Microbiology Immunology Lecture Notes PDF

Basic Immunology LECTUREs (2&3) Basic Immunology 1  Basic Immunology Is the study of the immune system Definition Including its responses to microbial pathogens and damaged...

Basic Immunology LECTUREs (2&3) Basic Immunology 1  Basic Immunology Is the study of the immune system Definition Including its responses to microbial pathogens and damaged tissues and its role in disease. Function Prevent or eradicate infections. A complex network of cells, tissues, and organs. Consists of Immune response (immunity). The body’s defense against infectious agents and other foreign The immune substances (antigens) in its environment. system Consists of: cells, tissues, and organs 2  Basic Immunology A. Primary lymphoid organs: B. Secondary lymphoid organs:  Trap and concentrate antigens. 1- Bone marrow (BM):  Include: 1. Site of B cell maturation. 1. Lymph nodes 2. Site of generation of all Blood cells from a common stem 2. Spleen. cell (hematopoiesis). 3. Mucosa-associated lymphoid tissues ( MALT)  2- Thymus a. Tonsils in the nasopharynx 1. Site of T cell maturation. b. Peyer`s patches in the sub-mucosal surfaces of small 2. Selection processes of T cells to discriminate between self intestine and non-self-antigen: Positive selection Negative selection  Also act as secondary lymphoid aggregates. Cells that are able to Cells that cannot recognize  Recognize self ag self ag  Developed in primary lymphoid organs Not bind to self Ag Efficiently bind self Ags  Reach the secondary lymphoid organs via Are autoreactive cells and Selected to grow. blood & lymphatic vessels undergo apoptotic cell death.  where they can meet, recognize antigen, and initiate the immune response 3  Basic Immunology 1. A common lymphoid progenitor 2. A common myeloid progenitor producing: producing: a. T lymphocytes a. Leukocytes. b. B lymphocytes b. Erythrocytes. c. Natural killer (NK) cells. c. Platelets 1. Lymphocytes: 2. Phagocytes: 3. Antigen presenting cells:  B lymphocytes  Macrophages  Macrophages  T lymphocytes  Neutrophils  Dendritic cells  NK cells  B lymphocytes 4  Basic Immunology Self/non-self.  The immune system has two lines of defense : 1. Innate (non-specific) immunity. 2. Adaptive (specific) immunity.  The innate and adaptive immune systems utilize cell-surface receptors to sense potential threats (microbes). 1. First line of defense against pathogens and give a rapid response. 2. Always present in healthy individuals. 3. Non specific 4. No memory. 5. Recognize and react against microbes only…PAMPs Barriers to Infection Innate Immunity Cells Soluble Defense 5  Basic Immunology  Epidermis and mucous membranes.  Nose Hair & Cilia in Respiratory tract  pH: the acidic pH of the skin, stomach, and vagina inhibit the growth of pathogens.  Microcidal molecules: α- and β- defensins), lysozyme, RNases and DNases  Are microbes that exist in a symbiotic relationship with the body  They colonize skin, GIT, upper respiratory, urogenital tracts and eyes  Inhibit the establishment of pathogenic microbes. a) Phagocytic cells: are cells having the ability to phagocytose (recognize, ingest, and kill) microbes and any foreign antigen (phagocytosis)  Macrophages,  Neutrophils b) Natural killer (NK) cells: function in killing tumor cells and virus infected cells 1. The complement system. 2. Cytokines of the innate immunity.  Proteins secreted by the immune cells and mediate the functions  e.g. TNF, IL 1 , IL 6 , IL 12 , IFN γ, IFN α, IFN β. 3. Other plasma proteins of innate immunity:  Mannose-binding lectin (MBL).  C-reactive protein (CRP) The circulating levels of these plasma proteins increase rapidly after infection. This protective response is called “acute phase response”. 