Immunology exam 1

UNT

Immunology

• how the body protects itself from disease

Advancements: Blood typing, immunotherapy, and monoclonal Antibody tech

Clinical: using tests to determine targets of infections, toxins, hormones, and other disease markers causing immune responses

Immunity

state of protection against foreign pathogens or substances (antigens)

Immune system

Network of cells, tissues, microenvironments

and molecules that:

• Defend against infection

• Eliminate abnormal cells

• Maintain homeostasis

Immunobiology

how the immune system works in

health and disease

immunogenetics

how genes influence the way the immune system

works including errors that affect immune response

Mammalian immune molecules

used to recognize pathogens from body's own cells

• PRRs

• B cell receptors

• T cell receptors

Pattern recognition receptors

• detect molecular patterns shared by many microbes such as viral RNA

B cells (Humoral response)

• adaptive immune response

• Recognizes specific structures on pathogens such as viral spike proteins/ unique structures on pathogens for targeting

• Produce antibodies that bind to pathogens, neutralizing them or marking them for destruction.

T cells (cell-mediated response)

• adaptive immune response

•  Recognize processed peptide fragments from pathogens

• Directly kill infected/abnormal cells or coordinate the activity of other immune cells.

Innate immunity

immune system mounts a fast initial defense (minutes/hrs)

• Nonspecific response- skin, mucous, 

* inflammatory response cells: mast cells, phagocytes, and natural killer cells activated

*activates PRRs

• No memory

Adaptive immunity

slower but more targeted response (days)

• Specific targets to unique antigens to avoid attacking own cells

• Has memory- for quicker response to future pathogens from past infections

-(lymphocytes) are left behind after antigen is cleared

• Includes B and T cells :lymphocytes antigen specific receptors, used to target specific pathogens and producing antibodies

• has primary and secondary response

Primary vs secondary response

Primary response- initiated upon first exposure to an antigen

Secondary response- initiated upon second exposure to the same antigen that stimulates memory lymphocytes

How does the immune system protect the host?

• Threat based activation

• Tolerance

• Regulatory controls

Threat based activation

• responds when damage signals are released

Tolerance

• immune system learns to target pathogens and not own cells

Regulatory Controls

• Built-in controls keep immune responses in check so they clear pathogens without harming healthy tissue

Steps to an immune response:

1.  pathogen enters the body

2. innate immune cells act immediately

3.  pathogen moved to lymphoid organs

4.  specialized B and T cells from adaptive immunity produced and matured by bone marrow recognize pathogen and prepare to fight

5. Activated lymphocytes leave lymph nodes and travel to infection site

6. Pathogen eliminated and memory cells created

Primary lymphoid organs

Bone marrow and thymus gland which train T and B cells to differentiate own cells from antigen via maturation

Secondary lymphoid organs

lymph nodes where B and T cells are replicated to respond to antigen

Microenvironments

specialized zones for immune cells to attack pathogens in lymphoid organs

Bone Marrow

primary site of immune cell development

Red bone marrow- infants-2yrs

Yellow bone marrow- adults

Hematopoiesis

the creation of blood stem cells (HSCs) in the bone marrow (self renewing)

Hematopoietic stem cells (HSCs)

• self renewing, originate in fetal tissues, differentiate into different cell types, found in bone marrow of adult vertebrates, (rare; 1 per 50,000 cells in bone marrow)

How is blood cell regulation done?

• The bone marrow sends signals to the HSCs to either self renew, rest, or start maturing. Production is adjusted to body's needs by cytokines and growth factors. 

HSCs stem cells then differentiate into what kind of different cells with specialized functions?

• Myeloid progenitors or Lymphoid progenitors in the bone marrow, which both can turn into dendritic cells

Myeloid progenitors (CMPs)

from HSCs in bone marrow

• RBCs

• Monocytes

• Macrophages

• Dendritic cells

• Granulocytes: 

• Megakaryocytes->platelets

Monocytes

circulate in blood, can turn into macrophages & dendritic cells (large kidney shaped nucleus)

• Macrophages:long lives/in tissues, utilize phagocytosis to destroy pathogens, display antigens to T cells

• Dendritic cells: concentrated in external areas of the body, take antigens to lymph nodes

Granulocytes

• Neutrophils: rapid responders/ most abundant granulocytes (segmented nucleus)

