1. Book, Abul K. Abbas: Basic Immunology
Gábor Koncz
Lectures 1-9, 25-26,29-30
Book, Abul K. Abbas: Basic Immunology

2. In this lecture:
General warm up, why do we need immune system
Simple schema of the immune system
3 lexical data

3. Do we need immune system?

4. GENERATION TIME OF PATHOGENS
PATOGENS
Virus
3 hrs
Bacteria
Viruses
Diversity
Fast development
In the active phase of the HIV 10billion viruses develop/day
Bacteria may divide in every 20 minutes
parasites

5. The human microbiome

6. HIV
Flu
S. aureus
Streptococus.
Salmonella
Mycobacterium tuberculosis
Lysteria
Pneumocystis carnii
Andida albicans
Trypanosoma brucei
Schistosoma mansoni
We live in a potentially hostile world filled with infectious agents of diverse size, shape, and composition which would very happily use us as „petri dishes”…

7. How can we survive????

8. 1. The interest of microbes

9. The human microbiome

10. Normal bacterial flora can be differnt in each person

11. Tightly regulated balance between commensal flora and the immunen system

12. Transplantation of bacteria?

13. 2. The immune system

14. THE TWO ARMS OF THE IMMUNE SYSTEM
Differentiation between harmless and harmful impacts
DETECTION OF STRESS AND DANGER SIGNALS
INNATE IMMUNITY
Differentiation between self and non-self structures
Antigen-specific recognition
ADAPTIVE IMMUNITY
INNATE IMMUNITY
immediate reaction
not antigen-specific
no memory
ADAPTIVE IMMUNITY
developes in several days
specific
has memory
Neutralization and elimination of foreign and harmful structures
COORDINATED AND REGULATED ACTIONS

15. Both the innate and adaptive arms of immunity are required for
elimination of pathogens

16. THE TWO ARMS OF THE IMMUNE SYSTEM
Monocytes, Macrophages, Dendritic cells, Granulocytes, NK cells and Complement components
Monocytes, Macrophages, Dendritic cells, Granulocytes, NK cells and Complement components
B and T cells
Defense against microbes is mediated by the early reactions of innate immunity and the later responses of adaptive immunity. Innate immunity (also called natural or native immunity) provides the early line of defense against microbes. It consists of cellular and biochemical defense mechanisms that are in place even before infection and are poised to respond rapidly to infections. These mechanisms react to microbes and to the products of injured cells, and they respond in essentially the same way to repeated infections. The principal components of innate immunity are (1) physical and chemical barriers, such as epithelia and antimicrobial chemicals produced at epithelial surfaces; (2) phagocytic cells (neutrophils, macrophages), dendritic cells, and natural killer (NK) cells; (3) blood proteins, including members of the complement system and other mediators of inflammation; and (4) proteins called cytokines that regulate and coordinate many of the activities of the cells of innate immunity. The mechanisms of innate immunity are specific for structures that are common to groups of related microbes and may not distinguish fine differences between microbes.
In contrast to innate immunity, there are other immune responses that are stimulated by exposure to infectious agents and increase in magnitude and defensive capabilities with each successive exposure to a particular microbe. Because this form of immunity develops as a response to infection and adapts to the infection, it is called adaptive immunity. The defining characteristics of adaptive immunity are exquisite specificity for distinct molecules and an ability to "remember" and respond more vigorously to repeated exposures to the same microbe. The adaptive immune system is able to recognize and react to a large number of microbial and nonmicrobial substances. In addition, it has an extraordinary capacity to distinguish between different, even closely related, microbes and molecules, and for this reason it is also called specific immunity. It is also sometimes called acquired immunity, to emphasize that potent protective responses are "acquired" by experience. The main components of adaptive immunity are cells called lymphocytes and their secreted products, such as antibodies. Foreign substances that induce specific immune responses or are recognized by lymphocytes or antibodies are called antigens.
Innate and adaptive immune responses are components of an integrated system of host defense in which numerous cells and molecules function cooperatively. The mechanisms of innate immunity provide effective initial defense against infections. However, many pathogenic microbes have evolved to resist innate immunity, and their elimination requires the more powerful mechanisms of adaptive immunity. There are many connections between the innate and adaptive immune systems. The innate immune response to microbes stimulates adaptive immune responses and influences the nature of the adaptive responses. Conversely, adaptive immune responses often work by enhancing the protective mechanisms of innate immunity, making them capable of effectively combating pathogenic microbes. 16

17. Immune system

18. Innate immunity Adaptive Immunity T cells B cells
The simplest Schema of the immune system
Innate immunity Adaptive Immunity
T cells B cells
Intracellular
pathogens
Extracellular

19. The main functions of the immune system:
Recognition
Communication
Elimination (effector functions)

20. Innate immunity Adaptive Immunity T cells B cells
The simplest Schema of the immune system
Innate immunity Adaptive Immunity
T cells B cells
Intracellular
pathogens
Extracellular
Recognition
Communication
Elimination

21. THE ANTIGEN Definition and properties Antigenic determinant (epitope)
Antigen recognition by B and T cells

22. DEFINITIONS
ANTIGEN (Ag) - any substance, which is specifically recognized by the mature immune system of a given organism
Any chemical structure
Soluble or corpuscle
Simple or complex
Originated from the body or comes from outside
Genetically self or non-self
Natural or artificial

23. DEFINITIONS
ANTIGENICITY– capability of an antigen to bind specifically with certain product of the adaptive immunity: TCR or BCR/antibody,
immunogenicity - capability of an antigen to induce an (adaptive) immune response,
tolerogenicity - capability to induce immunological tolerance, specific immune non-responsiveness
Autoimmunity/infections

24. FACTORS INFLUENCING IMMUNOGENICITY I.
From the aspect of our body:
Genetics (self/non-self)
species (evolutionarily nonconserved molecules)
individual differences (e.g. MHC polymorphism – see later)
Age
newborn – less reactive immune system
elderly – no new lymphocytes
Physiological condition (pl. immunodeficiencies, starvation)
Foreignness: evolutionary the farther the species are from each other the more their antigens induce immune response in another
Size: i.e. haptenes (too small to induce immune response without carriers)
Genetics: differences of the immune response between species from the same family/order and between individuals of the same species
Age: the old mainly rely on the immunological memory, they can hardly get over a new kind of infection. Moreover there are differences in the immune response generated by EBV and mumps viruses in childhood and adulthood

25. FACTORS INFLUENCING IMMUNOGENICITY II.
From the aspect of the antigen:
Physical-chemical properties of the Ag
size/complexity (bigger  more epitopes, role of carrier)
corpuscular (cell, colloid) or soluble
denatured or native (different epitopes!)
degradability (by APCs)
Availability (crystalline proteins of the eye are not presented to lymphocytes)

26. FACTORS INFLUENCING IMMUNOGENICITY III.
From the aspect of vaccination:
Dose
Route
intradermal/subcutan > intravenous > oral > intranasal (oral vaccine against polio virus!)

27. ANTIGENIC DETERMINANT (=EPITOPE)
Part of the antigen which directly interacts with the antigen-binding site of a defined immunoglobulin (BCR / antibody) or TCR

28. B cell epitope T cell epitope recognized by B cells proteins
polysaccharides
lipids
DNA
steroids
etc. (many artificial
molecules)
cell or matrix associated
or soluble
recognized by T cells
proteins mainly
(8-23 amino acids)
requires processing by
APC