6  Basic Immunology 1. Second line of defense. 2. Develops as a response to infection. 3. Specificity and memory are characteristic features of adaptive immunity:  The immune response is specific for a certain antigen Specificity ensures that different antigens elicit specific responses.  Is the ability to “remember” and respond more strongly to repeated exposure to the same microbe.  Produce antibodies that neutralize and  Eradicate intracellular microbes eliminate the extracellular microbes and  (Cell-mediated immunity). toxins  (Humoral immunity). B and T lymphocytes Recognize antigen by antigen specific receptors present on their surfaces  B lymphocytes  T lymphocytes 7  Basic Immunology 1. Antigen recognition by lymphocytes receptors. 2. Activation of lymphocytes leading to 3. proliferation & differentiation into effector cells (cells that carry the function) and memory cells. 4. Elimination of the microbes. 5. Decline and termination of the immune responses (homeostasis) once the pathogen is eliminated to avoid damaging host tissues. 6. Long-lived memory (memory cells).  1st line of defense  2nd line of defense  Immediate (hours)  Delayed (days) Non-specific Specific None Yes Yes Yes  Phagocytes: macrophages &  B lymphocytes neutrophils  T lymphocytes  NK cells  B cell receptor; BCR  Pattern recognition receptors  T cell receptor; TCR  Alternative & MBL pathways  Classical pathway  TNF, IL-1, chemokines, IFN-α,  IL-2, IL-4, IL-5, IFN-γ, IFN-β, IFN-γ, IL-12 IL-13, IL-17 8  Basic Immunology  B lymphocytes  Macrophages  Macrophages  T lymphocytes  Neutrophils  Dendritic cells  NK cells  B lymphocytes 1) Lymphocytes include:  B lymphocytes  T lymphocytes  NK cells 2) Morphologically similar. 3) Heterogeneous in phenotypes and functions. 4) They can be distinguished by surface proteins the Cluster of differentiation “CD” and a number :  CD markers: CD & number → CD1, CD2, CD3, CD4, CD8…......... etc. 5) Lymphocytes may be :  Mature  Proliferation  Carry the function  Never meet antigen  Differentiation 9  Basic Immunology 1. B lymphocytes 2. T lymphocytes Developed and mature in the BM. Developed & mature in the thymus B is derived from BM “T” refers to Thymus derived 10-15% of total blood lymphocytes 75% (The majority of blood lymphocytes). Phenotype markers: Phenotype markers: Antigen receptor (BCR) TCR, CD3, CD4, CD8. which is formed of IgM and IgD CD19, CD21, Recognize any antigen e.g. proteins, polysaccharides, lipids, nucleic acids Function: humoral immunity Function: cell-mediated immunity. (antibodies) Types of T lymphocytes: CD4 OR CD8 Recognize antigens, by B cell Helper T cells TH (CD4+) receptor (BCR) Cytotoxic T cells TC (CD8+) Stimulated by antigen leading to Regulatory T cells (Treg) their proliferation & differentiation into effector cells (plasma cells) which secrete antibodies and memory B cells. Antibodies destroy microbes 1. Help B lymphocytes to produce antibodies 2. Help macrophage activation to destroy ingested microbes. 1. Kill virus-infected cells. 2. Kill tumor cells. 3. Graft cells ….. Rejection. 10  Basic Immunology T lymphocytes don't recognize antigen directly as B lymphocytes do. Recognize antigen by TCRs formed of α and β chains Recognize protein antigens only. They recognize antigen only in the form of peptide fragments plus MHC molecules on the surface of APCs (MHC Restriction):  CD4+ cells recognize peptide + class II MHC molecules.  CD8+ cells recognize peptide + class I MHC molecules. A Proteasome: Degrade Proteins into Peptides 11  Basic Immunology B cell activation  Some antigens are activated B cells  Epitopes found on protein Ag. without help from T cells.  Engagement of TCR of a CD4 T cell,  Microbial LPS. interleukin-4 (IL-4). T-dependent activation  BCRs bind antigens.  