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Curs Introductiv

Istoric, Teorii selective si instructive, Sistem imun specific si nespecific, Echilibrul dintre fiziologic si patologic

The Immune System


Defends body against pathogens Can distinguish between self and non-self

General Defence System (innate)


Non-specific = acts against all pathogens Rapid

Specific Defence System (adaptive)

1. First line of general defence


Skin = barrier. Sweat (acidic pH) Clotting = also helps protect skin Lysozyme = enzyme in saliva, sweat, tears. Attacks bacterial cell walls Mucous (respiratory, digestive, urinary & reproductive tracts) = traps pathogens Cilia = little hairs that help clear mucous (and pathogens) from respiratory tract Alimentary canal = lysozyme in saliva, stomach HCl kills many pathogens, specialised immune areas in the GI tract, very high turnover of epithelial cells, antibodies

2. Second line of general defence


Phagocytic white blood cells (leukocytes) = destroy pathogens that enter Complement Inflammation

Phagocytes (Phago= eat; cyte=cell) attracted to a site of infection (chemotaxis) by chemicals released by injured cells Three types neutrophils (short lived), monocytes (short-lived..in blood) and macrophages (long-lived..in tissue)

Variola afectiune eradicata ca urmare a unei campanii de vaccinare

Vaccinare
14 mai 1796 Edward Jenner il imunizeaza pe James Phips, in varsta de 8 ani, cu materialul biologic extras din pustula unei mulgatoare, Sarah Nelmes, afectata de cowpox (vaccina). Peste cateva saptamani, baiatul este imunizat cu material biologic extras de la un pacient cu variola, dar nu dezvolta boala.

Figure 1-15

Immune organs

Macrophages very large white cells that can move around body, or remain in certain tissues. Long lived, act as scavengers

2. Second line of general defence cont.


Complement set of 30 proteins found in plasma that are activated by infection complicated chain reaction that leads to the bursting of viruses and bacteria made in the liver

Interferons set of proteins produced by virally infected cells cells to limit the spread of viral infections, by inducing a state of resistance in healthy cells. induced by viruses, bacteria and other signals from the immune system

Inflammation infected cells (mast cells) release histamine, which is a vasodilator. This causes localised swelling, redness, heat, pain. Can also cause high temperature. brings white cells to the area of infection Anti-histamines

Specific Defence System (Adaptive Immune System)


Antigens foreign molecules that generate antibody production Antibodies (immunoglogulins) proteins produced by lymphocytes in response to antigens

Monocytes develop into macrophages which phagocytose foreign particles (antigens) Lymphocytes -

Lymphocytes
B lymphocytes mature in Bone marrow lymphatic tissue, especially spleen and lymph nodes

T lymphocytes mature in the Thymus

Large nucleus

B-lymphocytes
B lymphocytes make antibodies = immunoglobulins Antibodies Can bind to pathogens and prevent them from infecting cells. Pathogens are then destroyed by phagocytes Can inactivate pathogens by causing them to clump together Can trigger the complement system, resulting in pathogens being burst

1000s of different B cells, each recognises a different antigen on the surface of a macrophage. Each antigen stimulates production of a single specific antibody B cells (along with T cells) come in contact with antigen. They are stimulated (by T cells) to produce many clones, plasma cells, which make antibodies. Memory B cells faster, more sensitive reaction = secondary response

How B-cells work


Pathogen (e.g. bacteria, virus) B-cells Each recognise a different antigen. The correct one develops into Plasma cells Clones of the correct B-cell, which produce antibodies

Macrophage

Macrophage Phagocytoses pathogen and displays antigens on surface

1st meeting a pathogen, this process takes 10-14 days Memory B cell= subesquent meetings, takes about 5 days

T-lymphocytes
Mature in Thymus, which is most active just before and after birth. The thymus starts to shrink during puberty. Killer T-Cell Destroy abnormal body cells, e.g. virus infected or cancer cells Stimulated by cytokines (THcells) Release perforin, which forms pores in target cells. This allows water and ions in = lysis Suppressor T-Cells Control the immune system when the antigen /pathogen has been destroyed Only recently discovered so little is known about them Memory T-Cells Can survive a long time and give lifelong immunity from infection Can stimulate memory B-cells to produce antibodies Can trigger production of killer T cells

Helper T-Cells Recognise antigens on surface of leukocytes, especially macrophages Enlagre and form a clone of T-helper cells Secrete interferon and cytokines which stimulate B-cells and stimulate killer -cells Can be infected by HIV

Abnormal cell e.g cancer cell, infected cell

Killer T-cell recognises antigen

How T-cells work

Antigen

X
Clones of killer T-cell attach to antigen Killer T-cells release perforin pores Helper T-cell stimulates correct killer T-cell to multiply Helper T-cell also stimulates B-cells to make antibodies

Normal cell

X
Memory Tcells stay in circulation

Abnormal cell gains water, swells and bursts

Suppressor T-cells turn off immune response

Duration of immunity
Memory B-cells circulate for a long time. If the same pathogen infects the body again, these B-cells can produce large amounts of specific antibody very quickly. This is why you usually dont suffer from the same infection twice. Memory T-cells survive a long time and trigger an immune response

Immune disorders
Sometimes the body produces antibodies against its own tissues e.g. autoimmune diseases e.g. rhumatoid arthritis, Crohns disease, SCID (bubble boy disease), asthma

Allergies occur when the body reacts to materials which should not be antigenic e.g. peanuts Tumours in most cases the body recognises tumours as being bad, because they express abnormal molecules on the cell surface. However sometimes the body doesnt notice and cancers can develop

Induced Immunity
Passive immunity An individual is given antibodies by another Short-term resistance (weeks- 6months)

Active immunity Production of a persons own antibodies. Long lasting

Natural Active Artificial Active When pathogen Vaccination usually enters body in the contains a safe antigen normal way, we from the pathogen. make antibodies Person makes antibodies without becoming ill

Natural Passive Baby in utero (placenta) Breast-fed babies

Artificial Passive Gamma globulin injection Extremely fast, but short lived (e.g. snake venom)

Edward Jenner

Macrofag

Figure 1-23

Patogenii care penetreaza prin barierele antomice si fiziologice sunt intampinati de sistemul imun nespecific. Ulterior, va intra in functiune, eventual, sistemul imun specific. Interactiunea dintre cele doua sisteme se realizeaza prin molecule de suprafata si citokine.

Trei faze ale apararii gazdei. Fiecare dintre ele implica o strategie distincta. 1) bariere preexistente; 2) sistemul imun innascut incepe sa lupte in mod activ; 3) intra in actiune sistemul imun specific. La un contact ulterior cu antigenul, limfocitele cu memorie vor facilita un raspuns mai rapid si mai eficient.

Organe limfoide primare: timusul si maduva osoasa Organe limfoide secundare: splina, ganglioni limfatici, MALT (tesut limfoid asociat mucoaselor)

Boala poate apare in situatia cand sistemul imun declanseaza un raspuns imun necorespunzator.

Figure 1-32