MMI 188
Medical Microbiology and Immunology
School of Medicine
HUMAN
IMMUNOLOGY
Spring Quarter 2020
CRN: 73239 Online
Instructor:
José V. Torres, PhD
Professor
Medical Microbiology and Immunology
School of Medicine
3226 Tupper Hall
(530) 752-3157
jvtorres@ucdavis.edu
Educator, Scientist, Tortoise Conservationist, Biotechnology Entrepreneur
Teaching Assistant:
Alicia Werner
awerner@ucdavis.edu
Molecular, Cellular and Integrative Physiology Graduate Group
Office Hours by Zoom:
Fridays from 4-6 PM
Wednesdays from 4-6 PM on the week before each exam (April 15, May 13 and June 3)
Elements of the Immune System and their
Roles in Defense
Based on:
Chapter 1 of the Parham Textbook (4th Edition)
MMI 188
Human Immunology
José V. Torres, PhD
Professor
Medical Microbiology & Immunology
School of Medicine
University of California
Davis, CA 95616
jvtorres@ucdavis.edu
Elements of the Immune System and Their
Roles in Defense
Learning Objectives for this Lecture:
Ø Understand the purpose of the immune system
Ø Learn how the body discriminates between self
and non-self
Ø Learn the differences between commensal and
pathogenic organisms
Ø Recognize the main elements of the humoral and
cellular immune responses
Ø Become familiar with specialized lymphoid tissues
Ø Learn the main differences between innate and
adaptive immunity
The purpose of the immune system
To defend the body against foreign invaders by:
ØRecognition of foreign organisms
ØPrevention of spread of pathogens
ØClearing invaders from body
ØHelping with the healing process
To keep you alive!
Introduction to Immunology
Important concepts and distinctions:
ØDiscrimination between self and non-self
ØAntigens versus immunogens
ØHumoral versus cell-mediated immunity
ØInnate versus adaptive immunity
ØGeneration of diversity and clonal selection
Discrimination between self and non-self
Ø Discrimination between self and non-self is
fundamental to survival.
Ø Clones of cells which have the capacity to recognize
self antigens are eliminated early in development.
Ø Tumor cells can be destroyed by immune
processes if they express antigens that are not
present on normal cells (tumor antigens).
Ø The magnitude of the immune response against an
antigen is proportional to the difference between its
structure and that of host antigens.
Antigen versus Immunogen
Antigen is the target of an adaptive immune response
Immunogen induces an adaptive immune response
How to make a small antigen more immunogenic?
-Conjugate it to a big foreign protein
Cell-mediated immune response to the carrier helps in the
induction of a humoral immune response to the hapten.
Humoral versus Cell-mediated Immunity
Adaptive immune response consists of two major branches:
• Humoral immunity: antibodies and associated accessory
systems
• Cell-mediated immunity: T lymphocytes and associated
accessory systems
Ø B lymphocytes secrete antibodies so are under
humoral.
Ø Some components of the innate immune response such
as complement and cytokines may also be involved in
both branches of the adaptive immune response.
Ø The major difference is whether the antigen specificity is
primarily determined by antibodies or T lymphocytes.
Success of Vaccination
Ø Best and more economical
solution to reduce infectious
diseases
Ø Protects against disease and not
against infection
Ø A vaccine induces memory that is
boosted by infection
Ø Reduced vaccination causes
increased susceptibility for
everyone!
Commensals are beneficial organisms
that inhabit the healthy human body
Ø Over 500 microbial species live in the healthy adult
human gut
Ø The community of microbial species that inhabits a specific
niche in the body is called the commensal flora
Ø Commensal organisms enhance human nutrition by
digesting food elements and making several vitamins
Ø They also protect against disease by competing with
pathogens for space
Ø E. coli (a commensal) secretes colicins, compounds that
inactivate other bacteria
Ø Eradication of commensals can have serious
consequences (colonization by pathogens)
Antibiotics kill beneficial bacteria
Example: Clostridium difficile – toxin – diarrhea – colitis – death
Time to appreciate
the extensive
diversity of human
pathogens…
Pathogen: an organism with the potential to cause disease
Opportunistic Pathogen: can colonize the body without ill effects but
can cause illness in the wrong tissue or when defenses are weak
lombrices
Innate immunity involves:
Ø
physical barriers
Ø
nonspecific responses to foreign invaders
Innate Immune System
Nonspecific recognition of pathogen followed by destruction
Example: the complement system
Innate Immunity: inflammation
Cells of the immune system appear in tissue during inflammation
Innate versus Adaptive Immunity
Recognition mechanisms
Innate
Adaptive
Adaptive Immunity
Based on Clonal Selection:
ØActivation of lymphocytes by a
pathogen
• Specific clones develop before antigen
exposure
• Self-reactive cells are deleted
• Cells that recognize foreign antigens
remain and are expanded and differentiate
following exposure
• Immunological memory – faster and
stronger second reaction to pathogens
Relative importance of innate and adaptive immunity
Innate immunity is required for survival.
