Poma Immunology

Self-Nonself Recognition:

• Autopoiesis: dynamic process of self-production
- Coherent internal relation among all the components operating in the process of self-production, i.e. hormone signaling
- internal and external coherence is maintained through two networks: the nervous systems (action and response) and immune system (defense against outside invasion)
• Adaptation: the maintenance of a mutually satisfactory relationship between the living entity and the medium in which it exists
• Immune system:
- Collection of organs, vessels, cells and molecules that participate in recognition of self while eradicate non-self pathogens (infections)
- It is dynamic and ever changing
- Able to access every part of the body (protect all body tissues) and responds to molecular shapes that maybe unusual (bacteria antigen, viral capsid) or in an unusual context (myocardium on streptococcal bacteria)
- Overall maintain an adequate relationship with organism’s environment
• Targets of recognition:
- Microbes: viruses, bacteria, fungi and yeast and parasites.
- Antigens: collection of antigens on a single biological structure such as protein or viruses, i.e. markers that the antibodies can recognized
- Dust particles
- Chemical polymers
- Cells from other people
- Anything above a certain size and complexity
• Innate and adaptive immunity:
- Innate: intrinsic components of the immune systems in which resistance is not improved with repeated infections, i.e they are non-specific. These include lysozyme and cytokines released by non-specific cells such as phagocytes, antigen-presenting cell and also acute phase proteins and natural killer cells.
- Adaptive: components of the immune system in which response is improved after repeated exposure to infections, i.e. they are specific. These are antibodies, cytokines released by lymphocytes, phagocytes and antigen-presenting cells and also complement.
• Roles of innate defense: acts as the first barrier and defense against pathogen invasion early in exposure and involved in invoke adaptive response later
- physical barrier (skins) to infectious agent,
- microbicidal factors in body fluids such as complement and lyzozyme
- antiviral proteins
- inflammatory response factors that lead to recruitment of phagocytic cells that recognized crudely the foreign particles and engulf them
• External body surfaces: exterior of the body presents an effective barrier to most organisms. Most infections enter the body via epithelial surfaces of nasopharynx, gut, lungs or genitourinary tract thus several physical and biochemical defenses are present for protection.
- Biochemical: lysozyme in saliva; commensal organisms in gut and vagina to compete with invading flora; spermine in semen; acid in stomach
- Physical: skin, cilia ling in respiratory tract that remove pathogens trapped inside the mucus
- Imp/ortance of skin: high risk of infection with damaged skin through burns etc
• Immune response: involving both cellular and humeral factors. The system, through two types of receptors that binding molecular shapes of foreign substances called antigen, is able to recognize and eradicate.
- Epitopes: structures of the pathogen antigen that is recognized by the antibodies or immune receptors
- While there is a huge range of shapes and sizes for the antigens, an antibody produced by the B lymphocyte or receptors on the surfaces of the cell (“hands” of cytotoxic lymphocytes) can only bind to one type of epitopes. Hence the number of lymphocytes in the body must in large as well and binding depends on affinity.
• Antibody affinity: the immune receptors not necessarily bind to epitopes with a perfect fit but instead the quality of binding is dependent on the affinity or ability to bind of the receptors to the antigen. Hence some antibodies with a high affinity for one antigen may also bind to non-identical but similar shape (but less well).
- Smallpox vaccination: cowpox and small pox have similar antigens thus vaccination against cowpox also allow protection for smallpox. This is called cross-reactivity.
• Role of adaptive immunity: response is directed specifically at the antigen of the agent involving high affinity of recognition and thus more effective killing. Diversity of response is wide and ultimately involved in the prevention and recovery of the infection.
- After the first contact with the non-self antigen, those antibodies that have high affinity for the antigens trigger the cells that is involved in their production to rapidly replicate to adapt to the infection while the expansion of the cell allows for an enhanced response in the future (memory)
- Problems with adaptive immunity include overreaction (allergy) to innocuous substances, autoimmunity and rejecting of transplanted organ or grafted parts.
• Immune recognitions: virtually all substances can act as antigen for the immune systems so the question now is how do the immune systems recognized self to non-self?
- Such distinguishing ability is very important feature of the immune systems that is established in early stages of development. A proposed theory is that the immune systems learn what is non-self.
- Acquired immunological tolerance: the continuous presence of non-self antigens at a times before the immunes systems has matures, leads to a permanent unresponsiveness to those particular non-self antigens.

