Week 1_b Flashcards

1
Q

Innate Immunity

A

Innate Immunity- non-adaptive host defense against pathogens.
• Conserved- same as eukaryotes.
• Genes encoding are present in the germ line-do not undergo rearrangement or hypermutation

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2
Q

Physical barriers to infection

A
  1. Physical- Skin and other epithelial surfaces (mucosal surfaces- GI tract, respiratory tract, urogenital tract)
    Skin- barrier for noxious insults such as infection (bacterial, fungal, or parasitic)- has multiple layers of keratinocytes.
    To infect skin there must be direct tissue damage
    Mucosal surfaces- are a primary site of infection (viral, bacterial. Fungal, parasistic)
    For protection these surfaces can secrete a thick mucus layer that acts as a physical barrier to cell surface interaction by microbes.
    Cilia movement of lung propels particulate matter and foreign material and prevents microorganisms for establishing infection
    Mucosal surfaces also secrete antibodies.

Also contain IgA that offers protection

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3
Q

Chemical barriers to infection

A
Skin- low moisture content and high acidity of sweat.
Lysosomes in tears and saliva which degrade the peptidoglycan layer of bacterial surfaces.
Antimicrobial peptides (AMPS) secreted by epithelial cells and phagocytes (defensins, cathelicidins, histatins)- ALL mess up pathogen membranes.
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4
Q

Phagocytic myelod cells important for innate responses

A

macrophages, neutrophils, and dendritic cells

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5
Q

Why are kearatinocytes impiortant as an impasse to pathogen invasion

A

skin is thick, multilayered, low moisture and acidic

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6
Q

Which Ab does mucosal surfaces have

A

IgA- acts as a dimer when active

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7
Q

what are the professional cells of the innate immune system

A

phagocytes- 3 major: neutrophil, macrophages, dendritic cells

  • Macrophages/Monocytes- long-lived widely distributed leukocytes, first to respond, mature circulating monocyte, increase in number at site of infection, secrete cytokines and chemokines for immune cell recruitment, are Antigen presenting cells for T cells.
  • Neutrophils- Short-lived leukocytes, most abundant white cell in the circulation, RARELY found in normal tissue. Quickly recruited to site of injury or infection, Primarily BACTERIALCIDAL- kills invading microorganisms.
  • Dendritic Cells- Found in most if not all tissue, have pattern recognition receptors, BROAD acting, APC, phagocytosis of pathogens. May be the most important cells of the immune system. They are the gateway to the adaptive immune response and determine the type of response to occur.
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8
Q

Describe Mediator Productiion- one of the main fucntions of phagocytes

A

When immune cells (especially macrophages) are activated and develop a response to a pathogen, they can produce cytokines, program cells for microbial combat, chemokines- chemical attractant molecules that recruit additional leukocytes, lipid mediators- prostaglandins that affect how cells behave, and hydrolytic enzymes and antimicrobial peptides that assist in the clearance of pathogens. This can act as a solely innate response or it can be amplified by the adaptive response.

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9
Q

Describe Pathogen Associated Molecular Pattern Recognition (PAMP)

A

MAny cells have highly conserved PAMP recognition receptors (PRRs) . PAMPS are present on most pathogens.- virus, bacteria, fungus, so PRRs can recognize these PAMPS to mount an immune response.

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10
Q

The PRR- TLR

A

Toll-like receptors are transmembrane receptors, and specifically recognize viral nuclei acids.

Also recognize bacteria, yeast, and fungi

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11
Q

The PRR-CLR

A

c-type lectin receptors- recognize sugar, mannose-conainigng structures. IT is transmembrane

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12
Q

The PRR- RIG-I-like

A

It is soluble and recognizes double stranded RNA and viruses.

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13
Q

What are Antimicrobial peptides (AMPS)

A

peptides made by epithelial cells and phagocytes that disrupt antigen membranes. The are small protein membranes that have electrostatic attractions that can insert into the membranes of microbes. (defensins, cathelicidins, histatins)

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14
Q

Major proinflammatory cytokines for fever, pain, and inflammation (local effects)

A

IL-1B, TNF-alpha (increases entry of IgG, complement, and cells and increased drainage of lymph nodes), IL6

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15
Q

PPR- NOD-like receptors

A

tracellular sensors of PAMPs that enter the cell via phagocytosis or pores an d DAMPs that are associated with cell stress. Soluble

