The humoral response involves B cells interacting with antigens and differentiating into antibody-secreting cells. The cell-mediated response involves various T lymphocyte subpopulations that can kill infected cells or secrete signals to direct other immune cells. Memory is a hallmark of adaptive immunity, allowing faster responses upon reexposure. Innate immunity provides initial defenses while adaptive immunity develops antigen-specific responses over days. Together they provide protective immunity, but can also cause issues if misdirected.

1. Kuby Immunology
EIGHTH EDITION
Lecture PowerPoint
CHAPTER 1
Overview of the Immune System
Copyright © 2019 by W. H. Freeman and Company
Punt • Stranford • Jones • Owen

2. A historical perspective of immunology
• What is immunity?
• Immunity is the state of protection against foreign pathogens
or substances (antigens)
• Latin term immunis, meaning “exempt,” is the source of the English
word immunity
• Observations of immunity go back over 2000 years
• Thucydides, an ancient historian, wrote in 430 BC of a plague in
Athens where those who had recovered could safely nurse the
currently ill

3. A historical perspective of immunology
• Can we generate immunity
without inducing disease?
YES…through vaccination
• Vaccination prepares the immune
system to eradicate an infectious
agent before it causes disease
• Widespread vaccine use has
saved many lives
• Classic examples: rabies vaccine
and eradication of smallpox

4. Table 1-1, Cases of selected infectious disease in the United States before and after the introduction of effective vaccines, Page 4
Disease
ANNUAL CASES/YR:
Prevaccine
CASES IN 2016:
Postvaccine
Reduction (%)
Smallpox 48,164 0 100
Diphtheria 175,885 0 100
Measles 503,282 79^ 99.98
Mumps 152,209 145* 98.90
Pertussis (“whooping cough”) 147,271 964* 99.35
Paralytic polio 16,316 0 100
Rubella (German measles) 47,745 0* 100
Tetanus (“lockjaw”) 1,314 (deaths) 1* (case) 99.92
Invasive Haemophilus
influenzae
20,000 356* 98.22

5. A historical perspective of immunology
• A portion of immunity involves both humoral and cellular
components
• Humoral immunity combats pathogens via antibodies
• Antibodies are produced by B cells
• Antibodies can be transferred between individuals to provide
passive immunity
• Cell-mediated immunity involves primarily T lymphocytes
• These can eradicate pathogens, clear infected self-cells, or aid
other cells in inducing immunity

6. Important concepts for understanding the
mammalian immune response
• Humoral and cell-mediated immunity relies on surface
receptors (B- and T-cell receptors)
• These are randomly generated by gene segment
rearrangements in B and T cells
• B cells that encounter antigen produce the antibody
specificity of their cell membrane immunoglobulin
• T-cell receptors bind specific peptides presented by MHC
molecules

7. The humoral response involves
interaction of B cells with foreign
proteins, called antigens, and their
differentiation into antibody-secreting
cells. The secreted antibody binds to
foreign proteins or infectious agents,
helping to clear them from the body.
The cell-mediated response
involves various subpopulations of T
lymphocytes, which can perform
many functions, including the
secretion of soluble messengers that
help direct other cells of the immune
system and direct killing of infected
cells.

8. Important concepts for understanding the
mammalian immune response
• Pathogens fall into four major categories
• Viruses
• Bacteria
• Fungi
• Parasites
• Immune responses are quickly tailored to the type of
organism involved and depend on the structure of the
pathogen and its location, i.e., intra- or extra-cellular

9. Table 1-3, Major categories of human pathogens, Page 13a
Viruses Rotavirus Poliovirus Poliomyelitis (polio)
Variola virus Smallpox
Human
immunodeficiency virus
AIDS
Measles virus Measles
Influenza virus Influenza
Rhinovirus Common cold
Ebola virus Hemorrhagic fever
Zika Virus Zika fever/virus disease
Bacteria
Mycobacterium
tuberculosis
Mycobacterium
tuberculosis
Tuberculosis
Bordetella pertussis Whooping cough (pertussis)
Vibrio cholerae Cholera
Borrelia burgdorferi Lyme disease
Neisseria gonorrhea Gonorrhea
Haemophilus influenzae Bacterial meningitis & pneumonia

10. Table 1-3, Major categories of human pathogens, Page 13b
Fungi Candida albicans Candida albicans Candidiasis (thrush)
Tinea corporis Ringworm
Cryptococcus neoformans Cryptococcal meningitis
Aspergillus fumigatus Aspergillosis
Blastomyces dermatitidis Blastomycosis
Parasites Filaria Plasmodium species Malaria
Leishmania major Leishmaniasis
Entamoeba histolytica Amoebic colitis
Schistosoma mansoni Schistosomiasis
Wuchereria bancrofti Lymphatic filariasis

11. Important concepts for understanding the
mammalian immune response
• Immune responses rely on recognition molecules
• Germ-line encoded (pattern recognition receptors, PRRs)
• These bind to pathogen-associated molecular patterns
(PAMPs)―generic molecules found on many different types of
pathogens (e.g., peptidoglycan)
• Randomly generated (B- and T-cell receptors)
• These bind to very specific antigens, rather than generic molecules
found on many pathogens

12. • Clonal selection and generation of diversity
• Individual B and T cells each have an individual specificity for a single
antigen
• This is due to each cell having many copies of a receptor on their surface that
only binds to one type of antigen
• When a B or T cell interacts with its specific antigen, it is selected and
becomes activated
• Activation results in a proliferation, producing a large number of clones
• Each clone is reactive against the antigen that initially stimulated the original
lymphocyte
Important concepts for understanding the
mammalian immune response

