4.2 Infectious diseases Flashcards

1
Q

What are pathogens, antigens and epitopes?

A

Pathogen: organisms invading the body to cause diseases
Antigen: substances that induce an immune response as they are recognised by cells of the immune system and antibodies
Epitope: parts on a single antigen that binds to the antigen-binding site of an antibody or T cell receptor AKA antigenic determinant

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2
Q

What does the immune system consist of? [hint: 2 main branches; each with 2 sub branches]

A
  1. Non-specific (innate) immune system
    - anatomical barriers
    - cellular component
  2. specific (adaptive) immune system
    - cellular component
    - humoral component
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3
Q

The cellular component of the INNATE immunity comprises phagocytes (cells capable of engulfing pathogens via phagocytosis); name 3 types of phagocytes

A

Macrophages
Dentritic cells
Neutrophils

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4
Q

What cells comprise the cellular component of the ADAPTIVE immunity? [hint: lymphocytes]

A

T lymphocytes

B lymphocytes

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5
Q

What are the 3 classifications of lymphocytes and what does each entail?

A
  1. Naive cells:
    have not encountered the specific antigen that they are programmed to respond to
    e.g. Naive B and T cells
  2. Effector cells:
    have been activated by APCs or antigens and ready to function in an immune response
    e.g. helper T cells, cytotoxic T cells, plasma cells
  3. Memory cells:
    generated following primary response to antigen; lymphocytes that mediate a secondary response to subsequent encounters with the antigen
    e.g. memory B and T cells
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6
Q

Where are B and T cells derived?

A

Haemotopoietic stem cells in the bone marrow
B cells: stem cells that remain in the bone marrow that undergo differentiation
T cells: stem cells that migrate to the Thymus and undergo differentiation

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7
Q

What are the hummoral components of the adaptive immunity?

A

Antibodies AKA immunoglobulins that are proteins secreted by plasma cells

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8
Q

Innate immunity: explain the first line of defense [anatomical barriers to infection]

A

Includes physical and chemical barriers to prevent entry of pathogens:
Physical barriers include:
epithelial cell layers such as skin
mucous membrane lining respiratory tract and gastrointestinal tract
secretions such as saliva and tears wash away potential invading microorganisms to prevent their attachment
Chemical barriers include:
antimicrobial substances in secretions to kill these microorganisms
acidic pH

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9
Q

Innate immunity: explain the second line of defense [cellular component]

A

comprises of phagocytes: macrophages, dendritic cells, neutrophils
macrophages and dendritic cells recognise and engulf these pathogens via phagocytosis; and act as APCs
macrophages also induce inflammation by secreting signalling proteins e.g. cytokines and chemokines that increase permeability of blood vessels, to recruit neutrophils from blood to the site of infection

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10
Q

Briefly describe the process of phagocytosis

A
  1. Bacterium becomes attached to membrane evaginations called pseudopodia
  2. Bacterium is ingested forming phagosome
  3. Phagosome fuses with lysosome
  4. Lysosomal enzymes digest captured material
  5. Digestion products are released from the cell
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11
Q

Define antigen presentation and antigen presenting cells

A

Antigen presentation is the display of peptides of antigen bound to membrane proteins called MHC (Major Histone Compatibility) complex proteins on the surface of an antigen-presenting cell; this allows specific recognition by T cell receptors on naive T cells and thus activation of these T cells to effector cells
APCs are a specialised group of cells that take up antigens and process them into short peptides before presenting the peptides on MHC to lymphocytes for recognition

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12
Q

Describe the process of antigen presentation; the role of macrophages and dendritic cells as APCs

A
  1. After an APC engulfs the pathogen by phagocytosis, it can process antigens from the surface of the pathogen into short peptides (inside phagolysosome)
  2. Peptides of antigens bind to MHC protein inside endoplasmic reticulum to form the peptide:MHC complex
  3. Peptide: MHC complex is transported to cell surface membrane of APC via vesicles
  4. Antigens of pathogen on cell surface membrane of APC are ready for presentation to naive T cells; this is possible because the antigen of pathogen on MHC protein is complementary in conformation to TCR
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13
Q

Upon naive T cell activation, T cell undergoes clonal expansion and differentiation into effector T cells; define clonal expansion

A

Clonal expansion occurs when a single cell is stimulated to undergo proliferation via mitosis to produce large numbers of genetically identical daughter cells
[cytokines stimulate proliferation and differentiation of T cells]

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14
Q

What comprises the adaptive immune response?