• Basophils:release histamine/ allergic inflammatory response (rare)(dark granules)

• Mast cells: (rare) in tissues near blood vessels, release histamines/ cytokines /enzymes (allergy/ anaphylaxis response)

• Eosinophils: target parasites/ antiviral defense, allergy/asthma response (Red/orange granules)

Lymphoid progenitors (LMPs)

from HSCs in bone marrow

Lymphocytes: (large nucleus minimal cytoplasm)

• B lymphocytes

• T lymphocytes

• Innate lymphoid cells (ILCs)

Lymphocytes

 (large nucleus minimal cytoplasm)

• B lymphocytes: pursuit antibodies, differentiate into plasma cells once activated

• T lymphocytes: coordinate responses (CD4⁺ helper, CD8⁺ cytotoxic to kill antigens)

• - NKT cells:

• - Cytotoxic T cells (TC): kill virus/cancer cells, use perforin/granzymes for cell death

• - Helper T cells: immune response to activate macrophages, B, and cytotoxic T cells

Innate lymphoid cells (ILCs): 

• NK cells: innate immune cells, destroy virus/ tumor cells

• ILC1, ILC2, ILC3

Total leukocytes (WBCs)

7.3x10^3

Innate Immune cells

macrophages, granulocytes, many dendritic cells

Adaptive immune cells

(use specialized receptors to detect antigens)- B cells,T cells (CD4⁺ helper, CD8⁺ cytotoxic)

Innate and adaptive immune cells

γδ T cells, Natural killer T (NKT) cells, Innate lymphoid cells (ILCs)

Phagocytic cells (engulf & destroy pathogens)

Macrophages, neutrophils, dendritic cells

What is the most abundant granulocyte?

Neutrophils

Antigen-presenting cells

(Present antigen to T cells):

Dendritic cells (most potent), macrophages, B cells

Cytotoxic cells

(kill infected or abnormal cells):

CD8⁺ T cells, NK cells, NKT cells

Mononuclear cells:

 lymphocytes, monocytes

Polymorphonuclear cells

Basophils, neutrophils, eosinophils

When would a peripheral blood smear (PBS) be performed?

When a CBC appears abnormal in order to get a closer look at the blood cells

Hematoxylin & Eosin (H&E) staining used for PBS

– Hematoxylin (basic) stains nuclei blue/purple

– Eosin (acidic) stains cytoplasm and granules pink/re

CD molecules:

cell membrane proteins that can be used to define immune cell type, lineage, and activation state.

What is used to detect CD molecules?

Flow cytometry

What characteristics distinguish hematopoietic cells (HSCs) from mature blood cells?

HSCs are more multipotent and capable of self renewal

what best distinguishes innate immunity from adaptive immunity?

innate immunity recognizes shared microbial features while adaptive recognizes specific structures

What are the primary lymphoid organs?

Bone marrow

thymus gland

Bone marrow

site of hematopoiesis and B cell maturation

B cells

mature in close contact with stromal cells in bone marrow

Stromal cells

structural support/ guide B cell development

B cells after maturation

develop functional B cell receptor, self tolerance by negative selection, ability to circulate secondary lymphoid organs

Thymus gland

site of T cell maturation

Pro-thymocytes

 migrate from bone marrow migrate via blood to thymus to mature into T cells through stepwise change

Thymus anatomy

divided into lobes via CT strands (trabeculae). Lobes have an outer cortex filled with naive T cells (thymocytes) and an inner medulla filled with mature T cells.

Thymic involution:

• shrinks and is covered with fat through aging limiting T cell development. 

Cells that support thymocyte development

stromal cell network, epithelial cells, dendritic cells, nurse cells (cortical epithelial cells), and macrophages.

T cells after maturation:

T cell receptors

MHC restriction

self-tolerance

lineage commitment

Secondary lymphoid organs

where lymphocytes clone, encounter antigens, and immune activation occurs. All connected through the lymphatic system.