We can survive even if some elements of the adaptive
immunity are defective.
Cells of the immune system
B cells – become Plasma cells that secrete antibodies
T cells – helper and cytotoxic
Dendritic cells:
ØIn tissues act as cellular messengers that call up an adaptive immune
response when needed.
ØMigrate from tissues to lymphoid organs to deliver antigens from
pathogens. They are antigen-presenting cells (APC).
Neutrophil – phagocytic, small, short life, white pus
Macrophage – phagocytic, large, long life
Ø first to detect infection
Ø secretes cytokines that recruit neutrophils and other leukocytes
Ø Antigen presenting cell (APC)
Eosinophil – parasite killer.
Ø In allergy, activated eosinophils secrete enzymes that damage the
respiratory epithelium.
Ø They also release active oxygen that injures cells.
Parasite control trio (mast cell, eosinophil, basophil) now associated with allergy.
Megakaryocyte – platelet producer (to stop bleeding)
Hematopoiesis
The generation of cellular elements of blood:
-Red blood cells
-White blood cells
-Platelets
The site of hematopoiesis
changes during human
development
Cells of the immune system arise from a common hematopoietic stem cell.
Hematopoietic stem cells divide for self-renewal.
Relative abundance of white blood cells in human
peripheral blood
Neutrophils are the most abundant white blood cells
Bacterial receptors on macrophages:
Bacterial binding induces:
Ø engulfment for degradation (phagocytic receptors)
Ø production of inflammatory cytokines (signaling receptors)
Structure of B and T cell Receptors and Antibodies
Ø No secreted form for the T cell receptor
Neutralization and Opsonization by Antibodies
Mechanisms by which antibodies fight
infection.
Neutralization: When antibodies bind
to a bacterial toxin and neutralize its
toxic activity by preventing the toxin
from interacting with its receptor on
human cells.
Opsonization: When a bacterium is
coated with IgG antibodies the
constant regions point outward and
can bind to receptors on a
macrophage, which then ingests and
degrades the bacterium.
Major sites of lymphoid tissues within the human body
Primary lymphoid
tissues:
Ø Bone marrow
Ø Thymus
Secondary lymphoid
tissues:
Ø Spleen
Ø Lymph nodes
Lymphocytes travel in the blood and lymph
Left subclavian vein:
Ø lymph returns to blood
Lymphocytes that encounter
pathogens in lymph nodes stop
circulating.
Lymph contains fluid that leaks from blood vessels.
It transports cells and proteins associated with the immune system.
The draining lymph nodes serve as specialized meeting
places for circulating lymphocytes and pathogens
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1
3
2
Lymph nodes are highly organized and dynamic structures
that optimize interactions of lymphocytes and pathogens
Activation of adaptive immunity in a draining lymph node
During an infection, lymphocytes proliferate in lymph nodes,
resulting in swollen or enlarged lymph nodes.
Ø Pathogens, pathogen components, and dendritic cells carrying
pathogens and molecules derived from them arrive in the afferent lymph
draining the site of infection.
Ø The dendritic cells specifically stimulate the division and
differentiation of pathogen-specific small lymphocytes (green) into
effector lymphocytes (blue).
Ø Some helper T cells and cytotoxic T cells leave in the efferent lymph
and travel to the infected tissue via the lymph and blood.
Ø Other helper T cells remain in the lymph node and stimulate the
division and differentiation of pathogen-specific B cells into plasma
cells (yellow).
Ø Plasma cells move to the medulla of the lymph node, where they
secrete pathogen-specific antibodies, which are taken to the site of
infection by the efferent lymph and subsequently the blood.
Ø Some plasma cells leave the lymph node and travel via the efferent
lymph and the blood to the bone marrow, where they continue to secrete
antibodies.
Green: Pathogen-specific small lymphocytes
Blue: Effector lymphocytes
Spleen: has aggregations of lymphocytes similar to those in lymph nodes
The red pulp is where old or
damaged red cells are removed
from the circulation.
The white pulp is secondary
lymphoid tissue, in which
lymphocyte responses to bloodborne pathogens are made.
Lymphoid follicle
Much of the secondary lymphoid tissue is associated with the gut
ØRegions of organized GALT such as Peyer’s patches
You Should Now Be Familiar With:
1) How and why the body distinguishes self from nonself
2) The difference between commensal and pathogenic
organisms
3) The differences between humoral and cellular
immune responses
4) The main differences between innate and adaptive
immunity
5) The major lymphoid tissues of the body
6) The major types of cells involved with innate and
adaptive immunity