The document discusses the adaptive immune system, specifically T cells and B cells. It describes how T cells mature in the thymus through positive and negative selection. It also explains the functions of CD4+ T cells, CD8+ T cells, and memory T cells. Regarding B cells, it summarizes their development in the bone marrow, maturation upon antigen exposure, and role in producing antibodies. The document also briefly discusses immune cell interactions and regulation of responses.
Slideshow is from the University of Michigan Medical
School's M1 Immunology sequence
View additional course materials on Open.Michigan:
openmi.ch/med-M1Immunology
this is a presentation on B lymphocytes and there role in humoral immune response . Dr Harshavardhan Patwal highlights on antibodies and B cell activation to name a few.
Slideshow is from the University of Michigan Medical
School's M1 Immunology sequence
View additional course materials on Open.Michigan:
openmi.ch/med-M1Immunology
this is a presentation on B lymphocytes and there role in humoral immune response . Dr Harshavardhan Patwal highlights on antibodies and B cell activation to name a few.
An accomplished entrepreneur-advisor and innovative tactician, New York resident Richard DiVenuto has served as a consultant to multiple organizations in the finance, biotechnology, and nutraceutical sectors across states and cities including Boston, Massachusetts, Florida, and California. Richard DiVenuto supports research into allogeneic Chimeric Antigen Receptor (CAR) T cells, which can involve the use of virus-specific memory T cells.
T cells helping the body fight infection. Memory T cells develop in response to specific foreign substances and remain in the body after healing. These cells can differentiate into multiple effector T cells when the body gets re-exposed to an infection. Effector T cells attack the foreign invaders. Due to these special functionalities, T cells are an important focus of multiple vaccines and cancer therapy research avenues.
Here are three common subtypes of T cells:
Naive T cells: Occurring in continuous circulation between the blood and secondary lymphoid organs, Naive T cells feature unique surface proteins that respond to various external signals, including those from foreign invaders.
Central memory T cells: While these cells have a high capacity to self-renew, they change over to effector cells poorly.
Effector memory T cells: Found in non-lymphoid peripheral tissues, such as the lung and liver, effector memory T cells play an important role in fighting viral, bacterial, and parasitic infections.
Describes the basic properties and mechanisms of T cells and B cells in maintaining Immune Response against foreign antigens or infections and covers the UG and PG portion of immunology.
Lymphocytic cells involved in human immune systemAbhay jha
This slide share was basically based on the immune system of human regarding the cellular activity involve to save human body against any pathogenic attack and we are talking about the lymphatic cells wich are T cells B cells natural kills T cell (NKT) innate lymphatic cells and their functions in our body.
T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response and are distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their cell surface.
B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system.. B cells produce antibody molecules.
In mammals, B cells mature in the bone marrow, which is at the core of most bones. In birds, B cells mature in the bursa of Fabricus.
B cells present antigens (they are also classified as professional antigen-presenting cells (APCs)) and secrete cytokines.
An accomplished entrepreneur-advisor and innovative tactician, New York resident Richard DiVenuto has served as a consultant to multiple organizations in the finance, biotechnology, and nutraceutical sectors across states and cities including Boston, Massachusetts, Florida, and California. Richard DiVenuto supports research into allogeneic Chimeric Antigen Receptor (CAR) T cells, which can involve the use of virus-specific memory T cells.
T cells helping the body fight infection. Memory T cells develop in response to specific foreign substances and remain in the body after healing. These cells can differentiate into multiple effector T cells when the body gets re-exposed to an infection. Effector T cells attack the foreign invaders. Due to these special functionalities, T cells are an important focus of multiple vaccines and cancer therapy research avenues.
Here are three common subtypes of T cells:
Naive T cells: Occurring in continuous circulation between the blood and secondary lymphoid organs, Naive T cells feature unique surface proteins that respond to various external signals, including those from foreign invaders.
Central memory T cells: While these cells have a high capacity to self-renew, they change over to effector cells poorly.
Effector memory T cells: Found in non-lymphoid peripheral tissues, such as the lung and liver, effector memory T cells play an important role in fighting viral, bacterial, and parasitic infections.
Describes the basic properties and mechanisms of T cells and B cells in maintaining Immune Response against foreign antigens or infections and covers the UG and PG portion of immunology.
Lymphocytic cells involved in human immune systemAbhay jha
This slide share was basically based on the immune system of human regarding the cellular activity involve to save human body against any pathogenic attack and we are talking about the lymphatic cells wich are T cells B cells natural kills T cell (NKT) innate lymphatic cells and their functions in our body.
T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response and are distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their cell surface.