A

Activation of T and B cells
antibody-mediated response
cell-mediated response

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15
Q

Briefly describe the cell-mediated response and humoral response

A

Cell-mediated immune response:
mediated by T cells; protect against intracellular pathogens by killing cells that contain these pathogens
Humoral response:
mediated by antibodies that are secreted by plasma cells; protect against extracellular pathogens and toxins secreted by pathogens into extracellular space

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16
Q

What are the key characteristics of the adaptive immunity?

A
  • High level of specificity for a particular pathogen
  • Shows memory (i.e. remembers the particular pathogen that previously invaded the body and responds more quickly to re-exposure to the same pathogen)
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17
Q

Role of T cells in the Specific/ Adaptive immunity: Describe the role of cytotoxic T cells

A

Cytotoxic T cells kill infected target cells and prevents reproduction of the intracellular pathogens
Cytotoxic T cells can recognise these infected host cells because these target cells display the same short peptides from antigen of pathogen presented earlier on MHC
The T cell receptor is complementary in shape to and thus binds to peptide:MHC complex found on target cells
Cytotoxic T cells kill infected host cells by releasing:
- Perforins: makes pores in the infected cell’s cell membrane
- Granzymes: diffuses in via the pores and activate enzymes involved in apoptosis
Cytotoxic T cells can also kill tumour cells

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18
Q

Role of T cells in the Specific/ Adaptive immunity: Describe the role of helper T cells

A

Helper T cells activate specific B cells to make antibodies by binding to peptide:MHC complex on cell surface membrane of B cells; specific T cell secretes cytokines that stimulate B cells to undergo clonal expansion and differentiation
After carrying out their respective functions, at least 90% of these effector cells die by apoptosis and the rest differentiate into memory T cells

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19
Q

Role of B cells in the Specific/ Adaptive immunity: Describe B cell activation

A
  1. Each B cell has one specific type of B cell receptor (BCR) on its cell surface that can recognise an epitope and bind to the specific antigen. When a B cell encounters the antigen with epitope complementary to its BCR, antigen binding occurs
  2. BCR together with bound antigen are endocytosed into the B cell; the antigen is processed into short peptides and attached to the MHC proteins
  3. The peptide: MHC complexes are transported to the cell surface membrane of the B cell where the peptide is recognised by antigen-specific helper T cells
  4. interaction between helper T cell and B cell stimulate cytokine secretion from helper T cell; cytokines activate the antigen-specfiic B cell to undergo clonal expansion and differentiation into effector cells: antibody secreting plasma cells and memory B cells
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20
Q

Explain the action of antibodies [hint: N&O]

A

Neutralisation (to prevent entry): antibodies recognise and bind to antigens on pathogens or bacterial toxins to prevent pathogen or toxin from attaching to specific host cell receptor and gain entry into host cell
Opsonisation (to promote phagocytosis): opsonisation is the binding of antibodies to antigens on pathogens to tag the pathogen for uptake by phagocytes
Fab portion of antibody binds to antigen while Fc portion of antibody binds to Fc receptor on phagocyte to promote phagocytosis

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21
Q

Define ACTIVE immunity based on mode of antibody production and duration of immunity

A

Antibody production: Antibodies are produced by the individual’s own immune system in response to antigens introduced naturally or artificially
Duration: immunity conferred is long-lasting since memory cells are formed in the individual after primary immune response to the antigen

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22
Q

Define PASSIVE immunity based on mode of antibody production and duration of immunity

A

Antibody production: Antibodies are transferred to the recipient without participation of the recipient’s immune system
Duration: immunity conferred is short-lived since there is no formation of memory cells

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23
Q

What are the four sub-types of immunity? [think of some examples]

A
  1. Active, Natural immunity: infected by the pathogen to stimulate memory cell production
  2. Passive, natural immunity
    e. g. fetus receives antibodies through placenta; newborn receives antibodies from milk
  3. Active, artificial immunity: receive vaccination to stimulate memory cells production
  4. Passive, artificial immunity: receive anti-serum with antibodies from another host
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24
Q

What are the 5 classes of antibodies?

A

IgG, IgM, IgA, IgD, IgE

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25
Q

What are the heavy chains and how many antigen-binding sites are there for the 5 classes of antibodies? [for all 5 classes, light chain is kappa chain/ lambda chain]

A
IgG: gamma chain; 2
IgM: mu chain; 10
IgA: alpha chain; 4
IgD: delta chain; 2
IgE: epsilon chain; 2
26
Q

What are the gene segments of a heavy chain gene and light chain gene?

