Principles of immune responses

Question 1

How can immune system lead to disease? (x2)

Answer 1

Immunodeficiency (failure of immune system e.g. HIV, AIDs, SCID (genetic)) – increased susceptibility to infection. Abnormal function of immune system e.g. autoimmune diseases, allergy.

Question 2

What interventions allow for exploitation of the immune system? (x3)

Answer 2

VID – Vaccination, Immunotherapy (treatment by enhancing or suppressing immune response), Diagnosis.

Question 3

How is there said to be an evolutionary ‘arms race’ between pathogen and host (x2)? How does host keep up in the race (x2(x1))?

Answer 3

The host exerts an evolutionary selection on the pathogen. Bacteria and viruses (less so) replicate millions of times faster so evolve faster. Pathogen exerts selection on the host (means those who are resistant to pathogen survive to reproduce). Host has flexible and rapid immune response. Our most polymorphic (variable) genes are genes that control immune response – therefore responsive to infectious diseases.

Question 4

What does immune system cells use to recognise danger? What are the two strategies [don’t talk about mechanism]?

Answer 4

Receptors

Strategy 1: receptors recognise MOLECULAR PATTERNS e.g. carbohydrates found in bacteria. They are germ-line encoded: meaning one gene, codes for one entire receptor protein for that immune cell.

Strategy 2: receptors recognise PRECISE MOLECULAR STRUCTURES. Millions of receptors, so cannot have their own individual gene as that would be tooooo many genes. Instead, are formed from RANDOM recombination of gene segments. So, combination of receptor proteins produced from single gene.

Question 5

Advantage and disadvantage of both strategies of receptor danger recognition? (x2 disadvantages of recombinant gene segments).

Answer 5

Germ-line encoded: Many cells can express same receptor, so response more rapid. BUT, limited receptor diversity – not all pathogens recognised this way. Recombinant gene segments: Massive diversity of receptors so all pathogens can potentially be recognised. BUT, initially, very few cells express the needed receptor, so there’s a process of expansion; and random nature of receptor generation means chance of autoimmunity.

Question 6

Germ-line encoded: What receptor type does this use? Two types of trigger (and two sources of DAMPs)?

Answer 6

Pattern Recognition Receptors (PRRs) Triggers: PAMPs (Pathogen-Associated Molecular Patterns) AND DAMPs (Damage-Associated Molecular Patterns – cell necrosis (cell injury from premature cell death) products and fragments from extracellular matrix). Reflects immune system functions: getting rid of foreign organisms, and identifying ‘danger’ signals (e.g. tissue damage).

Question 7

Recombinant gene segments: What receptor type does this use? Difference across immune cells?

Answer 7

Antigen-specific receptors on LYMPHOCYTES. B cell: receptor is membrane-bound ANTIBODY. Binds to intact antigens. T cell: T cell has 2 protein chains on surface which make the T cell receptor. Doesn’t recognise intact antigens, but binds to ‘processed’ antigen fragments that are PRESENTED on cell surfaces.

Question 8

What do recombinant gene segment receptors bind to on the antigen?

Answer 8

Each receptor binds to a particular site on the antigen called a EPITOPE.

Question 9

Difference between innate and adaptive immune responses? (x6 and x6)

Answer 9

INNATE: Independent of previous exposure (i.e. we are born with it). Depends on pre-formed and rapidly synthesised components of the immune system. Fast Limited specificity (pattern recognition) USES GERM-LINE RECEPTOR STRATEGY ADAPTIVE: Comes as a result of exposure (acquired immunity) Relies on clonal selection i.e. expansion of specific cell with antibody. Process called PRIMING. Slow Highly specific to antigen USES RECOMBINANT GENE SEGMENTS STRATEGY

Question 10

What is the difference in response time between adaptive and innate immune response?

Answer 10

Innate is an early response. Adaptive needs time to develop.

Question 11

What are the functions of the adaptive and innate immune response?