Structure of the Immune Systems:

• Phagocytes: cells that detect the presence of the foreign particles and engulf it. Neutrophils and blood monocytes travels in blood but can migrate out of the blood vessel travels in the tissue in which phagocytosis occurs.
- Chemotaxis and adherence to the particles
- Membrane activation forming ruffle border
- Extension of the cells encloses the particles in a phagosomes (vacuoles)
- Lysosomes in the cells fuses with the phagosomes and releases digestive enzymes to degrade the particle
- Exocytosis of the degraded particle
• Complement systems: set of circulating proteins that bind to bacterium and their enzymatic functions gets activated:
- Activates other complement compounds through an enzyme cascade and signal amplification
- Component 3A attract neutrophils
- Component 3B covalently bind to anything substances nearly with high chance of being bacterium and enhance phagocytosis in a process called opsonization.
• Recognition of innate phagocytes:
- Weakly attracted to common bacterial cell wall components
- Identify C3b complement component (complement mediated opsonization)
- Fc region of antibodies (immune mediates opsonization)
• Phagocytes of the reticuloendothelial systems:
- Localized phagocytes derived from bone marrow stem cells and are placed in specialized locations where they will encounter such particles, e.g. alveolar macrophages of the lungs.
- They are able to ingest but has the additional action of presenting the digested antigenic proteins to the lymphocytes
- The cells are characterized by long process hence are called dendritic cells at times
• Immune systems organization:
- Primary lymphoid organs: thymus and the bone marrow in which T lymphocytes and B lymphocytes are made respectively.
- Secondary lymphoid organs: organs into which the mature lymphocytes formed in the primary organs migrate. They are organs which filter foreign matter out of the body fluids and are places where immune responses to foreign antigens usually take places. These include spleen, lymph nodes, Peyer’s patches and skin.
- Lymphatics vessesl: systems of channels through the body tissues in which the lymph fluid flows and transport lymphocytes. It is lined with endothelial cells and anchored by anchoring filaments. Interstitial fluid flows through the endothelial cells and into the lymph
• Lymph nodes: a tissue filter organs. Lymphocytes enter the nodes in lymph fluids through the afferent lymphatic vessels or in blood which circulated through small vessels within the node called post-capillary venules. Lymphocytes can traverse these venules but RBC can not. Lymphocytes can leave the node via the efferent lymphatic system which empties into the blood streams at the thoracic duct
- Structures: the spleen has an outer cortex scattered with primary lymphoid follicles containing mostly B-cells, a paracortical area between cortex and medulla filled with T-lymphocytes, and a medullary cords located closely to the medulla sinus containing macrophages and plasma cells.
- Germinal centre: regions at the center of the primary follicles in which lymphocytes are actively differentiating and proliferating.
• Spleen: a blood immune organ that filters out antigens in the blood. Blood vessels such as arterioles are located within the white pulps which are surrounded by red pulps.
- White pulp: section of the spleen that is concentrated with lymphocytes. A peri-arteriolar lymphocyte sheath circulating the margin of the white pulps separates it into an inner zone of T and B lymphocytes and an outer rim called marginal zone filled with macrophages.
- Red pulp: the matrix of the spleen filled with red blood cells.
• Peyer’s patches: one of the Gut-Associated Lymphoid Tissue organs in the gut (mostly in the small intestine) located between the gut lumen and the gut wall. It functions as a lymph node in the gut to defend against pathogens of the gut. They are interconnected with the lymph systems and freely receive blood and lymph.
- Structure: a circular follicle of B cell area with a central germinal area. On either side of the germinal centers are T cell patches.
• Flow of lymph: lymph follows through the lymph vessels passively by other mechanism such as the contraction of the muscles. Valves located in the vessels helps to prevent backflow of fluids.
- Blocking of the lymph vessel by infections such as microfilaria parasitic worm causes intense swelling of the affected area such as the leg.
• Blood cells development: all blood cells are derived from the stems cells of long bone marrows. Cells are erthyrocytes
- Lymphocytes develop from pluripotent haemopoietic stem cells, which give rise to all of the blood cells, white blood cells and platelets regulated by factors such as cells surfaces molecules, cytokines and hormones.
- B cells mature in the bones marrows which are then exported through the bloodstreams to other lymphoid organs.
- Other stem progeny migrate from the bone marrow via blood to the thymus where T lymphocytes are made. These are then exported to other lymphoid tissues.
• Circulatory paths: continuous circulation of the lymphocytes ensures contact with the antigens ns severs to disperse the activated lymphocytes through the body’s lymphoid tissues. Circulation is increased with immune response.
- Both the T and B lymphocytes reside in the lymphoid organs but at any times 10% are circulating the body through the lymph and blood. They are capable of leaving the blood by squeezing through the capillaries at areas called high endothelial venules to enter tissues and lymph nodes.
- They accumulate in small lymphatic vessels after draining from a tissue which is connected to a series of lymph nodes downstream. Passing into progressively larger vessels, the lymphocytes eventually enter the main lymphatic vessel (the thoracic duct) which carries them back to the blood.

