR10: asthma connection
6
Q

What is the final transcription factor that is most commonly activated by inflammation?

A

Bad bug makes endotoxin&raquo_space; endotoxin is recognized by TLR&raquo_space; Signal cascade&raquo_space; Activates NF-KB&raquo_space; Inflammation

7
Q

Cytokines

A

Made by PAMP-stimulated cells. Small cell-signaling protein molecules that are secreted by the immune system for intercellular communication Helps inflammation

8
Q

Chemokine

A

Made by PAMP-stimulated cells. Family of small cytokines. Induce directed chemotaxis of WBC to site of injury.

9
Q

Innate to Adaptive Immune Response

A

At the wound site, immature DCs get activated by the cytokines and chemokines secreted by the innate immune response, and they take up anything they can find. Activated (mature) DCs leave the local wound and travel to the nearest lymph node. They “show” the antigen they have eaten to the lymphocytes, and the adaptive immune response develops with T cells, B cells and DCs.

10
Q

Dendritic Cells

A

Phagocytic cells at the interfaces between the body and the world (skin, lung, mucous membranes…). Immature DCs are the best phagocyte ever! Mature DCs are the best antigen presenting cell ever! (A change in phenotype occurs when the DC matures)

11
Q

T Lymphocytes

A

Start development in bone marrow, but mature in THYMUS. (Helper) T lymphocytes recognize and remove foreign substances. Two main classes: Helper T cells and Killer T cells.

12
Q

The epic journey of Helper T Cells

A

They recognize antigens using surface receptors which see antigens presented by the DC that is traveling via lymphatics. When the HTC recognizes the foreign material it becomes activated and proliferates. The daughter cells travel through the body until they reach where the antigen first invaded. There they are re-stimulated and release short-range mediators called lymphokines. These mediators call up much of the inflammatory response, attracting monocytes/macrophages

13
Q

Killer T Cells

A

Kill any body cell that they identify as containing abnormal molecules. Examine surface of incoming DCs, but they are also looking for fragments on MHC Class I antigen presenter, which are on ALL cells. Appropriate clones of Killer T cells proliferate and daughter cells circulate. When a daughter cell binds a cell showing the same peptide it delivers a lethal “hit” signaling the target cell to commit suicide.

14
Q

The role of B cells in immunity

A

Recognize and remove foreign substances and protect extracellular spaces of the body by releasing antibodies into tissue fluids, blood, and bodily secretions. They arrange for phagocytosis and recognize antigens via surface receptors and become activated and proliferate. They do NOT require recognition of MHC. Fully differentiated B cells are called plasma cells and are antibody producing “factories”

15
Q

What are the 5 immunoglobulin classes?

A

IgG, IgM, IgD, IgA, IgE

16
Q

IgG

A

most abundant antibody, 2 adjacent IgG molecules binding an antigen cooperate to activate COMPLEMENT. It is the only antibody that passes from mother to fetus. Phagocytic cells have receptors for the Fc of bound IgG>Opsonizing

17
Q

Complement

A

A system of proteins that enhances inflammation and pathogen destruction

18
Q

IgM

A

Even better at activating COMPLEMENT than IgG. First antibody to appear in blood after exposure to new antigen. Replaced by IgG in 1-2 weeks. It is the ONLY antibody made in the fetus.

19
Q

IgD

A

Antibody inserted into B cell membranes as their antigen receptor

20
Q

IgA

A

Most important antibody in secretions (tears, saliva, breast milk). Associated with SECRETORY COMPONANT which makes the antibody resistant to digestive enzymes and plays a role as the first line of defense against microorganisms

21
Q

IgE

A

Resistance to parasites and worms. Fc attaches to mast cells in tissues. Once attached, when it encounters and antigen it will cause the mast cell to make protaglandins, leukotrienes and cytokines and release its granules which contain mediators of inflammation (ie histamine). Also triggers Mast Cells to release Eosinophils to combat parasites

