Immunity. Basic princeples of humoral and cellular immune response.

1. Basic principles of humoral
and cellular immune reaction
Irene Tereshchenko
2nd Medical Faculty
Charles University in Prague

2. Immunity
Immunity is the ability of human body to resist almost all kinds of organisms
and toxins that tends to damage the tissues and organs.
→ Fungi, Protozoans, Bacteria and viruses are all potential pathogens.
Immune Response - reaction of the cells and fluids of the body to the
presence of a substance which is not recognized as a constituent of the body
itself.

3. 1. Pre-immune mechanisms
Ag penetrates tissues (vasodilatation, edema)
Adsorption of the Ag to immune tissue
2. Immune mechanisms
migration of APCs in T-or B-zone peripheral organs of the immune system
Processing of Ag: Stage 1 – Endocytosis of Ag
Stage 2 - cleavage (processing)
Stage 3 - expression of degraded particles Ag at the MTC in
complex with MHC I or MHC II
Stage 4 – presenting to TH
3. Suppression of the immune response (Autoimmune
diseases can run)
4. Immunological memory
Mechanism of IR

4. Goal: to stop pathogens from entering the body
→ Skin – acts as a barrier to invasion
→ Sweat – has chemicals which can kill different pathogens.
→ Tears - have lysozyme which has powerful digestive abilities that
render antigens harmless.
→ Saliva – also has lysozyme.
→ Mucus - can trap pathogens, which are then sneezed, coughed,
washed away, or destroyed by chemicals.
→ Stomach Acid – destroys pathogens
First line of defense

5. If a pathogen is able to get past the body's first line of defense,
and an infection starts, the body can rely on it's second line of
defense.
→ First there is a non-specific response (phagocytosis) followed
by an INFLAMMATORY RESPONSE.
Second line of defense
Phagocytosis =
ingestion + digestion of pathogens.

6. →Cell-mediated immunity is a type of immunity when body
develops large number of lymphocytes which are
specifically activated against foreign agent.
→These activated or sensitized lymphocytes have the
ability to attach to a foreign agent and to destroy it.
→CI is composed of sensitized T-lymphocytes.
Cellular Immunity

7. →In process of developing of CI phagocytic cells involved in the expulsion of
pathogens from the intercellular space.
→Phagocytic cells attack pathogens and destroy them. On intracellular level
macrophages are the main cell protectors which have specific receptors - Ig,
through which they effect on the pathogen.
→Its aim is to combine phagocytosis and specific antibodies to fight
pathogenic environment.
Cellular Immunity

8. → T-lymphocytes
→ Macrophages
→ NK-cells (type of CTL)
Cells involved in CI
* Macrophages present antigen via their surface MHC to T-cells
* T-cells recognize antigen through their specific receptors (TCR)
* A specific T-cell clone becomes activated and begins to proliferate
* Activated TH lymphocytes becomes effectors cells that secrete cytokines

9. → Protein Pathogen processed and converted into peptide to bind a
MHC molecules on APC to be presented on T-cell
AG Processing and presentation

10. → TH-cells express IL-2 receptors and secrete cytokines including IL-2
→ IL-2 auto activate TH-cells
→ APC release IL-I which acts on both APC and TH-cell to promote their
activation
→ All mentioned interactions lead to activation of mature TH-cells
→ Mature TH-cells proliferate and differentiate into effectors antigen specific
TH-cells releasing cytokines
→ Some of them become memory cells which provide secondary immune
response
→ Cytokine released from activated TH-cells activate macrophages, NK and B-
cells
T-cells activation

11. → Activated CD8 TC-cells proliferate and differentiate into a
clone of effectors cells CTLs
→ Effectors CTLs kill target cells i.e. nucleated cells (expressing
MHC-I) infected with viruses, tumor cells or graft cells
T-cells activation

12. → Activated TH-cells (TH1) secrete IFN-γ which activates
macrophages and increase their ability to kill ingested
intracellular pathogens
→ The process of activation of macrophages, NK cell and
cytotoxic T-cells, infiltration and proliferation of inflammatory
cells, stimulated by cytokines released from TH-cells (TH1) is
important protective mechanism against intracellular
pathogen
Macrophage activation

13. Cytokines stimulate other effectors cells of CMI and humoral immune response and
mediate the following:
1. Attract monocytes, macrophages and lymphocytes to the site
2. Activate macrophages to kill intracellular microbes
3. Promote activity of CD8 CTLs which directly kill virus infected cells, tumour cells,
and graft rejection
4. They activate NK cells increasing their cytotoxic functions
5. Stimulate B-cells to differentiate into plasma cells that secret antibodies

14. Sometimes the second line of defense is still not enough and the pathogen is
then heading for the body's last line of defense.
The immune system recognizes, attacks, destroys, and remembers each
pathogen that enters the body. It does this by making specialized cells
and antibodies that render the pathogens harmless.
For each type of pathogen, the immune system produces cells that are
specific for that particular pathogen.
Third line of defense

