Medical Microbiology Chapter 2

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Immune system

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-protect us from infections

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If an individual will be diseased or not depends on...

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immune system strength and amount of attacking pathogens.

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immune system failure occurs

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when amount of pathogens and their virulence/pathogenicity exceed the ability of immune system.

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Innate immune system

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non specific, first line of defense, generic

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Adaptive immune system

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acquired, B & T cells, context with pathogen induces specific clones, immunological memory, basis of vaccination

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Non-cellular innate system effectors

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cytokines (interferon) and complement

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Cellular innate system effectors

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Macro-phages and other phagocytes, nk cells

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Non cellular effectors of the adaptive immune system

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Antibodies

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Cellular effectors of the adaptive immune system

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T cells (CD4, CD8)

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Two main parts of blood

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Plasma and elements

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What are the "elements" blood

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White blood cells, red blood cells, platelets

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White blood cells (leukocytes) can be divided into what two categories?

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Granulocytes and A granulocytes

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Granulocytes

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- type of white blood cells that include: Neutrophils, basophils, Esinophils

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Agranulocytes

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- A type of white blood cells that include Monocytes, and lymphocytes

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Lymphocytes

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A type of Agranulocyte which includes, T cells, Bcells, and NK cells

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Dendritic cell

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A white blood cell in the category of agranulocyte and is the initiator of the adaptive immune response.

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Plasma cells

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are "descendants" of B cells which produce antibodies

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T cell function

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cell mediated iimmunity

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Natural killer (NK) cells

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Destroy target cells by cytolysis and apoptosis

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Monocytes

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- A type of whit blood cell in the category of Agranulocyte which performs phagocytosis when they full mature into macrophages

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Neutrophils

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make up about 60-70% of white blood cells. Phagocytes.

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Basophils

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Make histamine

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Eosinophils

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Production of toxic proteins against certain parasites and some of them are phagocytes.

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Immune responsive cells of the innate immune system

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Monocytes, Granulocytes, Lymphocytes

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Monocytes are located in

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the circulatory system and tissues

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In response to inflammation signals, monocytes can

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move quickly to sites of infection in the tissues and divide/differentiate into macrophages and dendritic cells

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Macrophages

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- Found in the circulatory system and tissues, possess surface receptors for manosse and fructose, recognize common surface antigens like LPS, perform phagocytosis

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Dendrite cells

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Found on the surface of structures like skin and mucous membranes. Star-like shape, surface recognition via PAMPS, phagocytosis followed by migration to lymphoid tissues

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Neutrophils (PolyMorphonuclear Neutrophils: PMN's)

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Mainly Phagocytes, more than 60%. Granules contain lytic enzymes and antimicrobial substances

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Eosinophils

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-No phagocytic, inflammatory reaction, and allergic reaction, Parasitic infection ( relsease of ROS)

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Basophils

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Not phagocytic, inflammatory reaction and allergic reaction,

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CD4

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helper T cells

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CD8

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Cytotoxic T cells

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Steps of phagocytosis

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1. Ingestion through phagoccytosis , and phagosome is formed. 2. The fusion of lysosomes with the phagosome creates a phagolysosome, the pathogen is broken down by enzymes 3. Waste material is expelled or assimilated.

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What is the cause of acute inflammation?

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Common pathogens or allergens

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Cells that are involved in acute inflammation

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Granulocytes and monocytes

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Mediators of acute inflammation

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Amines and Eicosanoids

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Eiosanoids

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Long fatty acid that acts on inflammatory pathways

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Onset of acute inflammation

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immediate ( results noticed in a couple of minuets)

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Duration of acute inflammation

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Few days to a couple of weeks

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Outcomes of acute inflammation

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Heal, abscess formation, or chronic inflammation

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Cause of chronic inflammation

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Non-degradable pathogens (virus)

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Cells involved in chronic inflammation

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Monocytes, Lymphocytes

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Mediators of chronic inflammation

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Cytokines and ROS

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Onset of chronic inflammation

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Delayed ( an acute phase if presents is usually not noticed)

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Duration of chronic inflammation

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Months to years

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Outcomes of chronic inflammation

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Tissue destruction and necrosis

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Lysozymes break what kind of bonds?

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Glycosidic bonds

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Glycosidic bonds are found...

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between sugar monomeric units

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Amount of digestive enzymes found in a lysosome:

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about 50

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Influx of immune-active components to the site results in

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inflammation/tissue swell

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The major function of the innate immune system

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recruiting immune cells to the site of infection by producing chemical factors and specialized chemical mediators called cytokines.