22
Q

Type I immunopathology

A

Immediate hypersensitivity. Patient makes too much IgE to environmental antigen

23
Q

Type II Immunopathology

A

Autoimmunity due to antibodies that react against self. Treat diseases with immunosuppressives

24
Q

Type III Immunopathology

A

Patient makes antibody against a soluble antigen. Antigen-antibody complex sometimes gets trapped in basement membrane of capillaries, where they activate Complement causing inflammation. (ie Systemic Lupus Erythemtosus and Rheumatoid Arthritis) Also, large doses of penicillin can cause Type III

25
Q

Type IV

A

T-cell mediated. Can be autoimmune or innocent bystander disease. Example: in TB most of the cavity formation in lungs is T cell mediated, not bacterium mediated

26
Q

AIDS

A

HIV infection of TH cells; binds to CD4 molecules they have on their surface. Uses reverse transcriptase to insert itself into the cells genome, where it remains latent until T cell is activated, leading to loss of TH cells

27
Q

Chronic frustrated immune response

A

Antigen is not to “self”, but something you can’t get rid of, like gut bacteria or gluten

28
Q

Leukocytes

A

Nucleated cells of the blood, white blood cells. The buffy coat when you centrefuge blood

29
Q

Mononuclear cells

A

Leukocytes whose nucleus has a smooth outline; monocytes and lymphocytes

30
Q

Polymorphonuclear cells

A

Cells whose nucleus is lobulated, also called granulocytes because they have prominent cytoplasmic granules; Eosinophils, Basophils and Neutrophils

31
Q

Mast Cells

A

Granules full of histamine, role in allergy and anaphyaxsis. Very Similar to basphil granulocytes

32
Q

Plasma

A

Yellow fluid portion of blood in which blood cells are suspended. 55% of blood volume

33
Q

Serum

A

The clear liquid that does not contain blood cells nor clotting factor. Includes electrolytes, antibodies, hormones, etc

34
Q

What are the central lymphoid organs

A

Organs where lymphocytes develop: Bone Marrow and Thymus

35
Q

What are the peripheral lymphoid organs

A

Organs where mature lymphocytes are organized to trap and respond to foreign invaders: lymph nodes, spleen, Peyer’s patch and mesenteric lymph nodes

36
Q

Describe the recirculation of lymphocytes from blood to lymph and back.

A

Lymphocyte in blood encounters the cells lining certain postcapillary venules in peripheral lymphoid tissue. Recirculating lymphocytes may bind to and pass between the endothelial cells into the lymph nodes. Lymph goes to large lymph channels (thorasic duct)&raquo_space; venous blood&raquo_space; circulatory loop starts again

37
Q

Antigen

A

Substance that can be recognized by the immune system

38
Q

Immunogen

A

An antigen in a form that can give rise to an immune response

39
Q

Antigenic determinant and epitope

A

small part of a large antigenic molecule, fits into lymphocytes receptor and activates lymphocyte

40
Q

Tolerogen

A

Antigen delivered in a form, or by a route, which does not give rise to an immune response, and which furthermore PREVENTS an immune response to subsequently administered immunogen which has the same epitopes

41
Q

Lymphocytic Activation

A

Each lymphocyte has many identical copies of a unique receptor. The antigenic determinant presented by Dendritic Cell fits into a particular lymphocyte receptor. To activate a T or B cell, the fit between receptor and antigen must be good enough and several nearby receptors must be simultaneously bound by antigen as well. (MHC must also be involved for T-cells to be activated).

42
Q

What are the receptors of T and B cells composed of?

A

T cells: alpha and beta chains

B cells: samples of the antibodies that the cell will eventually secrete

43
Q

Humoral Immunity

A

Antibody mediated response, occurs extra-cellularly where all the bacteria live. B lymphocytes are the main cell involved. B cells transform into plasma cells which secrete antibodies.Cytokines are also released. Can be transferred by serum.