B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system.. B cells produce antibody molecules.
In mammals, B cells mature in the bone marrow, which is at the core of most bones. In birds, B cells mature in the bursa of Fabricus.
B cells present antigens (they are also classified as professional antigen-presenting cells (APCs)) and secrete cytokines.
introduction of adaptive immunity. classification of adaptive immunity, factor affecting it and mechanism of adaptive immunity comparison between adaptive immunity and innate immunity. characteristic of adaptive immunity . cell mediated immune responses immunoglobulins
types of immunoglobulins. functions of immunoglobulins, hypersensitivity reactions
By DR. MANPREET KAUR BEHL.
Description of classificaton of immune system, immune cells, HLA, MHC complexes, antigen presentation, t-cell responses and b-cell responses, antibody, isotype switching, hypersenstivity reactions etc.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
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Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
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TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
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Introduction to immune system
1. Introduction to immune system
Dr R L Khare
Asso. Prof Medicine
Dept of medicine
Pt JNM Medical College raipur
2. THE ADAPTIVE I M M U N E SYSTEM
• Adaptive immunity is characterized by antigen-
specific responses to a foreign antigen or
pathogen.
• immunologic priming
• immunologic memory
• cellular (T cell)and humoral immunity(B cell)
3. T cell
• The pool of effector T cells is established in
the thymus
• maintained throughout life both by new T cell
production
– in the thymus and by antigen -driven expansion of
virgin peripheral T cells into "memory" T cells that
reside in peripheral lymphoid organs.
• The thymus exports -2% of the total number
of thymocytes per day throughout life
4. T cell
• Mature T lymphocytes constitute 70-80% of normal
peripheral blood lymphocytes
– Only 2% of the total-body lymphocytes are contaínd in
peripheral blood
• 90% of thoracic duct lymphocyte
• 30-40% of lymph node cells
• 20-30% of spleen lymphoid cells
• In lymph nodes, T cells occupy deep para-cortical
areas around B cell germinal centers and in the spleen
they are located in peri-arteriolar areas of white pulp
5. T cell
• T cells are the primary effectors of cell-mediated
immunity
• Maturing into CD8+ cytotoxic T cells capable of
lysis of virus-infected or foreign cells (short-lived
effector T cells)
• CD4+ T cells capable of T cell help for CD8+ T cell
and B cell development
• Two populations of long-lived memory T cells are
triggered by infections: effector memory and
central memory T cells
6. T cell
• Effector memory T cells reside in nonlymphoid organs
and respond rapidly to repeated pathogenic infections
with cytokine production and cytotoxic functions to
kill virus-infected cells.
• Central memory T cells home to lymphoid organs
where they replenish long- and short-lived and
effector memory T cells as needed.
• CD4+ T cells are also the primary regulatory cells of T
and B lymphocyte and monocyte function by the
production of cytokines and by direct cell contact
9. T cell function tuning
• positive selection
• negative selection
• As immature cortical thymocytes begin to express
surface TCR for antigen, autoreactive thymocytes are
destroyed (negative selection),
• thymocytes with TCRs capable of interacting with
foreign antigen peptides in the context of self-MHC
antigens are activated and develop to maturity
(positive selection),
• thymocytes with TCRs that are incapable of binding to
self-MHC antigens die of attrition (no selection).
10. • Mature thymocytes that are positively selected are either
CD4+ helper T cells or MHC class II–restricted cytotoxic (killer)
T cells
• CD8+ T cells destined to become MHC class I–restricted
cytotoxic T cells.
• MHC class I– or class II–restricted means that T cells recognize
antigen peptide fragments only when they are presented in
the antigen-recognition site of a class I or class II MHC
molecule
T cell function diffrentiation
11. T cell function diffrentiation
• In general, CD4+ T cells are also the primary
regulatory cells of T and B lymphocyte and monocyte
function by the production of cytokines and by direct
cell contact
• T cells regulate erythroid cell maturation in bone
marrow, and through cell contact (CD40 ligand) have
an important role in activation of B cells and induction
of Ig isotype switching
12. T cell function diffrentiation
• The earliest identifiable T cell precursors in bone marrow
are CD34+ pro-T cells (i.e., cells in which TCR genes are
neither rearranged nor expressed).
• In the thymus, CD34+ T cell precursors begin cytoplasmic
(c) synthesis of components of the CD3 complex of TCR-
associated molecules
• Within T cell precursors, TCR for antigen gene
rearrangement yields two T cell lineages, expressing either
TCR chains αβor TCR γδ chains.
