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Evy Sulistyoningrum

• Basic concept in immunology


• Immunology to pathogen
• Immunology in allergy & hypersensitivity
• Variety of cells, molecules that performed immune response
• Cellular components
• Immune-related cells: lymphocytes, macrophage, etc
• Lymphoid tissue or organs: thymus, lien, etc
• Humoral components
• Soluble protein:
• Complements: C1, C2, C3, factor D, Factor P etc
• Antibody: IgA, IgG, IgM, IgD, IgE

• Physical, mechanical, chemical barriers


Cell of the
immune
system
• Polimorphonuclear phagocyte
• Blood circulation
• Neutral granule
• First cell that come to the site of
infection
• Phagocytosis
• Non specific receptor
• Complement
• Opsonin (IgG)
• Major constituent of pus
• Defense against paracytes  antibody mediated
cytolysis
• Blood circulation
• Acidophillic granule
• Able to phagocyte (not main function)
• Blood circulation  mast cell in tissue
• Mast cell:
• Mucosal mast cell
• Connective tissue mast cell
• Basophilic granule
• Heparin
• Histamine
• Newly synthezysed mediators
• Function:
• Allergy & inflammation
• a: Neutrophilic granulocyte banded nucleus.
• b : Neutrophilic granulocyte with banded nucleus and beginning
segmentation
• c : Two neutrophilic granulocytes with segmented nuclei..
• d : Neutrophilic granulocyte, excessively segmented with five
segments.
• e - f: Eosinophilic granulocyte (eosinophil) with segmented
nucleus.
• g – h :Basophilic granulocyte (basophil).
• Giant eater
• Phagocytic mechanism = neutrophil
• Mononuclear phagocyte
• Derived from monocyte
• Monocytes (blood circulation ) macrophage (tissue)
• Locations: connective tissue, Microglial cell, Kupffer Cell, Dust
cell
• Extracelullar secretion:
• Cytokines
• Complements
• Hydrolytic enzymes
• Antigen presenting cells
• Locations
• Immature: skin (Langerhans cell, GIT, respiratory
tract)  phagocytosis
• Mature: Lymphoid tissue  Professional APC
• Myeloid bone marrow precursor
• Spine-like projection
• Take up, process and present all types of
antigen
• Activate T cell in secondary lymphoid organs
• Lymphoid progenitor
• Mononuclear leucocytes
• Able to recognize foreign molecules
• Adaptive immunity
• Subsets:
• T lymphocyte
• B lymphocyte
• Non B-non T lymphocyte/Large cell/NK cell
• Based on:
• Cluster of Differentiation (CD)
• Cytokine products
• No BCR- No TCR  Null cell
• Lymphoid progenitor
• Larger than B/T lymphocytes
• Cytoplasmic granules
• Able to kill certain virus and tumor cell
• Killing mechanism: release cytotoxic granules 
cell target death
• Innate immunity
• Response against pathogen infection
• 4 main tasks:
• Immunological recognition
• Immune effector function
• Immunological memory
• Immune regulation
• Resulted in immunity
• Distinguish self vs nonself
Innate/Natural/Native Adaptive /Acquired
Characteristics
Time Immediate (0-4 hours) Delayed (>96 hours)
Specificity Non-specific : Certain Specific : Specific parts
structure of all pathogens of the antigen
Memory (-) (+)
Components
Cellular & chemical Skin, mucosal epithelia, Lymphocytes in
barriers Antimicrobial chemicals epithelia, antibodies in
epithelial surfaces
Humoral Complements, acute phase Antibodies , cytokines
protein, cytokines
Cellular Phagocytes, NK cell Lymphocytes
• Infectious pathogen
• Mechanical barriers
• Tissue resident cells – pathogen
• Elimination of pathogen
• Inflammatory reaction
• Chemokine & cytokine
• Complement system
• Inflammatory cells
• Induction adaptive immune response
• PAMPS (Pathogen-
associated molecular
patterns)
• PRR (Pattern
recognition receptors)
• Activated macrophage
• Phagocytosis
• Release of cytokine &
chemokine
• Inflammatory process
• APC: Process & presents antigen to lymphocytes
in secondary lymphoid organs
• T cell activation
• B cell activation
• Proliferation  Differentiation into effector cell
• Cellular mechanism
• Humoral mechanism
• Immunological memory
Activation of
specialized antigen-
presenting cells (APC)
is a necessary first
step for induction of
adaptive immunity
• Antigen: substances that specifically bound
to lymphocytes
• Antigen was processed and presented by
APCs
• 2 pathways of antigen processing
• Recognized by:
• Antibody/B cell receptor
• T cell receptor +Major histocompatibility
Complex (MHC)
• APCs activate T cell  active T cell activates B cell
• Activation leads to proliferation & differentiation of T
cell & B cell into effector function
• Humoral
• Extracellular form of pathogen & its products
• B cell  antibody producing plasma cell
• Neutralization: preventing attachment of antigen
• Opsonization: coating pathogen  easy to be eaten
(phagocytosis)
• Complement activation
• Inflammation
• Lysis of target (MAC)
• Opsonization
• Cellular
• Intracellular pathogens
• T cell
• T cytotoxic/cytolitic :
• Destroy target cells
• Via action of perforin & granzymes
• T helper: Activate macrophages
 Induce formation of cytotoxic T cells
 Stimulate B cells to produce antibodies
T cytotoxic/CTL