Answer 11

Innate CONTROLS infection. Adaptive CLEARS infection and improves the efficacy of the innate immune response, focussing on site and organism.

Question 12

What cells are used in the innate and adaptive immune responses? Which are common in both? (x3)

Answer 12

INNATE: neutrophils, macrophages, eosinophils. ADAPTIVE: T and B cells. Basophils, dendritic cells, natural killer cells, used in both types.

Question 13

Where are T and B lymphocytes derived?

Answer 13

T are Thymus derived. B are bone marrow derived. All originate from foetal liver.

Question 14

What are innate immune response functions (x4)?

Answer 14

Invading Nucleic acids (e.g. viruses) in cytoplasm, activates Inflammatory pathways and releases relevant chemicals, and elicits type 1 Interferons for anti-viral defence. Buys Time for adaptive immune response. NIIT

Question 15

What are adaptive immune response functions (x2)? Two sub-types of immunity?

Answer 15

GENERAL FUNCTION: Target specific antigens and can form memory. TWO SUB-TYPES: Cellular immunity (uses T and B lymphocytes); Humoral immunity (uses antibodies). Humoral means SOLUBLE EFFECTORS!!!!!!!!

Question 16

Relative time course of primary immune response for adaptive and innate immunity?

Answer 16

Innate immunity much faster in responding.

Question 17

Where are most T cells found in the body?

Answer 17

Lymph circulation (98%).

Question 18

How does clonal selection occur?

Answer 18

Antigen binds to specific receptor on B or T cell. Causes selective expansion of that clone.

Question 19

What happens to number of lymphocytes when antigen is removed?

Answer 19

Most will die. Some will survive as memory cells – so re-exposure means rapid and GREATER immune response (secondary response).

Question 20

What are cytokines?

Answer 20

Small proteins secreted for LOCAL, short-lived cell-to-cell communication. They act as messengers of the immune system.

Question 21

How are the effects of cytokines mediated and controlled?

Answer 21

They have a biological effect at very low concentration, so need short half life to control effects.

Question 22

List the different types of cytokines. (x5)

Answer 22

INTERLEUKINS: INTERFERONS: CHEMOKINES: GROWTH FACTORS: CYTOTOXIC TUMOUT NECROSIS FACTORS:

Question 23

What are the functions of the different cytokines? (x5)

Answer 23

INTERLEUKINS: between leukocytes (denotes any WBC). INTERFERONS: anti-viral effects – interfere with replication. CHEMOKINES: chemotaxis (cell movement). GROWTH FACTORS: help stem cells to differentiate and proliferate. CYTOTOXIC (cytotoxic TUMOUR NECROSIS FACTORS): include programmed cell death in target cells.

Question 24

What is the mechanism by which cytokines are produced and work?

Answer 24

1. Stimulus in cytokine producing cell causes production of the cytokine, and granule fusion with the membrane (if present) resulting in exocytosis. 2. Cytokines bind to specific receptors on other cells, affecting gene expression in target cell causing biological effects.

Question 25

What are the three types of cytokine action?

Answer 25

AUTOCRINE: act on self. PARACRINE: works on nearby cells. ENDOCRINE: travel via circulation to distant cell.

Question 26

Why is it that only small amounts of cytokine can have a massive affect?

Answer 26

Cytokine binding to a receptor can up/down regulate hundreds of genes.

Question 27

What does a complement refer to in immunology?

Answer 27

Complements describe the complement system which ENHANCES and AMPLIFIES the ability of specific antibodies in lysing bacteria (by actually killing), AND phagocytic cells (aids their function) - those are its two functions. It is part of the innate immune system.

Question 28

What is the complement system composed of?

Answer 28

The complement system involves ~30 small proteins and glycoproteins, synthesised in the liver and found in the blood as inactive ENZYME precursors and found in high concentrations in the blood.

Question 29

What happens in the complement system?

