Immunology FInal Outline PDF

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Notes of Immunology Exam 1...

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Chapter 1: Elements of the Immune System and their Roles in Defense  Immunology is the study of physiological mechanisms that are used to defend the body from invasion by foreign or infectious agents  Innate immune response will be the same every time you run into a pathogen and won’t change (Dendritic cells, neutrophils, and etc.. will all work the same way)  In response to diseases caused by infectious agents, the body develops cells dedicated to defense – these form the immune system  We do not have long term immunity to certain pathogens  Protective/adaptive immunity takes time to develop, while microorganisms can rapidly multiply and cause disease 

Adaptive immunity includes lymphocytes like B and T cell lymphocytes

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It can change due to the lymphocytes

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Roughly 7 days to get adaptive immune system up and running again and creating a faster immune response

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The first time you get in contact with a pathogen will always be the worst and you are the most vulnerable because you do not have previous exposure to the pathogen and your immune system does not recognize it

 Immunity involves two responses: 1. Flexible but specific defenses of the adaptive immune response (our genes can change to adapt to new pathogens) 2. Fixed defenses of the innate immune response (genes that are given to us by our parents will not change with our innate immune system) Defenses Facing Invading Pathogens The Ubiquitous Enemy- Microbes  Microbes 

Can grow everywhere including in and on your bodies

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Help and/or cause no harm

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Survive on animal & plant products

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Release digestive enzymes

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Grow on living tissues (extracellular) where they are bathed in nutrients

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Other (intracellular) microbes infect animal/human cells, utilizing host-cell sources

 Some microbes are harmless (commensal organisms) and some even helpful 

e.g. E. Coli in our intestines (colicins are antimicrobial that helps protect against pathogens) (E.coli are naturally occurring. But can be harmful when they pick up a sugatoxin because it secretes a toxin that causes harm, as the bacteria is being killed by abx it release its LPS (which is found in the outer membrane of gram – bacteria) (If E.coli is found somewhere it should not be and its concentration is too high it can cause an opportunistic pathogens)

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Commensal microorganisms are fine until they become opportunistic by entering a space they don’t normally inhabit or the individual become immunocompromised

 Many others cause disease 

human pathogens (is not part of the normal flora)

 There is a constant battle between invading microbes and the immune system Immunity- The Immune Response  People who survive a specific infection become immune to it – protective immunity  To provide protective immunity, the immune system must first engage the microorganism 

There is lag time between infection and protection (~7days) which is the most dangerous time

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The first infection is the most dangerous one

 This understanding led to the concept of immunization or vaccination 

Disease is prevented by prior exposure to an attenuated/killed infectious agent

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Help creates immunity to that disease by presenting those attenuated cells (which are cells that are heat killed and aren’t virulent)

Historical Perspective  430 BC- Thucydides recognized that only those who had recovered from the plague could nurse the sick without becoming sick again.  Fifteenth century- Chinese and Turks used dried crusts from smallpox pustules (inhaled or inserted into small cuts in the skin “variolation” (inoculating people with that specific strain of disease) to induce immunity.  1796- Jenner realized milkmaids who had contracted cowpox (shares epitopes and antigens with smallpox) (mild disease symptoms compared to smallpox) were not susceptible to smallpox. 

He theorized that using fluid from a cowpox pustule would induce immunity to smallpox

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Tested theory on 8 yr old boy- inoculated boy with fluid from cowpox pustule then later injected the boy with smallpox. The boy didn’t contract smallpox.

 Origins of immunology attributed to Edward Jenner  Discovered in 1796 that cowpox “vaccinia” protected from human smallpox 

Base that was utilized by the tetanus vaccine

 Procedure called vaccination  Prevents severe disease by exposing the immune system to the infectious agent in a weakened or killed state.  Provides long term protection against the real pathogen with very little risk of becoming sick. The Nature of Pathogens  Any organism with potential to cause disease is a pathogen 

Influenza and typhoid bacillus are examples of what we call a pathogen.

