Microbiology and Immunology Block:

Introduction to the Block and Immunology

January 13, 2020

Bryce Chackerian
 Immunology Objectives

The block covers basic and clinical aspects of Immunology.

The primary objective of the Immunology block is to learn basic concepts
in immunology that can be applied to understanding host responses to
infection and disorders of the immune system.
Students will develop an understanding of the most important principles
governing the function of the human immune system, its cells and organ
systems.
 D2L Brightspace Information
• Syllabus and Objectives/Reading List for individual lectures are
posted under Block Information
 Immunology Course Level Objectives
• Learn the function of the cellular and soluble components of the innate and
adaptive immune systems and their role in protecting individuals from infection by
microbial pathogens.

• Describe the major mechanisms of pathology mediated by the immune system,

including the processes of acute and chronic inflammation, autoimmunity, and
allergy, and the drugs used to control these reactions.

• List the major congenital immunodeficiencies and their associations with

susceptibility to infection.

• Describe the immune mechanisms of graft rejection and the mechanisms of action
of immunosuppressive drugs used to control these reactions.
 Immunology Advice
• If you’re new to Immunology, don’t panic

• Boards and Beyond Videos may be useful

• Take advantage of the books (Abbas & Robbins)

(Reading List pdf on D2L)

Immunology Reference Materials:

• Robbins and Cotran Pathologic Basis of Disease,
https://www.clinicalkey.com/#!/browse/book/3-s2.0-C20110055734
• Basic Immunology, https://www.clinicalkey.com/#!/browse/book/3-s2.0-C20160052403

Microbiology Reference Material:

• Medical Microbiology, https://www.clinicalkey.com/#!/browse/book/3-s2.0-C2013019575X
 Immunology Advice
• If you’re new to Immunology, don’t panic

• Boards and Beyond Videos may be useful

• Take advantage of the books (Abbas & Robbins)

(Immunology Reading List pdf on D2L)

• Take the formative exams (questions and answers for each week are posted on D2L)

• Attend the review sessions

• Ask Questions (jlcannon@salud.unm.edu & bchackerian@salud.unm.edu), Give us feedback

We will often email good questions to the class
Week 1: Immunology Basics
Overview of Immunology
Cells and Organs
Innate Immunity
Abbas, Chapters 1-2

Antigen presentation and MHC

Lymphocyte receptors and development
Abbas, Chapters 3-4

Cell-mediated immunity
Humoral Immunity
Complement
Abbas, Chapters 5-8
 Week 2: Clinical Immunology

Tolerance and Autoimmunity

Abbas, Chapters 9 & 11 Cancer Immunology
Robbins, Chapter 6 Abbas, Chapter 10
Inflammation

Abbas, Chapter 11 Transplantation

Type I Hypersensitivity
Robbins, Chapter 3 Basic/Clinical science
(Allergy)
Abbas, Chapter 11 Abbas Chapter 10
Robbins, Chapter 6
Weeks 3-4: Microbiology
 Weeks 4 & 5: Review
Vaccines
Abbas, Chapter 8

Congenital and Acquired Immunodeficiency

Abbas, Chapter 12
Robbins, Chapter 6

Immunity to Microbes
Abbas, Chapter 8
 Pre-Work
• Check the pre-work tab for each session. Some (but not all)
instructors may require you to read material or watch a video
prior to the session
 Case-Based Learning Sessions
• Every Friday (9-11am) -- Attendance is mandatory. Check your room assignment!

• Case Based Learning (CBL) sessions are small group discussions facilitated by faculty members.
The cases reflect the material covered in the preceding week and are designed to allow students
to apply the basic science to a clinical case.

• Cases will be released immediately prior to CBL sessions -- students will be guided through the
case by faculty facilitators.

• After each session, students will be assigned a short homework assignment that is related to the
CBL session.