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16
Q

Describe antigen presentation

A

DC and macrophages engulf microbes and display antigen via MHC clas I and II molecules

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17
Q

difference between MHC I and II

A

I- presents peptides in cells (cytostolic peptides) MHC II- presents exogenous antigens-

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18
Q

Describe Innate Lymphiod Cells

A

Broad acting, invariant cells that are similiar to lymphocytes.
Type 1- NK cells- produce IFN-gamma and activate dendritic cells
Type 2- produce IL4 and secre antimicrobial peptids to shut down extracellular microbes
Type 3- produce IL-17 for immunity to worms

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19
Q

Major ILC

A

natural killer cells. (type I)

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20
Q

Major inflammatory cytokines produced during a viral infection

A

INF-alpha and INF- beta

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21
Q

Key Pathogen Recognition Receptors

A

Activate in minutes

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22
Q

How to TLR recognize and respond to lipid antigen

A

TLR bind to lipid side chains and this leads to dimerization and an activation response that activates NFKB

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23
Q

How is IL-1B activated

A

PAMPS activate inflammasome which activates capase I which cleaves the precursor IL-1B for form the mature form.

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24
Q

Function of NFKB

A

Activates genes encoding proinflammatory cytokines

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25
Q

What is a secreted PRR

A

Mannose binding lectin- which activates the complement system

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26
Q

Role of complement system in bridging innate and adaptive immunity

A

Augment AB responses
lyse foreign cells
clear immune complexes and apoptotic cells

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27
Q

Can PRRs produce ROS

A

yes- neutrophils engulf bacteria, phagosome is produced and fuse with primary and secondary granules and a NADPH oxidase in the membrane and ROS is produced for microbial killing

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28
Q

Key events of inflammatory response

A
  1. Alteration of blood flow- vasodilation
  2. Increaed vascular permeability- endothelial cells contract to enlarge junctions for increased leakage of serum contents into tissue
  3. Infliltration of WBCs- Neutrophils, then macrophages (dilate blood vessels), then lymphocytes arrive- blood clotting occurs at site of microvessels
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29
Q

Major problem in systemic infection

A

Systemic coagulation and break down of endothelium, swelling, fluid loss and drop in blood pressure.

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30
Q

Ig classes and side chains

A

IgG - predominant Ab induced in secondary response (gamma)
● IgA - predominant Ig in external secretions (alpha)
● IgM - predominant Ab induced in primary response (mu)
● IgD - found mainly on surface of B cells (delta)
● IgE - involvement in allergic hypersensitivities (epsilon)

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31
Q

Domain

A

series of repeating, homologous units, about 110 AA, fold independently

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32
Q

regions of chain

A
1. Constant region - amino
acid sequence in the Cterminal
regions of the H and
L chains is the same.
2. Variable region - amino
acid sequence in the Nterminal
regions of the H and
L chains is different. This
region provides antibodies
with unique specificity.
3. Hyper-variable regions are
regions within the variable
regions (greater
specificities).
The hinge region is the area of the Ig where the arms of the Abs form a ‘Y’,it is a flexible region. Igs also
have domains formed from folds of the globular region containing the intrachain disulphide bonds and
they are VL and CL (light chain domains) and VH and CH (heavy chain domains), seen in the three
dimensional images of the Ig
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33
Q

Light chain

A

Light chain- VL-about 100-110amino acids, CL-100-110 amino acids. There are two types of light chains,
kappa and lambda,

34
Q

Heavy chain

A
Heavy chains- VH-110 amino acids, CH-330-440 amino acids. There are 5 types of heavy chains which
defines the class of Igs, namely, Alpha, Gamma, Miu, Delta and Epsilon (α, γ,µ,δ,ε).the heavy chains are
between 53-75KDa.the variable region makes up a quarter of the entire heavy chain while ¾ of the
remaining chain is the constant region
35
Q

Antigen binding site

A

Combination of variable region of L and H chains

36
Q

Fab region

A

It contains the antigen binding site synonymous to VH and VL which is
particular to the kind of antigenic determinant the Ab will bind.

