ANS 150

immunology

The study of the physiological mechanisms that hosts use to defend their bodies from invasion by all sorts of other organisms

Immunity

The ability to resist infection

Antigen

Any foreign material that is specifically bound by specific antibody or specific lymphocytes, that causes an immune response

Antibody

Serum proteins formed in response to immunization and interact with antigens

Immune Response

All of the phenomena that result from specific interactions of cells of the immune system with antigen. Immune response is the result of clonal expansion of T and B cells

Robert Koch

-Grandfather of Immunology
-Tuberculosis

Emil Von Behring

-Grandfather of Immunology
-Serum therapy

Ilya Llich Mechnikov

-father of immunology
-phagocytosis

Paul Ehrlich

-father of immunology
-Antitoxin (immune therapy)

What are the two early concepts in immunology? (Term and definition)

1. Phagocytosis (cellular immunity)- immune cells engulfed by pathogen, which kills pathogen
2. Side Chain Theory (adaptive)- binding specifically with lock and key type mechanism

What are the 3 functions of immunity

1. immune defense
2. immune homeostasis
3. immune surveillance

Immune Defense (Normal vs. Abnormal)

Definition: Protect host against infection
Normal: Anti-infection (healthy) Just enough immune response to protect against pathogens
Abnormal: Hypersensitivity- attacks outside material (allergies) vs. immunodificiency- not able to defend against pathogens (HIV)

Immune Homeostasis (Normal vs. Abnormal)

Definition: When immune system is activated there are cells that are killed and tissues damaged, those cells need to be regenerated and repaired
Normal: Eliminate injured/senile cells and tolerate self components
Abnormal: immune dismodulation- can't remove bad cells vs. autoimmune disease- destroying healthy tissue/attacks host (lupus)

Immune surveillance (Normal vs. Abnormal)

Definition: Always on alert; detection of pathogens to know when to respond
Normal: Destroy transformed cells (anti-tumor) and prevent persistent infection
Abnormal: Tumor or persistent virus infection- not recognizing the presence of foreign material or bad cells

What are the two types of immunity

1. Innate Immunity:
2. Adaptive Immunity:

Innate Immunity

Definition: Doesn't need time to develop as it is already present(fast); non-specific, but pattern recognition; no memory
Aspects:
- Temperature (fever\=hostile to pathogens)
-pH (more acidic or basic to make hostile to pathogen)
-Barriers (skin, feathers)
- Microflora (microorgansims supposed to be present take the majority of the resources and make environment hostile for pathogen)
-cilia (physical barrier from getting into gut)
-cells (ie. leukocytes)
-serum proteins (antimicrobial properties within blood)
-complement (proteins that lead to the lysing of invading cells)

Adaptive Immunity

Definition: Takes time to develop(slow); specific; memory; transferrable; self-limitation
Aspects:
- B Cells- named for bursa of fabricius(primary source in avians); primary source in mammals\= bone marrow; humoral/antibody mediated immunity
- T cells- derived in thymus; cell mediated immunity
-killer and helper T cells

What are the time periods of host response to infections?

- 0-4 hours: immediate innate- pathogen is recognized by soluble/resident effector molecules
-4 hours - 4 days: induced innate- recruitment of effector cells to site for a greater defense against pathogen
-After 4 days: adaptive- B and T cells proliferate and mature to provide specific immune response

Hematopoiesis

Making immune cells

What makes the stem cells used for hematopoiesis?

During Gestation:
-initially the yolk sac
-majority the fetal liver and spleen
After birth:
-the bone marrow

In the bone marrow, what is the initial cell type that can be made into all needed cells for immunity?

Pluripotent hematopoietic stem cell

What are the two progenitors made from the Pluripotent hematopoietic stem cell?

1. Lymphoid progenitor
2. Myeloid progenitor

What does the lymphoid progenitor make?

Lymphocytes that go through the blood to the lymph nodes
1. B cells
2. T cells
3. Natural Killer Cells

What does the myeloid progenitor make?

1. granulocyte/ macrophage progenitor
2. Megakaryocyte/ erythrocyte progenitor
3. immature dendritic cells

What does the Granulocyte/macrophage progenitor make?

Granulocytes:
1. neutrophil
2. eosinophil
3. basophil
4. precursor of mast cell (in blood)--\> mast cell (in tissue)
5. Monocyte(in blood)--\> macrophage(in tissue)

What does the megakaryocyte/erythrocyte progenitor make?

