Chapter 1

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

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)

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

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

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

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

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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