Immunology

Question 1

What are the layers of immune defense?

Answer 1

Patogen invasion

1) Exterior defenses
- physical barriers
- mechanical barriers
- chemical barriers
- biological barriers (commensal organisms)

2) innate immune response through immune cells:
- rapid, non-specific, no memory, resistance does not improve according to the number of encounters.

3) adaptive immune response through immune cells:
- slow, specific, has memory, resistance improves according to the number of encounters

Pathogen is dead or suppressed.

Question 2

What are exterior defenses?

Answer 2

1) physical barriers:
- skin
- mucous
- epithelim and endothelium

2) mechanical barriers:
- cilia beating
- fluid flow
- flushing of urine tract
- exhaling and coughing

3) chemical barriers:
- very low pH in the stomach
- rapid pH change from stomach to small intestine
- acidic vagina
- lysozymes in tears
- lysozymes in saliva

4) commensal organisms (normal microflora: compete with pathogens and hence inhibit their growth)
- E. Coli
- Candida yeasts
- Staphylococcus aureus
- there are about 200 species in total

Question 3

What are leukocytes?

Answer 3

The general name for a big variety of immune cells.

There are lymphocytes (mostly agranulocytes) and non-lymphocytes (mostly granulocytes).

Question 4

What are the cells and chemicala of innate (non-specific) immune system?

Answer 4

Cells:
- neutrophils
- macrophages
- dendritic cells
- eosinophils
- basophils
- mast cells
- natural killer cells

Chemicals:
- complement system (complement cascade that eventually forms membrane attack complex)
- interferons
- inflammatory mediators

Question 5

What are the cells and chemicals of adaptive (specific) immune system?

Answer 5

Cells:
- B cells (differentiate into plasma cells after activation)
- Cytotoxic T cells
- Helper T cells
- Regulatory T cells

Chemicals:
- antibodies
- interleukins

Question 6

Which cells secrete inflammatory mediators?

Answer 6

Platelets, basophils and mast cells to attract more immune cells to the site of infection.

Question 7

Which cells mostly secrete interferon cytokines?

Answer 7

Tissue cells.

Their function to inhibit cell division and differentiation to decrease the spread of viral infection.

Question 8

Which cells secrete most of the cytokines?

Answer 8

T cells (all subtypes), large granular lymphocytes and phagocytes (all immune cells which can perform phagocytosis).

Question 9

Which cells release complement proteins?

Answer 9

Hepatocytes (liver cells) - most of them, some by macrophages.

Question 10

Where and how immune cells develop?

Answer 10

All start at bone marrow as hematopoietic stem cells.

Myeoloid progenitor gives rise to:
- dendritic cells
- granulocyte-monocyte progenitor (neutrophils and monocytes which develop into macrophages)
- eosinophil progenitor
- basophil progenitor (basophils develop into mast cells)
- megacaryocyte (fragments itself into plateletes)
- erythroid progenitor (erythrocytes)

Lymphoid progenitor gives rise to:
- natural killer cells
- T-cell progenitor (appears and differentiates into T Helper and T Cytotoxic cells in thymus)
- B cell progenitor
- also dendritic cells

The rest of precursors are still found in bone marrow.

Question 11

What are the features of macrophages?

Answer 11

• specialized for phagocytosis (bacteria and small parasites)
• antigen presentation (peptide at their MHC to trigger T cels) after phagocytosis
• release C-reactive proteins (acute phase protein) to assist in opsonisation; interleukin-1 and TNF to promote inflammation (recruitment of other immune cells and extravasation); interferon-alpha to activate antiviral response

Question 12

What are the features of dendritic cells?

Answer 12

• most important antigen presenting cells, only they can activate resting T cells which were not exposed to antigens before
• take antigens from other cells such as macrophages

Question 13

What are the features of neutrophils?