1. Megakaryocyte--\> platelets
2. Erythroblast--\> erythrocyte

Relative Abundance of Leukocyte cells in human blood

Neutrophil: 40-75%
Lymphocyte: 20-50%
Monocyte: 2-10%
Eosinophil: 1-6%
Basophil:

What are the 3 mechanisms of innate immunity?

1. Barriers
2. Humoral factors
3. Cells participating

Barriers of Innate Immunity

-Physical barrier: skin and mucosa
-chemical barrier: antimicrobial substances in secretion of skin and mucosa
-biotic barrier: normal flora existing on the surface of skin and mucosa
-anatomic barrier: blood-brain; blood-placental; blood-thymus

Humoral Factors of innate immunity

- complement
-lysozyme
-interferons
-C-reactive protein

Cells Participating in innate immunity

-Phagocytes (monocytes, neutrophils, eosinophils)
-natural killer cells
-dendritic cells
-basophils
-mast cells

Neutrophil

-Part of innate immunity
-Polymorphonuclear
-Short life span
-Does phagocytosis
-Does most of the fighting within innate immunity

Monocyte/Macrophage

-1st cell to sense pathogen
-Secretes cytokines that recruit other leukocytes
-long life span
-Antigen presenting
-Does phagocytosis
-Tissue specific

Dendritic Cell

-Antigen presenting cell in lymph nodes

Eosinophil

Killing of antibody-coated parasites

Basophil

kills parasites

Mast Cell

-release of granules containing histamine and active agents (cause of allergies)

Natural Killer Cells

-Functions:
1. kill virus-infected cells and therefore the virus
2.impede viral replication by secreting cytokines
-How it functions: attach to target cells and release cytotoxic granules onto target cells surface. Effector proteins (perforins) penetrate target cell membrane and induce programmed cell death

What are the steps of innate immunity?

1. Bacteria (pathogen) binds to macrophages and triggers macrophage to release cytokines and chemokines into blood
2. Cytokines and chemokines cause vasodilation and increased vascular permeability, which allows for other leukocytes to migrate to site of infection quickly
3. Inflammatory cells migrate to tissue, releasing inflammatory mediators causing pain

Innate system has broad specificity that provides initial discrimination between self and non-self. Describe

- Pathogen Associated Molecular Patterns (PAMP)- pathogen side receptor that allows the immune cell to recognize the pathogen
- Pattern Recognition Receptors (PRR)- host side receptors that defines responsiveness of host cells

Transferrable nature of Adaptive immunity

serum from recovered individuals can be used in another person to fight the same pathogen, since serum contains the proper antibodies

self limitation of adaptive immunity

Initially when activated by a pathogen there is a high level of antibodies that is sustained, over time the level of antibodies decreases as they are not being used and decay over time, thus decreasing immunity

Steps of Education of B and T Lymphocytes

1. A single lymphoid progenitor cell gives rise to a large number of immature lymphocytes (B or T cells), each with a different specificity
2. The different immature lymphocytes made are then "tested" with self antigens to remove potentially self-reacting immature lymphocytes via clonal deletion
3. After the clonal deletion step, the remaining lymphocytes are put into a pool of mature naive lymphocytes
4. Once presented an antigen, only the lymphocyte that is specific to that antigen will go through clone expansion and become a set of activated mature lymphocytes

3 Steps of Adaptive Immune Response

1. Antigen recognition- recognize specificity
2. Induction of response-generate immune response via clone expansion
3. Regulation of Response- maintain levels of antibody

What are the 3 antigen presenting cells

1. dendritic
2. macrophage
3. B cell

T-Cell Activation

1. Dendritic cell binds a small part(peptide) of the whole antigen to the T-cell receptor to send signal for activation
2. Activation of dendritic cell will send a second signal with release of the B7 molecule, which binds to the CD28 molecule of the T-cell
*T cell is now activated and will do clonal expansion

B-cell activation

1. Antigen binds to B-cell receptor and is internalized into cell and is then presented to the T-cell via peptide of antigen (held by MHC molecule on B-cell) binding to the T-cell receptor
2. Once T-cell is activated, it secretes a cytokine molecule to differentiate the B-cell
-IL10 to make plasma B-cell
-IL4 to make memory B-cell
*Clonal Expansion can now occur

