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Week 1_b Flashcards

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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
What is a secreted PRR
Mannose binding lectin- which activates the complement system
26
Role of complement system in bridging innate and adaptive immunity
Augment AB responses lyse foreign cells clear immune complexes and apoptotic cells
27
Can PRRs produce ROS
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
28
Key events of inflammatory response
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
29
Major problem in systemic infection
Systemic coagulation and break down of endothelium, swelling, fluid loss and drop in blood pressure.
30
Ig classes and side chains
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)
31
Domain
series of repeating, homologous units, about 110 AA, fold independently
32
regions of chain
``` 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 ```
33
Light chain
Light chain- VL-about 100-110amino acids, CL-100-110 amino acids. There are two types of light chains, kappa and lambda,
34
Heavy chain
``` 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
Antigen binding site
Combination of variable region of L and H chains
36
Fab region
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
Fc region
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
Heaviest Ig
IgM
39
Most abundant Ig in serum
IgG
40
Least abundant Ig in serum
IgE
41
Ig that crosses placenta
IgG- only get it from mom
42
Ig that does not activate complement
igD and IgE
43
Ig that binds to mast cells and basophils
IgE
44
major Ig class in external secretions
IgA
45
major ig in mucosal immunity
IgA
46
antigen epitope
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
3 ways Abs made by plasma cells that come from B cells mediate humoral immunity
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
Allergy response and IgE
cross-linking of IgE on mast cells leads to degradation
49
role of Fc receptors
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
Most b lymphocytes have what Ig classes
igM and IgD
51
there is approximately how many times mroe IgM and IgE in serum of normal individuals
100
52
Antibody fragment with a single combinging site is known as a
monoclonal
53
When are Ab levels reach
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
Ig with longest half life
IgG- the M (10 days); A (6 days); D (3 days) and E (2 days)
55
to make an antibody to what regoin would you targert
constant region (Fc) of Heavy chain
56
polyclonal vs monoclonal Ab
A Polyclonal Antibody represents a collection of antibodies from different B cells that recognize multiple epitopes on the same antigen.
57
common polyclonal Ab therapy
IVIG to treat inflammatory diseases
58
Types of antimicrobial peptids secreted by epithelial cells
serve as chemical barrier for innate immunity- defensins cathelicidins histatins
59
time of immune response
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
long-lived leukocytes, widely distributed in normal tissue, APC, first responder
macrophages
61
short lived, not present in normal tissue,s most abundant
neutrophil
62
freely roaming, display multiple types of pattern recognition, phagocytes
DC
63
gateway to adaptive immunitt
DC
64
factors produced by phagocytes
cytokines, chemokines, lipid mediators, hydrolytic enzymes, antimicrobial peptides
65
major inflammatory cytokines for macrophages
IL1B TNF-alpha IL6
66
other cells of innate immune system that are similar to T cells
NK NKT gamma delta T cells
67
types of PRRs
TLR, C-type lectin receptors, NOd-like and RIGIlike
68
cells PRRS mostly found on
macrophages, DC, monocytes
69
type of PRR that recognizes viruses
TLR
70
can multiple PRRs recognize a PAMP
yes
71
2 types of DC
myeloid and lymphoid
72
what recognizes lipopeptides
dimerized TLR
73
Inflammasome
requirement for ILB activation- job is to active caspase I, which cleaves pro-IL-1B
74
TLR activation is chieved by
NFKB
75
secreted PRRS have
mannose binding lectin
76
inflammatory response involves 3 elements
alteration in blood flow increased vascular permeability infiltration of WBCs into affected area
77
can the immune system be trained
yes- it can remember an infection and respond more strongly to a similar one inf the future due to epigenetic factors .
78
life span for tetanus antibody titers
11 yrs
79
life span for measles antibody titers
3014 yrs
80
examples of clinical monoclonal antibodies
monoclona end in mab
81
Polyclonal Ab used to treat many immune deficiencies and inflammatory diseases
IVIG

Immuno (3 decks)

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