Answer 13

• most abundant leukocytes (70%)
• like macrophages, can perform phagocytosis (bacteria are further degraded in phagosomes with help of NADPH oxidise and myeloperoxidase)
• very effective at fighting chronic and acute infections
• release pyrogens to promote inflammation
• release lactoferin to activate T cells
• multi-lobed cells, 3-5 segments
• have 3 types of granules (NADPH oxidise and myeloperoxidase in all granules):
  a) primary contains proteases
  b) secondary contain lactoferin
  c) tertiary contain metalloproteinases to separate metal ions from bacterial proteins)
• release NETs: neutrophil extracellular traps after death to further immobilize and kill bacteria

Question 14

What are the features of eosinophils?

Answer 14

• damage and phagocyte helminths (parasitic worms) with reactive oxygen proteins from cationic proteins
• helminths have to be covered with antibodies
• have role in asthma during an allergic response
• 2 lobed nucleus
• mostly found at GI tract

Question 15

What are the features of basophils?

Answer 15

• the largest immune cells
• cannot perform phagocytosis
• very rich in granules (containing histamine) which are released during allergic reaction or encounter with parasites
• slower response comparing to mast cells
• short life
• mostly reside in blood stream

Question 16

What are the features of the mast cells?

Answer 16

• like basophils, release histamine (to increase pembeability of capillaries)
• release chemotaxins to recruit more leukocytes
• like basophils, also involved in allergies and parasitic infections, but for immediate hypersensitivity
• mosly reside in tissues
• long life

Question 17

What are the features of natural killer cells?

Answer 17

• release lytic granules that kill virus-infected cells (or containing bacteria that invaded cytoplasm)
• target and kill cancerous cells
• are not specific, but act in the similar way to T Cytotoxic cells

Question 18

Are T and B cell present in all compex organisms?

Answer 18

No, only in vertebrates.

Question 19

What are the signs of inactive lymphocyte?

Answer 19

• very little cytoplasm
• condensed chromatin
• small size (8-10 micrones; when they become plasma cells increase to 9-15 micrones)

Question 20

What is the general way how innate immune response happens?

Answer 20

1) Tissue senses pathogens with pathogen recognition receptors using pathogen associated molecular patterns (peptidoglycan fragments, manose rich sugars, flagellin, teichoic and lipoteichoic acids)

1.5) Pathogens undergo opsonisations (both antibodies and opsonin proteins surround pathogen)

2) Triggered tissue releases cytokins (chemotaxins) in blood to attract myeloid cells from there. This is chemotaxis.

3) myeloids (especially neutrophils, macrophages and dendritic cells) perform extravasation (squeezing out from vessels) and migrate to infection site

4) neutrophils, macrophages and sometimes dendritic cells perform phagocytosis (in phagosome, pathogen is further destroyed by reactive oxygen species produced by myeloperoxidase from granules).

5) dead leukocytes form pus.

Question 21

Do innate and adaptive immunity work independently?

Answer 21

No, they must work together; basically, adaptive immunity enhances performance of innate immunity against specific pathogens.

Antibodies mark specific pathogen for phagocyte destruction.

Question 22

What is the role of Cytotoxic T cells in adaptive immunity?

Answer 22

1) form immunological synapse with normal tissue cell (T cells are activated by binding to antigen and MHC-I on normal cell surface)

2) Activated Cytotoxic T cell recognises infected cell

3) Pierce pores in the membranes of the infected cells with perforin

4) the pore allows Cytotoxic T cell to inject granzymes (caspases) to digest DNA and mitochondria of the infected cell

5) Infected cell dies due to apoptosis (addictionaly caused by activated Fas

Question 23

What is the role of Helper T cells in the adaptive immunity?

Answer 23

1) Form immunological synapse with cells containing MHC-II (antigen presenting dendritic cell mostly)

2) There are 3 types of Helper T cells: TH1, TH2 and TH17.

3) TH1 release IFN and interleukin-2 to activate Cytotoxic T cells, macrophages and B cells against bacteria.

3.5) Helper T cells may also form immunological synapse with B cells directly (MHC-II on B cell surface)

4) TH2 release interleukins (3, 5 and 13) to activate eosinophils and mast cells against helminths and allergies

5) TH17 release interleukins (17 and 22) to activate neutrophils against bacteria and fungi.