• T cells expressing the TCR chains constitute the majority of
peripheral T cells in blood, lymph node, and spleen and
terminally differentiate into either CD4+ or CD8+ cells
13. T CELL EXHAUSTION IN VIRAL INFECTIONS AND
CANCER
• In chronic viral infections such as HIV-1, hepatitis C virus, and
hepatitis B virus and in chronic malignancies, the persistence of
antigen disrupts memory T cell function, resulting in defects in
memory T cell responses.
• This has been defined as T cell exhaustion and is associated with T
cell programmed cell death protein 1 (PD-1) (CD279) expression.
• Exhausted T cells have compromised proliferation and lose the
ability to produce effector molecules, like IL-2, TNF-α, and IFN-γ.
• PD-1 downregulates T cell responses and is associated with T cell
exhaustion and disease progression.
• For this reason, inhibition of T cell PD-1 activity to enhance effector
T cell function is being explored as a target for immunotherapy in
both viral infections and certain malignancies.
14. B cell
• Mature B cells constitute 10–15% of human peripheral blood
lymphocytes, 20–30% of lymph node cells, 50% of splenic
lymphocytes, and ~10% of bone marrow lymphocytes.
• B cells express on their surface intramembrane immunoglobulin (Ig)
molecules that function as B cell receptors (BCRs) for antigen in a
complex of Ig-associated and signaling molecules with properties
similar to those described in T cells (Fig. 308-8).
• Unlike T cells, which recognize only processed peptide fragments of
conventional antigens embedded in the notches of MHC class I and
class II antigens of APCs, B cells are capable of recognizing and
proliferating to whole unprocessed native antigens via antigen
binding to B cell surface Ig (sIg) receptors.
15. B cell
• B cells also express surface receptors for the Fc region
of IgG molecules (CD32) as well as receptors for
activated complement components (C3d or CD21, C3b
or CD35).
• The primary function of B cells is to produce
antibodies.
• B cells also serve as APCs and are highly efficient at
antigen processing.
• Their antigen-presenting function is enhanced by a
variety of cytokines
• Mature B cells are derived from bone marrow
precursor cells that arise continuously throughout life
16. B lymphocyte development
• antigen-independent and antigen-dependent phases.
• Antigen-independent B cell development occurs in primary lymphoid
organs and includes all stages of B cell maturation up to the sIg+ mature
B cell.
• Antigen-dependent B cell maturation is driven by the interaction of
antigen with the mature B cell sIg, leading to memory B cell induction, Ig
class switching, and plasma cell formation.
• Antigen-dependent stages of B cell maturation occur in secondary
lymphoid organs, including lymph node, spleen, and gut Peyer's patches.
• In contrast to the T cell repertoire that is generated intrathymically
before contact with foreign antigen, the repertoire of B cells expressing
diverse antigen-reactive sites is modified by further alteration of Ig
genes after stimulation by antigen—a process called somatic mutation—
which occurs in lymph node germinal centers.
17. B cell
• During B cell development, diversity of the antigen-binding
variable region of Ig is generated by an ordered set of Ig gene
rearrangements that are similar to the rearrangements
undergone by TCR α, β, γ, and δ genes.
• The most immature B cell precursors (early pro-B cells) lack
cytoplasmic Ig (cIg) and sIg.
• The large pre-B cell is marked by the acquisition of the surface
pre-BCR composed of μ heavy (H) chains and a pre-B light chain,
termed V pre-B. V pre-B is a surrogate light chain receptor
encoded by the nonrearranged V pre-B and the γ5 light chain
locus (the pre-BCR).
18. B cell
• Pro- and pre-B cells are driven to proliferate and mature by
signals from bone marrow stroma—in particular, IL-7.
• Light chain rearrangement occurs in the small pre-B cell stage
such that the full BCR is expressed at the immature B cell stage.
• Immature B cells have rearranged Ig light chain genes and
express sIgM.
• As immature B cells develop into mature B cells, sIgD is
expressed as well as sIgM.
• At this point, B lineage development in bone marrow is
complete, and B cells exit into the peripheral circulation and
migrate to secondary lymphoid organs to encounter specific
antigens.
19. Editing of B cell
• Random rearrangements of Ig genes occasionally generate
self-reactive antibodies, and mechanisms must be in place
to correct these mistakes.
• One such mechanism is BCR editing, whereby
autoreactive BCRs are mutated to not react with self-
antigens.
• If receptor editing is unsuccessful in eliminating
autoreactive B cells, then autoreactive B cells undergo
negative selection in the bone marrow through induction
of apoptosis after BCR engagement of self-antigen.
