overview of the immune system immune system innate (nonspecific) cellular components humoral...
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OverviewOverview of the immune systemof the immune system
Immune System
Innate(Nonspecific)
Adaptive(Specific)
CellularComponents
HumoralComponents
CellMediated
Humoral(Ab)
Differences between:Differences between: Non specific (innate or natural immunity)
Response is antigen-independent.
There is immediate maximal response.
Not antigen-specific.
Exposure results in no immunologic memory
Specific Immunity (acquired or adaptive)
Response is antigen-dependent.
There is a lag time between exposure and maximal response.
Antigen-specific.
Exposure results in immunologic memory
Host DefensesHost Defenses
Mechanical Factors:Mechanical Factors:
Physical barriers to pathogens
Skin
Epidermis consists of tightly packed cells with keratin which is a protective protein.
Mucous membranes
First line of DefenseFirst line of Defense
Lacrimal apparatus: Washes eye
Saliva: Washes microbes off
Urine: Flows out, flushing.
Vaginal secretions: Flow out
Fungistatic fatty acid in sebum.
Low pH (3-5) of skin.
Lysozyme in perspiration, tears, saliva, and tissue fluids except CSF.
Low pH (1.2-3.0) of gastric juice and vaginal acidity.
Transferrins in blood reduce iron so inhibit microbial growth.
Chemical FactorsChemical Factors
Microbial antagonism/competitive exclusion:
Normal microbiota antagonize pathogen:
1-By competing with pathogens for nutrients, for colonization site by producing substances harmful to the pathogen.
2- By altering conditions that affect the survival of the pathogen. e.g. normal microbiota in vagina alters pH to prevent overpopulation of C.albicans which is a pathogenic yeast caused vaginitis.
Normal MicrobiotaNormal Microbiota
Second line of DefenseSecond line of Defense
1.Phagocytosis
2.Inflammation
3.Fever
4.Antimicrobial substances
Nonspecific DefensesNonspecific Defenses Nonspecific defenses deny pathogens access to the body or destroy them
without distinguishing among specific types.
Nonspecific DefensesNonspecific Defenses Nonspecific defenses deny pathogens access to the body or destroy them
without distinguishing among specific types.
Formed Elements In Blood (note functions)RBC’s
WBC’sAgranulocytes
1 .Monocytes and
2 .Lymphocytes Granulocytes
1 .Neutrophils (PMNs)
2 .Basophils and 3 .Eosinophils
Immune System
Myeloid Cells Lymphoid Cells
Granulocytic Monocytic T cells B cells
NeutrophilsBasophils
Eosinophils
MacrophagesKupffer cells
Dendritic cells
Helper cellsSuppressor cellsCytotoxic cells
Plasma cells
NK cells
Cells of the Immune System
Organs of the immune systemOrgans of the immune system
During embryonic life, haemopoeitic stem cells develop in fatal liver and other organs, these stem cells reside in the bone marrow in postnatal life.
There is primary lymphoidprimary lymphoid system which is responsible for the evolution and maturation of immune cells (Bone marrow and thymus).
and secondary lymphoidsecondary lymphoid system (tonsils, peyer patches, spleen and other lymph nodes all over the body), responsible for trapping of foreign antigen, residence of immune cells.
Phagocytosis
.
RednessPainHeatSwelling (oedema)In acute-phase proteins are activated (complement, cytokine, kinins) - chemical messengersVasodilation (histamine, kinins, prostaglandins, leukotrienes) - bring in more helpMargination and immigration of WBCsTissue repair
InflammationInflammation
Chemicals Released by Damaged CellsChemicals Released by Damaged Cells
•Histamine Vasodilation, increased permeability of blood vessels
•Kinins Vasodilation, increased permeability of blood vessels
•Prostaglandins Intensity histamine and kinin effect
•Leukotrienes Increased permeability of blood vessels, phagocytic attachment
In serum 30 proteins produced by the liver, activated in a cascade as previous catalyzes the next step.
Outcomes of Complement system1. Opsonization2. Chemotaxic3. Cell lysis
The Complement SystemThe Complement System
Effects of Complement ActivationEffects of Complement Activation
Opsonization or immune adherence: enhanced phagocytosis
Membrane attack complex: cytolysis
Attract phagocytes
Classical PathwayClassical Pathway
Alternative PathwayAlternative Pathway
Antiviral proteins
Alpha IFN & Beta IFN: Cause cells to produce antiviral proteins that inhibit viral replication
Gamma IFN: Causes neutrophils and macrophages to phagocytize bacteria
Interferons (IFNs)Interferons (IFNs)
Interferons (IFNs)Interferons (IFNs)
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2
3
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Viral RNA from an infecting virus enters the cell.
