General principles of immune response Flashcards

1
Q

What are the components of the innate immune response?

A

Barrier and chemical mechanisms.

PRR

Cellular (phagocytes and NK cells).

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2
Q

What are the components of the adaptive immune response?

A

Humoral and cellular.

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3
Q

What are the main PRRs?

A

Toll-like receptors (TLRs)

NOD-like receptors (NLR)

RIG-like receptors (RLRs)

C-type lectins

scavenger receptors.

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4
Q

What are the main antimicrobial peptides associated with the innate immune system?

A

Defensins

Cathelin

Protegrin

Granulysin

Histatin

Secretory leukoprotease inhibitor

Probiotics.

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5
Q

Which immune cells are involved in the innate response?

A

Macrophages

Dendritic cells

NK cells

NK-T cells

Neutrophils

Eosinophils

Mast cells

Basophils

Epithelial cells.

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6
Q

Which complement components are involved in the innate immune response?

A

Classic and alternative pathways and proteins that bind complement proteins.

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7
Q

What are pattern recognition receptors (PRRs)?

A

Inclusive term for antigen recognition receptor in innate system. Common theme is recognition of Pathogen-associated Molecular Patterns (PAMPs) but also Danger Associated Molecular Patterns (DAMP’s).

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8
Q

What are the two groups of PRRs?

A
  1. Cell surface (transmembrane) and intracellular receptors – TLRs, NLRs, RLR’s and CLR’s.
  2. Fluid-phase soluble molecules - C-type lectin
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9
Q

What are the main features of the C-type lectin family?

A

e.g. Mannose-binding Lectin

Recognition of microbial complex carbohydrates

Bind via Carbohydrate-Recognition Domains (CRDs)

Role in neutralisation of pathogen

Role in recruitment of adaptive response

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10
Q

What is the role of IL-1?

A

Endothelia

  • increased coagulation
  • increased inflammation

Hepatocytes
- increased acute phase proteins

Hypothalamus
- increased fever

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11
Q

What is the role of TNF?

A

Endothelia

  • increase coagulation
  • increased inflammation

Hepatocytes
- increase acute phase proteins

Neutrophils
- increase activation

Hypothalamus
- increased fever

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12
Q

What is the role of IL-6?

A

Hepatocytes
- acute phase proteins

B lymphocytes
- increased proliferation

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13
Q

What is the role of macrophages?

A

Phagocytose and kill bacteria

Produce antimicrobial peptides

Bind (LPS)

Produce inflammatory cytokines.

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14
Q

What are the roles of plasmacytoid dendritic cells (DCs)?

A

Produce large amounts of interferon- (IFN-) which has antitumor and antiviral activity, and are found in T cell zones of lymphoid organs; they circulate in blood.

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15
Q

What are the roles of NK cells?

A

Kill foreign and host cells that have low levels of MHC+ self peptides.

Express NK receptors that inhibit NK function in the presence of high expression of self-MHC.

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16
Q

What are the roles of myeloid dendritic cells?

A

Interstitial DCs

  • strong producers of IL-12 and IL-10
  • located in T cell zones of lymphoid organs
  • circulate in blood
  • present in the interstices of the lung, heart, and kidneys.

Langerhans DCs

  • strong producers of IL-12
  • located in T cell zones of lymph nodes, skin epithelia, and the thymic medulla
  • circulate in blood.
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17
Q

What are the roles of neutrophils?

A

Phagocytose and kill bacteria, produce antimicrobial peptides.

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18
Q

What is the role of eosinophils?

A

Kill invading parasites.

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19
Q

What are the roles of mast cells of basophils?

A

Release TNF-, IL-6, IFN- in response to a variety of bacterial PAMPs.

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20
Q

What are the roles of epithelial cells?

A

Produce anti-microbial peptides
- tissue specific epithelia produce mediators of local innate immunity, e.g. lung epithelial cells produce surfactant proteins (proteins within the collectin family) that bind and promote clearance of lung invading microbes.

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21
Q

What are the central features of the adaptive immune response?

A

Evolution in response to changing pathogen structures.

Unique antigen receptor found on each lymphocyte. In response to infection this lymphocyte undergoes clonal expansion.

22
Q

What are the primary lymphoid organs and what is their function?

A

Bone marrow (B cells) and thymus (T cells). Responsible for lymphocyte development and selection.

23
Q

What are the secondary lymphoid organs and what is their function?

A

Spleen, lymph nodes and mucosal surfaces. Take part in immune response.

24
Q

What is the range of antigenic variability estimated to be?

A

10^9

25
Q

How do the T and B cell receptors generate receptor diversity?

A

Recombination of the variable segments of the gene (V,D and J). Splicing together.

26
Q

What is the mechanism of Ag presentation for MHCII?

A

Antigens are internalised

Broken down to peptides

Peptides associate with newly synthesised Class 2 molecules and are brought to the cell surface.

If the peptides are foreign they are recognised by helper T cells which are then activated.

Helper T cells produce cytokines needed by B cells, T cells , etc.

27
Q

Which cells do MHCI proteins present to?

A

Cytotoxic T cells (CD8).

28
Q

Which cells do MHCII proteins present to?

A

Helper T cells (CD4).

29
Q

What are he functions of antibodies?

A

Precipitation of dissolved antigens, neutralization, agglutination and activation of complement.

30
Q

What are the cytokines of adaptive immunity?

A

IL-4

IL-5

IL-12

IL-13

IL-17

INF gamma

31
Q

What is immunosupression?

A

Immunosuppression: a natural or artificial process which turns off the immune response, partially or fully, accidentally or on purpose.