20. Somatic Hypermutation
• Antigen-driven B cell activation occurs through the
BCR, and a process known as somatic hypermutation
• IN this point mutations in rearranged H- and L-genes
give rise to mutant sIg molecules, some of which bind
antigen better than the original sIg molecules.
• Somatic hypermutation, therefore, is a process
whereby memory B cells in peripheral lymph organs
have the best binding, or the highest-affinity
antibodies. This overall process of generating the best
antibodies is called affinity maturation of antibody
21. Humoral Mediators of Adaptive Immunity:
Immunoglobulins
• Immunoglobulins are the products of differentiated B cells and
mediate the humoral arm of the immune response.
• The primary functions of antibodies are to bind specifically to
antigen and bring about the inactivation or removal of the
offending toxin, microbe, parasite, or other foreign substance
from the body.
• All immunoglobulins have the basic structure of two heavy and
two light chains
• Immunoglobulin isotype (i.e., G, M, A, D, E) is determined by the
type of Ig heavy chain present. IgG and IgA isotypes can be
divided further into subclasses (G1, G2, G3, G4, and A1, A2)
based on specific antigenic determinants on Ig heavy chains
22. Antibody structure
• 2 identical heavy chains
• 2 identical light chains
• Each heavy chain – has a
constant and a variable
region
• Each light chain has a
constant and a variable
regionH H
L L
ConstantregionVariableregion
24. Antibody: Fab
Fab region
• Variable region of the
antibody
• Tip of the antibody
• Binds the antigen
• Specificity of antigen
binding determined by
VH and VL
25. Antibody: Fc
Fc region
• Constant region
• Base of the antibody
• Can bind cell receptors
and complement
proteins
26. • Antibodies occur in 2 forms
– Soluble Ag: secreted in blood and tissue
– Membrane-bound Ag: found on surface of B-cell, also
known as a B-cell receptor (BCR)
Antibodies exist in two forms
27. CELLULAR INTERACTIONS IN REGULATION OF
NORMAL IMMUNE RESPONSES
• Activated TH1-type helper T cells secrete IL-2, IFN-γ, IL-3,
TNF-a, GM-CSF, and TNF-β
• Activated TH2-type helper T cells secrete IL-3, -4, -5, -6, -10,
and -13. TH1 CD4+ T cells, through elaboration of IFN-γ, have
a central role in mediating intracellular killing by a variety of
pathogens
• TH17 that secrete cytokines IL-17, -22, and -26. TH17 cells
have been shown to play a role in autoimmune
inflammatory disorders in addition to defense against
extracellular bacteria and fungi, particularly at mucosal
surfaces
28. Contd.
• TH9 cells are defined by their secretion of IL-9 and have
been shown to play a role in atopic disease, inflammatory
bowel disease, and in anti-tumor immunity
• the type of T cell response generated in an immune
response is determined by
– the microbe PAMPs presented to the DCs,
– the TLRs on the DCs that become activated,
– the types of DCs that are activated, and
– the cytokines that are produced
29. Contd.
• CD4+ and CD8+ T regulatory cells. These cells express the α
chain of the IL-2 receptor (CD25), produce IL-10, and suppress
both T and B cell responses.
• T regulatory cells are induced by immature DCs and play key
roles in maintaining tolerance to self-antigens.
• Loss of T regulatory cells is the cause of organ-specific
autoimmune disease in mice such as autoimmune thyroiditis,
adrenalitis, and oophoritis
• T regulatory cells also play key roles in controlling the
magnitude and duration of immune responses to microbes
30. Interaction
• T cell–B cell interactions that lead to high-affinity
antibody production require
(1) processing of native antigen by B cells and expression of
peptide fragments on the B cell surface for presentation to
THcells
(2) the ligation of B cells by both the TCR complex and the CD40
ligand
(3) induction of the process termed antibody isotype switching in
antigen-specific B cell clones
(4) induction of the process of affinity maturation of antibody in
the germinal centers of B cell follicles of lymph node and
spleen
31. X-linked hyper-IgM syndrome
• CD40 ligand expression by activated T cells is
critical for induction of B cell antibody isotype
switching and for B cell responsiveness to
cytokines.
• Patients with mutations in T cell CD40 ligand
have B cells that are unable to undergo
isotype switching, resulting in lack of memory
B cell generation and the immunodeficiency
syndrome of X-linked hyper-IgM syndrome
32. IMMUNE TOLERANCE AND AUTOIMMUNITY
• Immune tolerance is defined as the absence of
activation of pathogenic autoreactivity to self-
antigens.
• Autoimmune diseases are syndromes caused by the
activation of T or B cells or both, with no evidence of
other causes such as infections or malignancies.