13. Generation of diversity and clonal selection in T
and B lymphocytes. Maturation of T and B cells, which
occurs in primary lymphoid organs (bone marrow for B
cells and thymus for T cells) in the absence of antigen,
produces cells with a committed antigenic specificity,
each of which expresses many copies of surface
receptor that binds to one particular antigen. Different
clones of B cells (numbered 1, 2, 3, and 4) are
illustrated in this figure. Cells that do not die or become
deleted during this maturation and weeding-out process
move into the circulation of the body and are available
to interact with antigen. There, clonal selection occurs
when one of these cells encounters its cognate or
specific antigen. Clonal proliferation of an antigen-
activated cell (number 2, or pink in this example) leads
to many cells that can engage with and destroy the
antigen, plus memory cells that can be called on during
a subsequent exposure. The B cells secrete antibody, a
soluble form of the receptor, reactive with the activating
antigen. Similar processes take place in the T-
lymphocyte population, resulting in clones of memory T
cells and effector T cells; the latter include activated TH
cells, which secrete cytokines that aid in the further
development of adaptive immunity, and cytotoxic T
lymphocytes (CTLs), which can kill infected host cells.

14. Important concepts for understanding the
mammalian immune response
• Tolerance ensures that the immune system avoids
destroying host tissue
• Many of the random rearrangements used to create B- and
T-cell receptors could be anti-self
• Tolerance helps to keep these anti-self recognition
molecules/cells from circulating in the bloodstream

15. Important concepts for understanding the
mammalian immune response
• In response to pathogens, vertebrate immune systems
use two interconnected systems
• Innate immunity
• Adaptive immunity

16. Table 1-4, Comparison of innate and adaptive immunity, Page 18
Innate Adaptive
Response time Minutes to hours Days
Specificity Limited and fixed Highly diverse; adapts to
improve during the course of
immune response
Response to repeat
infection
Same each time More rapid and effective with
each subsequent exposure
Major components Barriers (e.g., skin);
phagocytes; pattern
recognition molecules
T and B lymphocytes; antigen-
specific receptors; antibodies

17. Important concepts for understanding the
mammalian immune response
• Innate immune responses
• First line of defense
• Fast, but nonspecific
• Uses germ-line–encoded recognition molecules
• Also uses phagocytic cells

18. Important concepts for understanding the
mammalian immune response
• Adaptive immune responses
• Humoral and cell-mediated responses
• Using B and T lymphocytes, respectively
• Slower to develop
• 5–6 days (or more)
• Use randomly generated antigen receptors
• Highly specific to individual antigen molecules

19. Important concepts for understanding the
mammalian immune response
• Innate and adaptive immunity work cooperatively
• Activation of innate immune responses produces signal
molecules (often cytokines)
• These signal molecules stimulate and direct adaptive
immune responses

20. Important concepts for understanding the
mammalian immune response
• Memory is the hallmark of adaptive
immunity
• Primary response is initiated upon
first exposure to an antigen
• Memory lymphocytes are left
behind after antigen is cleared
• A secondary response is initiated
upon second exposure to the same
antigen that stimulates memory
lymphocytes
• Stimulation yields faster, more
significant, better response
• Memory is NOT present in
innate immunity

21. The good, bad, and ugly of the immune
system
• Dysfunctions of immunity―two broad
categories
• Overly active or misdirected immune responses
• Allergies/asthma
• Autoimmune disease (e.g., multiple sclerosis, Crohn’s
disease)
• Immunodeficiency
• Primary (genetic) loss of immune function
• Secondary (acquired) loss of immune function
• Opportunistic infections (e.g., oral thrush) can occur in
people with impaired immune responses

22. The good, bad, and ugly of the immune
system
• Transplanted tissues
• A rare case where we want to AVOID an immune response
(rejection)
• The body’s natural response to foreign tissue is to attack it and destroy it
• Cancer
• A situation where the dangerous cells we want to target are our
own self-cells
• Generally tolerated and hard to generate immunity against

23. The Microbiome
• Commensal organisms that live in and on us that
cause no harm
• Function in metabolic and immune balance called
homeostasis
• Imbalance or dysbiosis leads to immune
overstimulation resulting in inflammation
• Due to dietary changes or environmental factors, e.g., stress

24. The proposed role of the microbiome in regulating
immune, metabolic, and neurologic function. Diet, exercise,
genotype, and environmental factors such as stress and the
body microflora have a significant influence on the composition
of the gut microbiome. In turn, this community of microbes
helps to maintain gut integrity and “tune” the extensive gut
immune system to create systemic homeostasis. Changes in
diet and other lifestyle factors can lead to disruption of this
community, or dysbiosis, resulting in immune imbalances that
feed forward into a state of immune overstimulation (chronic
inflammation, autoimmunity, and allergic disease). This state
results in increased gut permeability and proposed disruptions
to other body systems (metabolic and neurologic) and is
believed to contribute to conditions such as type 2 diabetes,
inflammatory bowel disease, and mood disorders, as well as
others.

25. Summary
• Immunity is a complex subject, broken down into many
different layers and areas
• This is just a quick summary of the basics of the field―there’s
MUCH more to come!
• Understanding how immunity works allows us to
• Exploit it to prevent infections (vaccination).
• Exploit it to treat illness (shutting down autoimmune disease or
ramping up anticancer responses).
• Provide safer organ and tissue transplants.