Question 24

What is the role of regulatory T cells?

Answer 24

Supress overactive immune cells with inhibitory cytokines (IL-10 and IL-35), cytolysis (granzymes A and B), metabolic disruption and stoping dendritic cells from maturation.

Question 25

What is the role of B cells in the adaptive immunity?

Answer 25

1) There are surface antibodies on B cells, to which antigens bind. But this is not enough to activate them 2) TH1 release interferons (IFN) to finally activate B cells 3) Activated B cells undergo clonal expansion (make multiple copies of themselves) 4) some cloned cells become plasma cells (short lived effector cells) and release soluble antibodies to inhibit pathogens and mark them for destruction 5) some cloned cells become long-lived memory cells which significantly enchanes specific immune response after second exposure

Question 26

What are the lymphoid tissues in the body?

Answer 26

In general, they are everywhere. Primary lymphoid (produce and mature leukocytes): - thymus - bone marrow Secondary lymphoid (encapsulated): - spleen - lymph nodes Secondary lymphoid (diffuse) - tonsils - gut associated lymphoid tissue (part of mucosa exposed to the external environment) - Peyer's patches (in small intestine)

Question 27

What are the features of the spleen?

Answer 27

- the largest lymphoid tissue in the body - found very close to stomach, on the left side Red pulp: - closely associated with blood vessels - full of macrophages which clean incoming blood from pathogens, worn off/damaged/abnormal erythrocytes - macrophages break down haemoglobin into amino acids, iron and billurubin, all send to the liver for excretion White pulp: - on the interior - full of lymphocytes

Question 28

What are the features of thymus gland?

Answer 28

- has two lobes - found just above the heart - size is age-dependent (biggest in adolescence, smallest in old age but replaced with fat) The site of T cell maturation (first two steps happen during embrionic period): - T cells with self reacting antibodies are eliminated (apoptosis) - other T cells undergo clonal expansion - where T cells differentiate - produces 3 peptide hormones (thymosin, thymopoetin, thymulin), all of them stimulate T cell development and release

Question 29

What are the features of lymph nodes?

Answer 29

- bean shaped organs in lymphatic system - full of various leukocytes which clean blood from pathogens coming from lymph artery - few afferent lymph vessels enter the cortex side - one efferent vessel on the base, parallel to lymph artery and vein

Question 30

What is lymph?

Answer 30

Extracellular fluid filtered from the blood and returned back to blood with lymphatic vessels with thoracic duct. 1) Naive lymphocytes enter lymph nodes from blood 2) antigens from the site of infection reach lymph nodes from lymphatic system 3) lymphocytes meet antigen in the lymph node and become activated 4) lymphocytes return to blood to find the site of infection All of this takes 4-6 days, but innate response is already happening from the beginning.

Question 31

What are the stages of extravasation?

Answer 31

1) Rolling on endothelium 2) Capture by endothelial receptors 3) Adhesion and activation 4) Spreading (flattening against endothelium) 5) extravasation (squeezing through capillary pores) Activated by chemokines released by neutrophils.

Question 32

What are the 3 key actions of complement?

Answer 32

- lysis - chemotaxis to activate phagocytes - opsonisation: C1q, C1r and C1s bind to 2 IgG antibodies which were already attached to protein surface. This activates the classical pathway of complementary systems: activates the sequence of events from 1C to 9C activation to finanally make membrane attack complex.

Question 33

How is membrane attack complex developed?

Answer 33

1) C1 cleaves C2 and C4 into C2a, C2b, C4a and C4b (a: smaller fragment, b: bigger fragment) 2) C2a combines with C4b: C2aC4b cleaves C3 into C3a and C3b. 3) C3b combines with C2aC4b: C2aC4bC3b cleaves C5 into C5a and C5b. 4) C5b recruits C6 and C7 without cleaving them. Instead, they just bind together and bind to cell membrane of the pathogen. 5) C5bC6C7 serve as a support for C8 to pierce pathogen cell membrane. 6) The longest C9 molecules insert each other in the membrane in the round row (up to 20 molecules), stretching the hole. 7) This creates 10 nm hole with rigid edges 8) ions leaks out from the hole, too much water gets inside 9) pathogen cell dies due to osmolysis (burst due to increased water pressure) and metabolic disturbances (due to loss of ion gradient)

Question 34

What 5 words define inflammation?

