Immunophysiology

Question 1

Organs of immune system

Answer 1

Primary (central): thymus, bursa, embryonic liver/ bone marrow
Secondary (peripheral): spleen, lnn, GALT, MALT

Question 2

Natural immunity

Answer 2

Non-antigen specific, less effective, rapid reactivity, no immunological memory, linear amplification
Molecular components: complement factors + receptors, heat shock proteins, histamine
Cellular components: macrophages, natural killer cells, granulocytes, dendritic cells
Humoral factors: lysozyme, interferon proteins from virus-infected cells (inhibits viral replication), C-reactive protein.

Question 3

Complement system

Answer 3

Activation:
- classic adaptive way: known Ag-Ab complex + C1, C2, C4
- natural hereditary alternative pathway: unknown Ag, microorg + B, D
- MBL (mannose binding lecithin): binds oligosaccharides of certain virus/bacteria + MASP1-2 (MBL Associated Serine Proteases)
C3 -> C3a + C3b, C2, C4

Cascade is activated like the blood-coagulation cascade

Question 4

C3a and C3b

Answer 4

C3a: provocation at inflammation
Histamine release (anaphylatoxin)

C3b: phagocytosis (opsonization); binds to glycoproteins and attracts monocytes + macrophages (C3b rec, C3b opsonin)
C5-C9 “Membrane drill” terminal reaction: C3b binds to C5 => allosteric changes -> attraction to C3/C5 convertase => membrane attack complex

Question 5

Functions of the complement

Answer 5

1. Intrinsic ability to LYSE bacterial membrane
2. Initiates CHEMOTAXIS (attract phagocytes to the site of reaction)
3. Stimulates opsonization (bacterial phagocytosis-> inflammation)

Question 6

Specific immune response

Answer 6

Humoral and Cellular immunity. Induced when an individual gets in contact with a non-self Ag.

• Active: when actively responds
• Passive: receiving cells/ immunoglobulins of an already immunized individual.

Question 7

Antigens

Answer 7

Non-self matter (belongs to the body of the pathogenic agent) , with large Mr and only epitope takes part in the binding of the antibody produced against it.
Recognized by T-/B-cell receptors and induces an active immune response or tolerance.
Classification: auto- (self matter), allo- (same spp), xeno- (another spp).
(a) Affinity (1 epitope): [Ag-Ab complex] X product of free Ag + Ab
(b) Avidity: 1< epitopes.

Question 8

Immunogenicity

Answer 8

(a) Ag reacts with the Ab
(b) Determined by the whole molecule: grade of foreignness, Mr (<4000 = weak, 100000< = strong), complexicity of structure

Immunogenicity increases with the complexicity.

Question 9

Immunoglobulins

Answer 9

Large glycoproteins, secreted by plasma cells and they act as Ab by binding with specific Ags.
During humoral immune response a selected Ag activates B-cells for the production of immunoglobulins. B-lymphocytes with cell surface immunoglobulins = “recognizing cells”.
Ag binding triggers cell differentiation => tranformation of B-lymphocytes into plasma cells.

Question 10

Antibodies

Answer 10

• FAB: fragment Ag binding
• FC: fraction crystallisable-> biological effect
• Variable region: 2 Ag binding sites
• Joint region (hinge): binding the Ag, more flexible, disulfide bond
• 2 H-chains (heavy), 2 different L-chains (light): λ,κ

Question 11

Function

Answer 11

• Non-specific cellular immunitity: immediate kills the Ag (natural killer cells)
• Humoral immune response -> dissolved Abs, lymphocytes can bind Abs at their FC region => recognition + immediately kills the invader. They cannot do it without Abs.

Question 12

Humoral immunity

Answer 12

Ab-dependent specific immune defense (B-cell defense)
Ag binding receptors (cell membr of B-lymphocytes) = Ab molecules, ONLY react with one paricular Ag epitope
Ag is immediately recognized by B-lymphocytes containing the proper Ag-binding receptor => lymphocytes start dividing rapidly.

