1.02 - Innate Immunity Flashcards

1
Q

Compare the Innate and Adaptive Immune System with respect to:

  • Presence in higher organisms
  • Specificity of receptors
  • Genetics behind the receptors
  • Presence of memory
A

Innate
- Present in earlier organisms
- Relies on receptors and molecules that recognise specific patterns on pathogens
- Structure of receptors and molecules encoded in the germline and is the same for all humans
- Induce the same response the first and 100th time they recognise their pathogen
Adaptive
- Only present in higher vertebrates (arisen through evolution)
- Relies on unique receptors on lymphocytes to identify specific pathogens
- Everyone has lymphocytes with different receptors and they are unique to each person
- Remembers past pathogens and gives a faster and better response with repeated challenges (memory)

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2
Q

Compare the difference(s) between Innate Immune Response, The Early Induced Innate Response and the Adaptive Immune Response

A

Innate Immunity (Immediate: 0-4 hours)
o Infection → Recognition by preformed, non-specific and broadly specific effectors → Removal of infectious agent
Early induced innate response (Early: 4-96 Hours)
o Infection → Recognition of microbial-associated molecular patterns → inflammation, recruitment and activation of effector cells → removal of infectious agent
Adaptive Immune Response
o Infection → Transport of antigen to lymphoid organs → Recognition by naive B & T Cells → Clonal expansion and differentiation to effector cells → removal of infectious agent

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3
Q

What are the three components of the innate immune system?

A

Barriers
Cells
Circulating Proteins

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4
Q

Describe the Epithelium as a barrier to infection

A

They are the first line of defence

Are a physical barrier but also aided by mucin, cilia, antimicrobial peptides and commensal bacteria

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5
Q

What are some common routes of entry for microbes?

A
Airways
GIT
Reproductive Tract
External Surface
Wounds and Abrasions
Insect Bites
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6
Q

Compare receptor characteristics of the Innate and Adaptive Immune systems

A

Innate (specific to the innate - not present in adaptive):
- Specificity is inherited in the genome
- Expressed by all cell of a particular type (e.g. macrophages
- Triggers immediate response
- Recognises broad classes of pathogens
- Interacts with a range of molecular structures of a given type
Adaptive (specific to adaptive - not present in innate):
- Encoded in multiple gene segments
- Requires gene rearrangement
- Clonal distribution
- Able to discriminate between even closely related molecular structures

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7
Q

Describe the Stages of infection through the skin and how, at each stage, infection is protected/prevented.

A

Adherence to epithelium
o Normal flora, Local chemical factors, Phagocytes
Penetration of epithelium, local infection
oWound healing induced
oAntimicrobial proteins and peptides, phagocytes and complement destroy microbes
Local infections of tissues
oComplement, cytokines, chemokines, phagocytes, NK cells
oActivation of macrophages
oDendritic cells migrate to lymph nodes to activate adaptive immunity
oBlood clotting helps limit spread of infection
Adaptive Immunity
oInfection cleared by specific antibody
oT cell dependent activation and cytotoxic T cells

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8
Q

Describe Macrophages

A

A tissue based phagocytic cell, derived from monocytes, that plays important roles in innate and adaptive immunity.
Microorganisms that cross the epithelial barrier are recognised by macrophages (through their surface receptors)
Phagocytosis then occurs
Activation of macrophages brings neutrophils to the site of infection.

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9
Q

Describe the basic process of phagocytosis

A

The microbe is surrounded by the cell membrane of the phagocyte (Macrophage) and is internalised into a phagosome.
The phagosome then merges with a lysosome to give a phagolysosome.
Within the lysosome are various proteins that produce hydrogen peroxide and hypochlorite
In this phagolysosome the microbe is then degraded.

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10
Q

Describe Neutrophils

A

Short lived cells from the blood (not present in normal tissue)
Play a key role in innate immunity as they phagocytose and remove a pathogen without the assistance of the adaptive immune system
They die soon after they have phagocytksed the pathogen
Major component of pus

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11
Q

Describe how Neutrophils enter the infected tissue

A

Chemical signals released by the activated macrophages and other tissue damage caused by the pathogen (chemokines/cytokines) activate receptors on the neutrophils and the cell wall to cause the neutrophil to leave the circulation and go to the inflamed tissue.