Ag are endocytosed.  The antigen is digested into fragments.  Ag are displayed at the cell surface inside a class II MHC to be presented to Th cells.  Th cells bind the B cell and secrete IL 4 that: 1. Stimulate the B cell to proliferate into a clone of cells with identical BCRs. 2. Differentiate into plasma cells that secrete antibodies. 12  Basic Immunology 3. Natural killer (Nk) cells ADCC A third population of lymphocytes. Antibody Dependent Cell- 10% of blood lymphocytes. Mediated Cytotoxicity) Cytoplasmic granules Phenotype markers: CD16 Antigen receptor: KARs and KIRs. Function: Killing tumor cells. Killing virus-infected cells. Antibody-dependent cellular cytotoxicity (ADCC) Produce IFN-γ which activate macrophages. Killer Inhibitory Receptors (-) signal Killer Activating Receptors (+) signal 13  Basic Immunology Phagocytes are cells having the ability to phagocytose (recognize, ingest, and kill) microbes and any foreign antigen. 1. Monocytes/Macrophages 2. Neutrophils 1. Monocytes circulate in blood … 1. Polymorphnuclear leukocytes PMNs ingest microbes in blood 2. The most numerous leukocytes in blood 2. Macrophages tissue resident of 3. Increase in No. in blood …acute infection monocytes …. Ingest microbes in 4. Ingest microbes and then die.. Pus cells tissues 1) Delivery of phagocytes to site of infection:  Diapedisis  Chemotaxis 2) Recognition of microbes 3) Phagocytic adherence to the target (opsonization) 4) Ingestion or engulfment of the target particle. Phagosome formation 5) Phagolysosome formation 6) Intracellular killing 14  Basic Immunology  Delivery of phagocytes to site of infection: Diapedisis Chemotaxis  Recognition of microbes: phagocytes recognize microbes in blood and tissues by surface receptors specific for microbes e.g. Toll-like receptors TLRs  Phagocytic adherence to microbes: Opsonization: coating of microbe by opsonin {antibody or complement C3b, C4b} Binding of microbe to receptors on phagocytic cells  Ingestion (engulfment) of microbe into cytoplasm of the cell within a membrane vesicle................. phagosome  Fusion of phagosome with lysosome of cell …. Phagolysosome {digestive vesicle}  Intracellular killing: a) Oxygen independent: lysosomal granules, lactoferrin, low ph and lysosomal enzymes. b) Oxygen dependent: toxic oxygen derived products and toxic nitrogen oxides 15  Basic Immunology 1. Dendritic cells 2. Macrophages 3. Some b cells  Epithelium of the skin, GIT, respiratory tract → Entry of microbes 1. Capture and transport antigens to peripheral lymphoid tissues 2. Process antigens into pieces (peptides) 3. Present peptides to T lymphocytes  They are rich in class II MHC molecules 16  Basic Immunology  Stem cells are undifferentiated (unspecialized) cells. Self-renewal:  Numerous cycles of cell division by mitosis  The capacity to differentiate into specialized cell types e.g. Muscle Potency: cell, Pancreatic beta cell, Red blood cell, Nerve cell, Brain cell, Liver cell, ….. etc 1. Embryonic  Isolated from the inner cell mass of blastocysts stem cells: 2. Adult stem  That are found in adult tissues (skin, muscles, umbilical cord blood, cells: brain, heart and bone marrow).  Stem cell therapy ……. Cell-based therapy  Treating patients by transplanting specialized cells that have been grown from stem cells in the laboratory (stem cell culture). Leukemia:  Bone marrow transplants Cardiovascular disease:  Repairing damaged heart cells after a heart attack.  Replacing damaged pancreatic beta cells by functional Type1 diabetes mellitus: beta cells which can secrete insulin. Spinal cord injuries:  Damaged neurons. Alzheimer's disease:  Replacing the damaged brain cells. Muscle damage. 17