Question 13

Daughter cells: Plasma cells, Memory cells

Answer 13

Plasma cells (larger than B-cells): produce + secrete Abs identical to the receptors on the B-cells. They die after a few days of intense Ab production. Most of the cells are differentiated into plasma cells, when a lymphocyte clone is activated by its Ag epitope

Memory cells: don’t participate in the immediate attack on the Ag, but they live for months/years after the Ag has been eliminated (if Ag is encountered => stimulation).

Question 14

Primary response

Answer 14

On first exposure to an Ag, several days elapse before the formation of Abs. The delay is due to the time required for the lymphocyte to come in contact with the antigen.
Before Abs production, the lymphocytes must undergo a proliferation phase.

Question 15

Secondary response

Answer 15

When Ags reenter the body, the Ab formation changes character.
Memory cells (ability to recognize Ag) will be present as a result of the previous attack. Memory cells and their progeny => Abs production

This response is quicker, more potent and lasts longer.

Question 16

T-cells

Answer 16

B-cell needs the assistance of a T-cell.
The complex formed bw the Ag + the membrane receptors of B-cells is transported into the cell (endocytosis) -> breaks down to epitopes -> carried back to the surface (with B-cells MHC class II proteins) -> recognized by helper T-cells -> activation -> production of cytokines => stimulation of B-cells to divide + differentiate into plasma cells

Question 17

B-cells maturation: Humoral acquired immunity

Answer 17

First phase (Ag-independent): pre B-lymphocytes -> maturation => virgin B-lymphocytes (surface: IgG-like molecule against a certain Ag structure)

Secondary phase (Ag-dependent): cell -> blood. If there is an APC Ag against which the virgin B-ly has an Ig => ly binds the Ag and gets activated. Activation can be Th-dependent / Th independent.
During binding of activated B-lys => interleukines, which settle in the B-dependent zones of the secondary lymphatic organs (through blastic transformation: the activated cell starts to reproduce intensively and a clone of the original cell carrying the original Ig structure appears).
Some cells -> memory cells
Mostly -> circulation => plasma cells produce free immunoglobulins

Question 18

Self restriction

Answer 18

Following Ag stimulus => potency + effieciency of immune response will decrease due to elimination of Ags and due to the immune response => costimulatory mechanisms, lymphokines,… which influence the response +/-.

Question 19

T-cells

Answer 19

Produced + matured in thymus, dark nucleus.
Tc-cells: Participate in cellular immunity by killing the virus + bacteria infected cells
Th-cells: Activation of Tc-cells + B-lys needed for the immune response.
Treg-cells: regulate the activation
Removing of these cells => autoimmune reaction

Question 20

Development of T-cells

Answer 20

Phase 1 (Ag-independent): pre-T-lys -> maturation => virgin-T-lys (surface: Ig).
Ti-initiator cell -> circulation -> 2nd phase begins

Phase 2 (Ag-dependent): Ti-cell carries a CD4 + IgG => recognition of Ag on the surface of an AP cell that has MHC-II as well -> primary stimulation.
Some Ti-cells have CD8 (Tc-cytotoxic) -> recognize Ags that are expressed beside MHC-I and immediate kill the cells carrying them.

Question 21

Maturation in Thymus

Answer 21

O: bone marrow, liver

1. TCR- T-cell receptors appear
2. Immature T-ly receptors can bind most MHC structures + Ags
3. (+) selection: bind self-MHC will survive, rest die.
4. (-) selection: bind self matters expressed together with self-MHC will be killed/ inactivated.

Afer selection procedure -> differentiate into self + non-self
More than 90% are destroyed in thymus.
Recognition of Ag and MHC => activated => recruits phagocytes with interleukines -> kill the pathogenic Ag

Question 22

MHC-System

Answer 22

Natural ability to distinguish self from non-self. Function: “ID card”

• MHC-I: EC component encoded by an MHC-gene + transmembrane + IC omponents. If the cell binds non-self Ag => Ags of the MHC-I group are recognized by cytotoxic T-ly.
• MHC-II: Ags similar to immunoglobulins (on APC). APC send parts of the non-self Ag + MHC-II structure onto the cell surface. Signal to helper T-cell: presence of MHC-II and non-self Ag.
• MHC-III: no direct role in immune response.