Chapter 1
Elements of the Immune system and their Roles in Defense
Introduction
Immunology is the study of physiological mechanisms that are used to defend the body from invasion by foreign or infectious agents
In response to diseases caused by infectious agents, the body develops cells dedicated to defense – these form the immune system
Protective immunity takes time to develop, while microorganisms can rapidly multiply and cause disease
Immunity involves two responses, the flexible but specific defenses of the adaptive immune response and the fixed defenses of the innate immune response
Defenses Facing Invading Pathogens
The Ubiquitous Enemy- Microbes
Microbes survive on animal & plant products Release digestive enzymes Grow on living tissues (extracellular) where they are bathed in
nutrients
Other intracellular microbes infect animal/human cells, utilizing host-cell sources
Some microbes are harmless and some even helpful (e.g. E. Coli in our intestines)
Many others cause disease (human pathogens) There is a constant battle between invading microbes and the
immune system
Immunity-The Immune Response
People who survive a specific infection become immune to it – protective immunity
To provide protective immunity, the immune system must first engage the microorganism There is lag time between infection and protection The first infection is the most dangerous one
This understanding led to the concept of immunization or vaccination
Disease is prevented by prior exposure to an attenuated infectious agent
Historical Perspective
Origins of immunology attributed to Edward Jenner
Discovered in 1796 that cowpox “vaccinia”
protected from human smallpox Procedure called vaccination Prevents severe disease by
exposing the immune system to the infectious agent in a form that cannot cause the disease
The Eradication of Smallpox by Vaccination
Vaccination was Initiated in 1796
WHO in 1979 announces eradication of smallpox
What are the risks to the human population should the virus emerge again? Naturally Deliberate act of human
malevolence
The Nature of Pathogens
Any organism with potential to cause disease is a pathogen Opportunistic pathogens cause disease if the body’s
defenses are weakened Constant evolutionary struggle between the host and the
pathogen REPLICATION TIMES favor the PATHOGEN!!!
The Four Kinds of Pathogen that Cause Human Disease
Refer to Figure 1.3: The Diversity of Human Pathogens
Candida albicans-normal inhabitant of the human body, thrush & systemic infections
Staphylococcus aureus-gram positive bacterium that colonizes human skin, pimples & boils (other strains = food poisoning)
Mycobacterium tuberculosis-causes tuberculosis
PseudohyphaeBlastophores (yeast-like cells) Cocci-grape like clusters
Avian Influenza (Bird Flu)• Bird flu or Avian
Influenza, is a contagious disease of animals caused by viruses that normally infect only birds
• By the middle of 2005, some 50 people had died from bird flu
• Virus can mutate to a more contagious form, experts continue to warn of the potential for a full-blown pandemic
Skin and Mucosal Surfaces -Physical Barriers Against Infection
Skin is first line of defense against infection Tough impenetrable barrier Skin continuous with epithelia lining
respiratory gastrointestinal urogenital tracts
The impermeable skin gives way to specialized tissues that are
more vulnerable to microbe attack; Known as mucosal surfaces or mucosae
When skin and mucosal barriers are breached - immune system responds
Skin and Mucosal Surfaces -Physical Barriers Against Infection
Mucosal surfaces are bathed in mucus; thick fluid containing glycoproteins, proteoglycans, and enzymes - protective
Lysozyme in tears and saliva – antibacterial Respiratory tract mucus is continuously removed to clear
unwanted material Stomach, vagina, skin acidic – protective
Secretions at Epithelial Surfaces
Site Source Specific secretions
Eyes Lacrimal glands (tears) Lysozyme, IgA and IgG
Ears Sebaceous glands Waxy secretion- cerumen
Mouth Salivary glands (saliva) Digestive enzymes, lysozyme, IgA, IgG, lactoferrin
Skin Sweat glands (sweat) Lysozyme, high NaCl, short chain fatty acids
Stomach Gastric juices Digestive enzymes (pepsin, rennin), acid (low pH, 1-2)
Secretions from epithelial surfaces at external sites of the body are important
for protection against entry of microbes
Physical Barriers that Separate the Body from its External Environment
Strong barriers to infection provided by the skin, hair, and nails are colored blueMore vulnerable mucosal membranes are colored red
Immune Defense-Innate Versus Adaptive Immunity
Innate immune system Is the first line of defense against infections It works rapidly Gives rise to the acute inflammatory response Has some specificity for microbes
Adaptive immune system Takes longer to develop Is highly specific for antigens, including those associated with
