Immune Response To Infection

Front 1

Name the two places extracellular infections occur and how they contribute to protective immunity.

Back 1

1. Interstitial spaces, blood, lymph: antibodies, complement, phagocytosis
2. Epithelial spaces: igA antibodies, Antimicrobial peptides

Front 2

Name the two places intracellular infections occur and how they contribute to protective immunity.

Back 2

1. Cytoplasm: cytotoxic T cells, NK cells
2. Vesicular: T-Cell, NK-cell activated macs

Front 3

What are the three distinct phases of the infectious process?

Back 3

1. Innate Immunity: 0-4hrs
2. Non-adaptive, early induced immunity: 4-96hrs
3. Adaptive immunity >96hrs

Front 4

Name 4 of the barriers/cells involved in the Innate immunity response [0-4hrs]?

Back 4

1. Epithelial barrier
2. Local chemical factors
3. Alternate complement pathway
4. Pre-formed, nonspecfic effector cells: Phagocytes [neutrophils, macs]

Front 5

Explain how neutrophils bind many bacterial constituents

Back 5

Surface receptors ex] mannose receptor, LPS, CR4, glycan, scavenger, CR3
-Neutrophils digest pathogens that cross-link these receptors

Front 6

What vesicular products are of functional significance in the innate immune response?

Back 6

1. Acids (drop vesicular pH to 3.5-4)
2. toxic oxygen derivatives (O2-, H2O2, OH radical, oxygen radical, Ocl-hypohalite, NO) 3. Peptides/proteins (defensins, cationic proteins)
4. Enzymes (myeloperoxidase, lysozyme, acid hydrolase)
5. Competitors (lactoferrin, B12 binding protein)

Front 7

What are Toll-like receptors [TLR's] and what stage of immunity are they involved in?

Back 7

they are found on cells likely to encounter pathogens first [like epithelial cells and phagocytic cells]
their receptors recognize different classes of pathogens [ie. viruses, bacteria, pathogens]. They often use a common pathway of signal transduction
Involved in non-adaptive, early immunity [4-96hrs]

Front 8

Name the mediators/cytokines that phagocytes release to induce an inflammatory response

Back 8

IL-1
IL-8
TNF-alpha
IL-6
IL-12
CXCL8

Front 9

What are the local and systemic effects of IL-1?

Back 9

LOCAL: activate vascular epithelium and lymphocytes
Local tissue destruction
Increase access to effector cells

SYSTEMIC: fever and production IL-6

-->also activates ACUTE PHASE RESPONSE

Front 10

What are the local and systemic effects of TNF-alpha? **

Back 10

LOCAL:
-activate vascular epithelium
-increase vascular permeability
-increase IgG entry-->complement
-increase fluid drainage to lymph nodes

SYSTEMIC:
-fever
-mobilization of metabolites
-SHOCK

-->can also activate ACUTE PHASE RESPONSE

Front 11

What are the local and systemic effects of IL-6?

Back 11

LOCAL:
-lymphocyte activation
-increase Ab production

SYSTEMIC:
-fever

-->can also activate ACUTE PHASE RESPONSE

Front 12

What are the local effects of IL-8, IL-12, and CXCL8?

Back 12

IL-8:
LOCAL:
-chemotactic factor for leukocytes (attracts them to the infection)
-increase access of effector cells
-activates binding of Beta 2 integrins --activation of PMNs--neutrophils, eosinophils, basophils--(along w/TNF-a)

IL-12:
LOCAL:
-Activate NK cells
-induce differentiation of CD4 T cells-->TH1 cells

CXCL8:
-chemotactic factor for neutrophils, basophils, and T cells (attracts them to infection)--BIG role in diapedesis

Front 13

What is diapedesis and what causes it?

Back 13

the migration of leukocytes from blood vessels

Caused by inflammatory mediators that activate adhesive reactions [endotoxins]--CXCL8 plays big role

-->there are a zillion types of chemicals used to attract molecules to site in inf--did he say we need to know these? fig 8.16, 8.19

Front 14

Explain how SHOCK occurs in the systemic infection

Back 14

Macs activated in the liver/spleen secrete TNF-alpha into BLOOD (instead of tissue)

Causes:
-systemic edema
-hypotension [leading to a collapse in vessels]
-neutropenia followed by neutrophilia
-Disseminate intravascular coagulation [DIC] leads to organ wasting and multiple organ failure
Result: death

Front 15

What are CHEMOKINES?

Back 15

Small, chemoattractant polypeptides that amplify immune response by recruiting more phag. and immunocompetent cells to the site of infection

Front 16

What induces the ACUTE PHASE RESPONSE?

Back 16

cytokines IL-1, IL-6, TNF-aplha

Front 17

What are two of the acute phase proteins and what is their function?

Back 17

1. C REACTIVE PROTEIN: bind to phsophorylcholine on bacterial surfaces, acting as an opsonin and activate complement cascade by binding to C1q

2. MANNAN-BINDING LECTIN: bind to mannose on bacteria and acts as oposin activating complement by the lectin activation pathway [via C4 and C2]

Front 18

8 important things occur in the non-adaptive, early induced immunity. What are they?

....you can do it!