The infecting virus replicates into new viruses.
The infecting virus also induces the host cell to produce interferon on RNA (IFN-mRNA), which is translated into alpha and beta interferons.
Interferons released by the virus-infected host cell bind to plasma membrane or nuclear membrane receptors on uninfected neighboring host cells, inducing them to synthesize antiviral proteins (AVPs). These include oligoadenylate synthetase, and protein kinase.
New viruses released by the virus-infected host cell infect neighboring host cells.
AVPs degrade viral m-RNA and inhibit protein synthesis and thus interfere with viral replication.
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Specific Defenses of the Host: The Immune Response
*Antigen (Ag) : A substances that causes the body to produce specific antibodies or sensitized T ells, also called immunogen.*Antibody (Ab): A proteins produced by the body in response to an antigen, and capable of combining specifically with that antigen.
Serology: Study of reactions between antibodies and antigens.
Antiserum: Generic term for serum because it contains Ab.Globulins: Serum proteinsGamma () globulin: Serum fraction containing Ab.
Serum ProteinsSerum Proteins
The Immune Response The Immune Response Two armsTwo arms
Acquired immunity:The ability obtained and developed during an individual's lifetime, to produce specific antibodies or T-cell.
The factors involved in this immunity known as:1. Humoral immunity: from humors, because they
were found in the body fluid, it Involves Ab produced by B cells (B lymphocytes).
2. Cell-mediated immunity: Involves specialized lymphocytes T cells or T lymphocytes
Acquired ImmunityAcquired ImmunityNatural Acquired:( Active and passive).Artificially Acquired:( Active and passive).
*Naturally acquired active immunityResulting from Antigen enter the body naturally (infection).
*Naturally acquired passive immunityAntibodies via transplacental or via colostrum
*Artificially acquired active immunityInjection of Antigen (vaccination)
*Artificially acquired passive immunityInjection of performed Antibody.
Antigenic DeterminantsAntigenic DeterminantsA specific region on the surface of an antigen to which antibodies recognize and react with, it is called epitopes.
HaptensHaptensit is a molecule too small to stimulate the antibody formation by itself but only when combine with a
carrier molecule. e. g. penicillin antibiotic.
Factors Influencing ImmunogenicityFactors Influencing ImmunogenicityA. The ImmunogenThe Immunogen
1- Foreignness The immune system normally discriminates between self and non-self such that only foreign molecules are immunogenic.
2- Size: the larger the molecule the more immunogenic it is likely to be.( generally substances with mol.wt.> 100,000 dalton are potent immunogenic).
3- Chemical Composition: The more chemical complexity of the substance is the more immunogenic it will be.
4- Physical form - In general particulate antigens are more immunogenic than soluble ones and denatured antigens more immunogenic than the native form.
5. Degradability - Antigens that are easily phagocytosed are generally more immunogenic. This is because for most antigens (T-dependant antigens) the development of an immune response requires that the antigen be phagocytosed, processed and presented to helper T cells by an antigen presenting cell (APC).
CHEMICAL NATURE OF IMMUNOGENS:A. Proteins -The vast majority of immunogens are
proteins. These may be pure proteins or they may be glycoproteins or lipoproteins. In general, proteins are usually very good immunogens.
B. Polysaccharides - Pure polysaccharides and lipopolysaccharides are good immunogens.
C. Nucleic Acids - Nucleic acids are usually poorly immunogenic. However, they may become immunogenic when single stranded or when complexed with proteins
.D. Lipids - In general lipids are non-immunogenic, although they may be haptens. In an antigen, the same antigenic determinant repeated many times .
TYPES OF ANTIGENS
T-independent Antigens - T-independent antigens are antigens which can directly stimulate the B cells to produce antibody without the requirement for T cell help .
In general, polysaccharides are T-independent antigens.
T-dependent Antigens - T-dependent antigens are those that do not directly stimulate the production of antibody without the help of T cells. Proteins are T-dependent antigens.
LYMPHOCYTESLYMPHOCYTESBoth B B cells and TT cells originate from stem
cells in adult red bone marrow or in the fetal liver. (RBCs, macrophages, neutrophiles, and other WBCs also originate from these same stem cell).
Some cells pass through the THYMUS THYMUS and
emerge as mature T-cells.T-cells.
Other cells probably remain in the Bone Bone marrow marrow and become B-cells.B-cells.
Both types of cells then migrate to lymphoid tissues, such as lymph nodes or spleen.
Once in these organs, B cells recognize antigens by means of antigen receptors antigen receptors which are antibody molecules on their surface (IgD).(IgD).
After antigen exposure, B-cells changed to memory cellsmemory cells and antibody-secreting plasma plasma cells.cells.