Answer 34

1) heat 2) pain 3) redness 4) swelling 5) loss of function Caused by bradykinin and histamine dilating blood vessels to increase blood flow (and hence transport more leukocytes) and make them more leaky (to allow more extravasation).

Question 35

How is inflammation different from the normal elimination of pathogens?

Answer 35

Mast cells are involved and they massively produce histamine to increase the pembeability of capillaries, so more and more phagocytes can arrive.

Question 36

What causes fewer?

Answer 36

1) Pyrogens such as TNF-alpha induce production of prostaglandin E2. 2) This acts on hypothalamus 3) More brown fat is used and there is vasoconstriction on the rest of body to prevent normal heat loss 4) high temperature = better adaptive immune response and phagocytosis

Question 37

How long-lived plasma cells are different from the normal plasma cells?

Answer 37

Long lived plasma cells secrete low levels of antibodies all the time.

Question 38

What is the structure of antibody?

Answer 38

- constant region: C-terminus, all stem (Fc region), part of bifork (Fab region). Consists of 4 segments (3 from heavy chain, 1 from light chain). - variable region (N-terminus, top of the bifork). Consists of 2 segments (1 from heavy chain, 1 from light chain) - disulphide bonds connect left and right side (two heavy chains) and light chains to the heavy chains

Question 39

What is the difference between antigen and epitope?

Answer 39

Antigen is a whole fragment from a pathogen. Called so because it is an antibody generation factor. Episode is a region on the surface of an antigen that is recognized by variable region of an antibody. One antigen can have several epitopes, so one antigen can bind several different antibodies.

Question 40

Which type of antibodies are activated during primary specific immune response?

Answer 40

IgM. There are lag phase, log phase, plateau and decline (assymetrical curve with well-defined peak).

Question 41

Which type of antibodies is activated during secondary immune response?

Answer 41

IgG. The graph of antibody concentration is symmetrical and round, like part of a circle.

Question 42

What are antibody classes?

Answer 42

- IgG: main class, mostly in blood, can pass through placenta, secondary response (deal with familiar pathogens), monomer - IgM: primary responce (deal with new unknown pathogens), pentamer - IgA: found at surfaces, opened to the external environment, dimer - IgE: against parasites and involved in allergies, monomer - IgD: least common, function is not clear

Question 43

What are the key functions of antibodies?

Answer 43

1) Neutralization: prevents pathogen entrance into tissues (by blocking their receptors, binding to toxins, clumping pathogens 2) Opsonisation: promotes phagocytosis (antibody stem bind to phagocyte receptors) 3) Complement activation: promotes formation of the membrane attack complex 4) Trigger degranulation from NK cells and eosinophils to kill target virus/bacteria infected or cancerous cell after making antigen-antibody-Fc receptor bridge. This is antigen-dependent cell-mediated cytotoxicity. 5) surface antibodies on B cells help to activate them

Question 44

How does T lymphocyte recognise an antigen?

Answer 44

1) Antigen is broken down into smaller peptide fragments 2) One of those fragments binds to MHC (major histocompatibility compex) 3) the fragment is sandwiched between MHC and T cell receptor (immunological synapse)

Question 45

Which immune cells does HIV attack?

Answer 45

Helper T cells

Question 46

What is the difference between immediate and delayed hypersensitivity?

Answer 46

Immidiate: - antibodies - happens in minutes Delayed: - macrophages - Helper T cells - takes few days to develop Allergies are caused by adaptive immune system

Question 47

What happens during anaphylaxis?

Answer 47

- IgE - massive release of histamine - brochoconstriction (becomes too difficult to breath) - vasodilation - shock