32
Q

What is immunodeficiency?

A

The lack of an efficient immune system-susceptibility to infections.

33
Q

What are the potential uses of immunosuppression?

A

Transplant rejection, autoimmunity and lymphoproliferative diseases.

34
Q

What might be the consequences of immunosuppression/immunodeficiency?

A

Loss if PRRs (pneumococcus, HSV)

Loss of macrophages/neutrophils (CGD, staph, aspergillus)

Loss of complement (meningococcus)

Loss of cytokines (mycobacterium)

Loss of B cells, (recurrent sino-pulmonary infections),

Loss of T-effector cells (SCID, opportunistic infections).

35
Q

What is hypersensitivity?

A

Undesirable, damaging, discomfort-producing and sometimes fatal reactions produced by the normal immune system (directed against innocuous antigens) in a pre-sensitized (immune) host.

36
Q

What are the features of type 1 (anaphalactic) hypersensitivity?

A

Immunopathogenesis -IgE Ab mediated mast cell and basophil degranulation- release of preformed and de novo synthesized inflammatory mediators

Clinical features -Fast onset (15-30 min). Weal and flare.

Can have 2nd phase (late) response

Common antigens - Pollen, bee venom, animal dander

Associated diseases - Hay fever, allergic asthma

37
Q

What is the mechanism behind type 1 hypersensitivity?

A

IgE mediated

Cross-linking of FceR by allergen

Release of pre-formed mediators e.g. histamine

Synthesis of lipid mediators e.g. leukotrienes

38
Q

What are the features of IgE?

A

Produced by plasma cells from class-switched B cells under the control of IL-4 and CD40L - CD40 interaction

Extremely low serum levels BUT

High affinity receptor for IgE (FceRI) on mast cells and basophils

Permits stable binding over long periods

39
Q

What is the early phase response?

A

MAST CELL

  • FceR1 present at high density
  • Cross-linking of FceR1 by allergen leads to activation of mast cell, resulting in :-

DEGRANULATION - Release of pre-formed mediators
SYNTHESIS OF LIPID MEDIATORS

40
Q

What are the functions of histamine?

A

Stimulation of irritant nerve receptors

Smooth muscle contraction

Increase in vascular permeability

41
Q

What is the function of kallikrein?

A

Activates bradykinin - similar actions to histamine.

42
Q

What are the pre-formed mediators?

A

Histamine, kallikrain and tryptase.

43
Q

What are the lipid mediators?

A

Arachidonic acid derivatives - leukotrines and prostoglandins (thromboxane)

44
Q

What are the features of the late phase response?

A

BASOPHILS -Similar properties to mast cells over longer time scale

EOSINOPHILS - GRANULES contain cytotoxic proteins (e.g. Eosinophil Cationic Protein)
Attracted to sites of allergic inflammation by chemokines (e.g. Eotaxin 1/2) In tissues, RELEASE CONTENTS OF GRANULES - major source of tissue damage in allergic response.

T CELL RESPONSES
Involved in both EARLY and LATE response to allergen
Cytokine production by activated T cells critical in ongoing response

CYTOKINE-DRIVEN ACTIVITY is the major source of PATHOGENESIS in allergic responses

45
Q

What are the features of type 2 hypersensitivity?

A

Antibody-mediated cytotoxic reactions

Binding of antibody to target antigen on cell membrane results in

  • Activation of the complement cascade resulting in cell lysis
  • Aggregation of Fc portions of immunoglobulin/C3b with binding to FcRs/C3bR resulting in opsonisation, phagocytosis & destruction

Initiated by IgM or complement-binding IgG

  • IgM&raquo_space; IgG1
  • IgM most efficient since pentavalent
  • IgG requires multiple binding

Cells usually affected are haematopoietic cells

46
Q

Give examples of type 2 hypersensitivity.

A

Blood group incompatibility

Autoimmune haemolytic anaemias

Affecting neutrophils

Affecting platelets

47
Q

What is type 3 hypersensitivity?

A

IMMUNE COMPLEX REACTIONS

  1. IgG + Ag = AgAb complex
  2. FcR in complex bind C1q
  3. Complement activation leads to generation of activated complement fragments
    4a. C5a - attractant for neutrophils
    4b. C3b - Opsonin
  4. Attempted phagocytosis of complexes - release of enzymes, oxygen radicals
  5. Consequence is tissue damage
    e. g. Farmer’s lung
48
Q

Give other examples of antibody-mediated immunopathology.

A

Direct inactivation - e.g. intrinsic factor -> B12 deficiency

Indirect inactivation - binding to e.g. hormone results in clearance of Ab/Ag complex

Receptor blockade - e.g. to AChR in Myasthenia Gravis

49
Q

What is the mechanism behind contact dermatitis?

A

e.g. Nickel, poison Ivy

Combination of DTH and cytotoxic reaction

Nickel acts as hapten with epidermal proteins

Antigen presentation by APC

Keratinocytes may present to CTL precursors

50
Q

What is a granulomatous reaction?

A

Focal collections of inflammatory cells in tissues -Macrophages, epithelioid cells (phagocytic cells containing foreign material), giant cells, lymphocytes

T cells are Th1-type - secrete IL2 & IFNg

Release of IL-12 by macrophages critical in initiation of response

51
Q

What is the difference between tuberculoid and lepromatous Leprosy?

A

Tuberculoid is Th1 weighted - protective.

Lepromatous is Th2 weighted - non-protective

52
Q

Give examples of granulomatous diseases.

A

Mycobacterial infections

Sarcoidosis

Wegener’s granulomatosis

Crohn’s.