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Flashcards in 5&6 - Immunopathology Deck (46):
1

Immune system categories

Innate or adaptive

2

Innate system categories

Barrier and chemical mechanisms
PRR
Cellular - phagocytes NK cells

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Adaptive system categories

Humoral
Cellular

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Lymphoid precursor can turn into what

NK cell
Plasmacytoid dendritic cell
T cell (from thymus)
B cell (from bone marrow)

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T cells can split into

CD8+ cytotoxic T cell
CD4+ T cell

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What does PRR stand for?

Pattern recognition receptors

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Examples of PRR

Toll-like receptors (TLR's), NOD-like receptors, Rigl-like receptors, C-type lectins (CLR's), scavenger receptors

8

Antimicrobial peptide examples

-defensins, cathelin, protegrin, granulysin, histatin, secretory leukoprotease inhibitor and probiotics

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Cells of the innate immune system examples

Macrophages, dendritic cells, NK cells, NK-T cells, neutrophils, eosinophils, mast cells, basophils and epithelial cells

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Complement components of the innate immune system

Classic and alternative complement pathways and proteins that bind complement components

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Cytokines of the innate immune system

Autocrine, paracrine, endocrine cytokines that mediates host defense and inflammation, as well as recruit, direct and regulate adaptive immune responses

12

What are PRR?

Inclusive term for antigen recognition receptor in innate system
2 groups of receptors either cell surface (transmembrane) and intracellular receptors, fluid-phase soluble molecules

13

Fluid phase recognition molecules' family

C-type lectin family

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Things belonging to C-type lectin family

Collectins - mannan-binding lectin; surfactant protein A&D
Recognition of microbial complex carbohydrates
Bind via carbohydrate-recognition domains
Role in neutralisation of pathogen
Role in recruitment of adaptive response

15

Complement pathways

Classical - antigen - Ig complexes
MB-lectin - mannose-binding lectin binds mannose on pathogen surfaces
Alternative - pathogen surfaces

16

Cells of the innate immune system

Macrophages
Plasmacytoid dendritic cells (DCs)
Myeloid dendritic cells
Natural killer cells (NK)
NK-T cells
Neutrophils
Eosinophils
Mast cells and basophils
Epithelial cells

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What are plasmacytoid dendritic cells? (DCs)

Produce large amounts of interferon (IFN) - antitumour and antiviral activity.

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What are myeloid dendritic cells

Interstitial DCs are strong producers of IL-2 and IL-10 in T cell zones.

19

What do mast cells and basophils release? why?

Release TNF-, IL-6, IFN- in response to bacteria

20

V(D)J recombination how does it work?

D to J recombination. So these are spliced.

V combines with DJ recombination.

21

Mechanism of antigen presentation

1. Antigens are internalised
2. Broken down to peptides
3. Peptides associated with newly synthesised class 2 molecules and brought to cell surface
4. If the peptides are foreign they are recognised by helper T cells which are then activated
5. Helper T cells produce cytokines needed by B cells, T cells etc.

22

Histocompatibility antigens

- Glycoproteins found on mammalian cells make us unique
- First found on white cells (called human leucocyte antigens or HLA)
- 6 families coded for by gene in MHC

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How many classes of histocompatibility?

Two

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Class one HLA receptors

HLA-A, HLA-B, HLA-C

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Class two HLA receptors

HLA-DP, HLA-DQ, HLA-DR

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Function of class 1 and 2 MHC proteins

T cells only see antigen in association with MHC proteins.
Proteins are there to present antigenic peptides
MHC1 = cytotoxic (CD8)
MHC2 = helper T (CD4)

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Ways inactivating antigens via antigens

Neutralisation (blocking viral binding sites)
Agglutination of microbes
Precipitation of dissolved antigens

Above 3 enhance phagocytosis

Activation of complement system (leads to cell lysis)

28

How do cytotoxic T cells work

1. Bind to infected cell
2. Perforin makes holes in infected cell's membrane and enzymes enter
3. Infected cell is destroyed

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What do Th1 cells activate

CD8+
IgG antibody from B cells
Macrophage activation

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What do Th2 cells activate

Eosinophil
Mast cell + basophil
B cells - IgM, G, A and E antibody

31

Types of hypersensitivity

I - IgE mediated reaction
II - Cytotoxic rxn
III - immune complex reaction
IV - cell mediated reaction

32

Type I hypersensitivity features

Anaphylactic
IgE mediated mast cell and basophil degranulation - released synthesised inflammatory mediators

Fast onset - 15-30 mins
Can have two phase response
Common antigens = pollen, bee venom, animal dander
Associated disease = hay fever, allergic asthma

33

What does degranulation mean?

Granules inside cells releasing their content to outside of cell e.g. release histamine, proteases, chemotactic factors

34

Why is there sometimes a late-phase rxn in type I hypersensitivity?

Synthesis of lipid mediators can turn into arachidonic acid which makes leukotrienes and prostalandins

35

What does histamine do

Stimulate irritant nerve receptors
Contract smooth muscle
Increase vascular permeability

36

What does the last phase response initiate?

Basophils and eosinophils

Basophils have similar properties to mast cells

Eosinophils contain cytotoxic proteins and attracted to sites of allergic inflammation by chemokines. They release the contents of their granules which = major source of tissue damage in allergic response.

Also initiates more T cells which make more cytokines

37

Type II rxn features

Antibody-mediated cytotoxic rxns

Binding of antibody to antigen results in:
1. activation of the complement cascade resulting in cell lysis
2. Aggregation of Fc portions of Ig/C3b binding to FcRs/C3bR resulting in opsonisation, phagocytosis and destruction

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What is type II activated by?

Initiated by IgM or complement-binding IgG

IgM most efficient since pentavalent whereas IgG requires multiple binding

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What cells are usually affected by type II rxn?

Haematopoietic cells

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What is type II rxn related to?

Blood group incompatibility
Autoimmune haemolytic anaemias
Affecting neutrophils
Affecting platelets

41

Type III rxns are...

Immune complex rxns

42

What are the immune complex rxns involved in type III?

1. IgG + Ag = AgAb complex
2. FcR in complex bind C1q
3. Complement activation leads to generations of activated complement fragments
4. C5a = attractant for neutrophils; C3b - opsonin
5. Attempted phagocytosis of complex - release of enzymes and O2 radicals
6. Consequence is tissue damage

43

Other antibody-mediated immunopathology

Inactivation = direct (B12 deficiency), indirect and receptor blockade

44

Type IV rxn features

T cell mediated - CD4+ cells (MHC Class II)
Delayed type e.g. Tuberculin skin rxn
Infiltration of lymphocytes and monocytes
Langerhan's cells present neo-antigen to T cells
Ag-specific T cells release cytokines
Activated macrophage cause tissue damage
Requires previous exposure to antigen

45

Granulomatous rxns

Granulomas - focal collections of inflammatory cells in tissues
T cells are Th1-type (secrete IL2 and IFNy)
Release of IL-12 by macrophages critical in initiation of response

46

Examples of granulomatous diseases

Infections: mycobacterial (TB, atypical mycobacteria, leprosy)

Unknown aetiology: sarcoidosis, Wegener's granulomatosis, Crohn's disease