15. →The humoral response is carried out by antibodies which are produced by
Plasma cells.
→Plasma cells are derived from activated B-cells that are produced in the bone
marrow.
→Humoral immunity promotes the development of normal operation antibodies.
→The aim of bacteria and viruses (pathogens) – is to enter the cell to destroy it
→The principle of action of antibodies is the interruption of receptor linkages
between the pathogen and the cell.
→The result is to breakdown of interaction between pathogen and cells due to
blocking it by the effector molecule or antibody.
Humoral Immunity

16. Antibodies
An antibody (Ab) is a protein produced by B cells that is used by the immune
system to identify and neutralize foreign objects such as bacteria and viruses.
→ Agglutination: Enhances phagocytosis and reduces number of infectious units
to be dealt with
→ Opsonization: Coating antigen with antibody enhances phagocytosis
→ Neutralization: blocks adhesion of bacteria and viruses to mucosa. Also blocks
active site of toxin
→ Activation of complement
→ Inflammation: Disruption of cells by complement/C-reactive protein attracts
phagocytic and other defensive immune system cells
→ AB-dependent cell-mediated cytotoxicity: Ab attached to target cells cause
destruction by non-specific immune cells

17. FunctionofAntibodies

18. Immunoglobins
Monomer
→ The most common, represents 75-80% of serum Ig.
→ The only antibody capable of crossing the placenta to
give passive immunity to the fetus.
→ Has longest half-life (23 days) among of all Igs.
→ Activates complement
→ Stimulates chemotaxis
→ Antigen receptor on surface B cells (together with
IgM).
→ Activate basophils and mast cells to produce
antimicrobial factors.
→ Bound to surface of mast cells and basophils
→ Destroys parasitic worms and participates in allergies
IgG
IgD
IgE
SS-bond

19. → Present in body secretions
→ Provides protection against proliferation of
microorganisms in this fluid
→ Aids in defense against microbes and foreign
molecules penetrating body via cell linings of
these cavities.
→ Provides passive immunity to infants through
mothers breast milk
Dimer (trimer)
IgA
Immunoglobins

20. Immunoglobins
Pentamer
→ First Ig class produced in a primary response to
an Ag
→ Found on surface on B cells (together with IgD)
→ Ag receptor of B cells
→ Has 10 antigen-binding sites
→ More effective at stimulating complement
→The FC receptors on phagocytes bind IgM
(opsonization)
IgM

21. Interferons (IFNs) are proteins made and released by host cells in response to
the presence of pathogens such as viruses, bacteria, parasites or tumor cells.
They allow for communication between cells to trigger the protective
defenses of the immune system that eradicate pathogens or tumors.
ϒ-IFNs are produced by NK cells that activate macrophages (Type II IFNs)
NK cells  ϒ-IFNs  Macrophage activation
Whereas, α and β IFNs are produced by virus infected
cells that activate NK cells. (Type I IFNs)
Virus infected cells  α, β IFNs  NK cell activation
Interferons

22. → The complement system helps the ability of Ab and phagocytic cells to
clear pathogens from an organism.
→ It is part of the innate immune system (not adaptable, doesn’t changes
during lifetime).
→ The complement system consists of a number of small proteins found in
the blood, in general synthesized by the liver, and normally circulating as
inactive precursors (pro-proteins). When stimulated by one of several
triggers, proteases in the system cleave specific proteins to release cytokines
and initiate an amplifying cascade of further cleavages.
Complement system

23. → The Microbial antigen is
ingested by an APC and partially
digested.
→ Fragments from microbe bind
with the MHC II to form a MHC II
/Ag complex on the surface of
the APC
Humoral Immunity

24. → TH-cell, specific for the
presented antigen, binds to
the MHC II/Ag complex
Humoral Immunity

25. → TH-cell then activates an
appropriate B cell by releasing
IL-2 to it.
Humoral Immunity
*IL-2 – growth factor for T and B cells

26. → The interaction between
the TH-cell and the B-cell
causes the B- cell to
differentiate into Plasma cells
and memory cells.
Humoral Immunity

27. Memory Cells
Memory T Cell
→ an infection fighting cell
Memory B cell
→ an antibody producing cell
Memory cells do not react right away but are held in reserve for later infections.
The secondary response that is carried out by memory cells is different in 3 ways.
→ Memory cells produce antibodies that bind with greater affinity
to their antigens than the antibodies produced in the initial
response.
→ The response time is much vaster than the primary response
→ A greater number of antibodies are produced.

28. Lymphicytos – organism fighting infection
G-вирус
М-бактерия A-бактерия
Proteins CD4 CD8 indexes shows the condition of CI
State of secondary immunodeficiency
Rheumatic process
17.12.2013

29. 25.02.2014