microbes Remembers that it has encountered a microbe previously, (i.e. shows
memory)
Immune Defense-Innate Versus Adaptive Immunity
The innate and adaptive immune systems work together…. through direct cell contact through interactions involving chemical mediators, cytokines and
chemokines
Many of the cells of the innate immune system are the same cells used by the adaptive immune system
Principle Characteristics of Innate and Adaptive Immunity
Immunological Memory
Cells of the Immune System
Lymphoid cells – 20-40% of white blood cells There are 1011 lymphocytes in the human body Mononuclear phagocytes – monocytes that circulate in the blood and
macrophages found in tissues Granulocytic cells, classified as neutrophils, eosinophils and basophils
based on morphology and cytoplasmic staining characteristics Dendritic cells, whose main function is the presentation of antigen to T
cells
Hematopoiesis
The generation of the cellular elements of blood, including: Red blood cells (RBC) White blood cells (WBC) or leukocytes Platelets
These cells originate from pluripotent hematopoietic stem cells (HSC) whose progeny differentiate and divide under the influence of various hematopoietic growth factors
HSC give rise to other cells in a process called self-renewal, becoming more mature stem cells that commit to different lineages
The pluripotent stem cell divides and differentiates into more specialized progenitor cells that give rise to the
lymphoid lineagemyeloid lineage erythroid lineage
Types of Hematopoietic Cells
The pluripotent stem cell divides and differentiates into more specialized progenitor cells that give rise to the
lymphoid lineagemyeloid lineage erythroid lineage
Types of Hematopoietic Cells
The pluripotent stem cell divides and differentiates into more specialized progenitor cells that give rise to the
lymphoid lineagemyeloid lineage erythroid lineage
Types of Hematopoietic Cells
Abundance of Leukocytes in Blood
Most abundant leukocytes are the neutrophils, followed by lymphocytes
Leukocyte Versus Lymphocyte
Leukocytes- a general term for a white blood cell Lymphocytes, granulocytes and monocytes are all leukocytes
Lymphocytes- a class of white blood cells that consist of small and large lymphocytes, two classes Small lymphocyte-
B lymphocytes (B cells) and T lymphocytes (T cells)
Large granular lymphocytes are natural killer (NK) cells, lymphocytes of innate immunity
Figure 1-9 part 1 of 6
Lymphoid Cells
Lymphocytes are divided into three classes, B cells, T cells and natural killer cells (NK cells)
Naïve lymphocytes or small lymphocytes are resting cells that have not interacted with antigen
Lymphoblasts are lymphocytes that have interacted with antigen and proliferate
Lymphoblasts eventually differentiate into effector cells or into memory cells
Effector cells eliminate antigen – plasma B cells that secrete antibody, cytokine-producing T helper cells (TH) and T cytotoxic cells (TC)
Figure 1-9 part 2 of 6
Natural Killer Cells
NK cells (large granular lymphocytes) are found throughout the tissues of the body but mainly in the circulation
Constitute 5-10% of lymphocytes in human blood Contain cytotoxic substances which are important for
protection against viruses and some tumors Secrete cytokines which prevent viral replication and helps to
activate T cell mediated immunity
Neutrophils
Effectors of innate immunity – specialized in the capture, engulfment and killing of microbes
Work in the anaerobic conditions found in damaged tissue Are short-lived and die at site of infection Are phagocytic cells with that contain toxic substances in
intracellular granuales Employ oxygen-dependent and oxygen-independent
pathways to destroy pathogens
Figure 1-9 part 5 of 6
Mononuclear Phagocytes
Granulocyte-monocyte progenitors in the bone marrow differentiate into pro-monocytes, which enter the blood, where these differentiate into monocytes
Monocytes circulate on the blood for about 8 hours, then migrate into tissues and become tissue specific macrophages or dendritic cells
Mononuclear Phagocytes
Differentiation of monocyte into macrophage requires changes
Cells enlarge 5-10 times; increased intracellular organelles, increased phagocytic ability; production of hydrolytic enzymes; secretion of soluble factors
There are tissue specific “fixed” macrophages and “free” macrophages
Figure 1-9 part 4 of 6
Dendritic Cells
Dendritic cells are so called because of their many surface membrane folds, similar in appearance to dendrites of the nervous system
These folds allow maximum interaction with other cells of the immune system
There are three main kinds of dendritic cells which are found in skin and in T cell and B cell areas of lymphoid tissue: Langerhans cells (LH) Interdigitating cells (IDC) Follicular dendritic cells (FDC)
Dendritic Cells (cont.)
