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Microbiology post midterm > Lecture 20-23 > Flashcards

Lecture 20-23 Flashcards

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1
Q

What are the physical barriers in the body?

A
  1. The skin
  2. Mucous membranes
  3. Lungs
    - lined with cilia and mucus.
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2
Q

To what are the physical barriers connected to?

A

-They are connected to lymphoid tissue in the body

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3
Q

What is the complement system in the body and what is its role?

A
  • The complement is a set of proteins made by the liver
  • They complement antibodies in the killing of bacteria
  • The proteins circulate in the blood and they enter tissues all over the body
  • They circulate inactively and they need to be cleaved to make them active
  • The complexes are named C1-C9
  • There are about 30 soluble and membrane-bound protein components of the complement system
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4
Q

What are the three complement activation pathways?

A
  1. The classical pathway
  2. The lectin pathway
  3. The alternative pathway
  • They all converge to the lytic pathway
  • Only the alternative pathway is connected to the innate system
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5
Q

Explain the alternative complement pathway

A

v

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6
Q

What is the immune system and how is it divided?

A
  • The immune system is a complex system of organs, tissues, cells, and cell products that work in concert to recognize and neutralize potentially pathogenic threats.
  • It is divided into innate and adaptive immune system
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7
Q

The innate immune system is what?

A
  • It is called a non-adaptive or non-specific
  • It is present at birth
  • It includes:
  1. Physical barriers
  2. Chemical and cellular responses
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8
Q

What is the best example of small molecule that is able to lyse most microbial cells and some enveloped viruses?

A

defensins-natural antimicrobial peptides

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9
Q

What is the role of defensins and where are they found in the body?

A
  • They are gound in the gut where there is a concentration gradient
  • Higher concentration in the close proximity to the crypts of the epithelium
  • Secretions is from the crypts
  • Keeps out even the normal microbiota
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10
Q

What sort of cells are found within blood?

A
  1. Red blood cells
  2. White blood cells
  3. Platelets (clotting)

White blood cells are part of the immune system

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11
Q

Development of white blood cell components of the immune system

A
  1. Hematopoietic stem cell (bone)
    Divides into
  2. Myeloid stem cell (bone)
    - Mast cell
    - Myeloblast (neutrophil)
    - Monoblast (macrophage and dendritic cell)
  3. Lymphoid stem cell (bone)
    - Natural killer cell
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12
Q

What do white blood cells include?

A
  • Polymorphonuclear leukocytes (PMNs granulocytes or polys)
  • Monocytes and macrophages
  • Dendritic cells
  • Mast cells
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13
Q

How does the amoeba eat?

A
  1. The bacterium binds to the surface of phagocytic cell
  2. Phagocyte pseudopods extend and engulf an organism
  3. The microbe is trapped
  4. Enzymes destroy the organism
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14
Q

What do myeloid bone marrow stem cells differentiate into?

A

They differentiate into phagocyte cells

-Cells that eat

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15
Q

How do neutrophils capture pathogens?

A
  • The capture pathogen with NETs
  • NETs-Neutrophil Extracellular Trap
  • An unusual form of cell death by the neutrophil called netosis
  • They are very mobile
  • They sense an invader and spew a latticework of chromatin and antimicrobial compounds into the vicinity
  • They prevent the spread of the pathogen
  • Allows rapid phagocytosis
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16
Q

What do monocytes differentiate into?

A

-Macrophages

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17
Q

What are monocytes?

A
  • They circulate the blood stream
  • Like neutrophils, they are attracted by chemical signals (cytokines) to sites where they are needed
  • As they travel through the blood vessels they differentiate into macrophages
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18
Q

Why are cytokines?

A

Cytokines are small proteins that are important for cell signaling

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19
Q

What is unique about monocytes?

A

They are large structures that can ingest many microbes at one time
-They secrete cytokines which would be dangerous in the blood vessels

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20
Q

What are dendrocytes?

A

-They possess long protrusions that can squeeze through tight spaces to sample microbes

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21
Q

what are the roles of cytokines, chemokines and interferons?

A
  • They are the language of our immune system
  • Close range acting hormone system
  • Allows cells of the body to communicate with each other
  • Particularly effective at signalling danger
  • Some are important for anti-inflammatory signals after the danger has passed
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22
Q

Why is inflammation important?

A

-Chronic inflammation can be bad

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23
Q

What are the antigen presenting cells?

A

-They are phagocytes
-Macrophages and dendrocytes are also antigen-presenting cells
-Process the antigens they ingest and display them on their surfaces for T-cells
-Form a link between innate and adaptive immune system
-

24
Q

What is the Peyers pathces?

A
  • Specialist sites within the small intestine
  • They are rich in M cells
  • Specialist sites of uptake of antigens in the gut for presentation to macrophages
  • Macrophages can enter M cells
25
Q

How do macrophages recognize microbial cells?