T helper
• General features
• Immunity to extracellular bacteria
• Immunity to intracellular bacteria
• Immunity to fungi
• Immunity to virus
• Immunity to parasite
• Defense against pathogen is mediated by effector
mechanism of innate & adaptive immunity
• Immune system responds in distinct ways to different
type of pathogen
• Pathogen try to evade the effector mechanism 
immune escape/immune evasion
• Sometimes, host response to pathogen may cause
greater tissue injury than the pathogen itself
• Ex:
• Staphylococcus aureus, Streptococcus pyogenes
• Mechanism of action
• Induce inflammation  tissue destruction  pus
formation
• Release toxin (endotoxin, exotoxin)
• Innate Immunity against extracellular bacteria
• Complement activation : lectin & alternative pathway
• Phagocytosis
• Inflammatory response
• Adaptive immunity against extracellular bacteria
• Main activity: humoral
• Actions: Neutralization, opsonization & phagocytosis,
classical pathway of complement activation
• Injurious effects
• Inflammation
• Septic shock
Mechanism of immune Examples
evasion
Antigenic variation Neisseria gonorrhoeae
Escherichia coli
Salmonella typhimurium

Inhibition of complement Many bacteria


activation
Resistance to phagocytosis Pneumococcus
Scavenging of reactive Catalase-positive
oxygen intermediates staphylococci
• Characteristic: capable of replication within phagocytes
• Examples : Mycobacterium tbc, Mycobacterium leprae
• Innate immunity:
• Phagocytes
• NK cell
• Macrophage activation in response to intracellular bacteria
can cause tissue injury
• Chronic antigenic stimulation  granulomas
• Adaptive immunity: T cell mediated immunity (most
effective)
Mechanism of immune Examples
evasion

Inhibition of phagolysosome Mycobacterium tuberculosis


formation Legionella pneumophilla

Inactivation of reactive Mycobacterium leprae


oxygen & nitrogen species

Disruption of phagosome Listeria monocytogenes


membrane, escape into
cytoplasm
• Obligatory intracellular organism
• Innate immunity to virus
• Inhibition by Type I IFN
• NK cell mediated killing
• Adaptive immunity to virus
• Antibody blocks virus binding
• CTL killing infected cell
• Immune evasion
• Alter antigen
• Inhibits antigen presentation by MHC molecules
• Secrete cytokine-binding protein
• Infect CD4 T cell
Mechanism of immune Examples
evasion
Antigenic variation Influenza virus, HIV

Inhibit of antigen processing HSV, CMV

Production of cytokine Vaccinia, poxvirus produce IL-


receptor homologs 1, IFN
CMV produce chemokine
Production of EBV produce IL-10
immunosuppressive cytokine

Infection of immunocompetent HIV


cells
• Innate immunity:
• Phagocytosis
• Adaptive immunity
• Th2 activation  IgE production  activation of
eosinophil  ADCC (large parasites)
• Cell mediated immunity to intracellular protozoan
• Immune evasion
• Resistant to phagocytosis
• Reduce immunogenicity
• Mycosis
• Endemic or opportunistic infection
• Maybe intracellular or extracellular
• Innate immunity
• Neutrophil & macrophage
• Adaptive immunity
• T cell mediated immunity  intracellular fungi (Histoplasma
capsulatum)
• Immune evasion:
• Inhibition of macrophage activation
• Gell and Coombs, 1968
• Type I: classical immediate hypersensitivity = allergy
• Type II: cytotoxic hypersensitivity
• Type III: immune-complex mediated hypersensitivity
• Type IV:cell mediated or delayed hypersensitivity
• Common among population in developed nations
• Immediate hypersensitivity or allergy or atopic
• Events:
• Exposure of antigens
• Activation of TH2 cells
• B cells class switching → IgE producing
• IgE binding
• Repeated exposure to allergen
• Mast cell activation
• Pathologic reaction
• Cytotoxic hypersensitivity reaction
• Minutes to hours
• Destruction of a target cell through the action of antibody
against antigen on plasma membrane.
• Antibodies involved are IgG (& IgM)
• Effector: phagocytes, NK Cell via ADCC
• Complement is also involved
• Ex: Drug reactions, miastenia gravis, blood transfusion reactions,
erythroblastosis fetalis, Grave’s disease
• Immune complex hypersensitivity
• Caused by antigen-antibody complexes formed in
circulation
• Mostly of the IgG class
• Antigen may be exogenous or endogenous
• The reaction may be general (e.g., serum sickness)
or may involve individual organs: skin (SLE, Arthus
reaction), kidneys (lupus nephritis), blood vessels
(polyarteritis), joints (rheumatoid arthritis)
• Antigen is soluble, released into blood or body
fluids  Deposited in cell wall  bound by
antibody & trigger immune reaction
• cell mediated or delayed type hypersensitivity (DTH).
• Usually takes 24 – 28 hours
• Caused by products of antigen-specific effector T cells
• T cells undergo blastogenesis and cellular division 
production of reactive cells
• Ex: tuberculin (Mantoux) , tuberculosis, leprosy,
blastomycosis, histoplasmosis, toxoplasmosis,
leishmaniasis