44
Q

Cell Mediated Immunity

A

T lymphocytes become activated. These in turn activate macrophages, NK cells, and cytotoxic T lymphocyte. Cytokines released when T cells become activated. Not transferred by serum

45
Q

H chain

A

Heavy chain of antibody. Each antibody has 2 H-chains, each H chain has 1 variable domain (VH) and 3-4 constant domains (CH1, CH2, CH3, (CH4)), 5 kinds of H chains (gamma, alpha mu, epsilon, delta) each corresponds to the appropriately named antibody: IgA has alpha chains

46
Q

L Chain

A

Light chain of antibody. Each antibody has 2 L-chains, each L chain has 1 variable domain (V1) and one constant domain (C1)

47
Q

Kappa and Lambda Chains

A

2 varieties of L chain, each cell that makes an antibody has a CHOICE, but uses ONLY ONE kind

48
Q

Hinge Region

A

Allows for flexibility so that when bound to an antigen, the constant part of the antibody can change conformation

49
Q

Fab

A

S-S bond between H chains fully reduced

50
Q

F(ab’)2

A

2 Fabs still joined by S-S bond

51
Q

Fc

A

Non-antigen binding region of the antibody, makes antibody participate in complement

52
Q

Complementarity-determining Regions (CDRs)

A

Light chain and heavy chain variable region is NOT uniformly variable, most of the variability is in the 3 regions called hyper-variable regions of CDRs, amino acids in this region comprise the actual antigen-binding site

53
Q

Hypervariable Regions

A

Areas on the variable region of light/heavy chain with amino acid availability

54
Q

Variable (V) Domain

A

A the N-terminal of the antibody, differences in amino acid sequences between antibodies of different specificites

55
Q

Constant (C) Domains

A

Region that is essentially identical on the antibodies, made up of compact, structurally similar domains called C domains

56
Q

Characteristic chains of IgG

A

2 light and 2 gamma (heavy)

57
Q

Characteristic chains of IgE

A

2 light and 2 epsilon (heavy)

58
Q

Characteristic chains of IgD

A

2 light and 2 delta (heavy)

59
Q

Characteristic chains of IgA

A

4 light 4 alpha (heavy), 1 Joining chain and 1 Secretory component (creates a dimer)

60
Q

Characteristic chains of IgM

A

10 light, 10 mu (heavy) and 1 Joining chain (creates a pentamer)

61
Q

Name immunoglobin classes from smallest to largest

A

IgG < IgE < IgD < IgA < IgM

62
Q

Combining Sites

A

Where the antibody binds to the antigen and is made up of the V domains of both the H and L chain

63
Q

Subclass of Immunoglobins

A

Immunoglobins are dived into subclasses because of slight differences in the amino acid sequences of their H chain C regions

64
Q

Allotypes of Immunoglobins

A

Minor allelic differences in the sequence of immunoglobins between individuals, determined by allotypes of your parents, useful in determining relatedness

65
Q

Idiotypes of Immunoglobins

A

Unique combining region, made up of CDR amino acids of its L and H chain, that each antibody has, Anti-idiotypes are antibodies made that recognize the unique sequence of that combining site.

66
Q

Valence

A

The valency of an antibody refers to the number of antigenic determinants that an individual antibody can bind. The valency of all antibodies is at least two (divalent) and in some instances more (multivalent)

67
Q

Affinity

A

The strength with which and antibody molecule binds to an epitope

68
Q

Precipitation

A

Large Immune complexes that are formed at or near equivalence tend to become insoluble and fall out of solution. When the antigen is a molecule, it is called precipitation

69
Q

Agglutination

A

Large immune complexes that are formed at or near equivalence tend to become insoluble and fall out of solution. When the antigen is a cell or cell-sized particle, it is called agglutination.