 Opportunistic pathogens cause disease if the body’s defenses are weakened or it gets into a part of the body it isn’t normally found.  Constant evolutionary struggle between the host and the pathogen 

REPLICATION TIMES favor the PATHOGEN!!!

The Four Kinds of Pathogen that Cause Human Disease  Examples of the types of pathogen are listed, along with the diseases they cause

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Mycobacterium tuberculosis  Tuberculosis

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HIV  Aids

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Candida albicans (fungi that causes problems in children and AIDS patient)  Thrush, systemic candidiasis

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Trypanosoma brucei  Sleeping sickness

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Viruses cannot grow on their own and they need host cells to replicate

The Diversity of Human Pathogens Blastophores (yeast-like cells)

Candida albicansnormal inhabitant of the human body, thrush & systemic infections

Cocci-grape like clusters

Staphylococcus aureus-gram positive bacterium that colonizes human skin, pimples & boils (other strains = food poisoning)

Mycobacterium tuberculosis-causes tuberculosis

Commensal Bacteria -

Over 1000 microbial species in the human gut (normal flora).

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These bacteria typically cause no harm to the host.

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Commensal = eat at the same table. Not harmful

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Abx do not know the difference between commensal bacteria and the pathogen

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When a round of antibiotics is taken, there is no specificity for the pathogen so a large percentage the bacteria (good and bad) are killed.

Skin and Mucosal Surfaces- Physical Barriers Against Infection  Skin is first line of external defense against infection  Tough impenetrable barrier  Skin continuous with epithelia lining (these are more vulnerable) 

Respiratory

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Gastrointestinal

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Urogenital tracts

 The impermeable skin gives way to specialized tissues that are more vulnerable to microbe attack; Known as mucosal surfaces or mucosae  Move from outer part  lower lip mucosal membrane  Upper Res  Lower Res –> GI tract  small or large intestine this is continuous meaning an open system( things will leave and come back)  A closed system means something will be leaving  Mucosal surfaces are bathed in mucus and are continuous with the skin; thick fluid containing glycoproteins, proteoglycans, and enzymes - protective  Lysozyme in tears (~ 40% of protein) and saliva – antibacterial  Respiratory tract mucus is continuously removed to clear unwanted material  Stomach, vagina, skin acidic – protective  Defensins – poke holes in the pathogen (amphipathic and embedded into outer mem.)

 When skin and mucosal barriers are breached - immune system responds Physical Barriers that Separate the Body from its External Environment

Innate Immune Response Leads to Inflammation

Strong barriers to infection hair,, and prov provided ided by the skin, hair nails are colored bl blue ue More vuln vulnerable erable mucosal membranes membr anes are colore colored d red

 The physical barriers have been breached. Now what? The innate immune system begin  This is known as the primary immune response (first time immune system has seen a pathogen)  Macrophage is the first one to recognize the pathogen, will send signals throughout the body including under the skin brings it in which will them make receptors to signal the immune response and get endothelial cells (blood vessels) and vasodilate (activate and become more permeability) which then call neutrophils (first leukocyte) in mass quantity and innate immune response will go and work and cause inflammation  The Innate Immune response starts to work to clear the new invader  This is the next line of defense after physical barriers are breached  Innate = determined by the genes you inherited from your parents 

Adaptive cells (T and B (lymphocytes) change the genes for their receptors)

 Innate response consists of two parts 

Recognition

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Recruitment of effect mechanisms (cells)

Complement (Innate) -

Is ubiquitous, molecules that can tag pathogens for destruction (land on surface of pathogen that our body can recognize the tag placed)

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Series of proteins that act to tag an invader for uptake (phagocytosis) by other immune cells or by poking holes in the microbe by completing the complement cascade.