A
Heavy chain gene:
V (variable)
D (diversity)
J (joining)
C (constant)

light chain gene:
V (variable)
J (joining)
C (constant)

27
Q

What are the 3 different methods of generating a vast repertoire of antibodies?

A
  1. Somatic recombination
  2. Somatic hypermutation
  3. Class switching
28
Q

Define somatic recombination

A

somatic recombination is a type of DNA rearrangement where DNA sequences that are initially separated from one another in the human genome are brought together by enzymatic removal of intervening sequences followed by rejoining of sequences

29
Q

When does somatic recombination occur?

A

during Bcell development in the bone marrow

30
Q

Explain what happens during VDJ recombination at the Ig heavy chain gene locus?

A

It involves the random rearrangement of one V gene segment, one D gene segment and one J gene segment to form a single VDJ exon;
the rearranged VDJ exon will code for variable region of heavy chain [Vh]
1. rearrangement of one D gene segment to one J gene segment forms DJ rearrangement
2. rearrangement of one V gene segment to DJ rearrangement forms VDJ rearrangement

31
Q

What occurs after the somatic recombination to form the heavy chain with the specific Vh?

A

transcription occurs:

  1. pre-mRNA contains VDJ exon and constant segments. The pre-mRNA undergoes RNA splicing so that VDJ exon and C exon are joined
  2. mature mRNA codes for a heavy chain that has specific Vh
32
Q

Explain what happens during VJ recombination at the Ig light chain gene locus?

A

It involves the random rearrangement of one V gene segment and one J gene segment to form a single VJ exon
The rearranged VJ exon will code for the variable region of the light chain [VL]
1. Rearrangement of one V gene segment to one J gene segment forms VJ rearrangment

33
Q

What occurs after the somatic recombination to form the light chain with the specific VL?

A

transcription occurs:

  1. pre-mRNA undergoes RNA splicing so that VJ exon and C light chain constant segment are joined
  2. mature mRNA codes for a C light chain that has specific VL
34
Q

Define somatic hypermutation

A

Somatic hypermutation is a random point mutation in the rearranged VDJ region of the heavy chain gene locus and rearranged VJ region of the light chain gene locus that further diversifies the variable regions [VH and VL] of the antibody for antigen binding

35
Q

Where does somatic hypermutation occur?

A

only on activated B cells outside the bone marrow

36
Q

What occurs during somatic hypermutation?

A

The B cells acquire slight amino acid difference in the variable region of Ig chains on the cell surface membrane [i.e changes in antigen-binding sites of BCR on cell surface membrane]
Some point mutations result in B cells expressing low affinity Ig on their cell surface membrane; other point mutations result in B cells expressing higher affinity Ig on their cell surface membrane

37
Q

Explain affinity maturation

A

When somatic hypermutation is used to make changes in the antigen-binding sites of BCR and BCR can be fine-tuned to express higher affinity for its specific antigen; these B cells that express higher affinity BCR are selected for clonal expansion and differentiation and differentiate into antibody-secreting plasma cells that secrete antibodies with high binding affinities for the specific antigen

38
Q

What is the difference between the BCR and the antigen-binding site of the antibody secreted from the plasma cells?

A

the only difference lies in their constant region of heavy chains due to class switching

39
Q

What is the difference between the different classes of antibodies?

A

different constant-region of heavy chains

40
Q

Where does class switching occur?

A

only on activated B cells in the presence of an antigen

41
Q

What is class switching?

A

the process of an individual B cell switching to synthesise different classes of antibodies e.g. IgM to IgG;
it refers to DNA rearrangement at the constant gene segment of Ig heavy chain gene locus [Ch][Vh remains unchanged]

42
Q

What is class switching induced by?

A

cytokines released from T helper cells during B cell activation

43
Q

Describe the process of class switching

A
  1. Before class switching, a B cell with Vh DNA linked to Cmu produced IgM antibodies
  2. During class switching, DNA rearrangement occurs and the Vh DNA becomes linked to another constant gene segment e.g. Cy of heavy chain gene locus Ch
  3. this results in a B cell that synthesises IgG antibodies
    Only the constant region of heavy chain of antibody changes from IgM to IgG due to the change of C gene segment from Cmu to Cy
44
Q

Describe the characteristics of a primary immune response

A
  1. Presence of a lag period (-3 to 6 days) between encountering the antigen and production of antibody; lag period reflects the time required for clonal expansion and differentiation of naive T cells to effector t cells and naive B cells to plasma cells
  2. Gradual increase in antibody concentration
  3. Lower peak concentration of antibodies that results in weaker response
45
Q

Describe the characteristics of a secondary immune response

A
  1. Faster increase in antibody concentration as there is no need to activate naive B and T cells; memory B and T cells can be reactivated easily and thus respond quickly to the same antigen
  2. Higher peak concentration of antibodies that leads to a stronger response
  3. high concentration of antibodies persists for a longer period of time
46
Q

Define vaccination

A

Vaccination is the intentional administration of an antigen, usually a harmless form of a pathogen, in order to induce a specific adaptive immune response that protects the individual against later exposure to the pathogen due to the production of memory cells

47
Q

What kind of immunity does vaccination confer?