70
Q

Epitope

A

The part of the antibody that actually interacts with the antigen, usually 10-20 amino acids long. Also known as antigenic determinant. Proteins have several epitopes which bind to different antibodies

71
Q

Why does a line of precipitate may form in agar gel when antigen and antibody diffuse towards each other

A

Precipitate forms in the agar when the antigen and antibody meet at optimal proportions (more immune complex forms and precipitates out of solution). This is called immunodiffusion

72
Q

Lectin Pathway

A

Part of INNATE IMMUNITY. Mediated by mannose-binding protein (MBO or MBL), a lectin. MBP binds certain mannose-containing structures found in carbohydrates of bacteria but not humans. MBP is similar to C1q so the lectin pathway goes: 4-2-3-5-6-7-8-9

73
Q

Classical Pathway

A

Activated by complexes of IgG or IgM antibody with antigen. Fc portion of antibodies change which allows binding and activation of C1q. C1q must interact with the 2 Fcs simultaneously. Pathway goes: 1-4-2-3-5-6-7-8-9.
Activating C3 and C5 is part of compliment because they are responsible for opsonizing, chemotaxis and anaphylastoxic

74
Q

Alternative Pathway

A

Part of Innate Immune response. Activated by IgA-antigen complex. Bacteria must activate C this way even in the absence of antibody. Complement activated by C3. IgA and cell wall structures provide a surface of binding C3b and factor B, properin and factor D, which can activate C5 (and thus C6-7-8-9)

75
Q

Oponizing

A

C3b adheres to membranes. Phagocytic cells have C3b receptors and so they get a firm grip on an antigen if opsonized with C3b. IgG is also opsonizing because phagocytes have receptor for its Fc end called FcR

76
Q

Lytic

A

If the membrane attack complex is activated when C5 activates C6-7-8-9. C8 and C9 form a lesion on the target cell membrane. Cell loses ability to regulate osmotic pressure and lyses

77
Q

Anaphylatoxic

A

C3a, C4a and C5a can all release histamine from mast cells by binding. This leads to and increase in blood flow to the area and a better chance for inflammatory cells to get out of blood and into tissues

78
Q

Chemotactic

A

The C5 activation product, C5a, is chemotactic for phagocytes, especially neutrophils

79
Q

Toxoid

A

Bacterial toxin (usually endotoxin) whose toxicity has been weakened or suppressed either by chemical (formalin) or heat treatment

80
Q

Cross-reactivity

A

The tendency of one antibody to react with more than one antigen (ie immunize a person with cow pox, the antigenic determinant of small pox will also be recognized and the person will be immunized)

81
Q

Low affinity B cell binding

A

B cells are typically activated when the antigen binds to B cell receptor and if the binding is strong enough, the B cell will be activated. If the binding is low affinity, the B cell is not activated but if another antigen comes along which binds AND activates, then the product of the cell (secreted antibody) may combine with the low affinity antigen well enough to be “inconveneint” (ie rheumatic heart disease)

82
Q

Clonal Selection Theory

A

Each cell of the immune system is programmed to make only one antibody. The choice of which antibody a cell makes is RANDOM. When it encounters a lymphocyte whose receptors bind it with a high affinity, the lymphocytes is activated and makes clones and antibodies. The best fitting clones are SELECTED by the antigen (Think K-mart example)

83
Q

Look at the diagram of heavy and light chain gene regions of human DNA

A

Okey dokey!

84
Q

Class switching

A

Single mature B cell starts by making IgM and IdD. Later, it may switch to IgG, IgE or IgA. In all cases, the V domain stays the same but the C region of the H chain changes. A cell can switch heavy chain, but cannot switch light chains. Switching classes involving excising of the gene cannot go back to the original class.

85
Q

Hypermutation

A

Each time a B cell divides after antigenic stimulation, there is a good chance 1 of the daughter cells will make a slightly different antibody, leading to mutants that are better (or worse) affinities during immune response

86
Q

N-region Diversity

A

Created by the sloppiness of V-D and D-J joining. 1)Exonucleases chew away a few nucleotides after the DNA is cut but before the gene segments are joined. 2)Enzyme TdT adds nucleotides WITHOUT A TEMPLATE. Lots of diversity produced, but the price is that frame shift mutations occur frequently. VDJ region is the most mutable out of the whole genome!