• Immune tolerance and autoimmunity are present
normally in health; when abnormal, they represent
extremes from the normal state
33. Multifactorial
• Multiple factors contribute to the genesis of
autoimmune disease syndromes, including
• genetic susceptibility (HLAB27 with ankylosing
spondylitis)
• environmental immune stimulants such as drug
(e.g., procainamide and phenytoin [Dilantin] with drug-
induced systemic lupus erythematosus
• infectious agent triggers (such as Epstein-Barr virus and
autoantibody production against red blood cells and
platelets)
• loss of T regulatory cells (leading to thyroiditis,
adrenalitis, and oophoritis)
34. Immunity at Mucosal Surfaces-MALT
• Contains 80% of all immune cells within the body and
constitutes the largest mammalian lymphoid organ
system
(1) to protect the mucous membranes from invasive
pathogens
(2) to prevent uptake of foreign antigens from food,
commensal organisms, and airborne pathogens and
particulate matter
(3) to prevent pathologic immune responses from foreign
antigens if they do cross the mucosal barriers of the body
36. THE CELLULAR AND MOLECULAR CONTROL OF
PROGRAMMED CELL DEATH
• Plays a crucial role in regulating normal immune responses to
antigen.
• A wide variety of stimuli trigger one of several apoptotic
pathways
– to eliminate microbe-infected cells,
– eliminate cells with damaged DNA, or
– eliminate activated immune cells that are no longer needed
• The largest known family of “death receptors” is the TNF receptor
(TNF-R) family
• (TNF-R1, TNF-R2, Fas [CD95], death receptor 3 [DR3], death receptor 4
[DR4; TNF-related apoptosis-including ligand receptor 1, or TRAIL-R1],
and death receptor 5 [DR5, TRAIL-R2]); their ligands are all in the TNF-α
family
37. MECHANISMS OF IMMUNE-MEDIATED DAMAGE TO MICROBES
OR HOST TISSUES
• Five general phases of host defenses:
– (1) migration of leukocytes to sites of antigen localization;
– (2) antigen-nonspecific recognition of pathogens by macrophages
and other cells and systems of the innate immune system;
– (3) specific recognition of foreign antigens mediated by T and B
lymphocytes;
– (4) amplification of the inflammatory response with recruitment of
specific and nonspecific effector cells by complement components,
cytokines, kinins, arachidonic acid metabolites, and mast cell–
basophil products; and
– (5) macrophage, neutrophil, and lymphocyte participation in
destruction of antigen with ultimate removal of antigen particles
by phagocytosis (by macrophages or neutrophils) or by direct
cytotoxic mechanisms
38. CLINICAL EVALUATION OF IMMUNE FUNCTION
• Clinical assessment of immunity requires investigation of the
four major components of the immune system that
participate in host defense and in the pathogenesis of
autoimmune diseases:
• (1) humoral immunity (B cells);
• (2) cell-mediated immunity (T cells, monocytes);
• (3) phagocytic cells of the reticuloendothelial system
(macrophages), as well as polymorphonuclear leukocytes; and
• (4) complement.
39. IMMUNOTHERAPY
• to specifically interrupt pathologic immune responses, leaving
nonpathologic immune responses intact.
• Novel ways to interrupt pathologic immune responses that are
under investigation include the
• use of anti-inflammatory cytokines or
• specific cytokine inhibitors as anti-inflammatory agents,
• the use of monoclonal antibodies against T or B lymphocytes as
therapeutic agents,
• the use of intravenous Ig for certain infections and immune
complex–mediated diseases,
• the use of specific cytokines to reconstitute components of the
immune system, and
• bone marrow transplantation to replace the pathogenic immune
system with a more normal immune system
40. • use of a monoclonal antibody to B cells (rituximab, anti-CD20 MAb) is
approved for the treatment of non-Hodgkin’s lymphoma and,
• in combination with methotrexate, for treatment of adult patients
with severe rheumatoid arthritis resistant to TNF-α inhibitors
• CTLA-4 inhibitors such as Ipilimumab and Tremelimumab and anti-PD-
1 antibodies such as Nivolumab have been shown to reverse CD8 T
cell exhaustion in melanoma and other solid tumors and induce
immune cell control of tumor growth.
• CTLA4 and PD-1 inhibitors are currently being studied in HCV or HIV-1
infection to reverse anti-viral CD8 T cell dysfunction and promote the
reduction of virus infected cells.
• A new technique that engineers autologous T cells to express
antibody receptors that target leukemic cells, termed T cells with
chimeric antigen receptors (T CARs), is currently showing promising
results in clinical trials for the treatment of certain types of leukemias
and lymphomas.
IMMUNOTHERAPY