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Flashcards in General principles of immune response Deck (52):
1

What are the components of the innate immune response?

Barrier and chemical mechanisms.

PRR

Cellular (phagocytes and NK cells).

2

What are the components of the adaptive immune response?

Humoral and cellular.

3

What are the main PRRs?

Toll-like receptors (TLRs)

NOD-like receptors (NLR)

RIG-like receptors (RLRs)

C-type lectins

scavenger receptors.

4

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

Defensins

Cathelin

Protegrin

Granulysin

Histatin

Secretory leukoprotease inhibitor

Probiotics.

5

Which immune cells are involved in the innate response?

Macrophages

Dendritic cells

NK cells

NK-T cells

Neutrophils

Eosinophils

Mast cells

Basophils

Epithelial cells.

6

Which complement components are involved in the innate immune response?

Classic and alternative pathways and proteins that bind complement proteins.

7

What are pattern recognition receptors (PRRs)?

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).

8

What are the two groups of PRRs?

1. Cell surface (transmembrane) and intracellular receptors – TLRs, NLRs, RLR’s and CLR’s.

2. Fluid-phase soluble molecules - C-type lectin

9

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

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

10

What is the role of IL-1?

Endothelia
- increased coagulation
- increased inflammation

Hepatocytes
- increased acute phase proteins

Hypothalamus
- increased fever

11

What is the role of TNF?

Endothelia
- increase coagulation
- increased inflammation

Hepatocytes
- increase acute phase proteins

Neutrophils
- increase activation

Hypothalamus
- increased fever

12

What is the role of IL-6?

Hepatocytes
- acute phase proteins

B lymphocytes
- increased proliferation

13

What is the role of macrophages?

Phagocytose and kill bacteria

Produce antimicrobial peptides

Bind (LPS)

Produce inflammatory cytokines.

14

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

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.

15

What are the roles of NK cells?

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.

16

What are the roles of myeloid dendritic cells?

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.

17

What are the roles of neutrophils?

Phagocytose and kill bacteria, produce antimicrobial peptides.

18

What is the role of eosinophils?

Kill invading parasites.

19

What are the roles of mast cells of basophils?

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

20

What are the roles of epithelial cells?

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.

21

What are the central features of the adaptive immune response?

Evolution in response to changing pathogen structures.

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

22

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

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

23

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

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

24

What is the range of antigenic variability estimated to be?

10^9

25

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

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

26

What is the mechanism of Ag presentation for MHCII?

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

Which cells do MHCI proteins present to?

Cytotoxic T cells (CD8).

28

Which cells do MHCII proteins present to?

Helper T cells (CD4).

29

What are he functions of antibodies?

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

30

What are the cytokines of adaptive immunity?

IL-4

IL-5

IL-12

IL-13

IL-17

INF gamma

31

What is immunosupression?

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

32

What is immunodeficiency?

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

33

What are the potential uses of immunosuppression?

Transplant rejection, autoimmunity and lymphoproliferative diseases.

34

What might be the consequences of immunosuppression/immunodeficiency?

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

What is hypersensitivity?

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

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

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

What is the mechanism behind type 1 hypersensitivity?

IgE mediated

Cross-linking of FceR by allergen

Release of pre-formed mediators e.g. histamine

Synthesis of lipid mediators e.g. leukotrienes

38

What are the features of IgE?

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

What is the early phase response?

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

What are the functions of histamine?

Stimulation of irritant nerve receptors

Smooth muscle contraction

Increase in vascular permeability

41

What is the function of kallikrein?

Activates bradykinin - similar actions to histamine.

42

What are the pre-formed mediators?

Histamine, kallikrain and tryptase.

43

What are the lipid mediators?

Arachidonic acid derivatives - leukotrines and prostoglandins (thromboxane)

44

What are the features of the late phase response?

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

What are the features of type 2 hypersensitivity?

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 >> IgG1
- IgM most efficient since pentavalent
- IgG requires multiple binding

Cells usually affected are haematopoietic cells

46

Give examples of type 2 hypersensitivity.

Blood group incompatibility

Autoimmune haemolytic anaemias

Affecting neutrophils

Affecting platelets

47

What is type 3 hypersensitivity?

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

5. Attempted phagocytosis of complexes - release of enzymes, oxygen radicals

6. Consequence is tissue damage

e.g. Farmer's lung

48

Give other examples of antibody-mediated immunopathology.

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

What is the mechanism behind contact dermatitis?

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

What is a granulomatous reaction?

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

What is the difference between tuberculoid and lepromatous Leprosy?

Tuberculoid is Th1 weighted - protective.

Lepromatous is Th2 weighted - non-protective

52

Give examples of granulomatous diseases.

Mycobacterial infections

Sarcoidosis

Wegener's granulomatosis

Crohn's.