Most dendritic cells possess high levels of surface MHC class II molecules process and present peptide antigens to T cells Their role is to recognize microbial antigens through innate receptors
and process and present them to T cells of the adaptive immune system
Follicular dendritic cells hold intact antigens in specialized areas of lymphoid tissues
Mast Cells
Mast cells are found in the skin, connective tissue and mucosal epithelial tissue of the respiratory and digestive tracts
The origin of mast cells is uncertain but precursors differentiate in the bone marrow and mature in tissues
When activated mast cells degranulate releasing pharmacological mediators which cause vasodilation increase vascular permeability and attract leukocytes to the site of degranulation
Figure 1-9 part 3 of 6
Eosinophils
These are granular leukocytes which stain with eosin (red) They are present at low levels in the circulation (2-5% of
blood leukocytes Eosinophils have some phagocytic activity but are primarily
responsible for extracellular killing of large parasites such as worms
They usually bind to an antibody-coated parasite and release the contents of their granules (degranulate) onto the parasite surface
Basophils
Basophils are granulocytes which stain with basic dyes (blue) and are present in very low numbers in the circulation (<0.2% of the granular leukocytes)
Basophils and mast cells are very similar in morphology Both contain and release large characteristic electron-dense
granules in their cytoplasm during allergic reactions Like all the granulocytes, basophils are produced from stem
cells in the bone marrow
Figure 1-9 part 6 of 6
Erythrocytes
Erythrocytes bind to immune complexes composed of antigen and antibody and carry these complexes to the liver where these are cleared are Kupffer cells
Erythrocytes have an important immunological role in clearing immune complexes from the circulation in persistent infections and in some autoimmune diseases
Kupffer cells = phagocytic cells of the liver that line the hepatic sinusoids
Pluripotent Hematopoietic Stem Cells
HSCs are multipotent or pluripotent – able to differentiate in various ways
There are fewer than one HSC per 5 x104 cells in the bone marrow
A normal mouse has 3 x108 bone marrow cells A lethal dose of radiation (x-rays, 950 rads) will kill mice
within 10 days unless they receive a bone marrow transplant from a genetically identical mouse
Infusion of 104-105 donor bone marrow cells will restore the hematopoietic system
HSCs growth is supported by stromal cells, which form the hematopoietic-inducing microenvironment (HIM), consisting of cellular matrix and factors
Figure 1-11The pluripotent stem cell divides and differentiates into more specialized progenitor cells that give rise to the lymphoid lineage, the myeloid lineage and the erythroid lineage
Site Of Hematopoiesis in Humans Changes During Development
The site for hematopoiesis changes with age
In early embryo, blood cells are first produced in the yolk sac and later in the fetal liver
From months 3-7 of fetal life the spleen is the major site of hematopoiesis
As bones develop (4-5 months) hematopoiesis shifts to the bone marrow
In adults hematopoiesis occurs mainly in the bone marrow
Hematopoiesis is active throughout life because blood cells are both vital and short-lived
Innate Immune Response
Innate refers to the fact that mechanisms are determined by the genes a person inherits from their parents
There are many families of receptor proteins expressed by immune cells that recognize pathogens
These receptors recognize chemically diverse ligands – peptides, proteins, glycoproteins, proteoglycans, peptidoglycans, carbohydrates, glycolipids, phospholipids and nucleic acids – produced by pathogens
Key Elements of Innate Immunity
Cells and molecules of the innate immunity identify common classes of pathogen and destroy them
Four key elements of innate immunity Molecules that noncovalently bind to surface macromolecules of
pathogens Molecules that covalently bond to pathogen surfaces, forming ligands
for phagocyte receptors Phagocytic cells that engulf and kill pathogens Cytotoxic cells that kill virus-infected cells
Innate Immune Response
Recognition that the pathogen is present Involves soluble proteins and cell surface receptors that bind
either to the pathogen and its products (ligands) human cells and serum proteins that become altered in the
presence of the pathogen
Recruitment of destructive effector mechanisms that kill and eliminate the pathogen Effector cells that engulf bacteria, kill virus-infected cells or attack
protozoan parasites Complement
serum proteins that help the effector cells by marking pathogens with molecular flags
complement also attack pathogens in their own right
Innate Immune Response-Inflammatory Response
Cells and proteins in damaged tissue “sense” the presence of bacteria Cells produce soluble proteins called cytokines that interact with other
cells to trigger the innate immune response
Overall effect of the innate immune response is to induce a state of inflammation in infected tissue Latin: Calor, dolor, rubor and tumor Heat, pain, redness and swelling
Inflammation is due to the innate immune response not the infection!!!