A
  • They have non specific receptors on their surgaces
  • Sticky but non specific
  • They also rely on circulating helper molecules
  • E.g complement, opsonization
26
Q

What is opsonization?

A
  1. Extracellular bacteria approach macrophage
  2. Osponization: Antibodies bind to bacteria and the Fc portion of the antibodies binds to receptors on the macrophage surface
  3. Ingestion by macrophage
    - Antibodies link bacteria and macrophage, aiding phagocytosis
27
Q

What part of bacteria interferes with the antigen recognition process?

A
  • Many pathogens are encapsulates to help them evade the innate system
  • CAPSULE
28
Q

How are the pathogens recognized by the immune system?

A
  • Innate system is the key
  • Cells of the innate immune system have specialized sets of receptors to recognize INVARIANT and ESSENTIAL microbial factors that are UNIQUE to the microbe (lipopolysaccharide, flagella, chitin)
  • These are referred to as PATTERN RECOGNITION RECEPTORS (PRRs)
  • PRR’s recognize MAMPS
  • MAMPS ARE MICROBE ASSOCIATED MOLECULAR PATTERNS
  • Don’t discriminate between good and bad microbes
29
Q

What are the TOLL LIKE RECEPTORS (TLRS)

A

-Transmembrane receptors on some immune cells that recognize viral and bacterial products
-On binding to ligand: (target)
-Use cytokines to signal inflammatory response (danger)
-Induce macrophages to produce antimicrobial proteins and peptides
TLR’S are useful to sense external MAMPS (Microbe associated molecular patterns)

30
Q

The NOD like receptors (NLR’s)

A

TLR’S are useful to sense external MAMPS (Microbe associated molecular patterns)

  • If the pathogen is in the inside of the host cell, the TLRs cannot sense them.
  • Instead, internal NOD like receptors (NLRs) bind MAMPS and
  1. Activate cytokine production
  2. Form a complex called an inflammasome that triggers apoptosis (good cell death)
31
Q

What are the examples of Toll like Receptors and NOD like Receptors?

A
  1. TLR1 (Lipopeptides, bacteria)
  2. TLR2 (Glycolipids, bacteria)
  3. TLR3 (Double stranded RNA, viruses)
  4. TLR4 (Lipopolysaccharides, bacteria)
  5. TLR5 (flagellin, bacteria)
  6. TL6 (Diacyl lipopeptides, mycoplasma)
  7. TLR9 (Unmethylated CpG residues in DNA, Bacteria)

NOD 1- Component of Gram negative peptidoglycan, Gram negative bacteria
NOD 2-Peptidoglycan component, bacteria

NLRP-3-Peptidoglycan, Bacteria
NLRP-4-Flagellin, ATP, dsRNA, Bacteria

32
Q

What are natural killer cells?

A
  • Not phagocytic
  • A lymphocytic cell, distinct from T cells and B cells
  • Large and granular
  • Make up 2%
  • Thought to be halfway house between innate and acquired immunity
  • Don’t attack pathogens themselves but instead attack host cells that have become overwhelmed by pathogens
33
Q

NK cells mechanism of action

A
  • NK cell alerted by interferons or macrophage generated cytokines
  • Infected host cell signals an altered response
  • NK cell binds to infected cell and perforin punches holes in the membrane
  • Granzyme induced infected cell to undergo apoptosis
34
Q

What is the adaptive immune response?

A
  • The branch of the immune system that has memory

- Develops as the need arises

35
Q

What are the two types of adaptive immune system

A
  1. Humoral immunity
    - Antibodies directly target microbial invaders (B-cell response)
    - tARGET INFECTIONS in the body’s fluids (humors)
  2. Cell-mediated immunity
    - Teams of T-cells (T lymphocytes) work together to recognize antigens displayed on infected cells
    - Target infections in the body’s cells

Both humoral and cell-mediated immunity are intertwined

36
Q

How does adaptive immunity develop?

A
  • Develops over a 3-4 day period following an exposure to an invading microbe
  • Immune system recognizes small pieces of a given antigen, called antigenic determinants or EPITOPES
  • Phagocytosis produces many epitopes for the adaptive immune system
  • Each B-cell recognizes one specific epitopes for the adaptive immune system
  • Each B cell recognizes one specific epitope
  • Response to an infection by a microbe involves thousands of different B cells each of which recognizes a particular epitope
37
Q

What are epitopes

A

-They are small pieces of a given antigen that the immune system learns to recognize.

38
Q

What are antigens?

A

-The are from antibody generators stimulate B cells to differentiate into antibody-producing cells

39
Q

Initiation of response

A
  • Humoral response starts when an antigen triggers the differentiation of B cells into antibody-producing factories
  • Cell mediate response starts when certain T-cells become activated by microbial antigens that are presented to them by macrophages
  • Activated T cells can directly kill an infected host cell
  • Also produce cytokines that initiate a macrophage feeding frenzy at the site of infection
40
Q

What is immunogenicity?