• Students should return a hard (printed) copy of the homework by the end of the class session on
the Tuesday following the CBL. (Note: that class ends at different times each Tuesday, so the
homework will be due at different times from week to week.) Late assignments will not be
accepted without a valid excuse. Homework should be completed independently, although
discussions with other students at the CBL session can contribute to your answer.
Review Sessions
• Every Friday
• Review of the previous week’s material
• Bring your iClickers
• A selection of Formative Exam questions will be discussed
• Case Studies
• A Comprehensive Review session will be held on Feb. 12, prior to
the Summative
 Assessment
1) Weekly Quizzes (4 Weekend Quizzes; 5% of grade/each)
30-36 Multiple-choice questions, covering material from the previous week

2) CBL Homework Assignment (4 Assignments; 2.5% of grade/each)

3) Summative Exam, Friday, Feb. 14 (70% of grade)

100-120 Questions, weighted by topics covered in the class
(~50% Immunology, ~50% Microbiology)
 Contact Us
Bryce Chackerian Judy Cannon
BRF 323D Fitz 379
bchackerian@salud.unm.edu jlcannon@salud.unm.edu
272-0269 272-5764

Michael Mandell
Fitz 351
mmandell@salud.unm.edu
504-0925
Please email if you’d like to meet with us!
 7 Key Concepts of Immunology
1. The immune system must strike a balance between Hypo- and Hyper-
reactivity
2. The immune system has two overlapping compartments, the innate immune
system and the adaptive immune system.
3. The antigenic specificity of the adaptive immune system is due to the
presence of antigen-specific receptors.
4. Antigen-receptors have tremendous diversity that is generated through a DNA
rearrangement process called VDJ recombination.
5. Specific adaptive immune responses are activated and expanded through a
process known as clonal selection.
6. The adaptive immune system has memory.
7. The immune system is tightly regulated.
1) The immune system must strike a balance between Hypo- and
Hyper-reactivity

A balancing act
Hypo-reactivity Health Hyper-reactivity

Immunodeficiency Immunopathology
 Immunodeficiency
Hyper-reactivity
Health

Hypo-reactivity

States Associated with Clinical Immunodeficiency:

• Congenital or Acquired Immunodeficiency
• Immune senescence (old age)
• Immunosuppression resulting from treatment (Iatrogenic)
• Malnutrition or metabolic imbalances
• Malignancies or infectious diseases
• Trauma or stress
 Example: Acquired Immunodeficiency
HIV infection leads to depletion of CD4+ T cells, which play a key role in adaptive
Immune responses.
HIV patients are susceptible to infections that are rarely seen in the normal
population.

• Kaposi’s Sarcoma is a rare disease that traditionally mainly

affected elderly men who lived near the Mediterranean.

• However, beginning in the mid-1980s it was observed

frequently in patients infected with HIV.

• In 1994 it was discovered that Human Herpes Virus-8 (KSHV)

was the cause of these lesions.

http://en.wikipedia.org/wiki/Kaposi%27s_sarcoma
 Immune Hyper-reactivity

Hypo-reactivity Health
Hyper-reactivity

States Associated with Clinical Hyper-reactivity:

• Systemic Autoimmunity
• Organ-Specific Autoimmunity
• Allergies and Asthma
• Infection-related Immunopathology
2. The immune system has two overlapping compartments, the innate
immune system and the adaptive immune system.
Innate Immunity: Provides an early line of defense against microbial infection
Consists of non-specific effectors

Acquired Immunity: Occurs as a response to infection.

Consists of specific responses to microbial antigens
 Innate Immune System
• Most primitive type of immune system; found in virtually all multicellular
animals.

• Innate Immunity is the first line of defense against infection--its elements are
constitutively expressed and are always present and active, and are constitutively
expressed (some components can be up-regulated).

• Innate Immunity encompasses broad immune mechanisms; it is not specifically

directed against any particular infectious agent or tumor (unlike adaptive
immunity).