Once re-exposure to antigen, memory cells quickly proliferate to produce more plasma cells.
Further differentiation of the activated B-cell into clone occurs, resulting in the formation of large antibody-secreting cells called plasma cells.
Plasma cells are relatively short-lived (less than 1 week) but excrete large amounts of antibody during this period.
Memory cells, in contrast, are very long-lived cells, and on re-exposure to the initial stimulating antigen, they quickly transform into plasma cells and begin secreting antibody.
Antibody Structure
Monomer
80% of serum antibodies
Fix complement
In blood, lymph, intestine
Cross placenta
Enhance phagocytosis; neutralize toxins & viruses; protects fetus & newborn
Half-life = 23 days
IgG antibodiesIgG antibodies
Pentamer
5-10% of serum antibodies
Fix complement
In blood, lymph, on B cells
Agglutinates microbes; first Ab produced in response to infection
Half-life = 5 days
IgM antibodiesIgM antibodies
C4
J Chain
Dimer
10-15% of serum antibodies
In secretions
Mucosal protection
Half-life = 6 days
IgA antibodiesIgA antibodies
J Chain
Secretory Piece
Monomer
0.2% of serum antibodies
In blood, lymph, on B cells
On B cells, initiate immune response
Half-life = 3 days
IgD antibodiesIgD antibodies
Monomer
0.002% of serum antibodies
On mast cells and basophils, in blood
Allergic reactions; lysis of parasitic worms
Half-life = 2 days
IgE antibodiesIgE antibodies
Bone marrow gives rise to B cells.Bone marrow gives rise to B cells.
Mature B cells migrate to lymphoid Mature B cells migrate to lymphoid organs.organs.
A mature B cells recognizes A mature B cells recognizes epitopes.epitopes.
Clonal SelectionClonal Selection
Clonal SelectionClonal Selection
Self-toleranceSelf-tolerance
Body doesn't make Ab against self
Clonal deletion
The process of destroying B and T cells that react to self antigens
The Results of Ag-Ab BindingThe Results of Ag-Ab Binding
Antibody titerAntibody titer
Is the amount of Ab in serum
Monoclonal AntibodiesMonoclonal Antibodies
Hybridomas are produced by fusing a cancer cell with an Ab-secreting plasma cells
Ideally, if an antibody-producing B cell could be grown by standard cell-culture method , it would produce the Highly specific, only only desired antibody in unlimited amounts. desired antibody in unlimited amounts.
Chemical Messengers of immune cells: Chemical Messengers of immune cells: CYTOKINESCYTOKINES
CYTOKINESCytokines are a diverse group of non-antibody proteins released by immune cells that act as intercellular mediators, especially in immune processes.A. Cytokines are clinically important as biological response modifiers. :1. Monokines - produced by mononuclear phagocytes2. Lymphokines - produced by activated T cells, primarily helper T cells3. Interleukins - name given to many cytokines, abbreviated as IL and given a number, serve as
Communicator between leukocytes .
Helper T Cells (THelper T Cells (THH))
TH1 Activate cells related to cell-mediated
immunity
TH2 Activate B cells to produce, IgM, and IgE
Cytotoxic T Cells ( TCytotoxic T Cells ( TCC))
Destroy target cells with perforin
Classification of T Cells according to function
Delayed Hypersensitivity T Cells (TDelayed Hypersensitivity T Cells (TDD))
Associated with allergic reaction, transplant rejection.
Suppressor T cells (TSuppressor T cells (TSS))
Turn off immune response when Ag no longer present.
Classification of T-cells according Classification of T-cells according to cell-surface receptorto cell-surface receptor
(CD)(CD)
CD4 : A molecule found on human helper T cells and delayed hypersensitivity T cells. It is involved in the interaction with MHC Class II molecules. CD4 is the 'receptor' by which the AIDS virus enters T cells.
CD8: A molecule found on most cytotoxic and suppressor T cells. It is involved in interacting with MHC Class I molecules.
Major histocompatibility complex
Tissue cells of each individual possess:
Uniqueness that is a function of certain surface glycoprotein molecules known as MHC or human leukocyte antigens (HLA), since they are also identified on the surface on WBCs.
Histocompatibility genes that are found on the short arm of chromosome No 6 in humans encodes such glycoprootein.
Class I MHC : encoding 2 polypeptide chains found on the surface of all nucleated cell. Tc and Ts (CD8) recognize antigens associated with MHC class I.
Class II MHC: encoding 2 polypeptide chains found on the surface of B cells,
T cells and macrophage (APC) .
The (CD4) recognize antigens in association with MHC class II.
T-independent AntigensT-independent Antigens
B cell