Inflammation
Cytokines induce the local dilation of blood capillaries
This increases blood flow and causes skin to warm and redden
Vasodilation increases leak of plasma into tissues, causing expansion of local fluid volume leading to swelling and pain
Inflammation
Phagocytosis/Endocytosis
If a microorganism crosses an epithelial barrier and begins to replicate, it is recognized by phagocytes- macrophages and neutrophils
Phagocytes can distinguish surface molecules on microorganims from surface molecules on host cells – called pattern recognition
Ingestion of microorganisms is called phagocytosis A cell’s membrane expands around particles to forms
vesicles called phagosomes Upon phagocytosis, phagocytes produce toxic products that
kill microorganisms, which include nitric oxide, superoxide anion and hydrogen peroxide
Phagocytes- Neutrophils- PMN
The most abundant mobile phagocyte (eating cell) is the neutrophil (polymorphonuclear cell, PMN) Phagocytosis is coupled to release of cytokines and other
inflammatory mediators Cytokines recruit neutrophils and other immune cells
Granular leukocytes comprise the majority of white blood cells Patrol the blood stream in search of invading microbes
Neutrophils are specialized killing machines, short-lived, when they die they produce pus
Eventually mopped up by macrophages
Neutrophils are Mobilized from the Bone Marrow, and Target (home) to Infection Sites
Mononuclear Phagocyte System
Mononuclear phagocyte system System of phagocytes located mainly in the organs and tissues Monocytes are present in the blood stream and settle in the tissues as
macrophages
Macrophage-like cells in the liver – Kupffer cells Macrophage-like cells in the brain – Microglia
Macrophage (pink)
E. Coli (green)
Process of Phagocytosis
Phagocytic process
Several stages Phagocyte attraction to the site of infection Phagocyte contact with the microbe Ingestion (endocytosis) Killing of the ingested microbe by means of oxygen and oxygen-
independent mechanisms
Opsonization Way of making microbes more palatable to the phagocyte Molecules coating a microbe, such as complement or antibody
facilitate contact and ingestion of the microbe
Macrophages are Key Players in the Innate and Adaptive Immune Response
PhagocytosisBacterial Killing
T Cell Activation
Release of Inflammatory Mediators
Macrophages Respond to Pathogens by Using Different Receptors to Stimulate
Phagocytosis & Cytokine Secretion
Bacterium (red) binds to cell-surface receptors of the macrophage (blue) Bacterium is engulfed into an
endocytic vesicle called a phagosome
Fusion of the phagosome with lysosomes forms an acidic vesicle called a phagolysome - Contains toxic molecules and
hydrolytic enzymes that kill the bacterium
Macrophages Respond to Pathogens by Using Different Receptors to Stimulate
Phagocytosis & Cytokine Secretion
Bacterial component binding to a cell-surface receptor sends a signal to the macrophage’s nucleus this initiates the transcription of genes
for inflammatory cytokines
The cytokines are synthesized and secreted into the extracellular space
Cytokine production
activate defense mechanisms including cytokine production
Macrophages Recognize a Array of Patterns, then
Virulence = the disease-
evoking power of a pathogen
Microbe
Macrophage
There are 10 expressed TLR genes in mice
Each recognizes a distinct set of molecular patterns not found in normal vertebrates
TLRs have limited specificity but can recognize a broad range of pathogenic microorganisms
Soluble Proteins also Mediate Innate Immunity
Plasma leaking into tissues brings in plasma proteins, including the mannose-binding protein (MBP) and complement proteins
Complement activation leads to covalent binding of complement proteins to bacterial surfaces
Complement receptors on macrophage cells promote phagocytosis of opsonized bacteria Complement kills bacteria Complement recruits additional phagocytes
Complement
Complement was discovered as a component of normal plasma that augments killing of bacteria by antibodies
Complement can be also be activated early in infection in the absence of antibodies
The Complement System
Serum proteins of the complement system are activated in the presence of a pathogen, forming a bond between complement protein and the pathogen
The attached piece of complement marks the pathogen as dangerous
The soluble complement fragment attracts a phagocytic white blood cell to the site of complement activation
The effector cell (macrophage) has a surface receptor that binds to the complement fragment attached to the pathogen
The receptor and its bound ligand are taken up into the cell by endocytosis, which delivers the pathogen to an intracellular vesicle called a phagosome, where it is destroyed
The Complement System
Mechanisms of Protection
