Summary Human and Veterinary Immunology + overview of all cells involved
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Course
Human and Veterinary Immunology (CBI30306)
Institution
Wageningen University (WUR)
Extensive summary of Human and Veterinary Immunology. It includes information of all the lectures and pictures, combined with the provided information in the text book. All processes are explained. It also includes an overview of all the different cell types and components with their function, wher...
Immunology
Main function of the immune system:
1. Protection against infectious microbes (non-self):
a. Intracellular (viruses, some bacteria and parasites)
b. Extracellular (most bacteria and parasites, fungi)
2. Protection against modified cells (self):
a. Cancer/tumor cells or transformed cells
Innate immunity Barrier defence
• Recognition of traits shared by broad range • Skin
of pathogens, using a small set of receptors • Mucous membranes
• Rapid response • Secretions
Internal defence
• Phagocytic cells
• Natural killer cells
• Antimicrobial proteins
• Inflammatory response
Adaptive immunity Humoral response
• Recognition of traits specific to particular • Antibodies defend against infection in body
pathogens, using a vast array of receptors fluids
• Slower response Cell-mediated response
• Cytotoxic cells defend against infection in
body cells
The physiological function of the immune system is defence against infectious microbes or non-
infectious foreign substances and products of damaged cells.
Immune system: A reaction to microbes as well as to molecules that are recognized as foreign, regardless
of the physiologic or pathologic consequence of such a reaction.
Cells and tissue of the immune system
Cells playing key role in innate and adaptive immune responses are phagocytes, dendritic cells, antigen-
specific lymphocytes and leukocytes function in eliminate antigens. These cells are almost all derived
from hematopoietic stem cells (HSC’s) in the bone marrow. The expression of various membrane
proteins is used to distinguish distinct populations of cells in the immune system.
• Most helper T cells express a surface protein called CD4
• Most cytotoxic T lymphocytes express a surface protein called CD8
➔ These are called markers since they identify and discriminate between different cell populations. The
markers have many functions in the cell types in which they are expressed. Whether a marker is
expressed on a cell can be determined by testing if the antibody specific for that marker binds to the
cell. The CD markers are found on all cell types in the body and have important functions in immune
responses as well being the target of therapeutic antibodies used in the treatment of inflammatory
diseases and cancer.
Natural antibodies (NAbs)
Antibodies are present in the circulation of ‘normal’ individuals and are produced without exposure to
pathogens. Antibodies have a low affinity and mainly consist of IgM. They are produced by B1 B cells
which are stimulated by bacteria from the gastrointestinal tract and by marginal zone B cells in the spleen.
Secreted antibodies inhibit continuing B cell activation by forming antigen-antibody complexes that
simultaneously bind to antigen receptors and inhibitory Fcy receptors on antigen-specific B cells. The
,NAbs recognize common molecular patterns (e.g. carbohydrate and (oxidised) lipid molecules) which
are found on bacteria and apoptotic cells.
• Antibodies against the A or B glycolipid blood group antigens are NAbs, and important in
transfusion.
• NAbs can activate the classical complement pathway leading to lysis of target cells.
Phagocytes
• Phagocytes: Cells whose primary function is to ingest and destroy microbes and remove
damaged tissues. Steps of phagocytes in host defence:
1. Recruitment of the cells to the sites of infection;
2. Recognition of and activation by microbes;
3. Ingestion of the microbes by phagocytosis;
4. Destruction of ingested microbes.
Neutrophils (Polymorphonuclear leukcoytes PMNs)
PMNs are produced in the bone marrow and migrate quickly to sites of infection. Their major function
is phagocytosis of microbes.
• Neutrophils: Most abundant population of circulating white blood cells and the principal cell
type in acute inflammatory reactions. Blood neutrophils are produced in the bone marrow, circulates
in the blood and are recruited to sites of inflammation.
• Basophils: Blood granulocytes with many structural and functional similarities to mast
cells.
• Eosinophils: Granulocytes that express cytoplasmic granules containing enzymes that are
harmful to the cell walls of parasites but can also damage host tissue.
Mononuclear phagocytes
The mononuclear phagocyte system includes monocytes, which become macrophages when they migrate
into tissue, and tissue resident macrophages, which are derived mostly from hematopoietic precursors
during foetal life.
• Monocytes: White blood cells produced in the bone marrow. They absorb pathogens during
phagocytosis.