Lymph nodes

Spleen

Stromal networks

Mucosa-associated lymphoid tissue

Lymph nodes

• filter/monitors lymph, hub for immune cells/ reaction

Spleen

• filters/ monitors blood for rapid immune response

MALT

• samples antigens from mucosal surfaces and initiates organized local immune responses

− Bronchus-associated lymphoid tissue (BALT)

− Nasal-associated lymphoid tissue (NALT)

− Gut-associated lymphoid tissue (GALT)

− Skin-associated lymphoid tissue (SALT)

Stromal networks:

• create supportive microenvironments that guide immune response

Flow of lymph

1. Plasma leaks from capillaries into

surrounding tissues, forming interstitial fluid.

2. Most interstitial fluid returns to blood; the rest

enters lymphatic capillaries and becomes

lymph.

3. Lymph flows through progressively larger

lymphatic vessels, eventually draining into the

thoracic duct.

4. Thoracic duct empties into the left subclavian

vein near the heart.

5. One-way valves in lymphatic vessels prevent

backflow.

6. Lymph movement is driven by skeletal

muscle contraction.

Lymph node structure-

• Cortex- B cell zone, B cells organize into follicles for proliferation/differentiation

• Paracortex- T cell zone, has dendritic cells and major site of activation

• Medulla- where plasma cells produce antibodies

Movement of lymphocytes and antigens in lymph nodes

• Afferent lymphatic vessels in LNs: take lymph from tissues with antigens, dnedritic cells and lymphocytes

• High endothelial venules: blood vessels in cortex for immature lymphocytes to enter the bloodstream

• Efferent lymphatic vessel: carry activated lymphocytes and antibodies out of the node to continue immune response

Lymph node stromal cell networks-

• Fibroblastic reticular cells: guide network for T cells and help T cell/antigen interaction

• Follicular dendritic cells: organize and activate B cells

Splenic structures

• Red pulp: for blood filtration, RBCs and macrophages present

• Marginal zone: between red/ white pulp for immune surveillance. First point of contact for blood borne antigens where specialized cells deliver them to lymphocytes

• White pulp: has T cells (PALS region) around arteries and B cells form adjacent follicles to support adaptive immune response to blood borne antigens (lymphocyte activation)

What are the implications of losing your spleen?

High risk for blood borne pathogens/ sepsis in children and bacteremia and blood borne pathogens in adults

What best distinguishes lymph nodes from the spleen?

lymph nodes monitor antigens draining from peripheral tissues

What best describes MALT?

organizes immune responses at epithelial and mucosal surfaces

Innate immunity barrier sites

Skin, resp tract, gut, urogenital tract

Innate immunity protection

Physical protection

Chemical protection

Early immune signaling to stop most pathogens and detect microbes early

Physical protection

• Lined with epithelial cells

• Physical barrier via tight junctions that prevent microbes/toxins from moving to other cells

• Mechanical clearance: cilia moves mucus and trapped microbes away from tissue surface

• Sentinel function: PRRs can detect microbes and signal local immune responses

Chemical protection

• Mucus: can trap/ limit movement of microbes toward epithelial cells for removal via coughing and sneezing

• AMPs can kill microbes

• Enzymes: lysosomes to break down microbial walls

• Ph- acidic environment inhibits microbe growth

Barrier maintenance

has healthy microbiota that protect against pathogens and strengthen epithelial barrier to reduce inflammation, and reduce immune responses

Innate immune cells

Neutrophils

Eosinophils

Basophils

Mast cells

Monocytes/macrophages

Conventional dendritic cells

Plasmacytoid dendritic cells

NK cells

Neutrophil

• most abundant WBC’s

• Expression: PRR’s detect local danger signals from damaged cells have Fc receptors and complement receptors to recognize and attack antimicrobials. 

• Activation: exit blood to phagocytose and kill pathogens by trapping the microbe by extracellular (NETs)  and degranulates to release antimicrobials. Produce cytokines/chemokines to active inflammatory response

Eosinophils

• parasite killing

• Expression : PRR’s, Fc receptors, complement receptors to attack parasites

• Activation: exits blood degranulates to release toxic proteins to destroy parasites and cast (EETs) to traps and immobilize parasites

Basophils

• Expression: needs Fc receptor to bind to antibody and allergen in order to activate

• Activation: leaves blood to respond by degranulating and release histamine and cast BETs to immobilize pathogens and secret cytokines, chemokines and lipid mediators for inflammation

Mast cells

• respond to toxins/ trauma/ stress

• Express PRRs, Fc receptors, complement receptors

• Activation: degranulate quickly to release histamine, proteases, and heparin and cast MCETs to kill microbes