Inflammation

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We get a breach, bacteria is recognized by receptors we call PRR (pattern recognition receptors) which are on the surface of our leukocytes and they recognize PAMPS (Pattern Associated Molecular Pathogens) an example being LPS which leads to phagocytosis or lead to signaling nucleus to tell macrophages to make cytokines which then releases neutrophils, complement etc. Neutrophils are the first leukocyte out into the blood stream by mass quantity which causes phagocytosis

Immune Defense- Innate Vs. Adaptive Immunity 1. Innate immune system 

Is the first line of defense against infections

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It works rapidly

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Gives rise to the acute inflammatory response

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Has some specificity (100 PRR’s) for microbes that are conserved like LPS (seen in gram- bacteria which is an example of a PAMP as well as LAS)

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Uses different receptors to recognize pathogens

2. Adaptive immune system 

Takes longer to develop (~7 days)

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Is highly specific for antigens, including those associated with microbes

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Uses one type of receptor to recognize many different pathogens because of the binding site that they have

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Primary immune response = first time the adaptive immune response is activated against a pathogen.

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Secondary immune response = any time the adaptive immune response is activated against a pathogen that it has been exposed to before (memory cells)

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Remembers that it has encountered a microbe previously 

(i.e. shows memory)

Innate and Adaptive Immunity Work Together  The innate and adaptive immune systems work together through…. 

Without the innate system there is no adaptive immune response 

The innate system sets up how the adaptive immune system will respond

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Direct cell contact

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Interactions involving chemical mediators 

Cytokines and Chemokines

 Many of the cells of the innate immune system are the same cells used by the adaptive immune system  Vaccinations require that the innate immune system is engaged in order to provide memory. 

Innate immune system activates and aids in the adaptive immune response.

Adaptive- lymphocyte selection and proliferation -

A single lymphocyte will have a receptor with a single specificity. One cell may have many receptors (~120,000) but all will recognize the same epitope.

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When a foreign epitope is recognized by the lymphocyte receptor (selected), the cell will proliferate (expansion).

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Want a lot of that specific receptor to recognize the invader. -

1 receptor specificity = 1 T or B cell

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Generally takes about a week before the benefits of a primary immune response are realized.

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Colonal selection = recognition to certain pathogen/antigen/epitope

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When it becomes activated it then proliferates (expands) and differentiates

Innate and Adaptive -

People lacking innate immunity can’t control the infection at all. Innate immunity cells are needed to activate the adaptive cells. They usually die earlier in life

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People lacking adaptive immunity can control the infection initially but can’t clear it. Innate immune response can keep the immune system in check

Principle Characteristics of Innate and Adaptive Immunity

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Different BCR recognize different epitopes. On the surface of the pathogen you have surface molecules that act as antigens. On those antigens you can have epitopes which will be the specific point that are recognized by paratopes on the BCR antibody (secreted BCR)

PRR- Pattern Recognition Receptors (surface of leukocytes, serve antigen on surface of bacteria)

PAMP- Pathogen Associated Molecular Pattern (surface molecules that have conserved over evolutionary time and allows the hundreds of PRR to be recognized by pathogens) PAMP (LPS (lipopolysaccharide) and LTA) Paratopes= the specific part of the BCR that binds to the epitope Affinity is how tight the paratopes bind to the epitopes -

Adaptive has high affinity

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Innate had low affinity

Immunoglobulin is the B cell receptor (BCR), if it is secreted it is referred to as an antibody but if it is membrane bound it will be referred as BCR -

Cytokines and chemokines are the “voice” of the leukocytes by telling other cells what’s going on

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Neutrophils are the most abundant of cells. They are the first ones to come out and see the pathogen

Cells of the Immune System 1. Lymphoid cells – 

20-50% of white blood cells

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T cells, B cells, and NK cells (part of the innate immune system)

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T and B cells are part of the adaptive immune cell

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Only B cells have paratopes

2. Mononuclear phagocytes – 

Monocytes that circulate in the blood and (can become macrophages by maturing into the blood cell, have more killing potential)