• The magnitude and kinetics of an innate response are the same every time;
unlike the adaptive immune system there are no memory responses.
 Components of the Innate Immune System

• Physical Barriers (i.e. skin)

• Protective Secretions (mucous, pH, anti-microbial peptides or lipids)

• Phagocytic Cells, such as Macrophages and Neutrophils, which engulf

and kill microbes

• Enzymes (i.e. digestive enzymes)

• Components of the Complement System, which recognize molecules

that are commonly found on microbes)

• Cytokines, soluble factors that promote defensive responses and also

help to shape the adaptive response
 Adaptive Immune System
• Found only in vertebrates

• Must be induced; usually triggered by component of innate immunity

• Usually highly specific to ANTIGENS derived from microbes.

Antigens are molecules that elicit immune responses. Antigens can be proteins,
carbohydrates, lipids, etc. Different arms of the adaptive immune system can
respond to different types of antigens. (Note: autoimmunity is due to adaptive
immunity against self-antigens).

• The adaptive immune system has memory – there is increased reactivity upon
subsequent exposures to a pathogen.

• The adaptive immune system is usually able to distinguish between self and
non-self
 Components of the Adaptive Immune System
• Antigen-presenting Cells (Dendritic Cells, Macrophages, etc.), components of
the innate response which prime adaptive immune responses.

• B lymphocytes, which produce antibodies

• T lymphocytes, which include T helper cells (which help other lymphocytes,

such as B cells and macrophages, respond to antigens) and Cytotoxic T cells,
which can bind to and kill infected cells

• Cytokines, soluble factors secreted by all of the above cells that can aid in
controlling the adaptive immune response.
3. The antigenic specificity of the adaptive immune system is due to
the presence of antigen-specific receptors.

B lymphocyte T lymphocyte
Immunoglobulin Molecule (B cell receptor) T cell Receptor

These receptors have high specificity for specific antigens

B lymphocytes T lymphocytes

APC

Antigen binding

Binding to peptide
presented by an
Antigen Presenting Cell

Secretion of antibodies Antigen-specific

specific for the antigen effector T cell
4. Antigen-receptors have tremendous diversity that is generated through a DNA
rearrangement process called VDJ recombination.

• The total number of antigenic specificities of lymphocytes in an individual is extremely large.

• B and T lymphocytes are estimated to recognize 107 – 109 distinct antigenic determinants.

• This diversity is the result of the variability of structures of the antigen binding sites sites of
lymphocyte receptors

• To encode all of these specificities would take a huge portion of the genome (107 genes > # of
genes in the human genome)

• The immune system solves this problem through a mix-and-match process that is known as VDJ
recombination
 VDJ Recombination

• The genome encodes a large, but limited

number of gene segments.

• Random selection and joining of gene

segments from this pool results in tens of
millions (or more) different receptor
sequences

• This process contributes to the diversity of

antibodies and T cell receptors
5. Specific adaptive immune responses are activated and expanded
through a process known as clonal selection.

1. Each lymphocyte bears a single type of

receptor with a unique specificity.
2. Receptor engagement is required for cell
activation.
3. The differentiated effector cells derived
from an activated lymphocyte will bear
receptors of identical specificity as the
parental cell.
4. There are multiple mechanisms for
inactivating lymphocytes bearing receptors
that recognize self-molecules.

Shown: B cells. The same principle applies to T cells

6. The adaptive immune system has memory.
• The adaptive immune response against an antigen is much
greater after the first exposure
• Essentially, each infection is a race between the pathogen and
the immune system
• With a kinetic advantage, the immune system can often control
infection
• This concept underlies the effectiveness of many vaccines

Antigen
Binding

Naive B cell
Memory B cells
Primary and Secondary Adaptive Immune Responses

Differences include:
• Magnitude of the response
• Speed of the response
• Type of response (for B cells)
7. The immune system is tightly regulated.

• The adaptive immune system has developed mechanisms to

eliminate or inhibit self-reactive B and T cells.

• These mechanisms are collectively known as immunological

tolerance

• Central Tolerance:
Elimination of potentially self-reactive cells during their
development

• Peripheral Tolerance:
A variety of different mechanisms that prevent the activation of
potentially self-reactive cells that escape central tolerance