87
Q

So, you will look at the diagram in the notes, but what ware some basics about the heavy and light genes

A

Variable domain is made of V, D, J for heavy chains (Light chains ONLY have V and J). One random D (1 to n) is brought to one random J (1 to n) and the intervening DNA is excised. Then V is brought to D-J and the intervening DNA is excised. After VDJ is put together, a primary RNA transcript is made, from just left of the chosen V all the way through the right of the Delta constant region gene. The primary transcript is alternatively spliced to make VDJmu and VDJdelta, for example. (The D goes between the VJ when its Hot and Heavy)

88
Q

Why do we write V(D)J instead of VDJ?

A

The variable domain region of heavy chains is composed of V, D, and J. The variable region of the light chain are only composed of V and J segments.

89
Q

Th1 Cells, and Downstream affects

A

Circulate until encounters antigen. Secrete lympohkines (INTERFERON GAMMA), which is chemotactic for monocytes and macrophages and turns them into ANGRY macrophages. The macrophages release their own cytokines (TNF and IL-1) that increase inflammation

90
Q

Th17 cells

A

Make pro-inflammatory lymphokine IL-17. Main job is inflammation, and make EVEN ANGRIER macrophages. Implicated in several autoimmune diseases.

91
Q

Th2 cells

A

Circulate through blood until discovering antigen. Secrete IL-4 and IL-3 which attract and activate macrophages involved in HEALING.

92
Q

Cytokine secreted by Th1 cells

A

Interferon Gamma- pro imflammatory and chemotatic for macrophages and monocytes, creating ANGRY macrophages

93
Q

Cytokine secreted by Th17 cells

A

IL-17- inflammation and makes even even ANGRIER macrophages

94
Q

Cytokine secreted by Th2 cells

A

IL-4 and IL-3, attracts and activates macrophages.
IL-4 is Chemotatic for eosinophils and pushes B cells to switch from IgM/IgD to IgE (antibody for parasites and allergies)

95
Q

What does T cell sibling rivalry mean?

A

A balance between Th1 and Th2. IFN gamma (made by Th2) suppresses Th2 differentiation. IL-4 (made by Th2) suppresses Th1

96
Q

Follicular helper T cells (Tfh)

A

Are activated by DC in lymph node, then migrate to follicles of cortex where B cells are present. Tfh secrete cytokines and direct B cells to switch from IgM to IgG, IgE, or IgA

97
Q

Regulatory T Cells (Treg)

A

Suppress the activation and function of other T helper cells. Most are CD4+/CD5+. Can suppress 1000 Th cells

98
Q

What cytokines are produced by Treg?

A

TGFbeta and IL-10. Suppresses Th cells

99
Q

Cytotoxic Killer T cells (CTL)

A

Signals target cells to commit suicide

100
Q

How to CTLs induce a cell to apoptos?

A
  1. Activate Fas (CD95) “death receptor” on target (CTLs have Fas ligand, CD95L)
  2. Secrete contents of lytic granules which contain proteases called granzymes and perforins that allow penetration into target cell
101
Q

What are the surface markers that can distinguish T and B cells?

A

T cells have CD2, CD4 and CD8 (different T cells have different markers; see further cards). B cells have antibody surface markers. Specific surface marker CD20

102
Q

What cells have CD3 surface marker?

A

virtually all T cells

103
Q

What cells have CD4 surface marker?

A

Th2, Th1, Treg cells

104
Q

What cells have CD8 surface marker?

A

CTL cells

105
Q

Define Lymphokine

A

short range mediators made by lymphocyte that affects behavior of the same or another cell. A subset of cytokines. Examples: IL-2, IFNgamma, IL-4, IL-5, IL-10

106
Q

Define Chemokine

A

Small, short range mediators made by any cell that causes inflammation. Examples: MIP-1 to -4, CCL28

107
Q

Define Cytokine

A

short range mediators made by any cell that affects behavior of the same or another cell. Examples: IL-1, TNFalpha, IL-12

108
Q

What is a mitogen?