A
  • The effectiveness by which an antigen elicits an immune response
  • Most efficient in recognizing proteins, then carbohydrates and lastly the nucleic lipids
41
Q

Antigen presentation

A

-Antigen is placed

42
Q

Antigen presentation

A
  • Antigen is placed on a major histocompability complex (MHC) protein
  • Binding of antigen to MHC protein needs to be strong for T-cell to recognize it properly
  • T-cell receptor binds antigen and MHC
  • Together with accessory molecules
  • This is the basis of vaccination
43
Q

What are the two types of effector T-cells

A
  1. T-helper cells/CD4+ cells
    - Associate with MHC class 1 proteins on APCs
  2. Cytotoxic T-cells/CD8+ cells
    - Associate with MHC Class 1 proteins on APCs
44
Q

What do the two different T cells do?

A
  1. T helper
    - detectives
    - trained to memorize databanks of antigens to alert b cells if circulating antigen is detected
  2. T cytotoxic cells
    - Trained to seek and destroy cells presenting noxious antigens on MHC
  • Both types are extensively educated in the thymus so that they don’t recognize self antigens too strongly
  • They are all tested before they leave and if they fail they are destroyed
45
Q

What are the two types of T helper cells?

A
  • T helper cell must determine which cytokines will allow the immune system to be most useful for the host during infection
  • On activation, TH cells differentiation into two types
  1. TH 1
    - most active against intracellular bacteria and protozoa
  2. TH 2
    - Most active against helminthic infections, parasitic worms
46
Q

Memory and Regulatory T cells

A

-Some Th cells differentiate into memory Th cells

  • Retain antigen affinity of the originally activated T cell
  • Used to act as later effector cells during reinfection
  • Some naive T cells differentiate into regulatory T cell (T-reg)
  • These do not promote an immune response but help to restore homeostasis after infection.
  • Lack of T reg cells is associated with chronic inflamation
47
Q

How do we learn to live with the antigens of our bodies/the foreign antigens of our microbiota?

A
  • Antigen does is important
  • If antigen dose is over a value, then B and T cells become over stimulated
  • T cells become non functional
  • B cells do not respond to subsequent antigen exposure to make antibodies

-T cells are educated and tested fro lack of sensitivity to self antigens

48
Q

Vaccination

A
  • Inducing immunity without disease
  • It uses killed, attenuated antigen sources to induce an immune response without causing disease
  • B cells are long lived and so immunity through vaccination lasts for years
49
Q

Anatomy of an Antibody

A
  • They are keys to immunological specificity
  • Typical antibody has 4 polypeptide chains
  • 2 large heavy chains
  • 2 smaller light chains
  • Bound together by disulphide bonds
50
Q

What are the constant and variable regions in an antibody?

A

-Contast regions of conserved amino acids sequences

  • 5 heavy chain types,
  • 2 light chain types, lambda and K

Heavy chain defines the antibody class

alpha-IgA
-Each class is common to a species (isotype)
51
Q

What does isotype, allotype, idiotype do?

A
  • It defines the various heavy chains of a species (human)
  • differences in the constant region shared by some but not all members of a species
  • difference in the hypervariable region within an individual
52
Q

IgG

A
  • Simples, smalles and most abundand antibody in blood and tissue fluids
  • A monomer with 4 classes
  • ach class varies in aa sequence and interchain cross linking

Function
1. Binds and opsonizes microbes (allows phagocytes to grab them more easily)

  1. Binds and neutralizes viruses
  2. Activates the classical complement pathway
53
Q

igA

A
  • Major secreted antibody of mucosal surfaces
  • Most commonly found as a dimer linked by disulfide bonds to the J (joining) chain protein
  • The secretory piece is wrapped around both molecules during secretion.
  • Secretory igA is found in tears, breast milk and mucosal surfaces
54
Q

igM

A
  • Can be found as monomers on the surface of B cells
  • But is most commonly found as pentamer held together by J protein
  • First antibody isotype detected during the course of an infection
55
Q

igD

A

-Present in trace amounts in the blood
-Exists in monomeric form on surface of B cells
-Plays a role in B cell activation
Function no well understood
-Does not bind complement
-May play a role in allergy as well as activation of the immune response to respiratory pathogens

56
Q

igE

A
  • present in trace amounts in the blood
  • found more prominently on the surfaces of mast cells and basophils
  • these are loads with inflammatory mediators (held in granules)
  • When 2 mast cells or basophils are cross linked by antigen via IgE mase cells degranulates and act to quickly amplify the immune response
  • Unfortunate side effect in some people-anaphylaxis

Microbiology post midterm (5 decks)

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