Antigens: Substances that can trigger an immune response – more specifically a substance that the immune system can recognize
Can be proteins, lipids, or sugers Can be found on the surface or secreted by microorganisms Antibodies (immunoglobulins): Proteins molecules
synthesized by cells of immune system that recognize antigens
Adaptive Immunity
Occasionally the infection outruns the innate immune response Innate immunity has a restricted number of receptors to recognize
pathogens
This activates the adaptive immune system The adaptive immune system is mediated by lymphocytes
which expand into effector cells and also persist as memory cells
The adaptive immune system generates a huge diversity of immunoglobulins (Ig) and T cell receptors
Upon infection, only the B cells with specific Ig or T cells with specific receptors are stimulated to proliferate and differentiate into effector cells
Clonal Expansion in the Adaptive Immune System:
Selection of lymphocytes by a
pathogen
Organs of the Immune System
Distinguished by function – primary and secondary lymphoid organs
Thymus and bone marrow are primary organs where maturation of lymphocytes takes place
Lymph nodes, spleen and mucosal-associated tissues are secondary organs which trap antigen and promote lymphocyte maturation
Lymphocytes and Lymphoid Tissues
Lymphocytes are Found in lymphoid tissues Activated in the secondary
lymphoid tissues Arise from stem cells in bone
marrow B cells - mature bone
marrow T cells - mature thymus Primary lymphoid tissues
Bone marrow and thymus Secondary lymphoid tissue
and lymphatics Spleen and lymph nodes
Thymus
Site of T cell development and maturation
T cells in the thymus are called thymocytes
It is a flat,bilobed organ situated above the heart
Function is to generate a diverse repertoire of T cells to protect the body from infections
Bone Marrow
Site of B-cell origin and development B cells proliferate and differentiate by interacting with stromal
cells and cytokines
Lymphatic System
Plasma from blood (interstitial fluid) seeps through to tissues and a portion (lymph) flows into lymphatic capillaries and lymphatic vessels
Antigens are carried to lymph nodes, as are lymphocytes, enabling interactions
Secondary Lymphoid Organs
Meeting place where lymphocytes circulating blood encounter antigens brought from sites of infection
Antigens derived from infections originating in connective tissues (as a result of skin wounds) are carried by the lymphatics to the nearest lymph node
Dendritic cells activated by infection also carry antigens
Circulating Lymphocytes Encounter Lymph-borne Pathogens in
Draining Lymph Nodes
Lymphocytes leave blood and enter lymph nodes where they are activated by pathogens
Pathogens drain from site of infection (example: foot) to LN via afferent lymphatic vessels
Activated lymphocytes stay in LN and divide and differentiate into effector cells, while non-activated cells leave through efferent lymphatics
Lymphocytes recirculate at a rate of 5 X 106 cells/min
Architecture of the Lymph Node
Kidney-shaped; packed with lymphocytes & macrophages through which lymph percolates
Pathogens and dendritic cells carrying pathogens arrive in afferent lymph
Pathogens are degraded and used to stimulate lymphocytes
Lymphocytes arrive at LN in arterial blood; extravasate from capillaries
Lymph is the mixture of extracellular fluid and cells that is carried by the lymphatic system
Architecture of the Lymph Node
In LN, there are discrete sites where B cells and T cells congregate
Effector B cells; plasma cells -secrete antibodies
LN increases in size due to dividing lymphocytes - “swollen glands”
Expansion occurs in lymphoid follicles
As lymphocyte development proceeds, follicle shape changes - germinal center
Lymph is the mixture of extracellular fluid and cells that is carried by the lymphatic system
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Cytotoxic T cells
Helper T cells
B cells
The Spleen
Filter for blood that removes old or damaged cells Site where blood-borne pathogens encounter lymphocytes
The Spleen
White pulp of spleen consists of sheath of lymphocytes called the periarteriolar lymphoid sheath (PALS) surrounding a central arteriole (CA)
T cells are closest to the CA, while B cells are more peripheral, forming a B cell corona
Germinal centers form between the T and B cell zonesThe marginal zone contains differentiated B cells
Mucosal-Associated Lymphoid Tissue (MALT)
Mucosal surfaces lining digestive, respiratory and urogenital tracts are the major sites of entry for pathogens and are defended by MALT
Range from loosely organized clusters of lymphoid cells to well-organized structures – tonsils, appendix
The gut associated lymphoid tissues (GALT) include tonsils, adenoids, appendix and Peyer’s patches that line the gut