Ig-like folds

37
Q

Fc region

A

Fc- this is also called fragment crystallizable because it is readily crystallized and it contains the
remainder of the two heavy chains. It contains different domains ands which mediate effector functions
of an Ig. Variations in the Fc determines the different classes of Igs

38
Q

Heaviest Ig

A

IgM

39
Q

Most abundant Ig in serum

A

IgG

40
Q

Least abundant Ig in serum

A

IgE

41
Q

Ig that crosses placenta

A

IgG- only get it from mom

42
Q

Ig that does not activate complement

A

igD and IgE

43
Q

Ig that binds to mast cells and basophils

A

IgE

44
Q

major Ig class in external secretions

A

IgA

45
Q

major ig in mucosal immunity

A

IgA

46
Q

antigen epitope

A

An epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells. For example, the epitope is the specific piece of the antigen to which an antibody binds.

47
Q

3 ways Abs made by plasma cells that come from B cells mediate humoral immunity

A
  1. Neutralization- makes it unharmful- prevents adherence
  2. Opsonixation- makes it for degradation- promoes phagocytosis
  3. Complement activation- recptors for Fc ad complement that enhances opsonization and lysis
48
Q

Allergy response and IgE

A

cross-linking of IgE on mast cells leads to degradation

49
Q

role of Fc receptors

A

Phagocytes, NK cells, eosinophils, basophils and mast cells all have Fc receptors on their surface. in order for them to be activated, a number of Fc carrying phagocytes must aggregate on the bad cell to activate cell killing

50
Q

Most b lymphocytes have what Ig classes

A

igM and IgD

51
Q

there is approximately how many times mroe IgM and IgE in serum of normal individuals

A

100

52
Q

Antibody fragment with a single combinging site is known as a

A

monoclonal

53
Q

When are Ab levels reach

A

IgG transferred passively from mother and drops at 6 months, it peaks again at age 4; IgM at 10 months; igG at 4 years and IgA at 10 years
MGA

54
Q

Ig with longest half life

A

IgG- the M (10 days); A (6 days); D (3 days) and E (2 days)

55
Q

to make an antibody to what regoin would you targert

A

constant region (Fc) of Heavy chain

56
Q

polyclonal vs monoclonal Ab

A

A Polyclonal Antibody represents a collection of antibodies from different B cells that recognize multiple epitopes on the same antigen.

57
Q

common polyclonal Ab therapy

A

IVIG to treat inflammatory diseases

58
Q

Types of antimicrobial peptids secreted by epithelial cells

A

serve as chemical barrier for innate immunity- defensins
cathelicidins
histatins

59
Q

time of immune response

A

innate immunity- 0-4 hours
early induced innate response- 4-96 hours ( recognition of PAMPS, recruitment of effector cells, removal of infectious agent
Adaptive immune response- >96 hours, transport ot lymphoid organse, recognition by B and T cells, conal expansion, ab

60
Q

long-lived leukocytes, widely distributed in normal tissue, APC, first responder

A

macrophages

61
Q

short lived, not present in normal tissue,s most abundant

A

neutrophil

62
Q

freely roaming, display multiple types of pattern recognition, phagocytes

A

DC

63
Q

gateway to adaptive immunitt

A

DC

64
Q

factors produced by phagocytes

A

cytokines, chemokines, lipid mediators, hydrolytic enzymes, antimicrobial peptides

65
Q

major inflammatory cytokines for macrophages

A

IL1B
TNF-alpha
IL6

66
Q

other cells of innate immune system that are similar to T cells

A

NK
NKT
gamma delta T cells

67
Q

types of PRRs

A

TLR, C-type lectin receptors, NOd-like and RIGIlike

68
Q

cells PRRS mostly found on

A

macrophages, DC, monocytes

69
Q

type of PRR that recognizes viruses

A

TLR

70
Q

can multiple PRRs recognize a PAMP

A

yes

71
Q

2 types of DC

A

myeloid and lymphoid

72
Q

what recognizes lipopeptides

A

dimerized TLR

73
Q

Inflammasome

A

requirement for ILB activation- job is to active caspase I, which cleaves pro-IL-1B

74
Q

TLR activation is chieved by

A

NFKB

75
Q

secreted PRRS have

A

mannose binding lectin

76
Q

inflammatory response involves 3 elements

A

alteration in blood flow
increased vascular permeability
infiltration of WBCs into affected area

77
Q

can the immune system be trained

A

yes- it can remember an infection and respond more strongly to a similar one inf the future due to epigenetic factors .

78
Q

life span for tetanus antibody titers

A

11 yrs

79
Q

life span for measles antibody titers

A

3014 yrs

80
Q

examples of clinical monoclonal antibodies

A

monoclona end in mab

81
Q

Polyclonal Ab used to treat many
immune deficiencies and
inflammatory diseases

A

IVIG