Back 18

1. Phagocytes release cytokines-->induce inflammatory response
2. Diapedesis of leukocytes from blood vessels-->infection
3. Release of TNF-alpha [double-edged sword b/c locally protective, systemically shock]
4. Release of chemokines-->rectruits more phagocytes to infection
5. Induction of acute phase response (IL-1, 6, TNF-alpha)
6. Production of interferon-alpha and interferon-beta [by virus infected cells]
7. Induction of natural killer cells
8. Induction of gamma, delta cell T cells-->important in early infection

Front 19

What cells are the major lymphoid population in epitheloid tissues and muscosa but only represent 1-5% of T cells in peripheral lymphoid organs?
Note: They are are restricted by MHC Class I molecules like CD-1...

Back 19

Gamma, delta T cells

Front 20

Who are the main players for adaptive immunity and when does it occur and why does it take so long to kick in?

Back 20

B lymph and T lymph

>96hrs

clonal expansion!

Front 21

What is the result of adaptive immunity?

Back 21

long lasting protection through induction of memory lymphocytes

Front 22

Who are the key players in humoral/adaptive mediated immunity?
where does it occur?
what cytokine induces this response?

Back 22

Ag. specific B cells and CD4 helper T cells TH2 type [and APC]
extracellular
induced by IL-4!

Front 23

Who are the key players in cell mediated immunity
where does it occur?
what cytokines induce it?

Back 23

CD4 inflammatory T cell [TH1]--releases IL-2, activating CD8 cytotoxic T cells
-intracellular
-induced by IL-12 and IFN gamma!

IL-12 activates NK cells-->NK cells make IFN-gamma-->activates TH1-->releases IL-2-->activates CD8!

Front 24

How are Tuberculoid leprosy and Lepromatous leprosy different?

Back 24

Tuberculoid leprosy: well controlled by TH1 cells that activate infected macs. Inflammation localized [dominant cytokines--IL2, interferon-gamma,TNF Beta]

Lepromatous leprosy: uncontrolled TH2 cells, thus leprosy widely disseminated and severe damage caused [dominant cytokines: IL4, 5, 10]

Front 25

What are cytokines released by each type of T-cell?

Back 25

TH1 (INFLAMMATORY)
-IL-2 (activates T CELL GROWTH-->including CD 8!)
-IL-3 (hematopoeisis--makes more LEUKOCYTES)
-IFN-GAMMA (enhances INFLAMMATION, activates phagocytes)
-TNF-ALPHA (enhances INFLAMMATION, increases vacular PERMEABILITY)

TH17 (INFLAMMATORY)
-IL-17 (Chemokines for NEUTROPHIL recruitment, activates IL-6, acute phase proteins, works w/IFN-GAMMA, TNF-ALPHA)

TH2 (Helper)
-IL-3 (hematopoeisis--makes more LEUKOCYTES)
-IL 4 (B cell ACTIVATION, IgM-->IgE isotype switch, SUPPRESSES TH1, TH17)
-IL-5 (B cell/eosinophil GROWTH)
-IL-10 (suppresses TH1 cytokines)
-TGF-BETA (suppresses TH1 cytokines)

Front 26

What ig shows up first during a primary infection [amount of ab and highest affinity]?

Back 26

IgM

Front 27

Which ig has the highest antibody amount and affinity in the secondary and tertiary infection?

Back 27

IgG [due to isotype switching]

Front 28

Which cell appears from 0-96hrs and is the 1st line defense against infection [bacteria, fungi, parasites]?

Back 28

Neutrophil

Front 29

What cell appears from 0-96hrs and also the first line of defense, but is involved in antigen presentation and is the link to adaptive immune response in pathogens?

Back 29

macrophages

Front 30

What cell is involved from 4-96hrs and is the first line of defense against VIRUSES

Back 30

Natural Killer

Front 31

A virus titer shows:
which cytokines are released in a burst as a result of infection?

These cytokines induce proliferation of what?

At the end of the titer [5 -10days], what cells are developing?

Back 31

IFN-gamma, TNK-alpha, IL-12

induce NK killing of infected cells [control virus replication and spread of infection]

effector CD8 T cells begin to develop after 5days

Front 32

What are the two mechanisms that extracellular bacteria cause disease?

Back 32

1. induce INFLAMMATION to destroy host tissue at the site of infection
2. produce TOXINS which have diverse pathological effects

Front 33

How do ENDOTOXINS differ from EXOTOXINS?

Back 33

ENDOTOXINS-a bacterial toxin found naturally inside pathogen. Not secreted but rather a structural component which is released when the bacteria is lysed
: ie bacterial cells wall like LPS

EXOTOXINS- soluble protein secreted by microorganisms. it is formed within the cell, but is released into the environment where it is rapidly active in extremely small amounts
ie] cholera toxin, teatnus toxin

Front 34

What are the cytokines released by phagocytes during the non-adaptive, early induced immunity?

Back 34

Phagocytes release:
IL-1, 6, 8, 12, TNF-alpha, CXCL8

Help induce inflammatory response and amplifies immune response.

Front 35

What is difference between cytokines and chemokines?

Back 35

cytokines--proteins made by cells that affect behavior of other cells. Can be released by lymphocytes or phagocytes.

chemokines--proteins released that guide WBC's to infection

Front 36

What factors determine whether an infection uses humoral vs. cell-mediated immunity?

Back 36

HUMORAL
--Induction of IL-4-->TH2 response!

CELL-MEDIATED
--Induction of dendritic cells-->IL-12-->activates NK cells-->NK cells make IFN-gamma-->TH1-->makes IL-2-->activates CD8 cells!