Small Resting Lymphocyte (not encountered antigen)

-small amount of cytoplasm
-No rough ER
-condensed chromatin

Lymphoblast (initial encounter with antigen)

-active cytoplasm
-enlarged nucleus with diffuse chromatin

Effector B cell or Effector T cell (encountered antigen)

-large amounts of cytoplasm
-prominent nucleoli
-Presence of ER

MHC Class 1 Antigen Processing Pathway

1. Virus infects cell
2. Viral proteins are synthesized, which break apart into smaller peptides
3. The smaller peptide binds with MHC 1 in Endoplasmic Reticulum
4. MHC 1 travels with peptide to infected cell surface
5. MHC 1 presents antigen peptide for binding to the T-cell receptor on the T cell

What are the two types of MHC molecules?

MHC 1 (1 stem) and MHC 2 (2 stems)

MHC Class 2 Processing Pathway (macrophage and B cell)

Macrophage:
1. Macrophage engulfs bacterium, which then enters a vesicle
2. The bacterium produce peptide fragments, which are then bound to MHC class 2 molecule within the vesicle
3. MHC class 2 travels to cell surface of macrophage
4. MHC class 2 presents peptide of antigen to allow binding to T-cell receptor of T-cell.
B-Cell:
1. Antigen binds to B cell receptor at the specific antigen binding site
2. The antigen is internalized and degraded into peptide fragments within a vesicle
3. MHC class 2 molecule binds to peptide of antigen in vesicle and travels to B cell surface
4. MHC class 2 molecule presents peptide to allow it to bind to a T-cell receptor on T-cell

What cells have MHC class 1 molecule?

virus infected body cell

What cells have MHC class 2 molecule?

antigen presenting cells: dendritic cell, macrophage, B cell

What does a cytotoxic T cell interact with and how?

Virus infected body cell via a MHC class 1 molecule with antigen presentation to T-cell receptor, which initiates T-cell to kill infected cell

What molecule on the cytotoxic T cell allows us to differentiate it from other T cells?

CD8

What does a helper T 1 cell interact with and how?

Infected macrophage that presents peptide of antigen via MHC class 2 molecule to T-cell receptor, which activates and makes phagocytosis in macrophage stronger

What does a helper T 2 cell interact with and how?

B cell has an antigen bind to B cell receptor, it gets internalized and a MHC class 2 molecule presents peptide antigen to T-cell receptor. This causes T cell to release either IL10 or IL4
-IL10 differentiates B cell to a plasma B cell
-IL4 differentiates B cell to a memory B cell

What are the receptors on a B cell?

1. immunoglobulins as cell-surface receptors (stick to membrane)
2. Soluble form\= antibodies secreted by plasma cell (does not stick to membrane)

What are the receptors on a T cell?

ONLY cell-surface receptors

What is the shape of B cell receptors and T-cell receptors?

B\= Y-shaped
T\= I- shaped

What are the 3 regions of a B or T cell receptor?

- constant region
- variable region (antigen binding site)
- transmembrane region (not in antibodies)

Which part of a B cell receptor is heavy vs. light chain?

Heavy: internal of variable region and all of constant region
Light: external of variable region

Is the constant region the same between isotypes of antibodies?

No, there are different constant regions depending on the isotype of the antibody (IgG, IgM, IgA, IgE, IgD)

What are the functions of Antibodies?

1. Neutralization- bind and kill
2. Opsonization- bind and label as bad
3. Complement activation- initiate complement system (lysis and ingestion)

IgG

- main antibody in blood (most abundant)
- smallest antibody (monomer) --\> can go everywhere
-Delayed response (2nd to be made)
-Attach to macrophage
-perform all 3 functions
-only antibody that can pass through placenta to defend fetus

IgM

- immediate response (1st to be made)
- 3rd most abundant in blood
-attach to macrophages
-pentameric (5 Y's)--\> Has more binding sites, so most efficient
- Perform all 3 functions
-Only antibody made by the fetus

IgA

- 2nd most abundant in blood
- monomer or dimer in serum, but secreted as a dimer
- Do only neutralization or opsonization
\-

IgE

-Least abundant in blood
- monomer (majority in mast cells)
-oponize ONLY
-Work with eosinophils to kill parasites
- Mast Cell + basophil (allergy)

IgD

- activate B cells
-Function not very clear

What is the difference between the primary and secondary immunization?

