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Pathobiology - BMS109 > Immunity > Flashcards

Flashcards in Immunity Deck (36):
1

What are the primary lymphoid organs?

Spleen
Thymus
Bone marrow

2

What are the peripheral lymphoid organs?

Lymph nodes

3

Who discovered innate immunity?

Ellie Metchnikoff - 1993

4

What is our innate immune system?

- Detects components (antigens) shared by all pathogens
- Fast, no memory
- Epithelial cells
- Phagocytes
- Dendritic cells
- Complement
- NK cells

5

What is adaptive immunity?

- Detections antigen specific to individual pathogens
- Slower, with lag phase, memory
- B lymphocytes
- T lymphocytes
- Production of antibodies

6

What type of barriers are involved in innate immune defence?

Physical
Cellular
Humoral

7

What type of barriers are involved in adaptive immune defence?

Cellular
Humoral

8

What is the first line of defence in an innate response?

Physical barriers:
- Mucus lining trachea
- Normal flora
- Lysozyme in tears
- Skin surface (physical barrier), fatty acids, normal flora

9

How do cells sense pathogens?

Pattern Recognition Receptors - toll like receptors

10

What are the main classes of innate immune PRR receptors?

1) Nucleotide oligomerisation domain-like receptors (NLRs)
2) Toll-like receptors (TLRs)
3) C-type lectin receptors (CLRs)
4) RIG-like receptors (RLRs)

11

What do each of the PRR receptors recognise and where are they found?

CLR and TLR on cell surface - sensing for pathogen molecules in EC environment
- TLR recognise pathogen molecules like flaggelin and LPS
- CLR recognise sugars on CS
- Different sets of TLRs recognise if a pathogen enters cell
- NLR and RLR in cytosol of host cell

12

How do PRRs sense pathogens?

Pathogen associated molecular patters
- PAMPs are specific to organism

13

What are defensins?
Features?

Anti-microbial peptides
- Produced by epithelial cells and phagocytes
- Bind pathogen phospholipid bilayers and form pores
- Bacteria cannot survive with pores
- Amphipathic
- On the surface of bacterial phospholipid bilayers - negatively charged phospholipids on surface, positive charge on AA on defensin stick to these

14

What is the complement system?

Complement refers to a system of inactive soluble proteins (C1-9+) in blood vessels

- Three activation pathways: alternative, classical and lectin
- Lead to activation by proteolytic cleavage of components C3
- C3a and C3b
- C3 convertase amplifies C3 cleavage
- 3 effector functions = outcome

15

What are interferons?

Interfere with life cycle of virus
- Best charactersed by IFNalpha and IFN-N-beta - single gene product
- Interferon synthesis response to viral single-stranded or double stranded RNA - PAMPs recognised by PRRs

16

What are natural killer cells?

- NK cells are activated by interferon to kill virally-infected or tumourigenic cells
- Kill by exocytosis of granules containing perforin and granzyme - induce apoptosis

17

What is involved in the cellular level of the adaptive immune response?

B lymphocytes
T lymphocytes

18

What are B lymphocytes?

Involved in creating antibodies
Attack invaders outside the cells
Mature in bone marrow

19

What are T lymphocytes?

- Attack invaders inside the cells
- Migrate to the thymus by thymotaxin
- Have variety of roles - T helper cells, T killer cells etc
- Mature in thymus

20

Who discovered the adaptive immune system?

Paul Erlich - 1897
Introduced lock and key

21

What is the antibody structure?

4 proteins in 1: 2 heavy chains, 2 light chains

22

How do antigens bind to antibodies?

Fab = Fragment antigen binding
- Binds antigen in lock and key manner
- Hypervariable regions
- Each hypervariable region recognises small regions
- Allows for small difference

23

What is the Fc fragment?

- Mediates interactions with immune system
- Fab region seeks target - Fc region directs effector functions
- Fc region triggers complement activation and cell lysis (bacteria, tumour cell)
- Fc region binds Fc receptors on effector cells (phagocytes like macrophages)

24

How are antibodies produced?

- B cell receptors bind intact antigen
- Present digested antigen on their MHC-II
- Find T cells specific for same antigen
- T cells help B cells

25

What is an antigen?

Any molecule that can be detected by adaptive immunity

26

What is an epitope?

Specific part of antigen recognised by an antibody

27

What do T cell receptors bind to?

Peptide fragment of antigen

28

How is the peptide fragment of an antigen presented?

Uses Major Histocompatibility Complex proteins (MHC)
- MHC = cell surface glycoprotein that bind antigens and present system cells
- MHC I - presents antigen, found in cytoplasm, to cytotoxic T cells
- MHC II - presents phagocytosed antigen to T helper
- Activated T cells become effectory or memory T cells
- Naive cells (never been exposed to antigen)

29

What is clonal expansion?

- B cell starts to divide, population of cells created from one precursor
- As immunoglobulins mature the pattern changes
- If antigen presenting cell displays antigen that binds with Ig attached to surface of B cell, then B cell matures
- Mature B cells begin to make antibodies
- Initially, cells make IgM, then make IgG
Igs binds to surface of bacterium
Igs also recognised by phagocytes

30

What do cytotoxic T cells and natural killer cells do?

They kill virally infected/tumorigenic cells
- Kill by exocytosis of granules containing perforin and granzyme - induce apoptosis
- Granzymes activating caspases (proteases which chop up DNA, cytoskeleton and fragments)
- Macrophages engulf products

31

What are follicular dendritic cells (FDC)?

Improve antibody quality
- FDCs reside in germinal centres where interact with activated B cells
- FDCs present native antigen to B cells whilst antibody genes mutate to improve affinity
- Help B cells produce better antibodies
- Mutate Ig genes to make better antibodies
- B cell becomes plasma cell when no better antibody that can be made - produce antibodies

32

What are the mediators of immune response?

- Vasoactive amine (histamine)
- Lipid products (prostaglandins)
- Cytokines (TNF, IL-1)
- Products of complement activation (plasma)

33

What do prostaglandins do?

- Regulate blood vascular system

34

What are the protein mediators?

Cytokines and Chemokines
- Produced following activation of PRRs

Cytokines (interleukins, interferons, tumour necrosis factors)
- Protein secreted by many cell types, activate receptors

Chemokines
- Small peptide chemoattractants for leukocytes, activates GPCRs and trigger a signalling cascade involved in adhesion for neutrophils near site of injury

35

What are the local effects of cytokines and chemokines?

- Endothelial site and leukocyte activation
- Recognise damage to tissue and produce TNF and IL-1
- Starts to fuse, hit blood vessels and tells endothelial cells to start releasing adhesion molecules
- Increased formation of inter-endothelial spaces, increased permeability to begin swelling
- Chemokines released by macrophages, telling neutrophils and monocytes where to go

36

What are the systemic effects of cytokines and chemokines?

- Associate with TNF and IL-1
- Enter blood stream and tell cells in thalamus to produce more cyclooxygenase, more prostaglandins
- Tells liver to produce C-reactive protein, and opsonin, decorates tissue damage and bacteria, which can easily be taken up by macrophage
- Premature release of leukocytes from bone marrow