Bronchial-associated lymphoid tissues (BALT)
Tonsils Found in three locations Nodular structures of reticular cells and fibers interspersed
with lymphocytes, macrophages, granulocytes and mast cells B cells are organized in follicles surrounded by T cells
A Region of GALT
Pathogens arrive through direct delivery across mucosa mediated
by specialized cells called M cells
Principles of Adaptive Immunity
Receptors that uniquely bind to a pathogen are selected and then amplified
Millions of different immunoglobulins and T cell receptors are made by B and T cells
Each receptor recognizes a different molecular structure
Immunoglobulins and T cell Receptors are Variable Recognition Molecules
Igs expressed on B cells -- bind pathogens Plasma cells (effector B cells) secrete antibodies (Igs) T cell receptors (TCRs) are not secreted Antigen (Ag) is any molecule detected by Ig or TCR; Igs and
TCRs have specificity for Ags Epitope (or antigenic determinant) is that part of the antigen
bound by Ig or TCR
Gene Rearrangement in Immunoglobulin & T-cell Receptors
In the unrearranged DNA there are three alternative ‘red’ segments and three alternative ‘yellow’ segments
A functional gene consists of one red segment joined to one yellow segment
This rearrangement is achieved by a process of ‘cut and paste’ in which the intervening DNA is removed
Gene Rearrangement in Immunoglobulin & T-cell Receptors
Different combinations of red and yellow segments can be brought together
The second red segment is brought together with the third yellow segment (L to R), but other combinations of a red and a yellow segment would have been equally possible
Major histocompatibility complex (MHC) is a cluster of genes on the short arm of human chromosome 6
That encodes a set of polymorphic membrane glycoproteins call the MHC molecules
Which are involved in presenting peptide antigens to T cells
Antigen Presentation
Antigen Processing and Generic Antigen
Presentation to T Cells
MHC class I presents antigens derived from the cytosol; intracellular pathogens like viruses and some bacteria
Most cells can present via MHC class I MHC class II presents peptides derived
from extracellular milieu (environment) by endocytosis and phagocytosis
Antigens are broken down within Ag presenting cells
Assembled into a complex with the MHC
Transported to cell surface Presented to TCR
MHC Class I Antigen Presentation To T Cells
MHC Class I Antigen Presentation to T Cells (cont.)
MHC Class II Antigen Presentation to T Cells
Cell-Mediated Immunity(the Effector Functions of T Cells)
Two main T Cell Classes CD8 T Cells CD4 T Cells
CD8 T cells – cytotoxic; kill virally infected cells CD8 binds MHC class I
Virally Infected Cell
CD8 T Cell
CD4 T Cells
CD4 T cells secrete cytokines that modulate other immune cells
CD4 T binds MHC class II Two classes of CD4 T cells;
TH1 cells mainly activate macrophages TH2 cells chiefly help B cells
Antibody – Based Adaptive Immunity
Antibody – Based Adaptive Immunity Antibody Production
Antibody Specificity
Mechanisms by Which Antibodies Combat Infection
Immunological Memory
Lymphocytes that expand persist, providing long term memory
First time infection results in a primary response Subsequent infections elicit a secondary response This is the basis of vaccination
Comparison of a Primary and Secondary Immune Response
Successful Vaccination Campaigns
Diphtheria, poliomyelitis and measles have been virtually eliminated from the USA
Sub acute sclerosing panencephalitis (SSPE) is a brain disease that is a late consequence of measles
Reduction of measles was paralleled by a reduction in SSPE 15 years later
Because these disease have not been eradicated worldwide, immunization must be maintained in much of the population to prevent disease recurrence
Immunodeficiency: Inherited or Infectious
Mutation in immune function genes leads to immunodeficiency -- different kinds…. Only one aspect of immune response is affected In others, adaptive immunity is completely absent
Leading to devastating vulnerability to all infections
Extreme example of immunodeficiency due to disease is the acquired immune deficiency syndrome (AIDS) Caused by infection with the human immunodeficiency virus (HIV)
The Misguided Immune System
Allergy: IgEs made against innocuous substances (foods, pollen, dust); constant regions bind to mast cells encounter allergen; triggers degranulation
Autoimmune disease: Immune response directed against normal host tissue Examples: autoimmune diabetes and reheumatoid arthritis
Transplantation: Organ transplantation stymied by tissue rejection Tissue rejection caused by extensive polymorphism of MHC class I
and II genes
Adaptive Immune Responses can be both Beneficial & Harmful
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