IMMUNITY .

Outline Anatomy of the Immune system Organization of the body’s defenses Humoral immunity Cell-mediated immunity Immune responses in Health and diseases

The Immune system Immunity refers to protection against infections, and the immune system is the collection of cells and molecules that are responsible for defending against the pathogenic microbes in environment

The Immune system Role: protect body against pathogens Pathogens; bacteria, bacterial toxin, viruses, parasites, and fungi.

Outline Anatomy of the Immune system Organization of the body’s defenses Humoral immunity Cell-mediated immunity Immune responses in Health and diseases

Anatomy Leukocytes - Phagocytes (phagocytosis): neutrophils, eosinophils, monocytes, macrophages, dendritic cells (skin) - Lymphocytes: Bs and Ts, natural killer cells - Mast cells Lymphoid tissues - primary lymphoid tissues (bone marrow and thymus) - secondary lymphoid tissues

Outline Anatomy of the Immune system Organization of the body’s defenses Humoral immunity Cell-mediated immunity Immune responses in Health and diseases

Organization of the body’s defenses Non-specific defenses: no need to decipher pathogen’s identity. Always present in the body. - Physical barriers - Inflammation - Interferons - Natural cell killers (NK cells) - Complement system Specific defenses:Based on recognition of the pathogen’s identity Humoral immunity Cell-mediated immunity

Non-specific defenses Physical barriers - skin - mucus - stream of tears or urine - Inflammation Chemical barriers pH (stomach, vagina) enzymes (stomach, tears) Interferons Complement system .

Inflammation Symptoms of inflammation: Redness heat Swelling - pain

Macrophage and phagocytosis

Interferon Protein secreted by a cell currently infected by a virus Interferon warns the neighboring cells of the impending viral infection The neighboring cells synthesize proteins that will block the virus from hijacking the cell DNA replication machinery

Complement system About 30 blood proteins They become activated either by direct contact with a pathogen or by contact with a bound antibody. In an activated state, they form a complex which opens a hole in a pathogen’s cell membrane  bacterial lysis Complement system also promotes inflammation

Natural Killer cells = NK cells Cytotoxic T cells, lacking markers Able to recognize a wide range of pathogens without prior exposure When recognition and binding occur, the NK cells destroy the pathogen through cell lysis .

Specific immunity Specificity: based on shape recognition of cell surface antigens Diversity: Any shape can be recognized by a B or T-lymphocytes and trigger an immune reaction Memory: once a pathogen has activated the immune system, memory cells remain and will protect against a secondary infection Self-tolerance: the immune system does not attack itself

Players of Specific immunity Macrophages (antigen presenting cell = APC): phagocytize pathogens and present antigens to helper-T lymphocytes Helper-T lymphocytes: secrete lymphokines and activate B and killer T lymphocytes B-lymphocytes: multiply and specialize into plasma cells  secrete antibodies Killer-T lymphocytes: kill (through lysis) infected or cancerous cells

Antibody-mediated (humoral) immunity = AMI Macrophages phagocytize a pathogen and present an antigen to a matching helper-T cell At the same time, some pathogens contact B-cells matching the pathogen’s antigens The helper-T cells multiply, secrete lymphokines which stimulate the B-cells to multiply and specialize into plasma cells The plasma cells secretes antibodies

.

What are antibodies? . Structures formed by 4 proteins Two main regions: the upper region is highly variable and bind to a specific shape (the antigen) The base region is constant for all antibodies this region, when the antibody is bound to its antigen, activates the complement system .

Role of the antibodies

Types of antibodies Antibody = immunoglobulin = Ig IgG Most abundant. mostly in blood, lymph. able to cross the placenta IgA  Found in tears, milk, blood, lymph IgM  Found in blood, lymph. unable to cross placenta IgE  Found on mast cells, basophiles. involved in allergic reaction. IgD  Found in blood, lymph, on B cells

First and second exposures to a pathogen

Clonal selection Once a T, B or killer lymphocytes have made contact with their specific antigen, they are triggered into action but they also divide and form a large amount of identical cells, called a clone.

Clonal deletion How can the DNA in the nucleus codes for each type of antibody? Since over a millions of different types are needed, how can the DNA in the nucleus code for each of them? There is clearly not enough DNA to accomplish that. During embryogenesis, several genes coding for the variable portion of the antibody (and each responsible for part of a shape) reshuffle so each combination of genes codes for a specific antibody (and shape). So a stem cell receives the capability to form one single type of antibody. Once formed, they circulate in the body. If they meet and bind to a shape (formed by a protein) present in the body, they are destroyed or deleted, so that only the stem cells responsible for antibodies aimed at foreign pathogens are left. A stem cell able to react with our own proteins and not deleted during fetal life might later trigger an autoimmune disease. .

Cell-mediated immunity Similar reaction to AMI The pathogen triggering the reaction is a virus infected cell or a cancerous cell. Killer T lymphocytes are sensitized by contact and activated by lymphokines secreted by activated helper T lymphocytes

CMI . Figure 23.11 (1 of 2)

Cell Mediated: MHC MHC occurs as two classes MHC I on virtually all tissue cells MHC II only on APC’s and Lymphocytes.

Cell Mediated: MHC display properties MHC I on virtually all tissue cells Display only proteins produced inside the cell Endogenous antigens = foreign proteins produced by the cell (viral / cancer) Stimulate the CD8+ cell population form cytotoxic T-cells (Killer T, TC)

.

Cell Mediated: MHC display properties MHC II found only on T-cells & APCs Display proteins derived from a phagocytized target Exogenous antigen: foreign protein from outside the cell – presented to surface Stimulates the CD4+ cell population form Helper T-cells (TH)

.

Clinical applications Immunization - Active and natural - Active and artificial - Passive and natural - Passive and artificial