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Molecular Virology > Immunology > Flashcards

Immunology Flashcards

1
Q

What is the overall function of the immune system?

A

The overall function of the immune system is to limit infection by microorganisms

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1
Q

What is the overall function of the immune system?

A

The overall function of the immune system is to limit infection by microorganisms

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2
Q

Name the three lines of Defence that the immune system uses.

A

Physical barriers
Innate defence
Adaptive defence

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3
Q

Physical barriers:

A

The virus needs to breach these barriers to gain entry for example the skin

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4
Q

Innate defence:

A

Immediate or develops rapidly

It is nonspecific and it has no memory

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5
Q

Adaptive defence:

A

Adaptive defence includes both cell mediated immunity and antibody mediated immunity.

It develops later.
It is pathogen specific and it has memory

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6
Q

Anatomical and chemical line of Defence:

A

The first line of Defence
It is continuous

It includes physical barriers such as:
Mucus
Saliva
Stomach acid
Tears
Skin
Scabs
Defensins
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7
Q

Intrinsic line of Defence:

A

It is immediate.
It includes intrinsic factors:
Apoptosis
Host restriction factors, e.g. APOBEC

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8
Q

Innate immunity:

A 
It occurs within minutes or hours.
The cells of the innate immune system:
Natural killer cells
Complement 
Antigen - presenting cells
Neutrophils
Cytokines
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9
Q

Acquired immunity:

A

It occurs within hours or days.
The cells of the adaptive immune system include:
T cells
B cells

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10
Q

Physical barriers:

A
  • First line of defence that the virus needs to get through.

* Example: skin, mucus, stomach acid, tears, scabs.

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11
Q

Intrinsic Host Defence:

A
  • Cellular-based antiviral defence mechanism.
  • Response is immediate and specific.
  • Does not fit into classical innate or adaptive response.
  • Example: Host restriction factors - host antiviral proteins that restrict viral replication, such as APOBEC3 which interferes with HIV replication to produce defective virus.
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12
Q

Cells of the immune system:

A

*Derived from hematopoietic stem cells found in the bone marrow
*Stem cells can become the following leukocytes (white blood cells; WBC):
Innate response
NK cell
Dendritic cell
Macrophage
Neutrophil

Adaptive response
B cell
Helper T cell
Killer T cell

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13
Q

Cells of the immune system: Innate response

A

a) Natural Killer cells (which destroy infected cells by cell lysis)

b) Phagocytic cells (which can engulf pathogens)
Monocytes (circulating “guard” cells)
Macrophages (ex-monocyte, engulf/destroy pathogen, present antigen)
Dendritic cells (ex-monocyte, engulf/destroy pathogen, present antigen)
Neutrophils (engulf pathogen, destroys pathogen and destroys itself)

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14
Q

Cells of the immune system: Adaptive response

A 
Lymphocytes (naïve in bone marrow, but are “taught” and become mature) 
B cells (can become plasma cells which secrete antibody)
T cells (can become specialized killer/cytotoxic (CD8) or helper (CD4) cells)
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15
Q

Define the term ‘Lysis’.

A

Lysis is the breaking down of the cell membrane. Antigen = processed piece of the virus

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16
Q

How does the innate system recognize microbes and not itself?

A

Immune cells such as macrophages have pathogen recognition receptors (PRR’s) that recognize pathogen associated molecular patterns (PAMP’s).

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17
Q

What are PAMP’s?

A

PAMP’s - certain types of conserved molecules or “patterns” commonly found on pathogens, but not in the host.

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18
Q

PRR’s can be:

A

(a) membrane receptors e.g. Toll-like receptors (TLR)

(b) cytoplasmic receptors e.g. RNA helicase (RIG) receptors

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19
Q

How is an immediate inflammatory response initiated?

A

Through complex molecular pathways, initiates an immediate inflammatory response that limits viral replication during the early stages of infection.

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20
Q

What are major targets of innate immune recognition?

