Post on 10-Nov-2014
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Macrophage Macrophage (Antigen Presenting Cell)(Antigen Presenting Cell)
Asbestos fibers engulfed by MacrophageAsbestos fibers engulfed by Macrophage4
Macrophage reaches out to ensure bacteria with pseudopod
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Killer T cell attack cancer cells6
Killer T cells appear remarkably alive as they attack a cancer cell
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MHC pada kromosom ke-6
Lokus A C B D/DR dst
Allel genetik : >20 >12 >20 >6
Penentu
Antigen HLA HLA A1 HLA Cw1 HLA B5 HLA Dw1 HLA A2 HLA Cw2 HLA B8 HLA Dw2
HLA Aw36 HLA Cw3 HLA Bw39 HLA Dw6
Contoh, HLA seseorang : HLA-A1, HLA-A3, HLA-B7, HLA-B8, HLA-Cw1, HLA-Cw2, HLA-Dw2, HLA-Dw3
NASE & NASAL PHARYNX OROPHARYNXStaphylococci StaphylococciDiphtheroids Streptococcus spNeisseria sp Neisseria spHaemophilus sp Haemophilus sp
MOUTH SKINStaphylococci StaphylococciStreptococci StreptococciActinomyces sp CorynebacteriumHaemophilus sp PropionibacteriumYeasts YeastsEnteric bacteria DiphtheroidsAnaerobic bacteria Enteric bacteria
(rare)Spirochaetes
NORMAL FLORA OF THE SKIN, MOUTH, NOSE AND NASOPHARYNX, AND THE OROPHARYNX
GASTROINTESTINAL SYSTEM :STOMACH LARGE INTESTINE
Normally sterile Anaerobic bacteria : Gram negative
SMALL INTESTINE Bacteroids sppLactobacilli Fusobacterium spp
Enterococci Gram positiveDiphtheroids Eubacterium sppYeasts (Candida) LactobacilliEnteric bacteria Clostridium sppAnaerobic gram BifidobacteriumNegative bacilli Streptococci
Facultative and aerobic organisms Staphylococci Enterococci Enteric bacteria Proteus spp Pseudomonas spp Yeasts (Candida)
NORMAL FLORA OF THE GASTROINTESTINAL SYSTEM
NORMAL FLORA OF THE GENITOURINARY TRACT
Predisposing Factor Effect on Immune system Type of infection
The Compromised host
Drug or X-rays in immunosuppression Allograft recipients (renal. Bone marrow, heart)VirusImmunosuppression e.g. Rubella, herpes, EB virus, hepatitis virus ,HIVTumours
Malnutrition
Smoking, inhalation of dust particles (e.g. Silica, Fungal spores)Chronic endocrine disease (e.g. Diabetes)Primary immune deficiency
Diminished cell- mediated and humoral immunity
Replication of virus in lymphoid cells with resulting impaired function
Replacement of cells of immune systemLymphoid hypoplasiaDecrease in circulating lymphocytesDecreased phagocytic abilityInflammatory lung changes, immune complex deposition to fungal spores
Decreased phagocytic activity
Diminished cell-mediated and/or humoral immunity
Lung infections, bacteraemia, fungal infections, urinary tract infectionsSecondary bacterial infections ( also fungal and protozoal in AIDS)
Bacteraemia, pneumonia, UTIMeasles, tuberculosis, respiratory infections, gastrointestinal infectChronic respiratory infections, allergic responses
Staph, infections Tuberculosis Respiratory infections, bacteraemia
Bacteria Viruses Fungi
M. tuberculosis Influenza Coccidioides
M. leprae Viral hepatitisCryptococcus
T. pallidum Herpes simplex Histoplasma
Brucella abortus Cytomegalovirus Candida
Salmonella spp. HIV
Measles
Mumps
Rubella
Infectious mononucleosis
Microorganisms affecting cell mediated immune function
Restoration of normal immmune function is likely to be of more importance in the recovery of the patient than spesific antimicrobial drug treatment.
Microorganism Effect
Microorganisms that interfere with induction of acquired immunity
Measles, rubella, herpes, Hepatitis virusesLymphadenopathy associated virus of AIDS (HIV)
Malaria paracites
Leprosy bacilli
Trichphyton fungi
Schistosomes
Influenza viruses
Herpes simplex and cytomegalovirus
Infection of cells of immune system and interference with induction of acquired immunity and expression of cell mediated immunity
Depressed lymphocytes responsiveness to mitogens and some antigensAlteration in T:B cell ratio wtih reduction in expression of complement receptors ( ? Bloked by immune complexes)Non-spesific impairment of cell-mediated immune responseRepeated exposure to tricophyton leads to relatively allergy to the fungal antigens and reduced inflamatory responseIncorporate host antigens and prevent recognition of their antigensSuppress mitogenic responses of lymphocytes? Disables macrophages leading to secondary bacterial infectionInduced Fc reseptors in infected cell that bind and thus inactivate antiviral antibody
IMMUNITY IN INFECTIONTo Understand the detailed cellular events and
differences in responses to infection of individulas it is necessary to take into account more recently acquired knowledge of the role of the major histocompability complex (MHC) in determining the outcome of an immune reponse.
The MHC is a highly polymorphic system of genes that control the expression of the cell surface molecules involved in immunity.
The existence of such a polymorphic system will inevitably result in individulas with different immunological potentials to respond to a given challege.
Whilst some individulas will be well prepared to resist an infectious agent others will be at risk.
It will come as no surprise to find that certain infective states are linked with the MHC.