Antibodies in Immunity:

• Interaction of antigen with immune system:
- Antigen entrance into the cells is detected and phagocytosed by much of the non-specific phagocytic cells such as the neutrophils. However presence of special APC macrophages will also engulf the antigen.
- Degraded antigens are presented on the cell surfaces of the APC with special structures called MHC proteins (Major Histocompatibility Complex). The cells leave the skin and enter the lymphatics systems.
- Antigen presenting cells enter the lymph nodes to becomes dendritic cells
- T cells with different antigen residing in the paracortically cluster around them and those with receptors specific for the antigen becomes stimulated and produce response.
• Response of the immune system to invasion: method of response depends on the natures of the substances and route entry i.e. non-infectious agent will be treated differently to infectious agents, and viruses infecting intracellularly will differ from extracellular bacteria and parasites.
• Lymphocytes subpopulation: subtypes of lymphocytes depending on their functions. Effector cells are involved in recognizing, responding and disposing of antigenic substances while regulator cells are involved in the control of the effector cells.
- B-lymphocytes: antibody producing cells.
- Antigen-specific cytotoxicity cells: CD8 T-lymphocytes involved in killing virus or tumour cells
- K-cells: antigen-dependent , cell mediated cytotoxicity
- NK cells: natural killer cells
- Helper T lymphocytes: stimulate and mediate the immune response, e.g. stimulate B-cells to differentiate and replicate.
• Lymphocytes activation:
- T-lymphocytes activation: T cell receptors locate on the surface of the T cells can only recognize short peptide antigens of 8 -20 amino acid long and activated by antigen presented by an APC.
- B-lymphocytes activation: activated by T-helper cells when the T-cell presents the antigen that corresponding to the B-cells surface immunoglobulin receptors.
• Primary and Secondary antibody response:
- Primary response: when the immune systems respond to an antigen that has not previously encountered. There is usually a lag period of few days before the antibodies which specific for that antigen is made by the body. In the absence of the antigen, the primary response gradually degrades.
- Secondary response: when the immune respond to the same antigen later in its life in which the body is already adapted with the memory cells for the antigen so the response is much more rapid and vigorous.
• Antibodies: immunoglobin proteins of the blood. All antibodies have a similar structure but the molecules is able to recognize a wide ranges of different antigens.
- Structures: four polypeptides chains forming a Y shape macromolecules which are held together by disulphide bonds and non-covalent interactions.
- Fab region: The end of the 2 heavy chains and 2 inner light chains form to the variable section with a hypervariable region that binds on to antigens and constant region just above the hinge area.
- Fc region: comprised of only the tail end of the 2 heavy chains divided into two constant regions of CH3 and CH2 with CH2 located just below the hinge region and function as a complement binding region
• B-cell proliferation
- Antigen in the secondary lymphoid organs select and become bounded with sufficient affinity by corresponding surface immunoglobin protein of certain antigen-selective B-lymphocyte to overcome the activation threshold. To reinforce the process, T-helper cell that also correspond to the same antigen secrete signal molecules and the B-cell differentiates into memory and plasma cells and replicates.
- Plasma cells are specialized to produce antibodies of the same antigen-binding specificity as was presented earlier by their precursor.
- Memory cells are specialized to mediate in a secondary response
• Function of antibodies:
- Direct neutralization: binding of the surface protein of the pathogen to directly inhibit the function of that protein, e.g. virus attaching proteins blocked so it can’t attach to host cell
- Opsonisation: binding of the antibody provides receptivity for the phagocytic cells Fc receptors and C3b (enhance recognition) allowing increase the efficiency of phagocytosis.
- Antibody-dependent cell-mediated cytotoxicity: this applies to populations of the lymphocytes that are not B or T types referred to as K-cells. Theses cells also have Fc receptors and C3b receptors on their surfaces and are thus able to recognize and bind to antibody-coated or C3b-coated foreign antigenic material. K cells functions by releasing short range cytotoxicity to kill cell material.
- Complement activation: initiate the enzymatic cascade of complement system
• Complement activation:
- Classic pathway: the antigen-antibody complex is recognized and bound by the first/early complement component (e.g. C1) at the CH2 region which becomes activated and through a series of complement cleaving and cascade activate C3-convertase. The C3-convertase cleaves protein C3 to produce C3a and C3b in which C3a are chemotaxic factors for phagocytics cells and increase vessel permeability and C3b used for opsonization
- Alternative pathway: activation of further C3-convertase stimulated by the hydrolysis of the first sets C3 proteins or pathogenic antigen thus does not require antibody presence. Aims to amplify complement signal and produce more C3a and C3b.
- Later complement: the main focus of complement system. C3b cleaves and activate further complement factors, e.g. C5, C6 etc which can form membrane pore complex and insert into the bacteria membrane causing it to lyse.