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Chemical mediators involved in the immune system

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Cationic proteins, complement system, cytokines

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Cationic proteins

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carthelicidin, defensins; usually ionophores which alter membrane permeability of pathogens; glycoproteins

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Complement system

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Glycoproteins; inserted into bacterial membranes resulting in lysis, facilitates antibody recognition which results in opsinization, attracts macrophages and neutrophils through chemotaxis,

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Cytokines

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Glycoproteins and proteins; signal molecules secreted by almost every nucelated cell, includes interluekins and inerferons

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Three pathways of complement action

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alternative pathway, MB lectin pathway, and classic pathway

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Classic complement pathway acctivation

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binding of antibodies formed during the adaptive immune response

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Mannose binding lectin ( Mb lectin) complement pathway activation

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Lectin binds to mannose which is a common surface component of bacteria, fungi, and some enveloped viruses. This opsonizes the pathogen and enhances phagocytosis.

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Alternative complement pathway activation

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Bacterial cell wall components with repetitive surface structures like LPS; formation of membrane attack complex which is inserted into the pathogens membrane.

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Complements are found in _______ and made by __________.

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the circulatory system, liver

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Formation of ionic pores by cathelicin and defensins cause

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disruption of the electron transport chain which results in the organism losing energy and motility.

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Antigen

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Any substance that can stimulate an immune response but not necessarily its entire structure is immunogenic.

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If a antigen is to large

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it is processed into small epitope units

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If an antigen is too small

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carrier proteins called heptans enhance recognition

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Epitopes

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Sub-region/structure of an antigen that is the actual antigenic determinants.

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Major histocompatibility complex:

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distinguish between self and non-self. Exists on the surface of almost all human cells. participants in antigen processing.

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MHC1

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found on almost all cells. Mostly respond to viral infections. Present proteins found within the cytoplasm of the cell.

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Events of viral infection detection involving MHC1

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viral invaison > cviral protein digestion > presents as MHC 1 viral protein complex on the surface of the cell > recognized by CD8 cells > cytotoxic T cell activation

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MHC 2

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- found on leukocytes (macrophaages, dendrite cells, some B and T cells), recognized by helper T (CD4) cells, presents contents found in the extracellular space

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Process of MHC 2 presentaion

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Extracellular pathogen > phagocytosis and digestion > presents as MHC2 digested protein fragment complex > recognized by Th CD4 cell, helper T cell activation > Tjh clonal multiplication

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Cytokine procuction from T cells modulates

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both specific and non specific host defenses

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T cell response steps

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Recognition of peptide epitope from MHC complex, Production of cytokines, Direct killing (cytotoxicity) of foreign cells and infected host cells.

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B cell response steps

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Antigen triggering from monomeric IgM, production of Ab

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T cell dependents B cell activation

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triggered by small foreign proteins, strog response, production of memory cells, boosted by immunization

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T cell independent B cell activation

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Triggered by large repeating surface structure like polysaccharides, weaker response, lower antibody affinity to antigens, no memory cell production, does not produce effective immunization

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What antibody is usually secreted first?

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Pentameric IgM

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IgG

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usually secreted second and is more specific that the primarily secreted antibody

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IgA

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Has a dimeric structure

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FAB

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contains variable region for antigen binding

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Fc

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contains constant region, effector function, interaction with complement components, interaction with phagocytes.

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Adverse effect of the immune system

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Tolerance: self antigen recognition due to the non fool proof mechanism which can be disrupted by genetic disposition, chronic infection, drugs and toxins, these can be organ specific or systemic

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Type one Hypersensitivity reaction: Immediate Hypersensitivity

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caused by reexposure to an antigen, the mediator is histamine from mast cell, and the antibody involved is IgE

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Type 2 hypersensitivity reaction: antibody mediated

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caused by antibody misbinding on host cells (Molecular mimicry), mediators are recruitment of phagocytic cells and cytotoxic T cells, antobodies involved are IgG and IgM, and some examples would be auto immue haemolytic anemia, acute rheumatic fever,

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Type 2 hypersensitivity reaction: Immune complex

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Caused by Excessive Ag-Ab complexes, mediators are the non cleared Ag-Ab complexes which eventually deposit in blood vessels, joints and organ, antibodies involves are IgG and some examples would be Lupus and Reactive arthritis

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Type 4 hypersensitivity reaction: Delayed type

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Hyper activated macrophage ( secreting too much TNF), mediated y TNF recruiting monocytes which create wall off but with significant local damaged, no antibodies are involved, and some examples would be Rheumatic arthritis and Chron's disease.