• Macrophages: Are activated to perform their functions by recognizing different microbial
molecules, as well as host molecules produced in response to infections and injury. They can acquire
distinct functional capabilities, depending on the types of activating stimuli they are exposed to.
Macrophages have different functions:
o Ingest microbes during phagocytosis an kill the ingested microbes
o Ingesting necrotic host cells, which is part of the cleaning up process after infection or tissue
injury.
o Activated by microbial substances to secrete several different cytokines that act on endothelial
cells lining the blood vessels, in order to enhance the recruitment of more monocytes and other
leukocytes from the blood into site of infection.
o Serving as antigen-presenting cells, displaying fragments of protein antigens to and activate T
lymphocytes.
o Promote the repair of damaged tissues by stimulating new blood vessel growth and synthesis of
collagen-rich extracellular matrix.
• Mast cells: Bone marrow-derived cells present in the skin and mucosal epithelia, which upon
activation, release many potent inflammatory mediators that defend against parasite infections, or
cause symptoms of allergic diseases.
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,• Dendritic cells (DC’s): DC’s are tissue resident and circulating cells that sense the presence of
microbes and initiate innate immune defence reactions and capture microbial proteins for display to
T cells to initiate adaptive immune responses.
o Classical DC are involved in capturing protein antigens of microbes that enter through epithelia
and presenting the antigens to T cells.
Active and passive immunity
The protective immunity against a microbe may be provided either by the host’s response to the microbe
or by the transfer of antibodies that defend against the microbe.
• Active immunity: The form of immunity that is induced by exposure to a foreign antigen.
• Passive immunity: Gaining immunity whereby antibodies from an immunized individual is
transferred to an individual who has not encountered
the antigen. The individual becomes immune
without being exposed to the antigen.
• Active immunity is conferred by a host response to
a microbe or microbial antigen, whereas passive
immunity is conferred by adoptive transfer of
antibodies or T lymphocytes specific for the
microbe. Both forms of immunity provide resistance
to infection and are specific for microbial antigens,
but only active immune responses generate
immunologic memory.
Innate and adaptive immunity
The defense against microbes is mediated by sequential and coordinated responses which are the innate
and adaptive immunity.
• Innate immunity: Essential for defending against microbes during the first hours of days after
infection, before the adaptive immune responses have developed. It is regulated by a mechanism
which is already present before the infection stars, and facilitates rapid responses to microbes.
• Adaptive immunity: Responses to an infection and adapts to it. It is stimulated by exposure
to infectious agents and increase in magnitude and defensive capabilities with each successive
exposure to a particular microbe. It recognizes and reacts to a large number of antigens. The adaptive
responses are stronger and more specialized compared to the innate responses.
o Antigen: A substance that elicits an immune response by binding to the B or T cell receptor.
Immunity is systemic since lymphocytes and other immune cells have the ability to circulate among
tissues. Even if an immune response is initiated in one sit, it can provide protection at distant site.
• Necessary for vaccination: a vaccination given in the arm is able to protect from infectious in the
whole body.
The immune responses are regulated by a system of positive feedback loops that amplify the reaction
and by control mechanisms that prevent inappropriate or pathologic reactions.
There are two phases of the immune response:
1. Pathogen recognition:
a. Innate: a-specific
b. Adaptive: Pathogen specific
2. Pathogen removal
a. Early response: Innate immunity (hours/days)
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, b. Later response: Lymphocyte generate adaptive immune response and memory
(days/weeks)
The mechanisms of innate immunity provide the initial defense against infections. adaptive immune responses
develop later and require the activation of lymphocytes. The kinetics of the innate and adaptive immune responses
are approximations and may vary in different infections.
Innate Adaptive
Characteristics
Specificity Molecules shared by groups of For microbial and non-microbial
related microbes and molecules antigens
produced by damaged host cells
Diversity Limited: recognition molecules Very large: receptor genes are formed
encoded by inherited genes by somatic recombination of gene
segments in lymphocytes.
Memory None or limited Yes
Nonreactivity to self Yes Yes
Components
Cellular and chemical Skin, mucosal epithelia; Lymphocytes in epithelia; antibodies
barriers antimicrobial molecules secreted at epithelial surface.
Blood proteins Complement, various lectins and Antibodies
agglutinins
Cells Phagocytes, dendritic cells, natural Lymphocytes
killer cells, mast cells, innate
lymphoid cells
Innate immunity
The primary functions of phagocytes is to rapidly identify, ingest and destroy microbes and remove
damaged tissue.
• Macrophages and neutrophilic granulocytes are phagocytes.
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