A

Major targets of innate immune recognition are viral nucleic acids. e.g. TLR 3, 7, 8 detect viral nucleic acids

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21
Q

Innate immune response is triggered in 2 ways:

A
  • Recognition of viral components by PRR’s on innate immune cells OR
  • activation of intracellular signalling mechanisms following virus entry and replication in cells.
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22
Q

Describe innate response.

A

Innate response is fixed, stereotyped, and continues to operate until the infection is eliminated. Innate response is same no matter how often individual is re-exposed to the same organism – no memory.

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23
Q

When is the innate immune response effective?

A

The innate immune response is effective at the limiting extent of infection in early stages (while a specific immune response is being generated).

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24
Q

Detection of viral pathogens by innate immune system has 2 major consequences:

A

leads to induction of the innate antiviral mechanisms most of which are mediated by type-I interferons (IFNs) AND
leads to activation of the adaptive immune response

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25
Q

What do immune cells use to communicate?

A

Immune cells use cytokines (soluble proteins) to communicate.

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26
Q

How are cytokines released?

A

Cytokines are released in short bursts in response to some stimulus (e.g. virus infected cell).

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27
Q

What do cytokines bind to and what do they induce?

A

Cytokines bind to receptors on nearby cells and induce response in the stimulated cell.

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28
Q

In addition to type I IFNs, many inflammatory cytokines play an important role in antiviral defence, by:

A
  • directly inducing antiviral effector molecules or
  • indirectly by stimulating cellular recruitment, phagocytosis of infected cells, and activating adaptive immune responses such as cytotoxic T lymphocytes and neutralizing antibodies.
29
Q

How can cytokines act?

A

Cytokines can act locally through autocrine and paracrine mechanisms or if produced at high enough levels they can gain access to the circulation and induce systemic effects such as acute-phase response or fever.

30
Q

What happens when a cytokine binds to its specific receptor?

A

When a cytokine binds to its specific receptor, it triggers a series of events in the cell which culminates in the cell changing in some way.
A signal is passed across the cell membrane.
Second messengers are activated in the cytoplasm which switch on the expression of specific genes. Proteins are synthesised and expressed.
The consequence of this may be that the cell becomes activated.
The cell may respond by releasing other cytokines, or undergoing differentiation or cell division or apoptosis even cause it to migrate

31
Q

An interferon is an…

A

important type of cytokine

32
Q

When is an interferon released?

A

*Interferon (IFN) is released after host PRRs interact with viral PAMPs e.g. the PAMP dsRNA is a potent inducer of interferon release.

Interferons released within hours of the host becoming infected and they limit the spread of viruses early, while adaptive immune response is developing.

33
Q

Types of interferons:

A

IFN α and β

34
Q

Where are IFN α and β released?

A

From virus - infected cells

35
Q

What do IFN α and β bind to and what do they lead to?

A
  • Bind to receptors on other cells in the environment and induce an antiviral state in those cells.
  • Leads to the expression of over 300 ISGs (interferon stimulated genes), which encode proteins that participate in antiviral defence.
36
Q

What do autocrine and paracrine signals induce?

A

Autocrine signals induce ISGs within same cell.

Paracrine signals induce an antiviral state in neighbouring cells, minimizing spread of infection.

37
Q

What does IFN α and β promote?

A

Promotes antigen processing and presentation in APCs

Promotes cytotoxic activity of NK cells and CD8 T cells

38
Q

Notes on PRRs:

A

PRRs on cell membrane, endosome and in cytoplasm that bind to dsRNA switch on activation cascade leading to translocation of active transcription factors IRF3 and NFkB to nucleus. These lead to transcription of interferon genes. Interferons are secreted from the cell and bind to high affinity receptors on nearby cells. Ligand binding leads to activation of transcription factor ISGF and translocation to the nucleus. This transcription factor induces the expression of multiple genes which alter the physiology of the cell to interfere with virus replication. The effect of IFN-abR signalling is different in infected and noninfected cells.