Monocytes/Macrophages

• monocytes move into tissues to become macrophages

• Expression: PRRs, Fc receptors, complement receptors

• Activation: Phagocytose and kill pathogens in phagolysosomes (strong response). Present antigen high expression of MHC II and costimulators for T cells. Secrete cytokines and chemokines that amplify inflammation and recruit other cells

Conventional Dendritic cells

• highly phagocytic cells

• Activated by: PRR’s recognizing PAMPs/DAMPs/ local inflammatory responses

• Activation: captures and processes antigen to load to MHC I &II and migrates via lymphatic system and secretes cytokines and chemokines

Plasmacytoid Dendritic cells

• specialized antiviral cells

• Activated by: PRRs that sense viral DNA/RNA/ inflammatory responses

• Rapidly release type I interferons to induce antiviral state

• Secrete cytokines and chemokines

• Short lived

NK cells

• lymphoid derived innate cells

• Activates by activating receptors and inhibiting receptors

• Kills target cells by releasing perforin and granzymes to induce cell death

• Releases cytokines

What is a receptor expressed by innate immune cells that allows them to recognize targets already y marked by the immune system

Fc receptors that bind antibodies coating a target

What cells mainly make up the PALS region?

T cells in arteries and B cells in follicles

What are fibroblastic reticular cells?

guided network for T cell and antigen interaction

What are follicular dendritic cells?

They organize and activate B cells

What are cytokines?

small regulatory proteins released by immune cells to help regulate communication and responses

act via: autocrine (acts on own cell) , paracrine (acts on neighboring cell) , endocrine signaling (travels to distant sites)

Cytokine properties

Pleiotropy- single cytokine can have diverse effects on many cell types

Redundancy- many cytokines can produce similar effects

Synergy/antagonism- cytokines can enhance or inhibit each-others effects

Cascade induction- a cytokine can produce other cytokines in cascade

Short half-life- act locally in a “quick burst”

Specific receptors- target cells have specific receptors to respond to cytokines

Types of cytokines

Pro inflammatory cytokines- promote inflammatory response

anti inflamatory cytokines- regulate inflammation

Lymphokines- made by T cells

Monokines- made by monocytes/ macrophages

Hematopoietic cytokines- regulate blood/ immune cells esp in bone marrow

Differentiation cytokines- direct immune cells (T cells) to have specific functions

Homeostatic cytokines- supports cell survival and maintains immune baseline

Six main cytokine families

Class I hematopoietin cytokines- regulate immune cells

Class II interferon cytokines- antiviral defense/immune regulation, has interferons

TNF- can trigger cell death, regulates immune responses/inflammation

Interleukin 1- mediates fever/inflammation and innate immune activation

Interleukin 2- important responder to extracellular pathogens

Chemokine- specialized cytokines guide immune cells to specific infection sites

innate immunity cytokines

• produced by macrophages, dendritic cells, neutrophils, and NK cells at presence of pathogens

• initiates and enhances immune responses

• can activate NK cells/ dendritic cells

adaptive immunity cytokines

produced by activated T cells, support B cell activation, enhance cytotoxic T cell responses, aid in memory formation, immune response regulation, act locally, and differentiate naive T cells into specific cytokines

cytokine receptors

receptors can be made of more than one protein, receptors can be shared or expressed at certain times. different receptors have different signals.

more about cytokines

Disease

• Excessive cytokine production can cause tissue damage

• Chronic cytokine signaling contributes to inflammatory and autoimmune disease

Diagnosis

• Cytokine levels can reflect immune activation and disease severity

• Used to assess responses to specific types of infection

Therapy

• Cytokines and their receptors are major drug targets

• Blocking cytokine signaling can reduce harmful inflammation

How does the innate immune system recognize patterns of antigens to generate quick immune responses?

PRRs

What are PRR’s?

detect patterns on microbes (PAMPs) and (DAMPs) detects signals from damaged cells.

located on the surface of innate immune cells, can signal rapid response to activate inflammation, cytokine/chemokines, immune cells, and the killing of microbes

activated by ligand binding

What are toll-like receptors?

specific PRR receptors on innate immune cells to activate signal cascades to activate antiviral/ inflammitory responses as well as dictates ligand specificity