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Macrophages found in tissues 

Phagocytosis and destruction

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Recognition and releasing the cytokines and chemokines

3. Granulocytic cells – These are called granulocytes 

Neutrophils (Neutral staining)

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Eosinophils (red/orange/pink)

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Basophils (dark purple/blue staining)

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based on morphology and cytoplasmic staining characteristics

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These are all innate cells

4. Dendritic cells – 

Main function is the presentation of antigen to T cells

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They activate T cells (bring in pathogen and put in surface and mi

Hematopoiesis  The generation of the cellular elements of blood, including: 

Red blood cells (RBC) or erythrocytes

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White blood cells (WBC) or leukocytes

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Megakaryocyte - Platelets

 These cells originate from pluripotent hematopoietic stem cells (HSC) whose progeny differentiate and divide under the influence of various hematopoietic growth factors  HSC give rise to other cells in a process called self-renewal, becoming more mature stem cells that commit to different lineages Types of Hematopoietic Cells  The pluripotent stem cell divides and differentiates into more specialized progenitor cells that give rise to the 

lymphoid lineage (leads to lymphocytes)

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myeloid lineage

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erythroid lineage

Abundance of Leukocytes in Blood  Most abundant leukocytes are the neutrophils  Circulatory leukocytes  Followed by lymphocytes  Finger stick, smear prep, and stain it and check your percentage

Leukocyte Vs. Lymphocyte  Leukocytes

A general term for a white blood cell 

Lymphocytes, granulocytes, monocytes, B cell and T cell are all leukocytes

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All lymphocytes are leukocytes but not all leukocytes are lymphocytes

 Lymphocytes

A class of white blood cells that consist of small and large lymphocytes

 Two classes of lymphocytes 

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Small lymphocyte (adaptive immunity cells) 

B lymphocytes (B cells) (mature in the blood stream)

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T lymphocytes (T cells) (mature in the thymus)

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Have not been activated yet (naïve)

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Turns into a plasma cell it is a mature cell and they secrete antibodies

Large granular lymphocytes 

Natural killer (NK) cells, lymphocytes of innate immunity

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Comes out of the bone marrow already matured

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They do not fall in the granulocyte category

Lymphoid Cells  Lymphocytes are divided into three different types 1. B cells (Ig’s – receptor) (have membrane bound immunoglobulins) 2. T cells (TCR) 3. NK cells (Natural killer cells)  Naïve lymphocytes or small lymphocytes are resting cells that have not interacted with antigen and have not yet matured ( have not been activated)  Lymphoblasts are lymphocytes that have interacted with antigen and proliferate (division taking place) 1. Lymphoblasts eventually differentiate into effector cells or into memory cells  Effector cells eliminate antigen 1. Plasma B cells that secrete antibody 2. Cytokine-producing T helper cells (TH) -CD4 cell  Co-receptors and surface molecules  Further differentiations 3. T cytotoxic cells (TC) – CD8 Cell  Co-receptors and surface molecules  Cytotoxic lymphocytes as effector cells  CD4 and CD8 are co-receptors B cell  Activation  Natural Killer Cells  NK cells (large granular lymphocytes) are found throughout the tissues of the body but mainly in the circulation 

Innate viral fighters

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Constitute 5-10% of lymphocytes in human blood

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Contain cytotoxic substances which are important for protection against viruses and some tumors

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Secrete cytokines which 

Prevent viral replication and

Neutrophils  Effectors of innate immunity – specialized in the capture, engulfment and killing of microbes 

Work in the anaerobic conditions found in damaged tissue

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Are short-lived and die at site of the infection – one the major reasons for pus formation at the site of injury 

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Pus former = pyogenic

Are phagocytic cells that contain toxic substances in intracellular granules (primary and secondary granules)

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Employ oxygen-dependent and oxygen-independent pathways to destroy pathogens

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