39
Q

What is IFN-γ secreted by and what does it induce?

A
  • secreted mainly by NK cells, CD8 T cells and T helper 1 cells
  • induces activation of genes involved in antigen processing and presentation, facilitating the activation of virus-specific T cells
40
Q

What have some viruses evolved?

A

Some viruses have evolved immune evasion strategies that protect them from interferons

41
Q

What are IFNs used as?

A

IFNs are used therapeutically as antiviral drugs to treat certain chronic viral infections, but they have proved to be rather disappointing therapeutic agents - have to be given intravenously and have lots of side effects

42
Q

Cells of the innate immune system
Natural Killer cells
Where are natural killer cells important? What don’t they recognize?

A

Important in the early stages of viral infection - recognize virus infected cells non-specifically.

Do not recognize specific antigens, rather they detect “an absence of self” – absent MHC I molecule

43
Q

Describe Natural Killer cells. State what they produce.

A

Cytotoxic – kill infected cells

Produce IFN-γ (type of cytokine) to induce other antiviral mechanisms

44
Q

Cells of the innate immune system
Natural killer cells and Apoptosis
What happens when natural killer receptors are triggered?

A

When NK receptors are triggered, a cascade of events occur in the cytoplasm of NK cell

45
Q

What does a cascade of events occur in the cytoplasm of NK cell [when NK receptors are triggered] lead to?

A

This leads to degranulation of vesicles containing perforin and granzymes, which are poured into the immunological synapse.

46
Q

What does perforin form?
What does this allow?
Leading to?

A

/Perforin forms a permeable pore in the cell membrane of the target cell
/Which allows entry of granzymes and loss of water (osmotic shock)
/Leading to cell death.
/Granzymes initiate apoptosis in the target cell.

47
Q

Cells of the innate immune system
Monocytes, Macrophages and Dendritic Cells – Professional Phagocytes
What do the Monocytes do?

A

Monocytes: circulating leukocytes that patrol blood & peripheral tissue for infection – Sentinel (“guard”) cells of innate immune system.

48
Q

Cells of the innate immune system
Monocytes, Macrophages and Dendritic Cells – Professional Phagocytes
What do the Monocytes do once they are inside the tissue?

A

Once inside tissue, monocytes differentiate into macrophages and dendritic cells.

49
Q

Cells of the innate immune system
Monocytes, Macrophages and Dendritic Cells – Professional Phagocytes
What are macrophages found as? What role do they in the body?

A

Macrophages found as specialized cell types in most organs e.g. Kupffer cells (liver), microglia (neuronal tissue), and osteoclasts (bone).

Play central role in inflammation, wound healing, tissue remodelling, clearing dying cells and viruses.

50
Q

Cells of the innate immune system
Monocytes, Macrophages and Dendritic Cells – Professional Phagocytes
Name the 2 types of dendritic cells and state where they reside.

A

Dendritic cells: 2 types: reside in blood & lymphoid tissues (blood DCs), reside in peripheral tissues (mucosa, skin, internal organs) (tissue DCs).

51
Q

Cells of the innate immune system
Monocytes, Macrophages and Dendritic Cells – Professional Phagocytes
Where are immature dendritic cells recruited?

A

Immature dendritic cells are recruited to areas of infection where they take up & process foreign antigen and then mature and migrate to the lymph nodes where they present antigen to T helper cells which organizes adaptive immune response.

52
Q

Cells of the innate immune system
Importance of Macrophages and Dendritic Cells in Immune Defence
Where are the macrophages and dendritic cells situated? What enables pathogen recognition?

A

The macrophages and dendritic cells are situated at the forefront of mucosal barriers. Pathogen recognition by pathogen recognition receptors (PRR’s), phagocytes that engulf and degrade pathogens

53
Q

Cells of the innate immune system
Importance of Macrophages and Dendritic Cells in Immune Defence
Why do macrophages and dendritic cells secrete cytokines?