Primary: lag phase before response to antigen (IgM before IgG)
Secondary: immediate response with no difference in timing of IgM and IgG; increase in the amount of IgG (slight increase in IgM)

Where is the immune response initiated?

primary or secondary lymphoid tissues

What are the primary lymphoid tissues?

-thymus
-bone marrow (mammals)
-bursa of Fabricius (avians)

What are the secondary lymphoid tissues?

-spleen
-lymph nodes (not in avians)
-MALT(mucosal mediated lymphoid tissues), BALT (bronchial), GALT(Gut)

What is the immune response in primary lymphoid tissues?

T and B cell education steps 1-3
1. Generation of receptor Diversity (immature B and T cells)
2. Central regulation of response to self antigens (process: clonal deletion)
3. maturation of responsive clones and MHC-restriction (mature naive B and T cells)

What is the immune response in secondary lymphoid tissues?

T and B cell education steps 4
1. Recognition of antigen, activation/proliferation of specific receptor cell (Process: clonal expansion), and differentiation (either B (memory or plasma) or T (cytotoxic or Helper T1 or Helper T2 or T regulatory)

Effect of Response to an infectious agent (normal vs. Deficient)

Normal response: protective immunity (beneficial)
Deficient response: Recurrent infection (harmful)

Effect of Response to an innocuous substance (normal vs. Deficient)

Normal response: Allergy (harmful)
Deficient response: no response (beneficial)

Effect of Response to an Grafted Organ (normal vs. Deficient)

Normal response: Rejection (harmful)
Deficient response: Acceptance (beneficial)

Effect of Response to an Self organ (normal vs. Deficient)

Normal response: Autoimmunity (harmful)
Deficient response: Self tolerance (beneficial)

Effect of Response to an Tumor (normal vs. Deficient)

Normal response: Tumor immunity (beneficial)
Deficient response: Cancer (harmful)

What are the parts of Koch's postulate?

1. The agent must be present in every case of the disease
2. The agent must be isolated and cultured in vitro
3. The disease must be reproduced when a pure culture of the agent is inoculated into a susceptible host
4. The agent must be recoverable from the experimentally-infected host

What is a microorganism? Characteristics of them...

Living thing which individually are too small to be seen with the naked eye (20nm -5mm)

-Grow exponentially
-has habitat
-live in populations
-communities are either free swimming or attached to a surface(biofilm)
Interact between communities (either harmful or beneficial)

What are the organisms considered microorganisms?

-bacteria
-archaea
-fungi
-protozoa
-microscopic algae
-viruses
-various parasitic worms

What is microbiology?

the study of microorganisms

What are the two main themes of microbiology?

Basic- cellular processes
Applied- concerning agriculture, industry and health

Where can infections occur?

-respiratory system
-nervous system
-GI tract
-Urinary tract
-Genital system
-Skin, soft tissues, wounds
-Joints and bones

Infections of the respiratory system

-nasopharynx
-pharynx (pharyngitis)
-Trachea
-Bronchi (bronchioli)- bronchitis
-Lungs- pneumonia
-bronchopneumonia
-pleura (pleuritis)
-lung abscess

Infections of the skin and soft tissues via a breach of skin caused by:

- minor abrasions
-hair follicles
-surgical incision
-wounds (trauma, surgical)

Bacteraemia

the presence of bacteria in the bloodstream that are alive and capable of reproducing

Can be detected in blood culture
-transient (single episode)
-intermittent (a few episodes)
-continuous (many)

What are the three types of microbes in terms of interactions with host?

1. pathogenic- cause disease
2. commensal- helps themselves without hurting host
3. Beneficial- helpful

What is the first microorganism to be recognized as a contagious agent?

Fungi

What is the taxonomic hierarchy?

1. Domain
2. Kingdom
3. Phylum
4. Class
5. Order
6. Family
7. Genus
8. Species

What is bacteria in taxonomic hierarchy? (2 of them)

Domain and kingdom

What is proteobacteria in taxonomic hierarchy?

Phylum

What is gammaproteobacteria in taxanomic hierarchy?

class

What is enterobacteriales in taxonomic hierarchy?

order

What is enterobacteriaceae in taxonomic hierarchy?

family

What is escherichia in taxonomic hierarchy?

genus