Answer 29

When stimulated, the glycoprotein enzyme precursors are cleaved into an active enzyme. The substrate of each enzyme is the next enzyme in the pathway (i.e. enzyme 1 cleaves precursor 2 into enzyme 2). Let’s say that each enzyme cleaves 10 precursors: This means that each step of the complement system, the enzyme cascade is amplified. The complement pathway leads to the activation of the C3b protein, which opsonises pathogens (by binding to its antigen) – opsonisation enhances phagocytosis remember, hence the functions of the complement system. FINAL COMMON PATHWAY: when C3b activated, there is a final common pathway – formation of a membrane attack complex that’s inserted into the cell membranes of all pathogens. Creates holes in bacterial cell membrane and causes loss of integrity – so bacteria lyses (another function of the complement system). ALSO NOTE: the molecules that are cleaved off the precursors are pro-inflammatory. Can bind to mast cells, causing them to degranulate, releasing histamines = pro-inflammatory. [Same as in Immunology: Organisation of the Immune System. Refer to this also for information on mast cells.]

Question 30

What are the three activation pathways in the complement system?

Answer 30

CLASSICAL PATHWAY: activation by antibody bound to antigen, forming an immune complex. LECTIN PATHWAY: lectin proteins that bind to carbs (e.g. CRPs or MBL) on bacteria to trigger complement system. ALTERNATIVE PATHWAY: bacteria directly trigger complement system. Three activation methods: all converge to activate C3b protein.

Question 31

What does the complement system induce such a massive response? (x2)

Answer 31

The precursors are found in high concentrations in the blood. At each stage, more precursors are cleaved – so process is amplified at each stage, so process can occur very quickly.

Question 32

How is the complement system controlled? (x3)

Answer 32

Short half-life. Diluted in biological fluids. Circulating and membrane-bound specific REGULATORY proteins that control the response.

Question 33

Why is it important to control the complement system?

Answer 33

You do not want the membrane attack complex to lyse normal healthy self-cells.

Question 34

What are the functions of the complement system – and link each to the mechanisms of the complement system? (x4)

Answer 34

Cell lysis (Membrane Attack Complex), opsonisation (C3b), pro-inflammatory effects (cleaved parts of the precursor), clearing of immune complexes like antibodies when they are not needed (phagocytes have complement receptors – look at photo).

Question 35

What is the systemic ‘acute phase response’ characterised by? (x2) How? (x2 points)

Answer 35

Characterised by fever and increased production of components to fight infection. HOW? This process is induced by cytokines. Prolonged innate immune responses may be accompanied by a systemic ‘acute phase response’.

Question 36

What are the components produced in the system ‘acute phase response’? (x2 (x1 and x4))

Answer 36

White blood cells (leukocytosis) and ‘acute phase’ proteins in the liver (C-reactive protein (CRP)) which activates complement (lectin pathway), Mannan binding lectin which activates complement (lectin pathway), complement, fibrinogen. REMEMBER: ALL PRODUCED TO FIGHT INFECTION.

Question 37

What are toll-like receptors? What do they recognise?

Answer 37

Protein receptors that play a key role in the innate immune system. They recognise microbes that have reached physical barriers like skin and mucosa (intestinal tract, airways…) and trigger an innate immune response – can link to adaptive immune response because TLRs are found on dendritic cells. They recognise CONSERVED MOLECULES of pathogens as LIGANDS: e.g. bacterial surface lipopolysaccharides, lipoproteins; double-stranded RNA of viruses…

Question 38

What is the mechanism of action of T-L receptors? In bacteria and viruses? (x1 and x2)

Answer 38

When they recognise pathogens, a cascade of reactions occurs in the cell of the TLR (gene upregulation and suppression) that result in inflammatory responses and cytokine production. If pathogen is BACTERIA: immune cell will phagocytose. If pathogen is VIRUS: immune cell will undergo apoptosis and may release interferons.

Question 39

Where are toll-like receptors found?

Answer 39

Expressed on macrophages, NK cells, dendritic cells, cells of the adaptive immune system, and epithelium.