A

Macrophages and dendritic cells secrete cytokines that stimulate the innate and adaptive response and present short peptides in association with major histocompatibility complex II (MHC II) in order to stimulate CD4 T-helper cells (therefore called antigen presenting cells).

54
Q

Cells of the innate immune system
Importance of Macrophages and Dendritic Cells in Immune Defence
What are complement proteins activated by apart from cytokines?

A

Apart from cytokines, complement (proteins activated by various pathways) also enhance the phagocytic activity of macrophages and dendritic cells.

55
Q

What are the 2 components of the adaptive immune system?

A

2 components of the adaptive immune system – cell mediated immunity and antibody mediated (humoral) immunity.

56
Q

Antigen specific, highly discriminating:

A

Antigen specific, highly discriminating – receptors of the cells of the adaptive immune system (B lymphocytes and T lymphocytes) only recognize the constituents/components (antigens) of a particular virus

57
Q

Describe the diversity of the adaptive immune system.

A

The adaptive immune system has remarkable diversity (can respond to millions of different antigens).

58
Q

Adaptive immune system

First encounter with a virus:

A

1st encounter with a virus: adaptive response takes days to evolve.

59
Q

Adaptive immune system

Repeat exposure/infection with particular virus/viral protein:

A

Repeat exposure/infection with particular virus/viral protein: results in a more rapid response of higher magnitude by the specific adaptive immune cells - phenomenon called immunological memory, the basis for vaccination.

60
Q

Lymphoid organs

What do the mature “resting” B and T lymphocytes do?

A

The mature “resting” B and T lymphocytes that leave their development site (bone marrow and thymus, respectively) enter the blood, and then migrate to secondary (peripheral) lymphoid organs (SLOs).

61
Q

Secondary lymphoid organs play a critical role in the …

Name the major secondary lymphoid organs.

A

SLOs - critical role in initiation of adaptive immune response to viruses/other microbes.
Major SLOs: lymph nodes (LNs), spleen, mucosal associated lymphoid tissue (MALT)

62
Q

What do secondary lymphoid organs localize?

A

SLOs localize adaptive immune cells (T and B cells) to distinct regions i.e. B cells localize to LN cortex, T cells localize to LN para-cortical area.

63
Q

What does the activation of B cells lead to?

A

Activation of B cells specific for a pathogen/antigen leads to their proliferation and formation of a germinal center within the LN cortex.

64
Q

Major histocompatibility complex(MHC) Class 1 vs 2

Where are they located and what is their function?

A
  • They are cell surface proteins found on most cells.
  • Their function is to present peptide antigen to T cells, but they are most famous for being the molecules responsible for graft rejection.

People express different variants of these molecules on their cells. These are the molecules that the immune system recognises as non self

65
Q

Where are MHC I molecules found?

A

MHC Class I molecules are found on the surface of all nucleated cells. They present peptides derived from proteins that were synthesised inside the cell.

66
Q

Where are MHC class II molecules found?

A

MHC class II molecules are found on the surface of antigen presenting cells. They bind peptides derived from phagocytosed antigen and present them to CD4 T cells.

67
Q

What are endogenous and exogenous peptides presented on?

A 
Endogenous peptides are presented on class I molecules and stimulate CD8 cells while 
Exogenous peptides are presented on class II molecules which stimulate CD4 cells
68
Q

CD8 cytotoxic T lymphocytes:

What does the T cell receptor of the CD8 T cell recognize?

A

T cell receptor (TCR) of CD8 T cell recognizes MHC class 1 viral peptide complexes

69
Q

CD8 cytotoxic T lymphocytes:

What are they killed by?

A

They are killed by either of 2 mechanisms - release of perforins and granzymes, or the induction of apoptosis by the death receptor pathway

70
Q

CD4 T helper lymphocytes

What are CD4 T helper cells important in?

A

CD4 T helper (Th) cells are important in stimulating both the humoral and cellular immune response.

Molecular Virology (26 decks)

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