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12
Q

Describe Dendritic Cells

A
Multiple different types
Bone marrow derived
Capture antigen and take to lymph node
Produce cytokines
Activate T cells and affect T cell differentiation
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13
Q

Describe Eosinophils

A

Bone marrow derived lymphocyte
Involved in allergic reactions
Important in defence against extracellular parasites such as helminths

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14
Q

Describe Mast Cells

A

Major effector cells of allergic reactions.
Have abundant granules containing histamine and other active agents
Have receptors for IgE antibodies.
Binding of antibodies stimulates release of their granule contents and production of other mediators –> Hypersensitivity (allergic) reactions

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15
Q

What is the purpose of the inflammatory response

A

To deliver effector molecules to the area to aid tissue macrophages
Induce local blood clotting to stop the spread of infection
Promotes repair of tissue

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16
Q

List the major cytokines in innate immunity

A

TNF-alpha
IL-12
Type 1 interferons (alpha and beta)
Pro-inflammatory cytokines: activate cells of the innate immune system, act on hypothalamus to cause fever, act on liver to make acute phase proteins

17
Q

What are PAMPs?

A

Pathogen Associated Molecular Patterns
These are proteins, nucleic acids or lipids which humans don’t have or which have modifications to make them dissimilar to ours
They are recognised by Pattern Recognition Receptors

18
Q

What structures recognise PAMPs and provide examples

A

Pattern Recognition Receptors

  • Toll Like Receptors (LPS and Nucleic Acid recognition)
  • C-Type Lectin Receptors (carbohydrate recognition)
  • Cytoplasmic Recognition Receptor (peptidoglycan and nucleic acid recognition)
19
Q

Describe an example of a Toll Like Receptor

A

TLR4
Found on the cell surface of phagocytes, DC, endothelial cells and many other cell types
Bind to LPS triggers a chain reaction that leads to transcription and translation of pro inflammatory cytokines

20
Q

Describe Toll Like Receptors

A

Cell surface and endosomal receptors expressed by many cell types.
Recognise PAMPs such as LPS and microbial nucleic acid
Initiate signalling cascade to nucleus to activate transcription of cytokines

21
Q

What is the Inflammasome?

A

Protein complexes that activate inflammatory signalling pathways and lead to the production of IL-1

22
Q

What major cytokines do activated macrophages secrete?

A
IL-1beta
TNF-alpha
IL-6
CXCL8
IL-12
23
Q

Describe the effects of IL-1beta when released from activated macrophages

A

Activates lymphocytes
Activates vascular endothelium
Increases access of effector cells

24
Q

Describe the effects of TNF-alpha when released from activated macrophages

A

Activates vascular endothelium and increases vascular permeability
Increases entry of IgG, complement and cells to tissues and increase fluid drainage to lymph nodes

25
Q

Describe the effects of IL-6 when released from activated macrophages

A

Lymphocyte activation

Increased antibody production

26
Q

Describe the effects of CXCL8 when released from activated macrophages

A

Chemotactic factor that recruits neutrophils, basophils and T cells to site of infection

27
Q

Describe the effects of IL-12 when released from activated macrophages

A

Activates NK cells

Induces the differentiation of CD4 T cells into Th1 cells

28
Q

Describe the process of Antiviral Immunity

A

Various viral components are recognised by PAMPs in virally infected cells
Triggers production of interferons (IFN-alpha, IFN-beta) to try to prevent spread of viral infection to adjacent cells.
Adjacent cells can put special measures in place that interfere with viral replication

29
Q

What are some of the effects of IFN-alpha and IFN-beta when released from viral infected cells?

A

Induce resistance to viral replication in all cells
Increase MHC Class I expression and antigen presentation in all cells
Activate dendritic cells and macrophages
Activate NK cells to kill virus-infected cells

30
Q

Describe the recognition of Virally Infected Cells by NK cells and how it compares to that in normal cells

A

MHC Class I on normal cells is recognised by inhibitory receptors on the NK that inhibit activating signals coming from other receptors on the NK cells –> NK cell does not kill the normal cells
Altered or absent MHC Class 1 cannot stimulate a negative signal. The NK is triggered by signals from the activating receptors –> Activated NK cell releases granule contents, inducing apoptosis in the target cell

31
Q

Describe the complement cascade

A

A system of serum and cell surface proteins that interact with one another and with other components of the immune system to generate important effectors of innate and adaptive immune responses.
A cascade of protein activation, with three different initiating pathways that all converge on a common protein, C3.

32
Q

What are the three pathways of complement activation and how are they each activated?

A

Classical: Antigen-Antibody complexes
Lectin Pathway: Mannose-binding lectin or ficolin binds carbohydrates on pathogen surfaces
Alternative: Microbial Surfaces

33
Q

What are some of the effects and effectors of the complement cascade?

A

C3a, C5a –> peptide mediators of inflammation, phagocyte recruitment
C3b –> binds to complement recpetors on phagocytes –> opsonisation of pathogens, removal of immune complexes
Terminal Complement Componets –> Formation of Membrane Attack Complex –> Lysis of certain pathogens and cells