T Cells in Immunity:

• Comparison humoral to cell-mediated immunity:
- Humoral immunity: focuses on antibody production with the proliferation of B-cells and is effective against antigens arising outside the cell, e.g. viruses, toxins, extracellular bacteria
- Cell-mediated immunity: focuses on the production of cytotoxic T-cells that effective against antigens arising inside cells such as virus infected cells, tumour cells, transplanted organs.
• Types of T-cells: both types of the T cells expresses the T cell receptors for antigen which recognize antigenic peptide fragments only when presented to them by MHC structures (HLA). And both cells also have the CD3 marker.
- Cytotoxic T cells: has a unique CD8 protein on the surface of the cell that interact with class I MHC determinants. These are able to kill cells when recognizing pathogenic proteins on the membrane.
- T-helper cells: has a unique CD4 on the surface of the cells and interacts with class II MHC determinants. These cells produce cytokines that assist other cells to respond.
• MHC (major histocompatibility complex) gene: genes that codes for the structures on the surface of cells which present antigens to T lymphocytes. They can be divided into two loci - class I and class II.
- Each locus has maternal and paternal version and are co-dominantly expressed.
- Genes are polymorphic so very difficult to find identical HLA.
- Class I MHC is presented in all cells that have a nucleus while class II MHC is only located in B lymphocytes and antigen presenting cells.
- Class I MHC presents intracellular peptides (e,g. viral) to the CD8 cytotoxicity cells) while class MHC II presents degraded antigenic peptides to CD4 helper cells.
• Process of antigen presentation:
- MHC class I: peptides originates intracellularly usually derived from an infectious process such as virus infection or as a result of normal breakdown of normal cell metabolic products. Infections usually creates virus-specified material by replication and these can be broken down within the cells and fragment appear on the surface presented by Class I MHC structures so cytotoxic cells destroy the cells by sending necrotic or apoptotic signals.
- MHC class II: antigenic materials can be taken up by antigen-presenting cells broken down into small fragments within the cell and then peptides is presented on the surface by class II MHC structures to helper T lymphocytes.
• Activation of Cytotoxic T cells:
- When cytotoxic T cells precursors are presented with antigens by the virus infected cells it will bind strongly to the antigen and become activated. Cytokine receptors will be expressed on the surfaces of the cell.
- With the aid of the helper T cell’s cytokine signal, these cells will differentiate into populations of effectors cells which can recognize specific target and kill them and memory cells that are longer lived and mediate secondary response (requires only a lower concentration of antigen to be activated)
• Activation of T helper cells:
- Very similar manner to that of the cytotoxic T cell and the B cells when interacting with the antigen presented by the class MHC II.
- Forms effector cells that secretes cytokines and memory cells
• Cytokines: low molecular weight glycoproteins secreted by CD4 T cells and other cells that have the paracrine functions of regulating immune and inflammatory responses e.g. amplitude, duration and quality.
- Often called interleukin as they are provide signaling between leukocytes and produced transiently and locally.
- Different cytokines can have multiple actions and overlapping effect depending on concentration, presence of other cytokines, cell type responding, history of the cell.
- Some cytokines are also produced by cells other than the blood cell lineages and also affect non-immune (e.g. nervous systems) cellular and system behaviors, e.g. fever response such as loss of appetite, rise in temperature, pain sensitivity.
• Problems of immunity:
- Over-reactive immunity to innocuous substances: strong antibody responses of a particular class (IgE antibodies) against relatively innocuous substances such as grass pollens or dust components. This is called allergy such as hay fever or asthma
- Immune-mediated tissue damage: excessive immune response to an infection can cause pathological damage to the host tissues. E.g. hepatitis B virus leads to liver damage through cytotoxic T lymphocyte attacking and killing virus-infected liver cells. Antigen-antibody complexes are produces in such high concentrations that they lodge in small vessels and cause vascular damage.
- Immune destruction by infectious agents: helper T lymphocytes are central to immune response. The HIV infects CD4 T cells and causes them to become targets for cytotoxic T cells. This can compromise the immune systems producing AIDS
• Autoimmunity: when the immunity system react to the body as if they are foreign pathogens, i.e. loss of self and non-self distinction. Usually occurs after an infection of an agents whose antigens are similar to that of the body, e.g. streptococcal antigen is similar to that of the heart antigens so immune response to the streptococcus will damage the heart valves and produce rheumatic heart disease.
- Hashimoto’s thyroiditis: immune systems make antibodies and cytotoxic T cells against thyroid antigens and damage or destroy the patient’s thyroid gland, leading to loss of thyroid hormones.
- Pernicious anemia: immune system-mediated damages to the parietal cells of the stomach compromise the ability of patients to absorb vitamin B12.
- Systemic Lupus Erythematosus: antibodies are made against DNA and other antigens from the nucleus of cells. Can cause damage to tissue throughout the body, particularly the kidney and joints and skin.

Unless otherwise stated, the content of this page is licensed under Creative Commons Attribution-ShareAlike 3.0 License