For example, the association between viral hepatitis and the HLA-A8 antigen on lymphocytes.
Individuals of blood group O are more susceptible than those of other blood groups to cholera.
In studies of a Children population it was found that people of blood group B had a 50% greater probability than non-B persons of contracting E.coli urinary tract infections.
Blood group B individuals are more susceptible to gonococccal infections.
Blood group B and AB non-secretors have been found to be three times more susceptible to urinary tract infections.
BACTERIAL INFECTIONMany microorganisms owe their pathogenic abilities to
the production of exotoxins.
Amongst diseases dependent on this type of mechanism are diphteria, cholera, tetanus, gas gangrene and botulism.
SCHEME SHOWING THE PROGRESS OF INFECTION AND THE IMMUNOLOGICAL DEFENCE MECHANISMS
MICROORGANISM
INVASION LOCAL PROLIFERATION
Spread via lymphatics Proliferation in local lymph
nodes
Toxin production (Toxigenic bacteria)
Intracellular growth (Chronic bacterial
infection and viruses)
ANTIBACTERIAL IMMUNITY ANTI TOXINS CELL MEDIATED
IMMUNITY
Innate immune mechanisms ( Mechanical barriers anti-bacterial substances phagocytic cells)
Inflammation, Polymorph infiltration Abscess formation
Bacterial toxins have been largely identified as enzymatic in nature and the antibody in some way is able to interfere with the ability of the enzyme to interact with its substrate.
This idea is supported by the finding that antibody is much more effective against enzymes which have high molecular weight substrates that it is against those with low molecular weight substrate.
This means that a bacterium coated with antibody and complement will adhere to a phagocytic cell and become susceptible to phagocytosis.
The phagocytic cell in many instances can then digest the microorganism by secreting into the phagocytic vacuole a variety of digestive enzymes carried in the intracellular lysosomes.
The streptococcus carries, as part of its cell wall, a substance known as M protein, which confers the ability to resist digestion by the enzymes.
Enteric infections such as those due to Salmonella typhi or Vibrio cholerae, antibodies can be secreted into the intestinal lumen and attack the organism before it invades the intestinal mucosa.
The IgA immunoglobulin is selectively produced in intestinal and respiratory mucous membranes.
T - Lymphosit – macrophage relationships
Natural Killer cell
T LymphositeIL-2 prodn
Macrophage
Altered tissue cell
(virus or Tumor)
Direct cytotoxic effect (NK cell)
Direct cytotoxic effect (Tc cell)
Production of cytotoxic factors
Chemotactic factor
macrofag inhibitory factor
macrofag activation factor
B cells
Kills along with antibody (ADCC)
Direct Effects of Ab
Processed antigen
Presented to T cell
Interleukin 1
Lymphocyte activating factorInterferon Antigen
Activated macrophag kills intracellular microorganisms
Microorganism
IMMUNE COMPLEXES IN VIRAL INFECTIONSIn infections of humans by hepatitis B virus the surface
antigens are shed into the blood stream and form complexes with antibody.
Persisting levels of hepatitis B antigen can lead to immune complex mediated damage such as polyarteritis nodosa and glomerulonephritis.
In Epstein Barr virus infections viral antigens have been found in immune complexes in the kidneys of patients with Burkitt’s lymphoma.
Deposition of complexes in the choroid plexus has been suggested as underlying behavioural disorder in asymptomatic virus infections.
The humoral immune response is probably the predominant form of immunity responsible for protection from reinfection by viruses.
For this reason immunisation procedures aim at producing circulating or mucous membrane antibody.
In volunteers infected with influenza virus a correlation was found between cytotoxic T cell activity and diminished shedding of virus.
Schematic view of virus infection and immune response, indicating some possible consequences
Virus Mucous membrane
Virus in blood stream
Virus infection target cell (viral replication)
Virus specified changes in cell surface
Release of new formed virus
Stimulation of humoral and cell mediated immunity to altered surface antigen
If target cell is component of immune system then alteration in immune reactivity
Stimulation of local IgA
Antiviral IgG immunization on passive administration
Neutralization of virus
Neutralization of virus
PROTECTION
PROTECTION
Neutralization of virusFormation of toxic complexes
PROTECTIONHYPERSENSITIVITY
Removal of virus infected cellsDamage to tissue cells
PROTECTION
HYPERSENSITIVITY
Inhibition of immune responseFailure of self tolerance
PERSISTENCE OF VIRUSLOSS OF IMMUNE SURVEILLANCE
? AUTOIMMUNITY
SCHEME SHOWING THE ROLE OF Ig E AND EOSINOPHILS IN HELMINTH IMMUNITY
HELMINTH ANTIGENS
T LYMPHOCYTES
LYMPHOKINES
EOSINOPHILSITUATION
Ig E STIMULATION
MAST CELL +Ig E
Ig G, Complement, Leucocytes at site
of infection
EosinophilIg G
Helminth
EOSINOPHIL
Chemotactic factorMediators of infllammtion
Destraction of parasite
Summary of role of B and T cells in infection
Antigens of microorganism
B cells T cells
Clonal expansion
Antibody producing cells
Antibody in blood lymph, tissue fluids mucous membranes
Clumping OpsonisationLysis of
microorganismInflammation chemotaxis
Memory cells
Lymphoid tissues and
blood
Respond to subsequent exposure
to microorganism
Clonal expansion
Cytotoxic T cell
Production of Immunoregulatory
substance
Memory cells
Macrophague activation and
localization
Chemotactic inflammation
Interferon
NK cell