A

Artificial Active immunity

48
Q

What basis does vaccination work on?

A

Immunological memory

49
Q

Explain what happens after vaccination

A
  1. A person is vaccinated against a specific disease. the vaccine contains antigens from the pathogen
  2. The modified pathogen is no longer able to cause disease, but it can still retain immunogenic effect (i.e. ability to elicit an immune response) because a characteristic surface antigen of a pathogen is still retained and can be recognised by APCs
  3. Adaptive immune response occurs. Naive B and T lymphocytes are activated to become effector lymphocytes
  4. The B lymphocyte with the specific BCR that is complementary in shape to the antigen undergoes clonal expansion by dividing repeatedly by mitosis to form genetically identical B lymphocytes which differentiate to become either memory B cells or antibody-secreting plasma cells
50
Q

Explain what happens after subsequent exposure to the pathogen [after vaccination]

A
  1. The virulent pathogen enters the vaccinated individual
  2. memory B and T cells will quickly recognise the antigen of the pathogen
  3. memory B and T cells rapidly undergo clonal expansion and
  4. differentiate into effector T cells and antibody-secreting plasma cells
  5. These plasma cells produce a high concentration of antibodies which prevent further infection by opsonisation/ neutralisation
51
Q

What are the 3 types of vaccines?

A
  1. Live, attenuated vaccine
  2. Inactivated vaccine
  3. Toxoid vaccine
52
Q

What does attenuation mean?

A

Attenuation refers to weakening of the pathogenic bacteria or virus by making it less virulent i.e. a modified pathogen that is not capable of causing disease

53
Q

Name some advantages and disadvantages of using a live, attenuated vaccine

A

Advantages:
The closest thing to a pathogen encountered in a natural infection; it contains a range of antigens that will elicit a strong immune response with just a low dosage
It is live and is able to replicate in the host, thus it will persist and continuously stimulate the immune system thus conferring longer-term protection
Disadvantages:
Possibility of their reversion to the virulent form by mutation and can cause disease
need to be refrigerated to stay viable and potent

54
Q

What does inactivation mean?

A

Inactivation involves killing the pathogenic bacteria or vrisu with chemicals, heat or radiation

55
Q

Name some advantages and disadvantages of using inactivated vaccine

A

Advantages:
Will not revert back to the virulent form and cause disease
usually do not require refrigeration and can be easily stored and transported in a freeze-dried form. This makes inactivated vaccine accessible to people in less accessible areas
Disadvantages:
May elicit weaker immune response, thus may need several doses (i.e. booster shots) to maintain protection

56
Q

What does toxoid mean?

A

Toxoid is a chemically modified toxin from pathogenic bacteria such that it is no longer toxic but is still able to elicit an immune response

57
Q

When is toxoid vaccine used?

A

When bacterial toxin is the main cause of illness. vaccination with toxoid induces production of anti-toxoid antibodies

58
Q

How does a toxoid vaccine work?

A

Vaccination with toxoid induces production of anti-toxoid antibodies which can bind the bacterial toxins and neutralise the toxins

59
Q

Name some advantages and disadvantages of using toxoid vaccine

A

Advantage:
Does not contain any pathogens thus there is no risk of reverting to vriulent form
Disadvantage:
May elicit weaker immune response, thus may need several doses to maintain protection
limited use when bacterial toxin is the main cause of illness but not all pathogenic bacteria produce toxin

60
Q

What are the benefits of vaccination?

A

vaccination protects inidividuals against diseases and increases herd immunity; if a large number of individuals in a population are vaccinated and are immune to an infectious agent, fewer susceptible individuals will contract the disease; transmission of the disease within the population is prevented

61
Q

What are the risks of vaccination?

A
  1. Live, attenuated vaccines may revert to virulent forms and cause disease
  2. Antigens used in some vaccines may cause allergy reactions
  3. Some vaccines may cause undesirable side effects
  4. Excessive vaccination may reduce the effectiveness of the immune system to respond to new infections