A

A protein that stimulates T cell division. They don’t actually bind to the antigen-binding site on T cell. Instead it binds to the CD3 domain that controls signal transduction.
Examples: PHA (binds CD3), pokeweed mitogen

109
Q

Mitogen vs Antigen

A

Antigens are specific, Mitogens are nonspecific.

110
Q

Specifics of T cell receptors

A

Made of 2 chains, alpha and beta. Each chain has common and variable portion. Receptor is made out of V,(D),J recombined and each chain has 2 CDRs (takes place in thymus). Both alpha and beta chains have trans-membrane domains (picture parallel lines as receptor)

111
Q

Specifics of B cell receptors

A

Bind antigen directly with surface antibodies. Receptors made of V,(D),J regions and recombination. Made of 2 heavy and 2 light chains, with constant and variable regions (picture y-shaped receptor)

112
Q

Class I Mediators

A

All nucleated cells have MHC Class I on their surfaces. Class I is recognized by CTLs. “Look what I’ve been making!”

113
Q

Class II Mediators

A

Class II products are only on dendritic cells, macrophages and B cells. Recognized by Th. “Look what I’ve been eating!”.

114
Q

Characteristics of T-independent antigens

A

Have the same epitope repeated over and over, common in carbohydrates. The carbohydrate chain binds to the B cell antibodies, activating the cell to diving. The response is almost all IgM

115
Q

Journey of a T cell

A

Bone Marrow…(Pre-T cells)…Stroma of Thymus….Divide and rearrange V(D)J, changing from CD4-/8- to 8+/4+. In the Thymus, T cells display CD1 surface marker….A T-cell that binds with high-affinity to peptide in the thymus dies. Also, cells with no affinity (to the MHC) also die. The ones that survive are ones what bind MHC but NOT the peptide!

116
Q

How is it that the T cells can be exposed to numerous body peptides will stuck in the Thymus?

A

AIRE! A gene that upregulates body genes so peptides can be loaded to MHC for T cell selection

117
Q

What are the phases of developing B cells?

A

Pro B cell…Pre B cell…Immature B cell…Mature B cell

118
Q

Pro B cell

A

Progenitors that are identifiable when they begin to made detectable cytoplasmic mu chains

119
Q

Pre B cell

A

A cell with cytoplasmic IgM but no surface IgM

120
Q

Immature B cell

A

A cell with surface IgM only and can interact with outside world. If immature B cell is exposed to antigen, the signal causes the cell to try receptor editing. If unsuccessful, cell will die (clonal abortion)

121
Q

What is clonal abortion/deletion?

A

Pre-B cells are differentiating into immature B cell and any cell whose receptor happens to be anti-self will almost surely encounter “self” in the bone marrow. If so, it will be destroyed. If it does not encounter an antigen in the marrow (cell is not anti-self), then it will mature further to slgM and slgD.

122
Q

Mature B cell

A

A cell with both IgM and IgD are on the cell surface. Present in the lymph nodes

123
Q

Know that sIgD appears on mature B cell 24 hours after sIgM

A

Ok

124
Q

What is the antibody response to a typical antigen in a primary and secondary response?

A

During primary B cell response to antigen, IgM is secreted first, then helper T cells help B cells switch to IgG (or IgA or IgE). Remember that after its switched from IgM, it cannot go back because the “mu” and “delta” have been spliced out!

125
Q

What is the antibody response to secondary (booster) immunizations?

A

IgM response is the same as in primary, but the IgG response (helped by T cells) is sooner, faster and higher and more prolonged because of immunological memory

126
Q

Whats up with a baby’s immune system?

A

IgM is made by fetus before birth. IgG is from the mother, and takes a huge spike ~6 months gestation and babies have 100% adult levels are full-term. Therefore, premature baby has low IgG (and lower than normal IgM). Half-life of IgG is 3 weeks, so the level from mother is depleted by 10 months. That ok though, because infants start making their own at about 3 months of age.

127
Q

Are kids born with compliment?

A

Yup.